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The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression. )] TJ ET BT 26.250 628.449 Td /F1 9.8 Tf [(PLOS Currents Muscular Dystrophy. 2017 Jun 27 . Edition 1. doi: 10.1371/currents.md.d18deef7dac96ed135e0dc8739917b6e.)] TJ ET q 15.000 32.231 577.500 593.837 re W n 0.271 0.267 0.267 rg BT 26.250 599.346 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 579.392 Td /F1 9.8 Tf [(Duchenne muscular dystrophy \(DMD or Duchenne\) is a progressive, life-limiting muscle-wasting disease that requires )] TJ ET BT 26.250 567.487 Td /F1 9.8 Tf [(comprehensive, multidisciplinary care. This care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic, )] TJ ET BT 26.250 555.582 Td /F1 9.8 Tf [(endocrine and rehabilitative interventions that address both the primary and secondary manifestations of the disease. The care )] TJ ET BT 26.250 543.678 Td /F1 9.8 Tf [(needs of patients evolve over the cdourse of the disease and as they transition from childhood into young adulthood. In the past )] TJ ET BT 26.250 531.773 Td /F1 9.8 Tf [(two decades, life expectancy has increased significantly by the use of corticosteroids and enhanced clinical management. )] TJ ET BT 26.250 519.868 Td /F1 9.8 Tf [(Nevertheless, each year, patients with Duchenne muscular dystrophy are admitted to emergency departments and intensive )] TJ ET BT 26.250 507.963 Td /F1 9.8 Tf [(care units where medical expertise thrives, but where expertise in rare diseases, such as Duchenne, may not. Emergency care )] TJ ET BT 26.250 496.059 Td /F1 9.8 Tf [(for patients with Duchenne can be as complex as the disease process itself. While any illness or injury may occur in a person )] TJ ET BT 26.250 484.154 Td /F1 9.8 Tf [(with Duchenne, some acute scenarios are much more common in the context of the disease. Making decisions about the )] TJ ET BT 26.250 472.249 Td /F1 9.8 Tf [(clinical care of a person with Duchenne who presents with an acute illness can be quite difficult in part, because of the )] TJ ET BT 26.250 460.344 Td /F1 9.8 Tf [(extensive use of corticosteroids, which can lead to adrenal suppression. The life of a person with Duchenne needing emergency )] TJ ET BT 26.250 448.440 Td /F1 9.8 Tf [(care may therefore depend upon the ability of the clinician on duty in the emergency department to recognize and mitigate )] TJ ET BT 26.250 436.535 Td /F1 9.8 Tf [(adrenal suppression resulting from corticosteroid dependence. With this in mind, and drawing from expertise and experience )] TJ ET BT 26.250 424.630 Td /F1 9.8 Tf [(with other steroid-dependent diseases, the PJ Nicholoff Steroid Protocol was developed. The purpose of this protocol is to )] TJ ET BT 26.250 412.725 Td /F1 9.8 Tf [(provide clinicians information regarding the safe management of corticosteroid during emergency situations in patients who may )] TJ ET BT 26.250 400.821 Td /F1 9.8 Tf [(have accompanying adrenal suppression. The protocol explains how to recognize the signs and symptoms of acute adrenal )] TJ ET BT 26.250 388.916 Td /F1 9.8 Tf [(crisis, how to prevent it with supplemental stress doses of corticosteroids, and how to taper doses after emergency care in order )] TJ ET BT 26.250 377.011 Td /F1 9.8 Tf [(to prevent corticosteroid withdrawal.)] TJ ET BT 26.250 340.409 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 320.454 Td /F1 9.8 Tf [(The authors received no specific funding for this work.)] TJ ET BT 26.250 291.352 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 271.398 Td /F1 9.8 Tf [(Duchenne Muscular Dystrophy \(DMD\) is the most common and severe muscle disease presenting in childhood. It is caused by )] TJ ET BT 26.250 259.493 Td /F1 9.8 Tf [(mutations in the dystrophin gene, located on the X chromosome, which causes a complete absence of dystrophin protein in )] TJ ET BT 26.250 247.588 Td /F1 9.8 Tf [(muscle. Becker Muscular Dystrophy \(BMD\) is caused by partial absence of dystrophin; this disease is less severe and less )] TJ ET BT 26.250 235.683 Td /F1 9.8 Tf [(common. As an X-linked disease, both diseases almost always affect males, though some females may be affected as well. )] TJ ET BT 26.250 223.779 Td /F1 9.8 Tf [(Duchenne and Becker have a prevalence of 1 in 5000 males, in about a 2:1 ratio.)] TJ ET 0.267 0.267 0.267 rg BT 376.363 225.286 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 381.181 227.667 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 383.591 225.286 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 204.374 Td /F1 9.8 Tf [(People with Duchenne Muscular Dystrophy have progressive muscle weakness, which generally begins proximally and spreads )] TJ ET BT 26.250 192.469 Td /F1 9.8 Tf [(to the legs, arms and other muscles. It is now known from a newborn screening study that the onset of disease is at birth, and )] TJ ET BT 26.250 180.564 Td /F1 9.8 Tf [(probably )] TJ ET BT 66.352 180.564 Td /F5 9.8 Tf [(in utero)] TJ ET BT 98.868 180.564 Td /F1 9.8 Tf [(.)] TJ ET 0.267 0.267 0.267 rg BT 101.578 182.072 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 106.397 180.564 Td /F1 9.8 Tf [( Boys with Duchenne are born with serum creatine kinase \(CK\) values over 2000 UL-1. The diagnosis is )] TJ ET BT 26.250 168.660 Td /F1 9.8 Tf [(typically made between 3 and 5 years of age. Progressive muscle weakness leads to the loss of ambulation at 10 to 12 years )] TJ ET BT 26.250 156.755 Td /F1 9.8 Tf [(old without treatment, though ambulation can be extended by one or two years through the use of corticosteroids. There is )] TJ ET BT 26.250 144.850 Td /F1 9.8 Tf [(progressive respiratory muscle weakness, which leads to hypoventilation, respiratory insufficiency, and respiratory failure in )] TJ ET BT 26.250 132.945 Td /F1 9.8 Tf [(adulthood. There is also a progressive cardiomyopathy leading to cardiac insufficiency. Prior to the use of corticosteroids, )] TJ ET BT 26.250 121.041 Td /F1 9.8 Tf [(assisted ventilation and other interventions, the median life expectancy was age 19; however, today most deaths are due to )] TJ ET BT 26.250 109.136 Td /F1 9.8 Tf [(heart disease and heart failure, and typically occur in the mid-20s, though survival into the 30s is no longer uncommon. )] TJ ET 0.267 0.267 0.267 rg BT 541.069 110.643 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 545.888 113.024 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 548.298 110.643 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 26.250 89.731 Td /F1 9.8 Tf [(In the late 1980s, it was established that corticosteroids could improve and prolong ambulation and slow the rate of decline in )] TJ ET BT 26.250 77.826 Td /F1 9.8 Tf [(both Duchenne and Becker.)] TJ ET 0.267 0.267 0.267 rg BT 147.111 79.334 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 151.930 77.826 Td /F1 9.8 Tf [( The use of corticosteroids has also reduced the incidence and severity of scoliosis. However, )] TJ ET BT 26.250 65.922 Td /F1 9.8 Tf [(chronic use of corticosteroids is associated with significant side effects that require monitoring and treatment.)] TJ ET BT 26.250 46.517 Td /F1 9.8 Tf [(International consensus recommendations on the comprehensive care for people living with Duchenne were published in Lancet )] TJ ET Q q 15.000 684.354 577.500 53.646 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(The PJ Nicholoff Steroid Protocol for Duchenne and Becker )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(Muscular Dystrophy and Adrenal Suppression)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(June 27, 2017)] TJ ET BT 74.846 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 79.721 675.088 Td /F3 9.8 Tf [(Advanced Diagnostics and Biomarkers)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Kathi Kinnett)] TJ ET 0.271 0.267 0.267 rg BT 81.532 667.135 Td /F1 8.7 Tf [(1)] TJ ET BT 86.351 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 91.772 663.247 Td /F1 9.8 Tf [(Garey Noritz)] TJ ET 0.271 0.267 0.267 rg BT 26.250 652.075 Td /F4 9.0 Tf [(1)] TJ ET BT 31.254 652.075 Td /F1 9.0 Tf [( Parent Project Muscular Dystrophy, Hackensack, New Jersey, USA)] TJ ET BT 26.250 640.353 Td /F1 9.8 Tf [(Kinnett K, Noritz G. The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression. )] TJ ET BT 26.250 628.449 Td /F1 9.8 Tf [(PLOS Currents Muscular Dystrophy. 2017 Jun 27 . Edition 1. doi: 10.1371/currents.md.d18deef7dac96ed135e0dc8739917b6e.)] TJ ET q 15.000 32.231 577.500 593.837 re W n 0.271 0.267 0.267 rg BT 26.250 599.346 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 579.392 Td /F1 9.8 Tf [(Duchenne muscular dystrophy \(DMD or Duchenne\) is a progressive, life-limiting muscle-wasting disease that requires )] TJ ET BT 26.250 567.487 Td /F1 9.8 Tf [(comprehensive, multidisciplinary care. This care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic, )] TJ ET BT 26.250 555.582 Td /F1 9.8 Tf [(endocrine and rehabilitative interventions that address both the primary and secondary manifestations of the disease. The care )] TJ ET BT 26.250 543.678 Td /F1 9.8 Tf [(needs of patients evolve over the cdourse of the disease and as they transition from childhood into young adulthood. In the past )] TJ ET BT 26.250 531.773 Td /F1 9.8 Tf [(two decades, life expectancy has increased significantly by the use of corticosteroids and enhanced clinical management. )] TJ ET BT 26.250 519.868 Td /F1 9.8 Tf [(Nevertheless, each year, patients with Duchenne muscular dystrophy are admitted to emergency departments and intensive )] TJ ET BT 26.250 507.963 Td /F1 9.8 Tf [(care units where medical expertise thrives, but where expertise in rare diseases, such as Duchenne, may not. Emergency care )] TJ ET BT 26.250 496.059 Td /F1 9.8 Tf [(for patients with Duchenne can be as complex as the disease process itself. While any illness or injury may occur in a person )] TJ ET BT 26.250 484.154 Td /F1 9.8 Tf [(with Duchenne, some acute scenarios are much more common in the context of the disease. Making decisions about the )] TJ ET BT 26.250 472.249 Td /F1 9.8 Tf [(clinical care of a person with Duchenne who presents with an acute illness can be quite difficult in part, because of the )] TJ ET BT 26.250 460.344 Td /F1 9.8 Tf [(extensive use of corticosteroids, which can lead to adrenal suppression. The life of a person with Duchenne needing emergency )] TJ ET BT 26.250 448.440 Td /F1 9.8 Tf [(care may therefore depend upon the ability of the clinician on duty in the emergency department to recognize and mitigate )] TJ ET BT 26.250 436.535 Td /F1 9.8 Tf [(adrenal suppression resulting from corticosteroid dependence. With this in mind, and drawing from expertise and experience )] TJ ET BT 26.250 424.630 Td /F1 9.8 Tf [(with other steroid-dependent diseases, the PJ Nicholoff Steroid Protocol was developed. The purpose of this protocol is to )] TJ ET BT 26.250 412.725 Td /F1 9.8 Tf [(provide clinicians information regarding the safe management of corticosteroid during emergency situations in patients who may )] TJ ET BT 26.250 400.821 Td /F1 9.8 Tf [(have accompanying adrenal suppression. The protocol explains how to recognize the signs and symptoms of acute adrenal )] TJ ET BT 26.250 388.916 Td /F1 9.8 Tf [(crisis, how to prevent it with supplemental stress doses of corticosteroids, and how to taper doses after emergency care in order )] TJ ET BT 26.250 377.011 Td /F1 9.8 Tf [(to prevent corticosteroid withdrawal.)] TJ ET BT 26.250 340.409 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 320.454 Td /F1 9.8 Tf [(The authors received no specific funding for this work.)] TJ ET BT 26.250 291.352 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 271.398 Td /F1 9.8 Tf [(Duchenne Muscular Dystrophy \(DMD\) is the most common and severe muscle disease presenting in childhood. It is caused by )] TJ ET BT 26.250 259.493 Td /F1 9.8 Tf [(mutations in the dystrophin gene, located on the X chromosome, which causes a complete absence of dystrophin protein in )] TJ ET BT 26.250 247.588 Td /F1 9.8 Tf [(muscle. Becker Muscular Dystrophy \(BMD\) is caused by partial absence of dystrophin; this disease is less severe and less )] TJ ET BT 26.250 235.683 Td /F1 9.8 Tf [(common. As an X-linked disease, both diseases almost always affect males, though some females may be affected as well. )] TJ ET BT 26.250 223.779 Td /F1 9.8 Tf [(Duchenne and Becker have a prevalence of 1 in 5000 males, in about a 2:1 ratio.)] TJ ET 0.267 0.267 0.267 rg BT 376.363 225.286 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 381.181 227.667 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 383.591 225.286 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 204.374 Td /F1 9.8 Tf [(People with Duchenne Muscular Dystrophy have progressive muscle weakness, which generally begins proximally and spreads )] TJ ET BT 26.250 192.469 Td /F1 9.8 Tf [(to the legs, arms and other muscles. It is now known from a newborn screening study that the onset of disease is at birth, and )] TJ ET BT 26.250 180.564 Td /F1 9.8 Tf [(probably )] TJ ET BT 66.352 180.564 Td /F5 9.8 Tf [(in utero)] TJ ET BT 98.868 180.564 Td /F1 9.8 Tf [(.)] TJ ET 0.267 0.267 0.267 rg BT 101.578 182.072 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 106.397 180.564 Td /F1 9.8 Tf [( Boys with Duchenne are born with serum creatine kinase \(CK\) values over 2000 UL-1. The diagnosis is )] TJ ET BT 26.250 168.660 Td /F1 9.8 Tf [(typically made between 3 and 5 years of age. Progressive muscle weakness leads to the loss of ambulation at 10 to 12 years )] TJ ET BT 26.250 156.755 Td /F1 9.8 Tf [(old without treatment, though ambulation can be extended by one or two years through the use of corticosteroids. There is )] TJ ET BT 26.250 144.850 Td /F1 9.8 Tf [(progressive respiratory muscle weakness, which leads to hypoventilation, respiratory insufficiency, and respiratory failure in )] TJ ET BT 26.250 132.945 Td /F1 9.8 Tf [(adulthood. There is also a progressive cardiomyopathy leading to cardiac insufficiency. Prior to the use of corticosteroids, )] TJ ET BT 26.250 121.041 Td /F1 9.8 Tf [(assisted ventilation and other interventions, the median life expectancy was age 19; however, today most deaths are due to )] TJ ET BT 26.250 109.136 Td /F1 9.8 Tf [(heart disease and heart failure, and typically occur in the mid-20s, though survival into the 30s is no longer uncommon. )] TJ ET 0.267 0.267 0.267 rg BT 541.069 110.643 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 545.888 113.024 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 548.298 110.643 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 26.250 89.731 Td /F1 9.8 Tf [(In the late 1980s, it was established that corticosteroids could improve and prolong ambulation and slow the rate of decline in )] TJ ET BT 26.250 77.826 Td /F1 9.8 Tf [(both Duchenne and Becker.)] TJ ET 0.267 0.267 0.267 rg BT 147.111 79.334 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 151.930 77.826 Td /F1 9.8 Tf [( The use of corticosteroids has also reduced the incidence and severity of scoliosis. However, )] TJ ET BT 26.250 65.922 Td /F1 9.8 Tf [(chronic use of corticosteroids is associated with significant side effects that require monitoring and treatment.)] TJ ET BT 26.250 46.517 Td /F1 9.8 Tf [(International consensus recommendations on the comprehensive care for people living with Duchenne were published in Lancet )] TJ ET Q q 15.000 684.354 577.500 53.646 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(The PJ Nicholoff Steroid Protocol for Duchenne and Becker )] TJ ET BT 15.000 693.094 Td /F2 21.0 Tf [(Muscular Dystrophy and Adrenal Suppression)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 675.088 Td /F3 9.8 Tf [(June 27, 2017)] TJ ET BT 74.846 675.088 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 79.721 675.088 Td /F3 9.8 Tf [(Advanced Diagnostics and Biomarkers)] TJ ET BT 26.250 663.247 Td /F1 9.8 Tf [(Kathi Kinnett)] TJ ET 0.271 0.267 0.267 rg BT 81.532 667.135 Td /F1 8.7 Tf [(1)] TJ ET BT 86.351 663.247 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 91.772 663.247 Td /F1 9.8 Tf [(Garey Noritz)] TJ ET 0.271 0.267 0.267 rg BT 26.250 652.075 Td /F4 9.0 Tf [(1)] TJ ET BT 31.254 652.075 Td /F1 9.0 Tf [( Parent Project Muscular Dystrophy, Hackensack, New Jersey, USA)] TJ ET BT 26.250 640.353 Td /F1 9.8 Tf [(Kinnett K, Noritz G. The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression. )] TJ ET BT 26.250 628.449 Td /F1 9.8 Tf [(PLOS Currents Muscular Dystrophy. 2017 Jun 27 . Edition 1. doi: 10.1371/currents.md.d18deef7dac96ed135e0dc8739917b6e.)] TJ ET q 15.000 32.231 577.500 593.837 re W n 0.271 0.267 0.267 rg BT 26.250 599.346 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 579.392 Td /F1 9.8 Tf [(Duchenne muscular dystrophy \(DMD or Duchenne\) is a progressive, life-limiting muscle-wasting disease that requires )] TJ ET BT 26.250 567.487 Td /F1 9.8 Tf [(comprehensive, multidisciplinary care. This care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic, )] TJ ET BT 26.250 555.582 Td /F1 9.8 Tf [(endocrine and rehabilitative interventions that address both the primary and secondary manifestations of the disease. The care )] TJ ET BT 26.250 543.678 Td /F1 9.8 Tf [(needs of patients evolve over the cdourse of the disease and as they transition from childhood into young adulthood. In the past )] TJ ET BT 26.250 531.773 Td /F1 9.8 Tf [(two decades, life expectancy has increased significantly by the use of corticosteroids and enhanced clinical management. )] TJ ET BT 26.250 519.868 Td /F1 9.8 Tf [(Nevertheless, each year, patients with Duchenne muscular dystrophy are admitted to emergency departments and intensive )] TJ ET BT 26.250 507.963 Td /F1 9.8 Tf [(care units where medical expertise thrives, but where expertise in rare diseases, such as Duchenne, may not. Emergency care )] TJ ET BT 26.250 496.059 Td /F1 9.8 Tf [(for patients with Duchenne can be as complex as the disease process itself. While any illness or injury may occur in a person )] TJ ET BT 26.250 484.154 Td /F1 9.8 Tf [(with Duchenne, some acute scenarios are much more common in the context of the disease. Making decisions about the )] TJ ET BT 26.250 472.249 Td /F1 9.8 Tf [(clinical care of a person with Duchenne who presents with an acute illness can be quite difficult in part, because of the )] TJ ET BT 26.250 460.344 Td /F1 9.8 Tf [(extensive use of corticosteroids, which can lead to adrenal suppression. The life of a person with Duchenne needing emergency )] TJ ET BT 26.250 448.440 Td /F1 9.8 Tf [(care may therefore depend upon the ability of the clinician on duty in the emergency department to recognize and mitigate )] TJ ET BT 26.250 436.535 Td /F1 9.8 Tf [(adrenal suppression resulting from corticosteroid dependence. With this in mind, and drawing from expertise and experience )] TJ ET BT 26.250 424.630 Td /F1 9.8 Tf [(with other steroid-dependent diseases, the PJ Nicholoff Steroid Protocol was developed. The purpose of this protocol is to )] TJ ET BT 26.250 412.725 Td /F1 9.8 Tf [(provide clinicians information regarding the safe management of corticosteroid during emergency situations in patients who may )] TJ ET BT 26.250 400.821 Td /F1 9.8 Tf [(have accompanying adrenal suppression. The protocol explains how to recognize the signs and symptoms of acute adrenal )] TJ ET BT 26.250 388.916 Td /F1 9.8 Tf [(crisis, how to prevent it with supplemental stress doses of corticosteroids, and how to taper doses after emergency care in order )] TJ ET BT 26.250 377.011 Td /F1 9.8 Tf [(to prevent corticosteroid withdrawal.)] TJ ET BT 26.250 340.409 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 320.454 Td /F1 9.8 Tf [(The authors received no specific funding for this work.)] TJ ET BT 26.250 291.352 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 271.398 Td /F1 9.8 Tf [(Duchenne Muscular Dystrophy \(DMD\) is the most common and severe muscle disease presenting in childhood. It is caused by )] TJ ET BT 26.250 259.493 Td /F1 9.8 Tf [(mutations in the dystrophin gene, located on the X chromosome, which causes a complete absence of dystrophin protein in )] TJ ET BT 26.250 247.588 Td /F1 9.8 Tf [(muscle. Becker Muscular Dystrophy \(BMD\) is caused by partial absence of dystrophin; this disease is less severe and less )] TJ ET BT 26.250 235.683 Td /F1 9.8 Tf [(common. As an X-linked disease, both diseases almost always affect males, though some females may be affected as well. )] TJ ET BT 26.250 223.779 Td /F1 9.8 Tf [(Duchenne and Becker have a prevalence of 1 in 5000 males, in about a 2:1 ratio.)] TJ ET 0.267 0.267 0.267 rg BT 376.363 225.286 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 381.181 227.667 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 383.591 225.286 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 204.374 Td /F1 9.8 Tf [(People with Duchenne Muscular Dystrophy have progressive muscle weakness, which generally begins proximally and spreads )] TJ ET BT 26.250 192.469 Td /F1 9.8 Tf [(to the legs, arms and other muscles. It is now known from a newborn screening study that the onset of disease is at birth, and )] TJ ET BT 26.250 180.564 Td /F1 9.8 Tf [(probably )] TJ ET BT 66.352 180.564 Td /F5 9.8 Tf [(in utero)] TJ ET BT 98.868 180.564 Td /F1 9.8 Tf [(.)] TJ ET 0.267 0.267 0.267 rg BT 101.578 182.072 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 106.397 180.564 Td /F1 9.8 Tf [( Boys with Duchenne are born with serum creatine kinase \(CK\) values over 2000 UL-1. The diagnosis is )] TJ ET BT 26.250 168.660 Td /F1 9.8 Tf [(typically made between 3 and 5 years of age. Progressive muscle weakness leads to the loss of ambulation at 10 to 12 years )] TJ ET BT 26.250 156.755 Td /F1 9.8 Tf [(old without treatment, though ambulation can be extended by one or two years through the use of corticosteroids. There is )] TJ ET BT 26.250 144.850 Td /F1 9.8 Tf [(progressive respiratory muscle weakness, which leads to hypoventilation, respiratory insufficiency, and respiratory failure in )] TJ ET BT 26.250 132.945 Td /F1 9.8 Tf [(adulthood. There is also a progressive cardiomyopathy leading to cardiac insufficiency. Prior to the use of corticosteroids, )] TJ ET BT 26.250 121.041 Td /F1 9.8 Tf [(assisted ventilation and other interventions, the median life expectancy was age 19; however, today most deaths are due to )] TJ ET BT 26.250 109.136 Td /F1 9.8 Tf [(heart disease and heart failure, and typically occur in the mid-20s, though survival into the 30s is no longer uncommon. )] TJ ET 0.267 0.267 0.267 rg BT 541.069 110.643 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 545.888 113.024 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 548.298 110.643 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 26.250 89.731 Td /F1 9.8 Tf [(In the late 1980s, it was established that corticosteroids could improve and prolong ambulation and slow the rate of decline in )] TJ ET BT 26.250 77.826 Td /F1 9.8 Tf [(both Duchenne and Becker.)] TJ ET 0.267 0.267 0.267 rg BT 147.111 79.334 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 151.930 77.826 Td /F1 9.8 Tf [( The use of corticosteroids has also reduced the incidence and severity of scoliosis. 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/Length 35460 >> stream 0.271 0.267 0.267 rg q 15.000 29.798 577.500 747.202 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Neurology in 2010. )] TJ ET 0.267 0.267 0.267 rg BT 110.792 768.983 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 115.611 771.364 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 118.020 768.983 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 122.839 767.476 Td /F1 9.8 Tf [( A summary listing the key elements of Duchenne care was published in this journal in 2015.)] TJ ET 0.267 0.267 0.267 rg BT 520.590 768.983 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 26.250 748.071 Td /F1 9.8 Tf [(Given the multi-systemic nature of the disease, there should generally be an interdisciplinary team of care providers with whom )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(to consult, including, at minimum, a coordinator, neurologist, doctor of physical medicine and rehabilitation, pulmonologist, )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(cardiologist, social worker, dietician and primary care doctor. However, one issue in the management of Duchenne is that due to )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(increased life expectancy, patients at some point need to transition out of pediatric care and on to adult care teams. Although )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(the transition into adult care should be a process, clinicians in the emergency department should be aware that it is sometimes )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(delayed or incomplete and may in fact be triggered by the very acute illness or clinical event that brings them to the )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(emergency room \(ER\).)] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(While any illness or trauma may occur in a person with Duchenne or Becker, certain clinical scenarios are more common. )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(These include exacerbations of the underlying respiratory or cardiac disease; kidney stones; and fractures as a result of low )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(bone mineral density. Patients with Duchenne also seem to be prone to a particularly devastating consequence of fracture, fat )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(embolism syndrome.)] TJ ET 0.267 0.267 0.267 rg BT 116.184 623.031 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 121.003 625.412 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 123.412 623.031 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 133.049 621.524 Td /F1 9.8 Tf [( Each medical crisis needs to be evaluated and responded to in the context of the expected )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(complications of the disease or medications used for disease management particularly the chronic use of corticosteroids, )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(which can lead to suppression of the hypothalamus-pituitary-adrenal axis \(HPA\).)] TJ ET BT 26.250 578.310 Td /F1 9.8 Tf [(One danger is that, as pressing medical emergencies emerge, issues of daily medical care \(including medications\) may be )] TJ ET BT 26.250 566.405 Td /F1 9.8 Tf [(pushed aside. However, the consequences of suddenly discontinuing or not appropriately dosing corticosteroids, particularly )] TJ ET BT 26.250 554.500 Td /F1 9.8 Tf [(during a crisis can be quite severe, as the patient may have little to no ability to produce cortisol in response to stress. An )] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(additional issue for emergency departments is that many patients with Duchenne or Becker use Deflazacort, a corticosteroid )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(that was recently approved in the United States but may be unfamiliar to doctors.)] TJ ET BT 26.250 511.286 Td /F1 9.8 Tf [(A recent case in point involved Phillip James PJ Nicholoff, a vibrant, 31-year-old man living with Duchenne muscular )] TJ ET BT 26.250 499.381 Td /F1 9.8 Tf [(dystrophy. PJ had been treated with daily corticosteroids since the age of 6. He endured several pathologic fractures, likely a )] TJ ET BT 26.250 487.476 Td /F1 9.8 Tf [(result of his steroid treatment and his non-ambulatory status. In November 2013, on a trip to Florida, he fractured his humerus )] TJ ET BT 26.250 475.572 Td /F1 9.8 Tf [(and hip, and was transported by plane to a hospital closer to his home in the north. PJ had orthopedic surgery to manage both )] TJ ET BT 26.250 463.667 Td /F1 9.8 Tf [(of these fractures. Following the surgery, however, he developed respiratory distress, tachycardia, hypotension, and later died. )] TJ ET BT 26.250 451.762 Td /F1 9.8 Tf [(A review of the medical record suggested that he had not received appropriate stress-doses of steroids during his )] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(hospitalization. While PJs death may have been attributed to many causes, inadequate corticosteroid doses may have been a )] TJ ET BT 26.250 427.953 Td /F1 9.8 Tf [(contributing factor.. Consequently, experts in the field held extensive discussions in order to develop a protocol on steroid )] TJ ET BT 26.250 416.048 Td /F1 9.8 Tf [(dosing during an acute illness or other emergency.)] TJ ET BT 26.250 396.643 Td /F1 9.8 Tf [(The protocol addresses several issues:)] TJ ET 0.271 0.267 0.267 RG 40.337 380.206 m 40.337 380.653 40.154 381.097 39.838 381.413 c 39.522 381.728 39.078 381.912 38.631 381.912 c 38.185 381.912 37.741 381.728 37.425 381.413 c 37.109 381.097 36.925 380.653 36.925 380.206 c 36.925 379.759 37.109 379.315 37.425 378.999 c 37.741 378.684 38.185 378.500 38.631 378.500 c 39.078 378.500 39.522 378.684 39.838 378.999 c 40.154 379.315 40.337 379.759 40.337 380.206 c f BT 45.750 377.238 Td /F1 9.8 Tf [(How to define HPA suppression in a patient using corticosteroids)] TJ ET 40.337 364.551 m 40.337 364.998 40.154 365.442 39.838 365.758 c 39.522 366.074 39.078 366.258 38.631 366.258 c 38.185 366.258 37.741 366.074 37.425 365.758 c 37.109 365.442 36.925 364.998 36.925 364.551 c 36.925 364.105 37.109 363.661 37.425 363.345 c 37.741 363.029 38.185 362.845 38.631 362.845 c 39.078 362.845 39.522 363.029 39.838 363.345 c 40.154 363.661 40.337 364.105 40.337 364.551 c f BT 45.750 361.584 Td /F1 9.8 Tf [(Appropriate corticosteroid stress doses for minor, moderate, and major stressors)] TJ ET 40.337 348.897 m 40.337 349.343 40.154 349.787 39.838 350.103 c 39.522 350.419 39.078 350.603 38.631 350.603 c 38.185 350.603 37.741 350.419 37.425 350.103 c 37.109 349.787 36.925 349.343 36.925 348.897 c 36.925 348.450 37.109 348.006 37.425 347.690 c 37.741 347.374 38.185 347.190 38.631 347.190 c 39.078 347.190 39.522 347.374 39.838 347.690 c 40.154 348.006 40.337 348.450 40.337 348.897 c f BT 45.750 345.929 Td /F1 9.8 Tf [(Recommendations for corticosteroid withdrawal)] TJ ET 40.337 333.242 m 40.337 333.688 40.154 334.132 39.838 334.448 c 39.522 334.764 39.078 334.948 38.631 334.948 c 38.185 334.948 37.741 334.764 37.425 334.448 c 37.109 334.132 36.925 333.688 36.925 333.242 c 36.925 332.795 37.109 332.351 37.425 332.035 c 37.741 331.719 38.185 331.536 38.631 331.536 c 39.078 331.536 39.522 331.719 39.838 332.035 c 40.154 332.351 40.337 332.795 40.337 333.242 c f BT 45.750 330.274 Td /F1 9.8 Tf [(How to test the HPA axis for continued suppression)] TJ ET 40.337 317.587 m 40.337 318.034 40.154 318.478 39.838 318.794 c 39.522 319.109 39.078 319.293 38.631 319.293 c 38.185 319.293 37.741 319.109 37.425 318.794 c 37.109 318.478 36.925 318.034 36.925 317.587 c 36.925 317.140 37.109 316.696 37.425 316.380 c 37.741 316.065 38.185 315.881 38.631 315.881 c 39.078 315.881 39.522 316.065 39.838 316.380 c 40.154 316.696 40.337 317.140 40.337 317.587 c f BT 45.750 314.619 Td /F1 9.8 Tf [(Symptoms of acute adrenal crisis)] TJ ET 40.337 301.932 m 40.337 302.379 40.154 302.823 39.838 303.139 c 39.522 303.455 39.078 303.639 38.631 303.639 c 38.185 303.639 37.741 303.455 37.425 303.139 c 37.109 302.823 36.925 302.379 36.925 301.932 c 36.925 301.486 37.109 301.042 37.425 300.726 c 37.741 300.410 38.185 300.226 38.631 300.226 c 39.078 300.226 39.522 300.410 39.838 300.726 c 40.154 301.042 40.337 301.486 40.337 301.932 c f BT 45.750 298.965 Td /F1 9.8 Tf [(Tests that can help diagnose adrenal crisis)] TJ ET 40.337 286.278 m 40.337 286.724 40.154 287.168 39.838 287.484 c 39.522 287.800 39.078 287.984 38.631 287.984 c 38.185 287.984 37.741 287.800 37.425 287.484 c 37.109 287.168 36.925 286.724 36.925 286.278 c 36.925 285.831 37.109 285.387 37.425 285.071 c 37.741 284.755 38.185 284.571 38.631 284.571 c 39.078 284.571 39.522 284.755 39.838 285.071 c 40.154 285.387 40.337 285.831 40.337 286.278 c f BT 45.750 283.310 Td /F1 9.8 Tf [(Corticosteroid conversions/equivalent doses)] TJ ET BT 26.250 260.155 Td /F4 9.8 Tf [(The PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 240.750 Td /F4 9.8 Tf [(1. Background/Assessment)] TJ ET BT 26.250 221.346 Td /F1 9.8 Tf [(The normal basal secretion of cortisol from the adrenal gland is approximately 5-7 mg/m2/day in children or 8 -10 mg/day for )] TJ ET BT 26.250 209.441 Td /F1 9.8 Tf [(adults.)] TJ ET 0.267 0.267 0.267 rg BT 54.974 210.948 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 64.611 213.329 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.020 210.948 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 76.658 209.441 Td /F1 9.8 Tf [( This amount increases during minor illnesses or surgery to approximately 50 mg/day \(5x normal physiologic )] TJ ET BT 26.250 197.536 Td /F1 9.8 Tf [(secretion\), and typically return to baseline in 24 hours. Severe illness, trauma, or major surgical procedures cause increased )] TJ ET BT 26.250 185.631 Td /F1 9.8 Tf [(cortisol production to about 75-150 mg/day \(10x normal physiologic secretion\), which return to baseline in about 5 days.)] TJ ET 0.267 0.267 0.267 rg BT 541.606 187.139 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 551.243 189.520 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 553.652 187.139 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 166.227 Td /F1 9.8 Tf [(Long-term administration of corticosteroids \(primarily prednisone, prednisolone or deflazacort\) may lead to suppression of the )] TJ ET BT 26.250 154.322 Td /F1 9.8 Tf [(hypothalamic-pituitary-adrenal \(HPA\) axis, such that the adrenal glands no longer produce endogenous cortisol. Rapid )] TJ ET BT 26.250 142.417 Td /F1 9.8 Tf [(reduction or abrupt withdrawal of corticosteroid therapy can cause secondary adrenal insufficiency and steroid withdrawal or )] TJ ET BT 26.250 130.512 Td /F1 9.8 Tf [(deprivation syndrome, which may progress to adrenal crisis. Adrenal crisis is characterized by hypotension and hypovolemic )] TJ ET BT 26.250 118.608 Td /F1 9.8 Tf [(shock, which may be life threatening.)] TJ ET 0.267 0.267 0.267 rg BT 186.111 120.115 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 195.748 118.608 Td /F1 9.8 Tf [( Recovery from suppression of the HPA axis after discontinuing corticosteroids can be )] TJ ET BT 26.250 106.703 Td /F1 9.8 Tf [(prolonged \(possibly 6 to 12 months\) and may vary based on doses, dosing schedules and duration of corticosteroid therapy.)] TJ ET 0.267 0.267 0.267 rg BT 561.135 108.210 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 94.798 Td /F1 9.8 Tf [(Since there is a great deal of individual variability, it is not possible to predict with confidence which patients will be affected by )] TJ ET BT 26.250 82.893 Td /F1 9.8 Tf [(adrenal suppression. Current practice is to administer supplemental \(stress\) doses of corticosteroids to patients with possible )] TJ ET BT 26.250 70.989 Td /F1 9.8 Tf [(suppression of the HPA axis in the perioperative period and during acute illness to prevent acute adrenal insufficiency, or )] TJ ET BT 26.250 59.084 Td /F1 9.8 Tf [(adrenal crisis.)] TJ ET Q q 15.000 29.798 577.500 747.202 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Neurology in 2010. )] TJ ET 0.267 0.267 0.267 rg BT 110.792 768.983 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 115.611 771.364 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 118.020 768.983 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 122.839 767.476 Td /F1 9.8 Tf [( A summary listing the key elements of Duchenne care was published in this journal in 2015.)] TJ ET 0.267 0.267 0.267 rg BT 520.590 768.983 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 26.250 748.071 Td /F1 9.8 Tf [(Given the multi-systemic nature of the disease, there should generally be an interdisciplinary team of care providers with whom )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(to consult, including, at minimum, a coordinator, neurologist, doctor of physical medicine and rehabilitation, pulmonologist, )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(cardiologist, social worker, dietician and primary care doctor. However, one issue in the management of Duchenne is that due to )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(increased life expectancy, patients at some point need to transition out of pediatric care and on to adult care teams. Although )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(the transition into adult care should be a process, clinicians in the emergency department should be aware that it is sometimes )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(delayed or incomplete and may in fact be triggered by the very acute illness or clinical event that brings them to the )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(emergency room \(ER\).)] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(While any illness or trauma may occur in a person with Duchenne or Becker, certain clinical scenarios are more common. )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(These include exacerbations of the underlying respiratory or cardiac disease; kidney stones; and fractures as a result of low )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(bone mineral density. Patients with Duchenne also seem to be prone to a particularly devastating consequence of fracture, fat )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(embolism syndrome.)] TJ ET 0.267 0.267 0.267 rg BT 116.184 623.031 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 121.003 625.412 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 123.412 623.031 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 133.049 621.524 Td /F1 9.8 Tf [( Each medical crisis needs to be evaluated and responded to in the context of the expected )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(complications of the disease or medications used for disease management particularly the chronic use of corticosteroids, )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(which can lead to suppression of the hypothalamus-pituitary-adrenal axis \(HPA\).)] TJ ET BT 26.250 578.310 Td /F1 9.8 Tf [(One danger is that, as pressing medical emergencies emerge, issues of daily medical care \(including medications\) may be )] TJ ET BT 26.250 566.405 Td /F1 9.8 Tf [(pushed aside. However, the consequences of suddenly discontinuing or not appropriately dosing corticosteroids, particularly )] TJ ET BT 26.250 554.500 Td /F1 9.8 Tf [(during a crisis can be quite severe, as the patient may have little to no ability to produce cortisol in response to stress. An )] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(additional issue for emergency departments is that many patients with Duchenne or Becker use Deflazacort, a corticosteroid )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(that was recently approved in the United States but may be unfamiliar to doctors.)] TJ ET BT 26.250 511.286 Td /F1 9.8 Tf [(A recent case in point involved Phillip James PJ Nicholoff, a vibrant, 31-year-old man living with Duchenne muscular )] TJ ET BT 26.250 499.381 Td /F1 9.8 Tf [(dystrophy. PJ had been treated with daily corticosteroids since the age of 6. He endured several pathologic fractures, likely a )] TJ ET BT 26.250 487.476 Td /F1 9.8 Tf [(result of his steroid treatment and his non-ambulatory status. In November 2013, on a trip to Florida, he fractured his humerus )] TJ ET BT 26.250 475.572 Td /F1 9.8 Tf [(and hip, and was transported by plane to a hospital closer to his home in the north. PJ had orthopedic surgery to manage both )] TJ ET BT 26.250 463.667 Td /F1 9.8 Tf [(of these fractures. Following the surgery, however, he developed respiratory distress, tachycardia, hypotension, and later died. )] TJ ET BT 26.250 451.762 Td /F1 9.8 Tf [(A review of the medical record suggested that he had not received appropriate stress-doses of steroids during his )] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(hospitalization. While PJs death may have been attributed to many causes, inadequate corticosteroid doses may have been a )] TJ ET BT 26.250 427.953 Td /F1 9.8 Tf [(contributing factor.. Consequently, experts in the field held extensive discussions in order to develop a protocol on steroid )] TJ ET BT 26.250 416.048 Td /F1 9.8 Tf [(dosing during an acute illness or other emergency.)] TJ ET BT 26.250 396.643 Td /F1 9.8 Tf [(The protocol addresses several issues:)] TJ ET 0.271 0.267 0.267 RG 40.337 380.206 m 40.337 380.653 40.154 381.097 39.838 381.413 c 39.522 381.728 39.078 381.912 38.631 381.912 c 38.185 381.912 37.741 381.728 37.425 381.413 c 37.109 381.097 36.925 380.653 36.925 380.206 c 36.925 379.759 37.109 379.315 37.425 378.999 c 37.741 378.684 38.185 378.500 38.631 378.500 c 39.078 378.500 39.522 378.684 39.838 378.999 c 40.154 379.315 40.337 379.759 40.337 380.206 c f BT 45.750 377.238 Td /F1 9.8 Tf [(How to define HPA suppression in a patient using corticosteroids)] TJ ET 40.337 364.551 m 40.337 364.998 40.154 365.442 39.838 365.758 c 39.522 366.074 39.078 366.258 38.631 366.258 c 38.185 366.258 37.741 366.074 37.425 365.758 c 37.109 365.442 36.925 364.998 36.925 364.551 c 36.925 364.105 37.109 363.661 37.425 363.345 c 37.741 363.029 38.185 362.845 38.631 362.845 c 39.078 362.845 39.522 363.029 39.838 363.345 c 40.154 363.661 40.337 364.105 40.337 364.551 c f BT 45.750 361.584 Td /F1 9.8 Tf [(Appropriate corticosteroid stress doses for minor, moderate, and major stressors)] TJ ET 40.337 348.897 m 40.337 349.343 40.154 349.787 39.838 350.103 c 39.522 350.419 39.078 350.603 38.631 350.603 c 38.185 350.603 37.741 350.419 37.425 350.103 c 37.109 349.787 36.925 349.343 36.925 348.897 c 36.925 348.450 37.109 348.006 37.425 347.690 c 37.741 347.374 38.185 347.190 38.631 347.190 c 39.078 347.190 39.522 347.374 39.838 347.690 c 40.154 348.006 40.337 348.450 40.337 348.897 c f BT 45.750 345.929 Td /F1 9.8 Tf [(Recommendations for corticosteroid withdrawal)] TJ ET 40.337 333.242 m 40.337 333.688 40.154 334.132 39.838 334.448 c 39.522 334.764 39.078 334.948 38.631 334.948 c 38.185 334.948 37.741 334.764 37.425 334.448 c 37.109 334.132 36.925 333.688 36.925 333.242 c 36.925 332.795 37.109 332.351 37.425 332.035 c 37.741 331.719 38.185 331.536 38.631 331.536 c 39.078 331.536 39.522 331.719 39.838 332.035 c 40.154 332.351 40.337 332.795 40.337 333.242 c f BT 45.750 330.274 Td /F1 9.8 Tf [(How to test the HPA axis for continued suppression)] TJ ET 40.337 317.587 m 40.337 318.034 40.154 318.478 39.838 318.794 c 39.522 319.109 39.078 319.293 38.631 319.293 c 38.185 319.293 37.741 319.109 37.425 318.794 c 37.109 318.478 36.925 318.034 36.925 317.587 c 36.925 317.140 37.109 316.696 37.425 316.380 c 37.741 316.065 38.185 315.881 38.631 315.881 c 39.078 315.881 39.522 316.065 39.838 316.380 c 40.154 316.696 40.337 317.140 40.337 317.587 c f BT 45.750 314.619 Td /F1 9.8 Tf [(Symptoms of acute adrenal crisis)] TJ ET 40.337 301.932 m 40.337 302.379 40.154 302.823 39.838 303.139 c 39.522 303.455 39.078 303.639 38.631 303.639 c 38.185 303.639 37.741 303.455 37.425 303.139 c 37.109 302.823 36.925 302.379 36.925 301.932 c 36.925 301.486 37.109 301.042 37.425 300.726 c 37.741 300.410 38.185 300.226 38.631 300.226 c 39.078 300.226 39.522 300.410 39.838 300.726 c 40.154 301.042 40.337 301.486 40.337 301.932 c f BT 45.750 298.965 Td /F1 9.8 Tf [(Tests that can help diagnose adrenal crisis)] TJ ET 40.337 286.278 m 40.337 286.724 40.154 287.168 39.838 287.484 c 39.522 287.800 39.078 287.984 38.631 287.984 c 38.185 287.984 37.741 287.800 37.425 287.484 c 37.109 287.168 36.925 286.724 36.925 286.278 c 36.925 285.831 37.109 285.387 37.425 285.071 c 37.741 284.755 38.185 284.571 38.631 284.571 c 39.078 284.571 39.522 284.755 39.838 285.071 c 40.154 285.387 40.337 285.831 40.337 286.278 c f BT 45.750 283.310 Td /F1 9.8 Tf [(Corticosteroid conversions/equivalent doses)] TJ ET BT 26.250 260.155 Td /F4 9.8 Tf [(The PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 240.750 Td /F4 9.8 Tf [(1. Background/Assessment)] TJ ET BT 26.250 221.346 Td /F1 9.8 Tf [(The normal basal secretion of cortisol from the adrenal gland is approximately 5-7 mg/m2/day in children or 8 -10 mg/day for )] TJ ET BT 26.250 209.441 Td /F1 9.8 Tf [(adults.)] TJ ET 0.267 0.267 0.267 rg BT 54.974 210.948 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 64.611 213.329 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.020 210.948 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 76.658 209.441 Td /F1 9.8 Tf [( This amount increases during minor illnesses or surgery to approximately 50 mg/day \(5x normal physiologic )] TJ ET BT 26.250 197.536 Td /F1 9.8 Tf [(secretion\), and typically return to baseline in 24 hours. Severe illness, trauma, or major surgical procedures cause increased )] TJ ET BT 26.250 185.631 Td /F1 9.8 Tf [(cortisol production to about 75-150 mg/day \(10x normal physiologic secretion\), which return to baseline in about 5 days.)] TJ ET 0.267 0.267 0.267 rg BT 541.606 187.139 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 551.243 189.520 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 553.652 187.139 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 166.227 Td /F1 9.8 Tf [(Long-term administration of corticosteroids \(primarily prednisone, prednisolone or deflazacort\) may lead to suppression of the )] TJ ET BT 26.250 154.322 Td /F1 9.8 Tf [(hypothalamic-pituitary-adrenal \(HPA\) axis, such that the adrenal glands no longer produce endogenous cortisol. Rapid )] TJ ET BT 26.250 142.417 Td /F1 9.8 Tf [(reduction or abrupt withdrawal of corticosteroid therapy can cause secondary adrenal insufficiency and steroid withdrawal or )] TJ ET BT 26.250 130.512 Td /F1 9.8 Tf [(deprivation syndrome, which may progress to adrenal crisis. Adrenal crisis is characterized by hypotension and hypovolemic )] TJ ET BT 26.250 118.608 Td /F1 9.8 Tf [(shock, which may be life threatening.)] TJ ET 0.267 0.267 0.267 rg BT 186.111 120.115 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 195.748 118.608 Td /F1 9.8 Tf [( Recovery from suppression of the HPA axis after discontinuing corticosteroids can be )] TJ ET BT 26.250 106.703 Td /F1 9.8 Tf [(prolonged \(possibly 6 to 12 months\) and may vary based on doses, dosing schedules and duration of corticosteroid therapy.)] TJ ET 0.267 0.267 0.267 rg BT 561.135 108.210 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 94.798 Td /F1 9.8 Tf [(Since there is a great deal of individual variability, it is not possible to predict with confidence which patients will be affected by )] TJ ET BT 26.250 82.893 Td /F1 9.8 Tf [(adrenal suppression. Current practice is to administer supplemental \(stress\) doses of corticosteroids to patients with possible )] TJ ET BT 26.250 70.989 Td /F1 9.8 Tf [(suppression of the HPA axis in the perioperative period and during acute illness to prevent acute adrenal insufficiency, or )] TJ ET BT 26.250 59.084 Td /F1 9.8 Tf [(adrenal crisis.)] TJ ET Q q 15.000 29.798 577.500 747.202 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Neurology in 2010. )] TJ ET 0.267 0.267 0.267 rg BT 110.792 768.983 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 115.611 771.364 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 118.020 768.983 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 122.839 767.476 Td /F1 9.8 Tf [( A summary listing the key elements of Duchenne care was published in this journal in 2015.)] TJ ET 0.267 0.267 0.267 rg BT 520.590 768.983 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 26.250 748.071 Td /F1 9.8 Tf [(Given the multi-systemic nature of the disease, there should generally be an interdisciplinary team of care providers with whom )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(to consult, including, at minimum, a coordinator, neurologist, doctor of physical medicine and rehabilitation, pulmonologist, )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(cardiologist, social worker, dietician and primary care doctor. However, one issue in the management of Duchenne is that due to )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(increased life expectancy, patients at some point need to transition out of pediatric care and on to adult care teams. Although )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(the transition into adult care should be a process, clinicians in the emergency department should be aware that it is sometimes )] TJ ET BT 26.250 688.548 Td /F1 9.8 Tf [(delayed or incomplete and may in fact be triggered by the very acute illness or clinical event that brings them to the )] TJ ET BT 26.250 676.643 Td /F1 9.8 Tf [(emergency room \(ER\).)] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(While any illness or trauma may occur in a person with Duchenne or Becker, certain clinical scenarios are more common. )] TJ ET BT 26.250 645.333 Td /F1 9.8 Tf [(These include exacerbations of the underlying respiratory or cardiac disease; kidney stones; and fractures as a result of low )] TJ ET BT 26.250 633.429 Td /F1 9.8 Tf [(bone mineral density. Patients with Duchenne also seem to be prone to a particularly devastating consequence of fracture, fat )] TJ ET BT 26.250 621.524 Td /F1 9.8 Tf [(embolism syndrome.)] TJ ET 0.267 0.267 0.267 rg BT 116.184 623.031 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 121.003 625.412 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 123.412 623.031 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 133.049 621.524 Td /F1 9.8 Tf [( Each medical crisis needs to be evaluated and responded to in the context of the expected )] TJ ET BT 26.250 609.619 Td /F1 9.8 Tf [(complications of the disease or medications used for disease management particularly the chronic use of corticosteroids, )] TJ ET BT 26.250 597.714 Td /F1 9.8 Tf [(which can lead to suppression of the hypothalamus-pituitary-adrenal axis \(HPA\).)] TJ ET BT 26.250 578.310 Td /F1 9.8 Tf [(One danger is that, as pressing medical emergencies emerge, issues of daily medical care \(including medications\) may be )] TJ ET BT 26.250 566.405 Td /F1 9.8 Tf [(pushed aside. However, the consequences of suddenly discontinuing or not appropriately dosing corticosteroids, particularly )] TJ ET BT 26.250 554.500 Td /F1 9.8 Tf [(during a crisis can be quite severe, as the patient may have little to no ability to produce cortisol in response to stress. An )] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(additional issue for emergency departments is that many patients with Duchenne or Becker use Deflazacort, a corticosteroid )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(that was recently approved in the United States but may be unfamiliar to doctors.)] TJ ET BT 26.250 511.286 Td /F1 9.8 Tf [(A recent case in point involved Phillip James PJ Nicholoff, a vibrant, 31-year-old man living with Duchenne muscular )] TJ ET BT 26.250 499.381 Td /F1 9.8 Tf [(dystrophy. PJ had been treated with daily corticosteroids since the age of 6. He endured several pathologic fractures, likely a )] TJ ET BT 26.250 487.476 Td /F1 9.8 Tf [(result of his steroid treatment and his non-ambulatory status. In November 2013, on a trip to Florida, he fractured his humerus )] TJ ET BT 26.250 475.572 Td /F1 9.8 Tf [(and hip, and was transported by plane to a hospital closer to his home in the north. PJ had orthopedic surgery to manage both )] TJ ET BT 26.250 463.667 Td /F1 9.8 Tf [(of these fractures. Following the surgery, however, he developed respiratory distress, tachycardia, hypotension, and later died. )] TJ ET BT 26.250 451.762 Td /F1 9.8 Tf [(A review of the medical record suggested that he had not received appropriate stress-doses of steroids during his )] TJ ET BT 26.250 439.857 Td /F1 9.8 Tf [(hospitalization. While PJs death may have been attributed to many causes, inadequate corticosteroid doses may have been a )] TJ ET BT 26.250 427.953 Td /F1 9.8 Tf [(contributing factor.. Consequently, experts in the field held extensive discussions in order to develop a protocol on steroid )] TJ ET BT 26.250 416.048 Td /F1 9.8 Tf [(dosing during an acute illness or other emergency.)] TJ ET BT 26.250 396.643 Td /F1 9.8 Tf [(The protocol addresses several issues:)] TJ ET 0.271 0.267 0.267 RG 40.337 380.206 m 40.337 380.653 40.154 381.097 39.838 381.413 c 39.522 381.728 39.078 381.912 38.631 381.912 c 38.185 381.912 37.741 381.728 37.425 381.413 c 37.109 381.097 36.925 380.653 36.925 380.206 c 36.925 379.759 37.109 379.315 37.425 378.999 c 37.741 378.684 38.185 378.500 38.631 378.500 c 39.078 378.500 39.522 378.684 39.838 378.999 c 40.154 379.315 40.337 379.759 40.337 380.206 c f BT 45.750 377.238 Td /F1 9.8 Tf [(How to define HPA suppression in a patient using corticosteroids)] TJ ET 40.337 364.551 m 40.337 364.998 40.154 365.442 39.838 365.758 c 39.522 366.074 39.078 366.258 38.631 366.258 c 38.185 366.258 37.741 366.074 37.425 365.758 c 37.109 365.442 36.925 364.998 36.925 364.551 c 36.925 364.105 37.109 363.661 37.425 363.345 c 37.741 363.029 38.185 362.845 38.631 362.845 c 39.078 362.845 39.522 363.029 39.838 363.345 c 40.154 363.661 40.337 364.105 40.337 364.551 c f BT 45.750 361.584 Td /F1 9.8 Tf [(Appropriate corticosteroid stress doses for minor, moderate, and major stressors)] TJ ET 40.337 348.897 m 40.337 349.343 40.154 349.787 39.838 350.103 c 39.522 350.419 39.078 350.603 38.631 350.603 c 38.185 350.603 37.741 350.419 37.425 350.103 c 37.109 349.787 36.925 349.343 36.925 348.897 c 36.925 348.450 37.109 348.006 37.425 347.690 c 37.741 347.374 38.185 347.190 38.631 347.190 c 39.078 347.190 39.522 347.374 39.838 347.690 c 40.154 348.006 40.337 348.450 40.337 348.897 c f BT 45.750 345.929 Td /F1 9.8 Tf [(Recommendations for corticosteroid withdrawal)] TJ ET 40.337 333.242 m 40.337 333.688 40.154 334.132 39.838 334.448 c 39.522 334.764 39.078 334.948 38.631 334.948 c 38.185 334.948 37.741 334.764 37.425 334.448 c 37.109 334.132 36.925 333.688 36.925 333.242 c 36.925 332.795 37.109 332.351 37.425 332.035 c 37.741 331.719 38.185 331.536 38.631 331.536 c 39.078 331.536 39.522 331.719 39.838 332.035 c 40.154 332.351 40.337 332.795 40.337 333.242 c f BT 45.750 330.274 Td /F1 9.8 Tf [(How to test the HPA axis for continued suppression)] TJ ET 40.337 317.587 m 40.337 318.034 40.154 318.478 39.838 318.794 c 39.522 319.109 39.078 319.293 38.631 319.293 c 38.185 319.293 37.741 319.109 37.425 318.794 c 37.109 318.478 36.925 318.034 36.925 317.587 c 36.925 317.140 37.109 316.696 37.425 316.380 c 37.741 316.065 38.185 315.881 38.631 315.881 c 39.078 315.881 39.522 316.065 39.838 316.380 c 40.154 316.696 40.337 317.140 40.337 317.587 c f BT 45.750 314.619 Td /F1 9.8 Tf [(Symptoms of acute adrenal crisis)] TJ ET 40.337 301.932 m 40.337 302.379 40.154 302.823 39.838 303.139 c 39.522 303.455 39.078 303.639 38.631 303.639 c 38.185 303.639 37.741 303.455 37.425 303.139 c 37.109 302.823 36.925 302.379 36.925 301.932 c 36.925 301.486 37.109 301.042 37.425 300.726 c 37.741 300.410 38.185 300.226 38.631 300.226 c 39.078 300.226 39.522 300.410 39.838 300.726 c 40.154 301.042 40.337 301.486 40.337 301.932 c f BT 45.750 298.965 Td /F1 9.8 Tf [(Tests that can help diagnose adrenal crisis)] TJ ET 40.337 286.278 m 40.337 286.724 40.154 287.168 39.838 287.484 c 39.522 287.800 39.078 287.984 38.631 287.984 c 38.185 287.984 37.741 287.800 37.425 287.484 c 37.109 287.168 36.925 286.724 36.925 286.278 c 36.925 285.831 37.109 285.387 37.425 285.071 c 37.741 284.755 38.185 284.571 38.631 284.571 c 39.078 284.571 39.522 284.755 39.838 285.071 c 40.154 285.387 40.337 285.831 40.337 286.278 c f BT 45.750 283.310 Td /F1 9.8 Tf [(Corticosteroid conversions/equivalent doses)] TJ ET BT 26.250 260.155 Td /F4 9.8 Tf [(The PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 240.750 Td /F4 9.8 Tf [(1. Background/Assessment)] TJ ET BT 26.250 221.346 Td /F1 9.8 Tf [(The normal basal secretion of cortisol from the adrenal gland is approximately 5-7 mg/m2/day in children or 8 -10 mg/day for )] TJ ET BT 26.250 209.441 Td /F1 9.8 Tf [(adults.)] TJ ET 0.267 0.267 0.267 rg BT 54.974 210.948 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 64.611 213.329 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.020 210.948 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 76.658 209.441 Td /F1 9.8 Tf [( This amount increases during minor illnesses or surgery to approximately 50 mg/day \(5x normal physiologic )] TJ ET BT 26.250 197.536 Td /F1 9.8 Tf [(secretion\), and typically return to baseline in 24 hours. Severe illness, trauma, or major surgical procedures cause increased )] TJ ET BT 26.250 185.631 Td /F1 9.8 Tf [(cortisol production to about 75-150 mg/day \(10x normal physiologic secretion\), which return to baseline in about 5 days.)] TJ ET 0.267 0.267 0.267 rg BT 541.606 187.139 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 551.243 189.520 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 553.652 187.139 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 166.227 Td /F1 9.8 Tf [(Long-term administration of corticosteroids \(primarily prednisone, prednisolone or deflazacort\) may lead to suppression of the )] TJ ET BT 26.250 154.322 Td /F1 9.8 Tf [(hypothalamic-pituitary-adrenal \(HPA\) axis, such that the adrenal glands no longer produce endogenous cortisol. Rapid )] TJ ET BT 26.250 142.417 Td /F1 9.8 Tf [(reduction or abrupt withdrawal of corticosteroid therapy can cause secondary adrenal insufficiency and steroid withdrawal or )] TJ ET BT 26.250 130.512 Td /F1 9.8 Tf [(deprivation syndrome, which may progress to adrenal crisis. Adrenal crisis is characterized by hypotension and hypovolemic )] TJ ET BT 26.250 118.608 Td /F1 9.8 Tf [(shock, which may be life threatening.)] TJ ET 0.267 0.267 0.267 rg BT 186.111 120.115 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 195.748 118.608 Td /F1 9.8 Tf [( Recovery from suppression of the HPA axis after discontinuing corticosteroids can be )] TJ ET BT 26.250 106.703 Td /F1 9.8 Tf [(prolonged \(possibly 6 to 12 months\) and may vary based on doses, dosing schedules and duration of corticosteroid therapy.)] TJ ET 0.267 0.267 0.267 rg BT 561.135 108.210 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 26.250 94.798 Td /F1 9.8 Tf [(Since there is a great deal of individual variability, it is not possible to predict with confidence which patients will be affected by )] TJ ET BT 26.250 82.893 Td /F1 9.8 Tf [(adrenal suppression. Current practice is to administer supplemental \(stress\) doses of corticosteroids to patients with possible )] TJ ET BT 26.250 70.989 Td /F1 9.8 Tf [(suppression of the HPA axis in the perioperative period and during acute illness to prevent acute adrenal insufficiency, or )] TJ ET BT 26.250 59.084 Td /F1 9.8 Tf [(adrenal crisis.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(2)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular Dystrophy)] TJ ET 0.39 w 1 J 1 j Q endstream endobj 83 0 obj << /Type /Annot /Subtype /Link /A 84 0 R /Border [0 0 0] /H /I /Rect [ 110.7922 768.1817 115.6109 777.0000 ] >> endobj 84 0 obj << /Type /Action >> endobj 85 0 obj << /Type /Annot /Subtype /Link /A 86 0 R /Border [0 0 0] /H /I /Rect [ 118.0203 768.1817 122.8389 777.0000 ] >> endobj 86 0 obj << /Type /Action >> endobj 87 0 obj << /Type /Annot /Subtype /Link /A 88 0 R /Border [0 0 0] /H /I /Rect [ 520.5902 768.1817 525.4088 777.0000 ] >> endobj 88 0 obj << /Type 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endobj 149 0 obj << /Type /Page /Parent 3 0 R /Annots [ 151 0 R 153 0 R 155 0 R 158 0 R 160 0 R 162 0 R 165 0 R 167 0 R 169 0 R 171 0 R 173 0 R 175 0 R 177 0 R 179 0 R 181 0 R 183 0 R 185 0 R 187 0 R ] /Contents 150 0 R >> endobj 150 0 obj << /Length 16004 >> stream 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG q 15.000 30.910 577.500 746.090 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F4 9.8 Tf [(2. Defining HPA Suppressed Patients:)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Recommendations differ slightly in defining a suppressed patient, but general guidelines are as shown in table 1.)] TJ ET 0.267 0.267 0.267 rg BT 511.274 749.579 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 520.911 748.071 Td /F1 9.8 Tf [( These )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(recommendations are primarily based on expert opinion and practice, as little data in this area have been published, but are )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(based on the degree of medical/surgical stress and the likelihood of adrenal suppression.)] TJ ET 0.267 0.267 0.267 rg BT 410.478 725.769 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 420.115 724.262 Td /F1 9.8 Tf [( Consultation with an )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(endocrinologist is recommended for questions or concerns.)] TJ ET 0.965 0.965 0.965 rg 26.250 524.254 555.000 178.223 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 702.476 m 581.250 702.476 l 581.250 701.726 l 26.250 701.726 l f 26.250 524.254 m 581.250 524.254 l 581.250 525.004 l 26.250 525.004 l f q 435.000 0 0 116.250 35.250 576.476 cm /I3 Do Q q 35.250 535.504 537.000 34.973 re W n 0.271 0.267 0.267 rg BT 35.250 559.487 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 68.849 559.487 Td /F1 9.8 Tf [(: Defining Adrenal Suppression.)] TJ ET 0.267 0.267 0.267 rg BT 205.953 562.460 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 215.590 559.487 Td /F1 9.8 Tf [( Note: doses for prednisone and prednisolone are equivalent; conversion is )] TJ ET BT 35.250 545.751 Td /F1 9.8 Tf [(required for patients taking deflzacort \(5 mg prednisone or prednisolone = 6 mg deflazacort\))] TJ ET Q BT 26.250 507.230 Td /F1 9.8 Tf [(Patients receiving disease appropriate corticosteroid doses \(at least 10 times above the physiologic cortisol dose\) generally do )] TJ ET BT 26.250 495.325 Td /F1 9.8 Tf [(not need stress doses if usual daily dose is continued. Patients who are on maintenance physiologic dose of hydrocortisone for )] TJ ET BT 26.250 483.420 Td /F1 9.8 Tf [(primary disease of the HPA axis do require supplemental therapy.)] TJ ET 0.267 0.267 0.267 rg BT 310.199 484.928 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 319.837 483.420 Td /F1 9.8 Tf [( Recommendations for supplemental doses are generally )] TJ ET BT 26.250 471.516 Td /F1 9.8 Tf [(divided by the severity of the stress the patient may experience \(medical or surgical\).)] TJ ET BT 26.250 452.111 Td /F4 9.8 Tf [(3. Corticosteroid Stress Doses for Patients Using Chronic Daily Corticosteroids)] TJ ET 0.965 0.965 0.965 rg 26.250 151.744 555.000 290.486 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 442.230 m 581.250 442.230 l 581.250 441.480 l 26.250 441.480 l f 26.250 151.744 m 581.250 151.744 l 581.250 152.494 l 26.250 152.494 l f q 432.000 0 0 242.250 35.250 190.230 cm /I4 Do Q q 35.250 162.994 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 173.241 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 68.849 173.241 Td /F1 9.8 Tf [(: Corticosteroid Stress Dosing)] TJ ET Q BT 26.250 134.720 Td /F1 9.8 Tf [(For patients using a high dose, twice-weekly corticosteroid)] TJ ET BT 278.219 138.608 Td /F1 8.7 Tf [(*)] TJ ET BT 281.591 134.720 Td /F1 9.8 Tf [(:)] TJ ET 0.271 0.267 0.267 RG 40.337 118.283 m 40.337 118.729 40.154 119.173 39.838 119.489 c 39.522 119.805 39.078 119.989 38.631 119.989 c 38.185 119.989 37.741 119.805 37.425 119.489 c 37.109 119.173 36.925 118.729 36.925 118.283 c 36.925 117.836 37.109 117.392 37.425 117.076 c 37.741 116.760 38.185 116.576 38.631 116.576 c 39.078 116.576 39.522 116.760 39.838 117.076 c 40.154 117.392 40.337 117.836 40.337 118.283 c f BT 45.750 115.315 Td /F1 9.8 Tf [(If patients are unable to take their usual corticosteroids by mouth due to nausea, vomiting, or npo status, they should take )] TJ ET BT 45.750 103.410 Td /F1 9.8 Tf [(stress doses intravenously as indicated above.)] TJ ET 40.337 90.723 m 40.337 91.170 40.154 91.614 39.838 91.930 c 39.522 92.246 39.078 92.429 38.631 92.429 c 38.185 92.429 37.741 92.246 37.425 91.930 c 37.109 91.614 36.925 91.170 36.925 90.723 c 36.925 90.277 37.109 89.833 37.425 89.517 c 37.741 89.201 38.185 89.017 38.631 89.017 c 39.078 89.017 39.522 89.201 39.838 89.517 c 40.154 89.833 40.337 90.277 40.337 90.723 c f BT 45.750 87.756 Td /F1 9.8 Tf [(During a moderate or major medical or surgical stressor, a cortisol level should be drawn prior to stress dosing.)] TJ ET BT 26.250 64.601 Td /F4 9.8 Tf [(4. Recommendation for withdrawal of Corticosteroid Therapy:)] TJ ET 40.337 48.164 m 40.337 48.610 40.154 49.054 39.838 49.370 c 39.522 49.686 39.078 49.870 38.631 49.870 c 38.185 49.870 37.741 49.686 37.425 49.370 c 37.109 49.054 36.925 48.610 36.925 48.164 c 36.925 47.717 37.109 47.273 37.425 46.957 c 37.741 46.641 38.185 46.457 38.631 46.457 c 39.078 46.457 39.522 46.641 39.838 46.957 c 40.154 47.273 40.337 47.717 40.337 48.164 c f BT 45.750 45.196 Td /F1 9.8 Tf [(It is recommended that patients electing to discontinue the use of corticosteroids do so under the guidance of a )] TJ ET Q q 15.000 30.910 577.500 746.090 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F4 9.8 Tf [(2. Defining HPA Suppressed Patients:)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Recommendations differ slightly in defining a suppressed patient, but general guidelines are as shown in table 1.)] TJ ET 0.267 0.267 0.267 rg BT 511.274 749.579 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 520.911 748.071 Td /F1 9.8 Tf [( These )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(recommendations are primarily based on expert opinion and practice, as little data in this area have been published, but are )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(based on the degree of medical/surgical stress and the likelihood of adrenal suppression.)] TJ ET 0.267 0.267 0.267 rg BT 410.478 725.769 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 420.115 724.262 Td /F1 9.8 Tf [( Consultation with an )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(endocrinologist is recommended for questions or concerns.)] TJ ET 0.965 0.965 0.965 rg 26.250 524.254 555.000 178.223 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 702.476 m 581.250 702.476 l 581.250 701.726 l 26.250 701.726 l f 26.250 524.254 m 581.250 524.254 l 581.250 525.004 l 26.250 525.004 l f q 435.000 0 0 116.250 35.250 576.476 cm /I3 Do Q q 35.250 535.504 537.000 34.973 re W n 0.271 0.267 0.267 rg BT 35.250 559.487 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 68.849 559.487 Td /F1 9.8 Tf [(: Defining Adrenal Suppression.)] TJ ET 0.267 0.267 0.267 rg BT 205.953 562.460 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 215.590 559.487 Td /F1 9.8 Tf [( Note: doses for prednisone and prednisolone are equivalent; conversion is )] TJ ET BT 35.250 545.751 Td /F1 9.8 Tf [(required for patients taking deflzacort \(5 mg prednisone or prednisolone = 6 mg deflazacort\))] TJ ET Q BT 26.250 507.230 Td /F1 9.8 Tf [(Patients receiving disease appropriate corticosteroid doses \(at least 10 times above the physiologic cortisol dose\) generally do )] TJ ET BT 26.250 495.325 Td /F1 9.8 Tf [(not need stress doses if usual daily dose is continued. Patients who are on maintenance physiologic dose of hydrocortisone for )] TJ ET BT 26.250 483.420 Td /F1 9.8 Tf [(primary disease of the HPA axis do require supplemental therapy.)] TJ ET 0.267 0.267 0.267 rg BT 310.199 484.928 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 319.837 483.420 Td /F1 9.8 Tf [( Recommendations for supplemental doses are generally )] TJ ET BT 26.250 471.516 Td /F1 9.8 Tf [(divided by the severity of the stress the patient may experience \(medical or surgical\).)] TJ ET BT 26.250 452.111 Td /F4 9.8 Tf [(3. Corticosteroid Stress Doses for Patients Using Chronic Daily Corticosteroids)] TJ ET 0.965 0.965 0.965 rg 26.250 151.744 555.000 290.486 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 442.230 m 581.250 442.230 l 581.250 441.480 l 26.250 441.480 l f 26.250 151.744 m 581.250 151.744 l 581.250 152.494 l 26.250 152.494 l f q 432.000 0 0 242.250 35.250 190.230 cm /I4 Do Q q 35.250 162.994 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 173.241 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 68.849 173.241 Td /F1 9.8 Tf [(: Corticosteroid Stress Dosing)] TJ ET Q BT 26.250 134.720 Td /F1 9.8 Tf [(For patients using a high dose, twice-weekly corticosteroid)] TJ ET BT 278.219 138.608 Td /F1 8.7 Tf [(*)] TJ ET BT 281.591 134.720 Td /F1 9.8 Tf [(:)] TJ ET 0.271 0.267 0.267 RG 40.337 118.283 m 40.337 118.729 40.154 119.173 39.838 119.489 c 39.522 119.805 39.078 119.989 38.631 119.989 c 38.185 119.989 37.741 119.805 37.425 119.489 c 37.109 119.173 36.925 118.729 36.925 118.283 c 36.925 117.836 37.109 117.392 37.425 117.076 c 37.741 116.760 38.185 116.576 38.631 116.576 c 39.078 116.576 39.522 116.760 39.838 117.076 c 40.154 117.392 40.337 117.836 40.337 118.283 c f BT 45.750 115.315 Td /F1 9.8 Tf [(If patients are unable to take their usual corticosteroids by mouth due to nausea, vomiting, or npo status, they should take )] TJ ET BT 45.750 103.410 Td /F1 9.8 Tf [(stress doses intravenously as indicated above.)] TJ ET 40.337 90.723 m 40.337 91.170 40.154 91.614 39.838 91.930 c 39.522 92.246 39.078 92.429 38.631 92.429 c 38.185 92.429 37.741 92.246 37.425 91.930 c 37.109 91.614 36.925 91.170 36.925 90.723 c 36.925 90.277 37.109 89.833 37.425 89.517 c 37.741 89.201 38.185 89.017 38.631 89.017 c 39.078 89.017 39.522 89.201 39.838 89.517 c 40.154 89.833 40.337 90.277 40.337 90.723 c f BT 45.750 87.756 Td /F1 9.8 Tf [(During a moderate or major medical or surgical stressor, a cortisol level should be drawn prior to stress dosing.)] TJ ET BT 26.250 64.601 Td /F4 9.8 Tf [(4. Recommendation for withdrawal of Corticosteroid Therapy:)] TJ ET 40.337 48.164 m 40.337 48.610 40.154 49.054 39.838 49.370 c 39.522 49.686 39.078 49.870 38.631 49.870 c 38.185 49.870 37.741 49.686 37.425 49.370 c 37.109 49.054 36.925 48.610 36.925 48.164 c 36.925 47.717 37.109 47.273 37.425 46.957 c 37.741 46.641 38.185 46.457 38.631 46.457 c 39.078 46.457 39.522 46.641 39.838 46.957 c 40.154 47.273 40.337 47.717 40.337 48.164 c f BT 45.750 45.196 Td /F1 9.8 Tf [(It is recommended that patients electing to discontinue the use of corticosteroids do so under the guidance of a )] TJ ET Q q 15.000 30.910 577.500 746.090 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F4 9.8 Tf [(2. Defining HPA Suppressed Patients:)] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Recommendations differ slightly in defining a suppressed patient, but general guidelines are as shown in table 1.)] TJ ET 0.267 0.267 0.267 rg BT 511.274 749.579 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 520.911 748.071 Td /F1 9.8 Tf [( These )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(recommendations are primarily based on expert opinion and practice, as little data in this area have been published, but are )] TJ ET BT 26.250 724.262 Td /F1 9.8 Tf [(based on the degree of medical/surgical stress and the likelihood of adrenal suppression.)] TJ ET 0.267 0.267 0.267 rg BT 410.478 725.769 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 420.115 724.262 Td /F1 9.8 Tf [( Consultation with an )] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(endocrinologist is recommended for questions or concerns.)] TJ ET 0.965 0.965 0.965 rg 26.250 524.254 555.000 178.223 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 702.476 m 581.250 702.476 l 581.250 701.726 l 26.250 701.726 l f 26.250 524.254 m 581.250 524.254 l 581.250 525.004 l 26.250 525.004 l f q 435.000 0 0 116.250 35.250 576.476 cm /I3 Do Q q 35.250 535.504 537.000 34.973 re W n 0.271 0.267 0.267 rg BT 35.250 559.487 Td /F4 9.8 Tf [(Table 1)] TJ ET BT 68.849 559.487 Td /F1 9.8 Tf [(: Defining Adrenal Suppression.)] TJ ET 0.267 0.267 0.267 rg BT 205.953 562.460 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 215.590 559.487 Td /F1 9.8 Tf [( Note: doses for prednisone and prednisolone are equivalent; conversion is )] TJ ET BT 35.250 545.751 Td /F1 9.8 Tf [(required for patients taking deflzacort \(5 mg prednisone or prednisolone = 6 mg deflazacort\))] TJ ET Q BT 26.250 507.230 Td /F1 9.8 Tf [(Patients receiving disease appropriate corticosteroid doses \(at least 10 times above the physiologic cortisol dose\) generally do )] TJ ET BT 26.250 495.325 Td /F1 9.8 Tf [(not need stress doses if usual daily dose is continued. Patients who are on maintenance physiologic dose of hydrocortisone for )] TJ ET BT 26.250 483.420 Td /F1 9.8 Tf [(primary disease of the HPA axis do require supplemental therapy.)] TJ ET 0.267 0.267 0.267 rg BT 310.199 484.928 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 319.837 483.420 Td /F1 9.8 Tf [( Recommendations for supplemental doses are generally )] TJ ET BT 26.250 471.516 Td /F1 9.8 Tf [(divided by the severity of the stress the patient may experience \(medical or surgical\).)] TJ ET BT 26.250 452.111 Td /F4 9.8 Tf [(3. Corticosteroid Stress Doses for Patients Using Chronic Daily Corticosteroids)] TJ ET 0.965 0.965 0.965 rg 26.250 151.744 555.000 290.486 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 442.230 m 581.250 442.230 l 581.250 441.480 l 26.250 441.480 l f 26.250 151.744 m 581.250 151.744 l 581.250 152.494 l 26.250 152.494 l f q 432.000 0 0 242.250 35.250 190.230 cm /I4 Do Q q 35.250 162.994 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 173.241 Td /F4 9.8 Tf [(Table 2)] TJ ET BT 68.849 173.241 Td /F1 9.8 Tf [(: Corticosteroid Stress Dosing)] TJ ET Q BT 26.250 134.720 Td /F1 9.8 Tf [(For patients using a high dose, twice-weekly corticosteroid)] TJ ET BT 278.219 138.608 Td /F1 8.7 Tf [(*)] TJ ET BT 281.591 134.720 Td /F1 9.8 Tf [(:)] TJ ET 0.271 0.267 0.267 RG 40.337 118.283 m 40.337 118.729 40.154 119.173 39.838 119.489 c 39.522 119.805 39.078 119.989 38.631 119.989 c 38.185 119.989 37.741 119.805 37.425 119.489 c 37.109 119.173 36.925 118.729 36.925 118.283 c 36.925 117.836 37.109 117.392 37.425 117.076 c 37.741 116.760 38.185 116.576 38.631 116.576 c 39.078 116.576 39.522 116.760 39.838 117.076 c 40.154 117.392 40.337 117.836 40.337 118.283 c f BT 45.750 115.315 Td /F1 9.8 Tf [(If patients are unable to take their usual corticosteroids by mouth due to nausea, vomiting, or npo status, they should take )] TJ ET BT 45.750 103.410 Td /F1 9.8 Tf [(stress doses intravenously as indicated above.)] TJ ET 40.337 90.723 m 40.337 91.170 40.154 91.614 39.838 91.930 c 39.522 92.246 39.078 92.429 38.631 92.429 c 38.185 92.429 37.741 92.246 37.425 91.930 c 37.109 91.614 36.925 91.170 36.925 90.723 c 36.925 90.277 37.109 89.833 37.425 89.517 c 37.741 89.201 38.185 89.017 38.631 89.017 c 39.078 89.017 39.522 89.201 39.838 89.517 c 40.154 89.833 40.337 90.277 40.337 90.723 c f BT 45.750 87.756 Td /F1 9.8 Tf [(During a moderate or major medical or surgical stressor, a cortisol level should be drawn prior to stress dosing.)] TJ ET BT 26.250 64.601 Td /F4 9.8 Tf [(4. Recommendation for withdrawal of Corticosteroid Therapy:)] TJ ET 40.337 48.164 m 40.337 48.610 40.154 49.054 39.838 49.370 c 39.522 49.686 39.078 49.870 38.631 49.870 c 38.185 49.870 37.741 49.686 37.425 49.370 c 37.109 49.054 36.925 48.610 36.925 48.164 c 36.925 47.717 37.109 47.273 37.425 46.957 c 37.741 46.641 38.185 46.457 38.631 46.457 c 39.078 46.457 39.522 46.641 39.838 46.957 c 40.154 47.273 40.337 47.717 40.337 48.164 c f BT 45.750 45.196 Td /F1 9.8 Tf [(It is recommended that patients electing to discontinue the use of corticosteroids do so under the guidance of a )] TJ ET Q q 435.000 0 0 116.250 35.250 576.476 cm /I3 Do Q q 432.000 0 0 242.250 35.250 190.230 cm /I4 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(3)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular Dystrophy)] TJ ET 0.39 w 1 J 1 j Q endstream endobj 151 0 obj << /Type /Annot /Subtype /Link /A 152 0 R /Border [0 0 0] /H /I /Rect [ 511.2735 748.7769 520.9108 757.5952 ] >> endobj 152 0 obj << /Type /Action >> endobj 153 0 obj << /Type /Annot /Subtype /Link /A 154 0 R /Border [0 0 0] /H /I /Rect [ 410.4780 724.9674 420.1153 733.7858 ] >> endobj 154 0 obj << /Type /Action >> endobj 155 0 obj << /Type /Annot /Subtype /Link /A 156 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 576.4762 470.2500 692.7262 ] >> endobj 156 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/md/files/2016/11/Table-1.png) >> endobj 157 0 obj << /Type /XObject /Subtype /Image /Width 580 /Height 155 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 3 /Columns 580 /BitsPerComponent 8>> /ColorSpace /DeviceRGB /BitsPerComponent 8 /Length 54154>> stream xWp]Gv۫{s9`Ι(ь*oypu[~*ؿǷh4hH $@0 3prܻ{݇s GdR5{Nاiя~D„ &L.F0a„ )o}oLa(7]0/,wvv >.N?R~Όu-Uo UU'&&~!鲄y1.--rUU揔G&3!D~~~CC[# B"(5442>OyQ ',}TW (OP(&2 = >ɛ?U K?!e1DTUU$AȆvʪy&I~)` nuxBUAˡ*++*j%6WU,w +%YOzOU@$$3"Jh֙ـ+y78xK ĢTkkFrKn3>/&9}B!ĺ\/W#=c^[wO9J I/.LCEPWƇ&g< yTa*(Y+Tи+@-g D(,Y= -vL6ͺ,)9'G FgBJ-M@<80RB aJ+.Kz؆([wn`(,(+NP_CaߖzZ>wڄ[[=+eU{6 bd\vuE$arLfCC]_?PIb@3*S% IE ɩȪZ/|F4[vgV75DJ뎯 DISVXڐ&L6=L)0DgWkHGKJѮ}[,vT՘]ov4ĸ@BSCGNMj P3k* D!8"LD\eѹsAdA.QFs$R@R(9"0FG1B43FE`۴BBP(jQ@%e. !c r }V0_ BqL ;}jEѭqC1 xHI#"3IJ)cdʯ#眄@$1Js|>r.HsAhP PpA(cp *)=p/l |!r!(c@pMUCPp9pszPfs ֢d`j$.C2Fkß! 1F@PJ}˟?;(c_а~LYMorGB%(p9LY< Qyd@CB$¾<348N?eN @KFA~6[{M&"s SP3[}D Y%  .\ou1_R5پBt & (\3Gk;u:$Kwʵ;_H2;s]Tzm()@>c~Ι>ٽΩ9)lPV?ro+RJ) &e߾fY4K/7ڨezW:韶sk'srTiPMViMME[[Y}b&"r$>OC@WPYd2mkv$&j"iwbM25gC`yp7OL@Ns~LIPIu蛲#99KCu#ظ*ǔydnv12&ap޽RHWkW;sw՗h.]ꚶjL U rcopĊːYwrGԢ%!h/vݹv@Y1Roi5i l>J$Ib%UgKE=:J9~C5Q礴l#v4ͳ%):N2}'^*aQ?w~[UmL~_nQ8峿m ,hH,N{OeבSOGg6}v֫4>bL}ɱvgfJ{tHkxlHHl1nCׇCyWϼ >4[4,0tjgLdֿx|SM\/ݿ7zw[i]st= Pd& .LugV=>sz|*pPg[G{˵{w PJd[*BYrȂ" |Ԙlꕋ7Wn6^sw;:L5!3D:hL_LVMnK2zښv.e NY'E̪Ie9,ȊAkk ._. ]" xKo!2ă7+LfuEgzG1U9Eg\z~aeuSaa} ?o>uD[܄TVY>$GǭN]nizRvI?xRnj2aU%(,ܹnmaxh2,@ WWlvYUY}w|ْZX_v$`xaBʫ/Lw,&XOtOs"81exi/LFj_^ eL n(l1%mD\B"!8hY+)Pt9.3BHU) "tWTɶ r ߻د2m^`o P-{Aj D<+thuڐ2 (m$mYU(lew';wo "*l8ₜ=;IݍDNSaRUu["ޠ@*~SJ ?7 :8sǎ7ʖ[RDDv2FowFLrrrv]h5cB"ӥ9gq $P(Eէۇ\R *}ŽTcPWWiF=ymV22_qǩ(d9!9 IRZgr2N|r~.i!]HAA fQnBBI0SL!ק wUeˣR&8~E#xr -Bnj,%@&]s1B(1"?MK`SM*N]ۊ&:fl%1-,eo|X*ɩڹo]^!4&IV:FE$/Oqgh`G@ۃ[V[kc*UO&Jpjh@PYuzzgE"'E%ȄxcȎ/i9>}ջ ,n|U?1)In]HTd Ii&/x RKYfbOoOmkuzW,^\Xzu <*(\xL΅;WoTZ]LՓY sLRbl-.a(qNonk֕>ʎ s>Qo"1&)/מ(Xl6F%Sb=fьkUs].WWh-"PP11Pg;gF3^k NOki<6Y8ZXrr(B(P ИS2^"h".1zc\ritЁ%9>*0e #>ۊS­+7U&!h6*nu3g5Y=FZ&i.9u]KK\N#BLI&Ҋ*n]С}ٱ:\1)}(eA2%GEjii*{ QgIuhfuZΊK{R( 0lݪy|_ulTBzpMtޝVܓbM/9x`ObDp"@YP a퇏m+KOtC/(M6g?zļ~wh@J=| s9Q{^::L6#S LEDD KRήï=G,xcsbK[t݇d'ǏN6GEfmmn3>*&*+o9d؞@MTo9o$=Xemo{ssBRVnؽ֤.nǑcUqzs=Bb;ZS3؟uohh9͸n 길=/́$!fݕFSBRqѲK[R#LQIZPR%;;l/͈079Zlj 0nVVa-|ѣE{+#1$`-6 Q:4j]겒l)d D{,*::2*fx$Q@ӗl?kYtddlB,V B0s꾣'jrcŋyk¶mvСΞ~6Lk6cnFZ婩E7eLxgMeqF߽kfWQV25hw,MO,OMf,NfPN((-)H6֦ )+)-dы8ʴvqbl٥PL3 3$?Ǩ7]9 (LO:J c%g{{rL%ve`AtQyŅZ-+^uqlh+rSy9p?9...~׊O;U d͎;JwufhҞTP\Rk7&G0:(;9rmfc[( wx9Pi2V&'zYr/L/&:(/K |v͏ .sKqII^Nok?Fѳ01ku&WH~qiAn:YvF2h1Gdfd'ƫSV`14=2m JJ s36|bӜKD%d䦘:nZg'I%9ftƤ]ߣ?tuupdee=(p?"(7#fy67RZZtҲB3;2&o%ei=W>6T$Kjeǔ[V韾|ڤ5 ͌;|1NXsKv.% x}x" `J*[[ώ/+Y%eyYz'VLMfmrt'@uF3.NmH`jd؆Q她 H630`1DjՉI=C w|pCXɤg mtzAhoZv;$ЈhT ⢼TfgX|^4}ZgWV}mz^IIQ^d)G! 7ݿ<>~.N{Eя~?[__9& UTC [m]BC~\@)PIbDUTJ\p#%BUC2Sƒ`T2)UN(!DMGBp%R B`8l :1qu? 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56.425 668.569 56.609 668.125 56.925 667.809 c 57.241 667.493 57.685 667.309 58.131 667.309 c 58.578 667.309 59.022 667.493 59.338 667.809 c 59.654 668.125 59.837 668.569 59.837 669.015 c s BT 65.250 666.048 Td /F1 9.8 Tf [(Continue until dose is near physiologic dose \(3mg/m2/day of prednisone or 3.6mg/m2/day of Deflazacort\))] TJ ET 40.337 649.611 m 40.337 650.057 40.154 650.501 39.838 650.817 c 39.522 651.133 39.078 651.317 38.631 651.317 c 38.185 651.317 37.741 651.133 37.425 650.817 c 37.109 650.501 36.925 650.057 36.925 649.611 c 36.925 649.164 37.109 648.720 37.425 648.404 c 37.741 648.088 38.185 647.904 38.631 647.904 c 39.078 647.904 39.522 648.088 39.838 648.404 c 40.154 648.720 40.337 649.164 40.337 649.611 c f BT 45.750 646.643 Td /F1 9.8 Tf [(When near physiologic dose, substitute corticosteroids with short acting form of corticosteroid or hydrocortisone \(12 )] TJ ET BT 45.750 634.738 Td /F1 9.8 Tf [(mg/m2/day of hydrocortisone\))] TJ ET 40.337 622.051 m 40.337 622.498 40.154 622.942 39.838 623.258 c 39.522 623.573 39.078 623.757 38.631 623.757 c 38.185 623.757 37.741 623.573 37.425 623.258 c 37.109 622.942 36.925 622.498 36.925 622.051 c 36.925 621.604 37.109 621.160 37.425 620.844 c 37.741 620.529 38.185 620.345 38.631 620.345 c 39.078 620.345 39.522 620.529 39.838 620.844 c 40.154 621.160 40.337 621.604 40.337 622.051 c f BT 45.750 619.083 Td /F1 9.8 Tf [(This will also enable the patient to have a supply of hydrocortisone to be used for stress doses if needed in times of stress )] TJ ET BT 45.750 607.179 Td /F1 9.8 Tf [(after coming off steroids )] TJ ET 0.39 w 1 J 1 j 59.837 594.491 m 59.837 594.938 59.654 595.382 59.338 595.698 c 59.022 596.014 58.578 596.198 58.131 596.198 c 57.685 596.198 57.241 596.014 56.925 595.698 c 56.609 595.382 56.425 594.938 56.425 594.491 c 56.425 594.045 56.609 593.601 56.925 593.285 c 57.241 592.969 57.685 592.785 58.131 592.785 c 58.578 592.785 59.022 592.969 59.338 593.285 c 59.654 593.601 59.837 594.045 59.837 594.491 c s BT 65.250 591.524 Td /F1 9.8 Tf [(Continue to taper off by 20-25% each week \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 578.837 m 59.837 579.283 59.654 579.727 59.338 580.043 c 59.022 580.359 58.578 580.543 58.131 580.543 c 57.685 580.543 57.241 580.359 56.925 580.043 c 56.609 579.727 56.425 579.283 56.425 578.837 c 56.425 578.390 56.609 577.946 56.925 577.630 c 57.241 577.314 57.685 577.130 58.131 577.130 c 58.578 577.130 59.022 577.314 59.338 577.630 c 59.654 577.946 59.837 578.390 59.837 578.837 c s BT 65.250 575.869 Td /F1 9.8 Tf [(Give every other day for 2 weeks \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 563.182 m 59.837 563.629 59.654 564.073 59.338 564.389 c 59.022 564.704 58.578 564.888 58.131 564.888 c 57.685 564.888 57.241 564.704 56.925 564.389 c 56.609 564.073 56.425 563.629 56.425 563.182 c 56.425 562.735 56.609 562.291 56.925 561.975 c 57.241 561.660 57.685 561.476 58.131 561.476 c 58.578 561.476 59.022 561.660 59.338 561.975 c 59.654 562.291 59.837 562.735 59.837 563.182 c s BT 65.250 560.214 Td /F1 9.8 Tf [(Stop)] TJ ET 0.39 w 1 J 1 j 59.837 547.527 m 59.837 547.974 59.654 548.418 59.338 548.734 c 59.022 549.050 58.578 549.233 58.131 549.233 c 57.685 549.233 57.241 549.050 56.925 548.734 c 56.609 548.418 56.425 547.974 56.425 547.527 c 56.425 547.081 56.609 546.637 56.925 546.321 c 57.241 546.005 57.685 545.821 58.131 545.821 c 58.578 545.821 59.022 546.005 59.338 546.321 c 59.654 546.637 59.837 547.081 59.837 547.527 c s BT 65.250 544.560 Td /F5 9.8 Tf [(Watch very carefully for signs of adrenal crisis \(see below\))] TJ ET 40.337 528.122 m 40.337 528.569 40.154 529.013 39.838 529.329 c 39.522 529.645 39.078 529.829 38.631 529.829 c 38.185 529.829 37.741 529.645 37.425 529.329 c 37.109 529.013 36.925 528.569 36.925 528.122 c 36.925 527.676 37.109 527.232 37.425 526.916 c 37.741 526.600 38.185 526.416 38.631 526.416 c 39.078 526.416 39.522 526.600 39.838 526.916 c 40.154 527.232 40.337 527.676 40.337 528.122 c f BT 45.750 525.155 Td /F1 9.8 Tf [(Alert patients and parents to signs/symptoms of adrenal crisis)] TJ ET 40.337 512.468 m 40.337 512.914 40.154 513.358 39.838 513.674 c 39.522 513.990 39.078 514.174 38.631 514.174 c 38.185 514.174 37.741 513.990 37.425 513.674 c 37.109 513.358 36.925 512.914 36.925 512.468 c 36.925 512.021 37.109 511.577 37.425 511.261 c 37.741 510.945 38.185 510.761 38.631 510.761 c 39.078 510.761 39.522 510.945 39.838 511.261 c 40.154 511.577 40.337 512.021 40.337 512.468 c f BT 45.750 509.500 Td /F1 9.8 Tf [(If patients have symptoms of adrenal insufficiency during the taper, the patient should return to the previous steroid dose, )] TJ ET BT 45.750 497.595 Td /F1 9.8 Tf [(which should be maintained longer)] TJ ET BT 26.250 474.441 Td /F5 9.8 Tf [(If the patient has a serious illness/injury during the taper, they may need a stress dose of corticosteroids:)] TJ ET 40.337 458.003 m 40.337 458.450 40.154 458.894 39.838 459.210 c 39.522 459.526 39.078 459.710 38.631 459.710 c 38.185 459.710 37.741 459.526 37.425 459.210 c 37.109 458.894 36.925 458.450 36.925 458.003 c 36.925 457.557 37.109 457.113 37.425 456.797 c 37.741 456.481 38.185 456.297 38.631 456.297 c 39.078 456.297 39.522 456.481 39.838 456.797 c 40.154 457.113 40.337 457.557 40.337 458.003 c f BT 45.750 455.036 Td /F1 9.8 Tf [(Encourage parents to continue to report any serious events until 1 year post-taper )] TJ ET 0.39 w 1 J 1 j 59.837 442.349 m 59.837 442.795 59.654 443.239 59.338 443.555 c 59.022 443.871 58.578 444.055 58.131 444.055 c 57.685 444.055 57.241 443.871 56.925 443.555 c 56.609 443.239 56.425 442.795 56.425 442.349 c 56.425 441.902 56.609 441.458 56.925 441.142 c 57.241 440.826 57.685 440.642 58.131 440.642 c 58.578 440.642 59.022 440.826 59.338 441.142 c 59.654 441.458 59.837 441.902 59.837 442.349 c s BT 65.250 439.381 Td /F1 9.8 Tf [(The stress doses of hydrocortisone is 30-50 mg/m2/day, or higher, for major stress \(see Table 2\))] TJ ET 0.39 w 1 J 1 j 59.837 426.694 m 59.837 427.141 59.654 427.585 59.338 427.901 c 59.022 428.216 58.578 428.400 58.131 428.400 c 57.685 428.400 57.241 428.216 56.925 427.901 c 56.609 427.585 56.425 427.141 56.425 426.694 c 56.425 426.247 56.609 425.803 56.925 425.487 c 57.241 425.172 57.685 424.988 58.131 424.988 c 58.578 424.988 59.022 425.172 59.338 425.487 c 59.654 425.803 59.837 426.247 59.837 426.694 c s BT 65.250 423.726 Td /F1 9.8 Tf [(Patients need to go to the emergency room if they are having signs or symptoms of adrenal crisis. Serum electrolytes )] TJ ET BT 65.250 411.822 Td /F1 9.8 Tf [(with blood glucose and cortisol level should be obtained.)] TJ ET 0.39 w 1 J 1 j 59.837 399.134 m 59.837 399.581 59.654 400.025 59.338 400.341 c 59.022 400.657 58.578 400.841 58.131 400.841 c 57.685 400.841 57.241 400.657 56.925 400.341 c 56.609 400.025 56.425 399.581 56.425 399.134 c 56.425 398.688 56.609 398.244 56.925 397.928 c 57.241 397.612 57.685 397.428 58.131 397.428 c 58.578 397.428 59.022 397.612 59.338 397.928 c 59.654 398.244 59.837 398.688 59.837 399.134 c s BT 65.250 396.167 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress )] TJ ET BT 65.250 384.262 Td /F1 9.8 Tf [(dose of hydrocortisone.)] TJ ET 0.39 w 1 J 1 j 59.837 371.575 m 59.837 372.022 59.654 372.466 59.338 372.782 c 59.022 373.097 58.578 373.281 58.131 373.281 c 57.685 373.281 57.241 373.097 56.925 372.782 c 56.609 372.466 56.425 372.022 56.425 371.575 c 56.425 371.128 56.609 370.684 56.925 370.368 c 57.241 370.053 57.685 369.869 58.131 369.869 c 58.578 369.869 59.022 370.053 59.338 370.368 c 59.654 370.684 59.837 371.128 59.837 371.575 c s BT 65.250 368.607 Td /F1 9.8 Tf [(Patients should see an endocrinologist for evaluation of HPA axis during the process of corticosteroid therapy )] TJ ET BT 65.250 356.703 Td /F1 9.8 Tf [(withdrawal.)] TJ ET BT 26.250 329.798 Td /F1 9.8 Tf [(Testing the HPA axis:)] TJ ET 0.267 0.267 0.267 rg BT 119.996 331.305 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.655 38.631 311.655 c 39.078 311.655 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(After reaching half the physiological dose \(5-6 mg/m2/day of hydrocortisone or 1-1.5 mg/m2/day of prednisone\), monthly )] TJ ET BT 45.750 298.488 Td /F1 9.8 Tf [(morning serum cortisol and ACTH should be assayed \(may do less frequently\), until they reach normal levels.)] TJ ET 40.337 285.801 m 40.337 286.248 40.154 286.692 39.838 287.008 c 39.522 287.324 39.078 287.508 38.631 287.508 c 38.185 287.508 37.741 287.324 37.425 287.008 c 37.109 286.692 36.925 286.248 36.925 285.801 c 36.925 285.355 37.109 284.911 37.425 284.595 c 37.741 284.279 38.185 284.095 38.631 284.095 c 39.078 284.095 39.522 284.279 39.838 284.595 c 40.154 284.911 40.337 285.355 40.337 285.801 c f BT 45.750 282.834 Td /F1 9.8 Tf [(When baseline monthly morning serum ACTH and cortisol are normal, discontinue the corticosteroid and carry out the )] TJ ET BT 556.192 282.834 Td /F1 9.8 Tf [(rapid )] TJ ET BT 45.750 270.929 Td /F1 9.8 Tf [(ACTH stimulation test \(may also be called cosyntropin, tetracosactide or Synacthen tests\) monthly until post-stimulation )] TJ ET BT 45.750 259.024 Td /F1 9.8 Tf [(cortisol response is normal \(post-stimulus level > 20 mcg/dL\). When this point is reached, it can be considered that the )] TJ ET BT 45.750 247.119 Td /F1 9.8 Tf [(HPA axis has recovered.)] TJ ET 40.337 234.432 m 40.337 234.879 40.154 235.323 39.838 235.639 c 39.522 235.955 39.078 236.139 38.631 236.139 c 38.185 236.139 37.741 235.955 37.425 235.639 c 37.109 235.323 36.925 234.879 36.925 234.432 c 36.925 233.986 37.109 233.542 37.425 233.226 c 37.741 232.910 38.185 232.726 38.631 232.726 c 39.078 232.726 39.522 232.910 39.838 233.226 c 40.154 233.542 40.337 233.986 40.337 234.432 c f BT 45.750 231.465 Td /F1 9.8 Tf [(It may be appropriate to recheck the rapid ACTH stimulation test after 1 year, to establish continued full recovery of the )] TJ ET BT 45.750 219.560 Td /F1 9.8 Tf [(HPA axis.)] TJ ET BT 26.250 179.207 Td /F4 12.0 Tf [(Modification of above protocol:)] TJ ET 40.337 162.221 m 40.337 162.667 40.154 163.111 39.838 163.427 c 39.522 163.743 39.078 163.927 38.631 163.927 c 38.185 163.927 37.741 163.743 37.425 163.427 c 37.109 163.111 36.925 162.667 36.925 162.221 c 36.925 161.774 37.109 161.330 37.425 161.014 c 37.741 160.698 38.185 160.515 38.631 160.515 c 39.078 160.515 39.522 160.698 39.838 161.014 c 40.154 161.330 40.337 161.774 40.337 162.221 c f BT 45.750 159.253 Td /F1 9.8 Tf [(Omit monthly AM cortisol and ACTH and perform an ACTH stimulation test in 3 months after discontinuation of )] TJ ET BT 45.750 147.348 Td /F1 9.8 Tf [(corticosteroids)] TJ ET 40.337 134.661 m 40.337 135.108 40.154 135.552 39.838 135.868 c 39.522 136.184 39.078 136.368 38.631 136.368 c 38.185 136.368 37.741 136.184 37.425 135.868 c 37.109 135.552 36.925 135.108 36.925 134.661 c 36.925 134.215 37.109 133.771 37.425 133.455 c 37.741 133.139 38.185 132.955 38.631 132.955 c 39.078 132.955 39.522 133.139 39.838 133.455 c 40.154 133.771 40.337 134.215 40.337 134.661 c f BT 45.750 131.694 Td /F1 9.8 Tf [(During this time \(3 months before getting ACTH stimulation test\), patients will need to take stress dose at the time of stress)] TJ ET 40.337 119.006 m 40.337 119.453 40.154 119.897 39.838 120.213 c 39.522 120.529 39.078 120.713 38.631 120.713 c 38.185 120.713 37.741 120.529 37.425 120.213 c 37.109 119.897 36.925 119.453 36.925 119.006 c 36.925 118.560 37.109 118.116 37.425 117.800 c 37.741 117.484 38.185 117.300 38.631 117.300 c 39.078 117.300 39.522 117.484 39.838 117.800 c 40.154 118.116 40.337 118.560 40.337 119.006 c f BT 45.750 116.039 Td /F1 9.8 Tf [(If ACTH stimulation test result is abnormal \(peak cortisol <20\), patients will need to continue taking stress doses of )] TJ ET BT 45.750 104.134 Td /F1 9.8 Tf [(hydrocortisone at the time of stress. \(Patients should have a repeat ACTH stimulation test again in 1-2 months later and )] TJ ET BT 45.750 92.229 Td /F1 9.8 Tf [(families would need to have teaching on this with an endocrine nurse.\))] TJ ET BT 26.250 69.075 Td /F1 9.8 Tf [(Alternatively, when laboratory tests cannot be carried out:)] TJ ET 40.337 52.637 m 40.337 53.084 40.154 53.528 39.838 53.844 c 39.522 54.160 39.078 54.344 38.631 54.344 c 38.185 54.344 37.741 54.160 37.425 53.844 c 37.109 53.528 36.925 53.084 36.925 52.637 c 36.925 52.191 37.109 51.747 37.425 51.431 c 37.741 51.115 38.185 50.931 38.631 50.931 c 39.078 50.931 39.522 51.115 39.838 51.431 c 40.154 51.747 40.337 52.191 40.337 52.637 c f BT 45.750 49.670 Td /F1 9.8 Tf [(Patients who have used corticosteroids for prolonged periods can be considered as having suppression of the HPA axis up )] TJ ET Q q 15.000 35.384 577.500 741.616 re W n 0.271 0.267 0.267 rg BT 45.750 767.476 Td /F1 9.8 Tf [(neuromuscular provider and/or endocrinologist.)] TJ ET BT 26.250 744.321 Td /F1 9.8 Tf [(Weaning from corticosteroids, and reactivating the adrenal glands, may take several months to achieve. A recommendation for )] TJ ET BT 26.250 732.417 Td /F1 9.8 Tf [(tapering chronic corticosteroids \(generally managed in an outpatient setting\) is as follows:)] TJ ET 0.271 0.267 0.267 RG 40.337 715.980 m 40.337 716.426 40.154 716.870 39.838 717.186 c 39.522 717.502 39.078 717.686 38.631 717.686 c 38.185 717.686 37.741 717.502 37.425 717.186 c 37.109 716.870 36.925 716.426 36.925 715.980 c 36.925 715.533 37.109 715.089 37.425 714.773 c 37.741 714.457 38.185 714.273 38.631 714.273 c 39.078 714.273 39.522 714.457 39.838 714.773 c 40.154 715.089 40.337 715.533 40.337 715.980 c f BT 45.750 713.012 Td /F1 9.8 Tf [(First, starting on a Monday, giving 20-25% lower corticosteroid dose for 2 weeks \(or longer\))] TJ ET 40.337 700.325 m 40.337 700.771 40.154 701.215 39.838 701.531 c 39.522 701.847 39.078 702.031 38.631 702.031 c 38.185 702.031 37.741 701.847 37.425 701.531 c 37.109 701.215 36.925 700.771 36.925 700.325 c 36.925 699.878 37.109 699.434 37.425 699.118 c 37.741 698.802 38.185 698.619 38.631 698.619 c 39.078 698.619 39.522 698.802 39.838 699.118 c 40.154 699.434 40.337 699.878 40.337 700.325 c f BT 45.750 697.357 Td /F1 9.8 Tf [(Next, if multiple daily doses are taken, start first to reduce to a single morning dose )] TJ ET 0.39 w 1 J 1 j 59.837 684.670 m 59.837 685.117 59.654 685.561 59.338 685.877 c 59.022 686.192 58.578 686.376 58.131 686.376 c 57.685 686.376 57.241 686.192 56.925 685.877 c 56.609 685.561 56.425 685.117 56.425 684.670 c 56.425 684.223 56.609 683.779 56.925 683.463 c 57.241 683.148 57.685 682.964 58.131 682.964 c 58.578 682.964 59.022 683.148 59.338 683.463 c 59.654 683.779 59.837 684.223 59.837 684.670 c s BT 65.250 681.702 Td /F1 9.8 Tf [(Cut the dose 20-25% again for 2 weeks \(or longer\); continues this schedule)] TJ ET 0.39 w 1 J 1 j 59.837 669.015 m 59.837 669.462 59.654 669.906 59.338 670.222 c 59.022 670.538 58.578 670.721 58.131 670.721 c 57.685 670.721 57.241 670.538 56.925 670.222 c 56.609 669.906 56.425 669.462 56.425 669.015 c 56.425 668.569 56.609 668.125 56.925 667.809 c 57.241 667.493 57.685 667.309 58.131 667.309 c 58.578 667.309 59.022 667.493 59.338 667.809 c 59.654 668.125 59.837 668.569 59.837 669.015 c s BT 65.250 666.048 Td /F1 9.8 Tf [(Continue until dose is near physiologic dose \(3mg/m2/day of prednisone or 3.6mg/m2/day of Deflazacort\))] TJ ET 40.337 649.611 m 40.337 650.057 40.154 650.501 39.838 650.817 c 39.522 651.133 39.078 651.317 38.631 651.317 c 38.185 651.317 37.741 651.133 37.425 650.817 c 37.109 650.501 36.925 650.057 36.925 649.611 c 36.925 649.164 37.109 648.720 37.425 648.404 c 37.741 648.088 38.185 647.904 38.631 647.904 c 39.078 647.904 39.522 648.088 39.838 648.404 c 40.154 648.720 40.337 649.164 40.337 649.611 c f BT 45.750 646.643 Td /F1 9.8 Tf [(When near physiologic dose, substitute corticosteroids with short acting form of corticosteroid or hydrocortisone \(12 )] TJ ET BT 45.750 634.738 Td /F1 9.8 Tf [(mg/m2/day of hydrocortisone\))] TJ ET 40.337 622.051 m 40.337 622.498 40.154 622.942 39.838 623.258 c 39.522 623.573 39.078 623.757 38.631 623.757 c 38.185 623.757 37.741 623.573 37.425 623.258 c 37.109 622.942 36.925 622.498 36.925 622.051 c 36.925 621.604 37.109 621.160 37.425 620.844 c 37.741 620.529 38.185 620.345 38.631 620.345 c 39.078 620.345 39.522 620.529 39.838 620.844 c 40.154 621.160 40.337 621.604 40.337 622.051 c f BT 45.750 619.083 Td /F1 9.8 Tf [(This will also enable the patient to have a supply of hydrocortisone to be used for stress doses if needed in times of stress )] TJ ET BT 45.750 607.179 Td /F1 9.8 Tf [(after coming off steroids )] TJ ET 0.39 w 1 J 1 j 59.837 594.491 m 59.837 594.938 59.654 595.382 59.338 595.698 c 59.022 596.014 58.578 596.198 58.131 596.198 c 57.685 596.198 57.241 596.014 56.925 595.698 c 56.609 595.382 56.425 594.938 56.425 594.491 c 56.425 594.045 56.609 593.601 56.925 593.285 c 57.241 592.969 57.685 592.785 58.131 592.785 c 58.578 592.785 59.022 592.969 59.338 593.285 c 59.654 593.601 59.837 594.045 59.837 594.491 c s BT 65.250 591.524 Td /F1 9.8 Tf [(Continue to taper off by 20-25% each week \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 578.837 m 59.837 579.283 59.654 579.727 59.338 580.043 c 59.022 580.359 58.578 580.543 58.131 580.543 c 57.685 580.543 57.241 580.359 56.925 580.043 c 56.609 579.727 56.425 579.283 56.425 578.837 c 56.425 578.390 56.609 577.946 56.925 577.630 c 57.241 577.314 57.685 577.130 58.131 577.130 c 58.578 577.130 59.022 577.314 59.338 577.630 c 59.654 577.946 59.837 578.390 59.837 578.837 c s BT 65.250 575.869 Td /F1 9.8 Tf [(Give every other day for 2 weeks \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 563.182 m 59.837 563.629 59.654 564.073 59.338 564.389 c 59.022 564.704 58.578 564.888 58.131 564.888 c 57.685 564.888 57.241 564.704 56.925 564.389 c 56.609 564.073 56.425 563.629 56.425 563.182 c 56.425 562.735 56.609 562.291 56.925 561.975 c 57.241 561.660 57.685 561.476 58.131 561.476 c 58.578 561.476 59.022 561.660 59.338 561.975 c 59.654 562.291 59.837 562.735 59.837 563.182 c s BT 65.250 560.214 Td /F1 9.8 Tf [(Stop)] TJ ET 0.39 w 1 J 1 j 59.837 547.527 m 59.837 547.974 59.654 548.418 59.338 548.734 c 59.022 549.050 58.578 549.233 58.131 549.233 c 57.685 549.233 57.241 549.050 56.925 548.734 c 56.609 548.418 56.425 547.974 56.425 547.527 c 56.425 547.081 56.609 546.637 56.925 546.321 c 57.241 546.005 57.685 545.821 58.131 545.821 c 58.578 545.821 59.022 546.005 59.338 546.321 c 59.654 546.637 59.837 547.081 59.837 547.527 c s BT 65.250 544.560 Td /F5 9.8 Tf [(Watch very carefully for signs of adrenal crisis \(see below\))] TJ ET 40.337 528.122 m 40.337 528.569 40.154 529.013 39.838 529.329 c 39.522 529.645 39.078 529.829 38.631 529.829 c 38.185 529.829 37.741 529.645 37.425 529.329 c 37.109 529.013 36.925 528.569 36.925 528.122 c 36.925 527.676 37.109 527.232 37.425 526.916 c 37.741 526.600 38.185 526.416 38.631 526.416 c 39.078 526.416 39.522 526.600 39.838 526.916 c 40.154 527.232 40.337 527.676 40.337 528.122 c f BT 45.750 525.155 Td /F1 9.8 Tf [(Alert patients and parents to signs/symptoms of adrenal crisis)] TJ ET 40.337 512.468 m 40.337 512.914 40.154 513.358 39.838 513.674 c 39.522 513.990 39.078 514.174 38.631 514.174 c 38.185 514.174 37.741 513.990 37.425 513.674 c 37.109 513.358 36.925 512.914 36.925 512.468 c 36.925 512.021 37.109 511.577 37.425 511.261 c 37.741 510.945 38.185 510.761 38.631 510.761 c 39.078 510.761 39.522 510.945 39.838 511.261 c 40.154 511.577 40.337 512.021 40.337 512.468 c f BT 45.750 509.500 Td /F1 9.8 Tf [(If patients have symptoms of adrenal insufficiency during the taper, the patient should return to the previous steroid dose, )] TJ ET BT 45.750 497.595 Td /F1 9.8 Tf [(which should be maintained longer)] TJ ET BT 26.250 474.441 Td /F5 9.8 Tf [(If the patient has a serious illness/injury during the taper, they may need a stress dose of corticosteroids:)] TJ ET 40.337 458.003 m 40.337 458.450 40.154 458.894 39.838 459.210 c 39.522 459.526 39.078 459.710 38.631 459.710 c 38.185 459.710 37.741 459.526 37.425 459.210 c 37.109 458.894 36.925 458.450 36.925 458.003 c 36.925 457.557 37.109 457.113 37.425 456.797 c 37.741 456.481 38.185 456.297 38.631 456.297 c 39.078 456.297 39.522 456.481 39.838 456.797 c 40.154 457.113 40.337 457.557 40.337 458.003 c f BT 45.750 455.036 Td /F1 9.8 Tf [(Encourage parents to continue to report any serious events until 1 year post-taper )] TJ ET 0.39 w 1 J 1 j 59.837 442.349 m 59.837 442.795 59.654 443.239 59.338 443.555 c 59.022 443.871 58.578 444.055 58.131 444.055 c 57.685 444.055 57.241 443.871 56.925 443.555 c 56.609 443.239 56.425 442.795 56.425 442.349 c 56.425 441.902 56.609 441.458 56.925 441.142 c 57.241 440.826 57.685 440.642 58.131 440.642 c 58.578 440.642 59.022 440.826 59.338 441.142 c 59.654 441.458 59.837 441.902 59.837 442.349 c s BT 65.250 439.381 Td /F1 9.8 Tf [(The stress doses of hydrocortisone is 30-50 mg/m2/day, or higher, for major stress \(see Table 2\))] TJ ET 0.39 w 1 J 1 j 59.837 426.694 m 59.837 427.141 59.654 427.585 59.338 427.901 c 59.022 428.216 58.578 428.400 58.131 428.400 c 57.685 428.400 57.241 428.216 56.925 427.901 c 56.609 427.585 56.425 427.141 56.425 426.694 c 56.425 426.247 56.609 425.803 56.925 425.487 c 57.241 425.172 57.685 424.988 58.131 424.988 c 58.578 424.988 59.022 425.172 59.338 425.487 c 59.654 425.803 59.837 426.247 59.837 426.694 c s BT 65.250 423.726 Td /F1 9.8 Tf [(Patients need to go to the emergency room if they are having signs or symptoms of adrenal crisis. Serum electrolytes )] TJ ET BT 65.250 411.822 Td /F1 9.8 Tf [(with blood glucose and cortisol level should be obtained.)] TJ ET 0.39 w 1 J 1 j 59.837 399.134 m 59.837 399.581 59.654 400.025 59.338 400.341 c 59.022 400.657 58.578 400.841 58.131 400.841 c 57.685 400.841 57.241 400.657 56.925 400.341 c 56.609 400.025 56.425 399.581 56.425 399.134 c 56.425 398.688 56.609 398.244 56.925 397.928 c 57.241 397.612 57.685 397.428 58.131 397.428 c 58.578 397.428 59.022 397.612 59.338 397.928 c 59.654 398.244 59.837 398.688 59.837 399.134 c s BT 65.250 396.167 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress )] TJ ET BT 65.250 384.262 Td /F1 9.8 Tf [(dose of hydrocortisone.)] TJ ET 0.39 w 1 J 1 j 59.837 371.575 m 59.837 372.022 59.654 372.466 59.338 372.782 c 59.022 373.097 58.578 373.281 58.131 373.281 c 57.685 373.281 57.241 373.097 56.925 372.782 c 56.609 372.466 56.425 372.022 56.425 371.575 c 56.425 371.128 56.609 370.684 56.925 370.368 c 57.241 370.053 57.685 369.869 58.131 369.869 c 58.578 369.869 59.022 370.053 59.338 370.368 c 59.654 370.684 59.837 371.128 59.837 371.575 c s BT 65.250 368.607 Td /F1 9.8 Tf [(Patients should see an endocrinologist for evaluation of HPA axis during the process of corticosteroid therapy )] TJ ET BT 65.250 356.703 Td /F1 9.8 Tf [(withdrawal.)] TJ ET BT 26.250 329.798 Td /F1 9.8 Tf [(Testing the HPA axis:)] TJ ET 0.267 0.267 0.267 rg BT 119.996 331.305 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.655 38.631 311.655 c 39.078 311.655 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(After reaching half the physiological dose \(5-6 mg/m2/day of hydrocortisone or 1-1.5 mg/m2/day of prednisone\), monthly )] TJ ET BT 45.750 298.488 Td /F1 9.8 Tf [(morning serum cortisol and ACTH should be assayed \(may do less frequently\), until they reach normal levels.)] TJ ET 40.337 285.801 m 40.337 286.248 40.154 286.692 39.838 287.008 c 39.522 287.324 39.078 287.508 38.631 287.508 c 38.185 287.508 37.741 287.324 37.425 287.008 c 37.109 286.692 36.925 286.248 36.925 285.801 c 36.925 285.355 37.109 284.911 37.425 284.595 c 37.741 284.279 38.185 284.095 38.631 284.095 c 39.078 284.095 39.522 284.279 39.838 284.595 c 40.154 284.911 40.337 285.355 40.337 285.801 c f BT 45.750 282.834 Td /F1 9.8 Tf [(When baseline monthly morning serum ACTH and cortisol are normal, discontinue the corticosteroid and carry out the )] TJ ET BT 556.192 282.834 Td /F1 9.8 Tf [(rapid )] TJ ET BT 45.750 270.929 Td /F1 9.8 Tf [(ACTH stimulation test \(may also be called cosyntropin, tetracosactide or Synacthen tests\) monthly until post-stimulation )] TJ ET BT 45.750 259.024 Td /F1 9.8 Tf [(cortisol response is normal \(post-stimulus level > 20 mcg/dL\). When this point is reached, it can be considered that the )] TJ ET BT 45.750 247.119 Td /F1 9.8 Tf [(HPA axis has recovered.)] TJ ET 40.337 234.432 m 40.337 234.879 40.154 235.323 39.838 235.639 c 39.522 235.955 39.078 236.139 38.631 236.139 c 38.185 236.139 37.741 235.955 37.425 235.639 c 37.109 235.323 36.925 234.879 36.925 234.432 c 36.925 233.986 37.109 233.542 37.425 233.226 c 37.741 232.910 38.185 232.726 38.631 232.726 c 39.078 232.726 39.522 232.910 39.838 233.226 c 40.154 233.542 40.337 233.986 40.337 234.432 c f BT 45.750 231.465 Td /F1 9.8 Tf [(It may be appropriate to recheck the rapid ACTH stimulation test after 1 year, to establish continued full recovery of the )] TJ ET BT 45.750 219.560 Td /F1 9.8 Tf [(HPA axis.)] TJ ET BT 26.250 179.207 Td /F4 12.0 Tf [(Modification of above protocol:)] TJ ET 40.337 162.221 m 40.337 162.667 40.154 163.111 39.838 163.427 c 39.522 163.743 39.078 163.927 38.631 163.927 c 38.185 163.927 37.741 163.743 37.425 163.427 c 37.109 163.111 36.925 162.667 36.925 162.221 c 36.925 161.774 37.109 161.330 37.425 161.014 c 37.741 160.698 38.185 160.515 38.631 160.515 c 39.078 160.515 39.522 160.698 39.838 161.014 c 40.154 161.330 40.337 161.774 40.337 162.221 c f BT 45.750 159.253 Td /F1 9.8 Tf [(Omit monthly AM cortisol and ACTH and perform an ACTH stimulation test in 3 months after discontinuation of )] TJ ET BT 45.750 147.348 Td /F1 9.8 Tf [(corticosteroids)] TJ ET 40.337 134.661 m 40.337 135.108 40.154 135.552 39.838 135.868 c 39.522 136.184 39.078 136.368 38.631 136.368 c 38.185 136.368 37.741 136.184 37.425 135.868 c 37.109 135.552 36.925 135.108 36.925 134.661 c 36.925 134.215 37.109 133.771 37.425 133.455 c 37.741 133.139 38.185 132.955 38.631 132.955 c 39.078 132.955 39.522 133.139 39.838 133.455 c 40.154 133.771 40.337 134.215 40.337 134.661 c f BT 45.750 131.694 Td /F1 9.8 Tf [(During this time \(3 months before getting ACTH stimulation test\), patients will need to take stress dose at the time of stress)] TJ ET 40.337 119.006 m 40.337 119.453 40.154 119.897 39.838 120.213 c 39.522 120.529 39.078 120.713 38.631 120.713 c 38.185 120.713 37.741 120.529 37.425 120.213 c 37.109 119.897 36.925 119.453 36.925 119.006 c 36.925 118.560 37.109 118.116 37.425 117.800 c 37.741 117.484 38.185 117.300 38.631 117.300 c 39.078 117.300 39.522 117.484 39.838 117.800 c 40.154 118.116 40.337 118.560 40.337 119.006 c f BT 45.750 116.039 Td /F1 9.8 Tf [(If ACTH stimulation test result is abnormal \(peak cortisol <20\), patients will need to continue taking stress doses of )] TJ ET BT 45.750 104.134 Td /F1 9.8 Tf [(hydrocortisone at the time of stress. \(Patients should have a repeat ACTH stimulation test again in 1-2 months later and )] TJ ET BT 45.750 92.229 Td /F1 9.8 Tf [(families would need to have teaching on this with an endocrine nurse.\))] TJ ET BT 26.250 69.075 Td /F1 9.8 Tf [(Alternatively, when laboratory tests cannot be carried out:)] TJ ET 40.337 52.637 m 40.337 53.084 40.154 53.528 39.838 53.844 c 39.522 54.160 39.078 54.344 38.631 54.344 c 38.185 54.344 37.741 54.160 37.425 53.844 c 37.109 53.528 36.925 53.084 36.925 52.637 c 36.925 52.191 37.109 51.747 37.425 51.431 c 37.741 51.115 38.185 50.931 38.631 50.931 c 39.078 50.931 39.522 51.115 39.838 51.431 c 40.154 51.747 40.337 52.191 40.337 52.637 c f BT 45.750 49.670 Td /F1 9.8 Tf [(Patients who have used corticosteroids for prolonged periods can be considered as having suppression of the HPA axis up )] TJ ET Q q 15.000 35.384 577.500 741.616 re W n 0.271 0.267 0.267 rg BT 45.750 767.476 Td /F1 9.8 Tf [(neuromuscular provider and/or endocrinologist.)] TJ ET BT 26.250 744.321 Td /F1 9.8 Tf [(Weaning from corticosteroids, and reactivating the adrenal glands, may take several months to achieve. A recommendation for )] TJ ET BT 26.250 732.417 Td /F1 9.8 Tf [(tapering chronic corticosteroids \(generally managed in an outpatient setting\) is as follows:)] TJ ET 0.271 0.267 0.267 RG 40.337 715.980 m 40.337 716.426 40.154 716.870 39.838 717.186 c 39.522 717.502 39.078 717.686 38.631 717.686 c 38.185 717.686 37.741 717.502 37.425 717.186 c 37.109 716.870 36.925 716.426 36.925 715.980 c 36.925 715.533 37.109 715.089 37.425 714.773 c 37.741 714.457 38.185 714.273 38.631 714.273 c 39.078 714.273 39.522 714.457 39.838 714.773 c 40.154 715.089 40.337 715.533 40.337 715.980 c f BT 45.750 713.012 Td /F1 9.8 Tf [(First, starting on a Monday, giving 20-25% lower corticosteroid dose for 2 weeks \(or longer\))] TJ ET 40.337 700.325 m 40.337 700.771 40.154 701.215 39.838 701.531 c 39.522 701.847 39.078 702.031 38.631 702.031 c 38.185 702.031 37.741 701.847 37.425 701.531 c 37.109 701.215 36.925 700.771 36.925 700.325 c 36.925 699.878 37.109 699.434 37.425 699.118 c 37.741 698.802 38.185 698.619 38.631 698.619 c 39.078 698.619 39.522 698.802 39.838 699.118 c 40.154 699.434 40.337 699.878 40.337 700.325 c f BT 45.750 697.357 Td /F1 9.8 Tf [(Next, if multiple daily doses are taken, start first to reduce to a single morning dose )] TJ ET 0.39 w 1 J 1 j 59.837 684.670 m 59.837 685.117 59.654 685.561 59.338 685.877 c 59.022 686.192 58.578 686.376 58.131 686.376 c 57.685 686.376 57.241 686.192 56.925 685.877 c 56.609 685.561 56.425 685.117 56.425 684.670 c 56.425 684.223 56.609 683.779 56.925 683.463 c 57.241 683.148 57.685 682.964 58.131 682.964 c 58.578 682.964 59.022 683.148 59.338 683.463 c 59.654 683.779 59.837 684.223 59.837 684.670 c s BT 65.250 681.702 Td /F1 9.8 Tf [(Cut the dose 20-25% again for 2 weeks \(or longer\); continues this schedule)] TJ ET 0.39 w 1 J 1 j 59.837 669.015 m 59.837 669.462 59.654 669.906 59.338 670.222 c 59.022 670.538 58.578 670.721 58.131 670.721 c 57.685 670.721 57.241 670.538 56.925 670.222 c 56.609 669.906 56.425 669.462 56.425 669.015 c 56.425 668.569 56.609 668.125 56.925 667.809 c 57.241 667.493 57.685 667.309 58.131 667.309 c 58.578 667.309 59.022 667.493 59.338 667.809 c 59.654 668.125 59.837 668.569 59.837 669.015 c s BT 65.250 666.048 Td /F1 9.8 Tf [(Continue until dose is near physiologic dose \(3mg/m2/day of prednisone or 3.6mg/m2/day of Deflazacort\))] TJ ET 40.337 649.611 m 40.337 650.057 40.154 650.501 39.838 650.817 c 39.522 651.133 39.078 651.317 38.631 651.317 c 38.185 651.317 37.741 651.133 37.425 650.817 c 37.109 650.501 36.925 650.057 36.925 649.611 c 36.925 649.164 37.109 648.720 37.425 648.404 c 37.741 648.088 38.185 647.904 38.631 647.904 c 39.078 647.904 39.522 648.088 39.838 648.404 c 40.154 648.720 40.337 649.164 40.337 649.611 c f BT 45.750 646.643 Td /F1 9.8 Tf [(When near physiologic dose, substitute corticosteroids with short acting form of corticosteroid or hydrocortisone \(12 )] TJ ET BT 45.750 634.738 Td /F1 9.8 Tf [(mg/m2/day of hydrocortisone\))] TJ ET 40.337 622.051 m 40.337 622.498 40.154 622.942 39.838 623.258 c 39.522 623.573 39.078 623.757 38.631 623.757 c 38.185 623.757 37.741 623.573 37.425 623.258 c 37.109 622.942 36.925 622.498 36.925 622.051 c 36.925 621.604 37.109 621.160 37.425 620.844 c 37.741 620.529 38.185 620.345 38.631 620.345 c 39.078 620.345 39.522 620.529 39.838 620.844 c 40.154 621.160 40.337 621.604 40.337 622.051 c f BT 45.750 619.083 Td /F1 9.8 Tf [(This will also enable the patient to have a supply of hydrocortisone to be used for stress doses if needed in times of stress )] TJ ET BT 45.750 607.179 Td /F1 9.8 Tf [(after coming off steroids )] TJ ET 0.39 w 1 J 1 j 59.837 594.491 m 59.837 594.938 59.654 595.382 59.338 595.698 c 59.022 596.014 58.578 596.198 58.131 596.198 c 57.685 596.198 57.241 596.014 56.925 595.698 c 56.609 595.382 56.425 594.938 56.425 594.491 c 56.425 594.045 56.609 593.601 56.925 593.285 c 57.241 592.969 57.685 592.785 58.131 592.785 c 58.578 592.785 59.022 592.969 59.338 593.285 c 59.654 593.601 59.837 594.045 59.837 594.491 c s BT 65.250 591.524 Td /F1 9.8 Tf [(Continue to taper off by 20-25% each week \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 578.837 m 59.837 579.283 59.654 579.727 59.338 580.043 c 59.022 580.359 58.578 580.543 58.131 580.543 c 57.685 580.543 57.241 580.359 56.925 580.043 c 56.609 579.727 56.425 579.283 56.425 578.837 c 56.425 578.390 56.609 577.946 56.925 577.630 c 57.241 577.314 57.685 577.130 58.131 577.130 c 58.578 577.130 59.022 577.314 59.338 577.630 c 59.654 577.946 59.837 578.390 59.837 578.837 c s BT 65.250 575.869 Td /F1 9.8 Tf [(Give every other day for 2 weeks \(or longer\))] TJ ET 0.39 w 1 J 1 j 59.837 563.182 m 59.837 563.629 59.654 564.073 59.338 564.389 c 59.022 564.704 58.578 564.888 58.131 564.888 c 57.685 564.888 57.241 564.704 56.925 564.389 c 56.609 564.073 56.425 563.629 56.425 563.182 c 56.425 562.735 56.609 562.291 56.925 561.975 c 57.241 561.660 57.685 561.476 58.131 561.476 c 58.578 561.476 59.022 561.660 59.338 561.975 c 59.654 562.291 59.837 562.735 59.837 563.182 c s BT 65.250 560.214 Td /F1 9.8 Tf [(Stop)] TJ ET 0.39 w 1 J 1 j 59.837 547.527 m 59.837 547.974 59.654 548.418 59.338 548.734 c 59.022 549.050 58.578 549.233 58.131 549.233 c 57.685 549.233 57.241 549.050 56.925 548.734 c 56.609 548.418 56.425 547.974 56.425 547.527 c 56.425 547.081 56.609 546.637 56.925 546.321 c 57.241 546.005 57.685 545.821 58.131 545.821 c 58.578 545.821 59.022 546.005 59.338 546.321 c 59.654 546.637 59.837 547.081 59.837 547.527 c s BT 65.250 544.560 Td /F5 9.8 Tf [(Watch very carefully for signs of adrenal crisis \(see below\))] TJ ET 40.337 528.122 m 40.337 528.569 40.154 529.013 39.838 529.329 c 39.522 529.645 39.078 529.829 38.631 529.829 c 38.185 529.829 37.741 529.645 37.425 529.329 c 37.109 529.013 36.925 528.569 36.925 528.122 c 36.925 527.676 37.109 527.232 37.425 526.916 c 37.741 526.600 38.185 526.416 38.631 526.416 c 39.078 526.416 39.522 526.600 39.838 526.916 c 40.154 527.232 40.337 527.676 40.337 528.122 c f BT 45.750 525.155 Td /F1 9.8 Tf [(Alert patients and parents to signs/symptoms of adrenal crisis)] TJ ET 40.337 512.468 m 40.337 512.914 40.154 513.358 39.838 513.674 c 39.522 513.990 39.078 514.174 38.631 514.174 c 38.185 514.174 37.741 513.990 37.425 513.674 c 37.109 513.358 36.925 512.914 36.925 512.468 c 36.925 512.021 37.109 511.577 37.425 511.261 c 37.741 510.945 38.185 510.761 38.631 510.761 c 39.078 510.761 39.522 510.945 39.838 511.261 c 40.154 511.577 40.337 512.021 40.337 512.468 c f BT 45.750 509.500 Td /F1 9.8 Tf [(If patients have symptoms of adrenal insufficiency during the taper, the patient should return to the previous steroid dose, )] TJ ET BT 45.750 497.595 Td /F1 9.8 Tf [(which should be maintained longer)] TJ ET BT 26.250 474.441 Td /F5 9.8 Tf [(If the patient has a serious illness/injury during the taper, they may need a stress dose of corticosteroids:)] TJ ET 40.337 458.003 m 40.337 458.450 40.154 458.894 39.838 459.210 c 39.522 459.526 39.078 459.710 38.631 459.710 c 38.185 459.710 37.741 459.526 37.425 459.210 c 37.109 458.894 36.925 458.450 36.925 458.003 c 36.925 457.557 37.109 457.113 37.425 456.797 c 37.741 456.481 38.185 456.297 38.631 456.297 c 39.078 456.297 39.522 456.481 39.838 456.797 c 40.154 457.113 40.337 457.557 40.337 458.003 c f BT 45.750 455.036 Td /F1 9.8 Tf [(Encourage parents to continue to report any serious events until 1 year post-taper )] TJ ET 0.39 w 1 J 1 j 59.837 442.349 m 59.837 442.795 59.654 443.239 59.338 443.555 c 59.022 443.871 58.578 444.055 58.131 444.055 c 57.685 444.055 57.241 443.871 56.925 443.555 c 56.609 443.239 56.425 442.795 56.425 442.349 c 56.425 441.902 56.609 441.458 56.925 441.142 c 57.241 440.826 57.685 440.642 58.131 440.642 c 58.578 440.642 59.022 440.826 59.338 441.142 c 59.654 441.458 59.837 441.902 59.837 442.349 c s BT 65.250 439.381 Td /F1 9.8 Tf [(The stress doses of hydrocortisone is 30-50 mg/m2/day, or higher, for major stress \(see Table 2\))] TJ ET 0.39 w 1 J 1 j 59.837 426.694 m 59.837 427.141 59.654 427.585 59.338 427.901 c 59.022 428.216 58.578 428.400 58.131 428.400 c 57.685 428.400 57.241 428.216 56.925 427.901 c 56.609 427.585 56.425 427.141 56.425 426.694 c 56.425 426.247 56.609 425.803 56.925 425.487 c 57.241 425.172 57.685 424.988 58.131 424.988 c 58.578 424.988 59.022 425.172 59.338 425.487 c 59.654 425.803 59.837 426.247 59.837 426.694 c s BT 65.250 423.726 Td /F1 9.8 Tf [(Patients need to go to the emergency room if they are having signs or symptoms of adrenal crisis. Serum electrolytes )] TJ ET BT 65.250 411.822 Td /F1 9.8 Tf [(with blood glucose and cortisol level should be obtained.)] TJ ET 0.39 w 1 J 1 j 59.837 399.134 m 59.837 399.581 59.654 400.025 59.338 400.341 c 59.022 400.657 58.578 400.841 58.131 400.841 c 57.685 400.841 57.241 400.657 56.925 400.341 c 56.609 400.025 56.425 399.581 56.425 399.134 c 56.425 398.688 56.609 398.244 56.925 397.928 c 57.241 397.612 57.685 397.428 58.131 397.428 c 58.578 397.428 59.022 397.612 59.338 397.928 c 59.654 398.244 59.837 398.688 59.837 399.134 c s BT 65.250 396.167 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress )] TJ ET BT 65.250 384.262 Td /F1 9.8 Tf [(dose of hydrocortisone.)] TJ ET 0.39 w 1 J 1 j 59.837 371.575 m 59.837 372.022 59.654 372.466 59.338 372.782 c 59.022 373.097 58.578 373.281 58.131 373.281 c 57.685 373.281 57.241 373.097 56.925 372.782 c 56.609 372.466 56.425 372.022 56.425 371.575 c 56.425 371.128 56.609 370.684 56.925 370.368 c 57.241 370.053 57.685 369.869 58.131 369.869 c 58.578 369.869 59.022 370.053 59.338 370.368 c 59.654 370.684 59.837 371.128 59.837 371.575 c s BT 65.250 368.607 Td /F1 9.8 Tf [(Patients should see an endocrinologist for evaluation of HPA axis during the process of corticosteroid therapy )] TJ ET BT 65.250 356.703 Td /F1 9.8 Tf [(withdrawal.)] TJ ET BT 26.250 329.798 Td /F1 9.8 Tf [(Testing the HPA axis:)] TJ ET 0.267 0.267 0.267 rg BT 119.996 331.305 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.655 38.631 311.655 c 39.078 311.655 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(After reaching half the physiological dose \(5-6 mg/m2/day of hydrocortisone or 1-1.5 mg/m2/day of prednisone\), monthly )] TJ ET BT 45.750 298.488 Td /F1 9.8 Tf [(morning serum cortisol and ACTH should be assayed \(may do less frequently\), until they reach normal levels.)] TJ ET 40.337 285.801 m 40.337 286.248 40.154 286.692 39.838 287.008 c 39.522 287.324 39.078 287.508 38.631 287.508 c 38.185 287.508 37.741 287.324 37.425 287.008 c 37.109 286.692 36.925 286.248 36.925 285.801 c 36.925 285.355 37.109 284.911 37.425 284.595 c 37.741 284.279 38.185 284.095 38.631 284.095 c 39.078 284.095 39.522 284.279 39.838 284.595 c 40.154 284.911 40.337 285.355 40.337 285.801 c f BT 45.750 282.834 Td /F1 9.8 Tf [(When baseline monthly morning serum ACTH and cortisol are normal, discontinue the corticosteroid and carry out the )] TJ ET BT 556.192 282.834 Td /F1 9.8 Tf [(rapid )] TJ ET BT 45.750 270.929 Td /F1 9.8 Tf [(ACTH stimulation test \(may also be called cosyntropin, tetracosactide or Synacthen tests\) monthly until post-stimulation )] TJ ET BT 45.750 259.024 Td /F1 9.8 Tf [(cortisol response is normal \(post-stimulus level > 20 mcg/dL\). When this point is reached, it can be considered that the )] TJ ET BT 45.750 247.119 Td /F1 9.8 Tf [(HPA axis has recovered.)] TJ ET 40.337 234.432 m 40.337 234.879 40.154 235.323 39.838 235.639 c 39.522 235.955 39.078 236.139 38.631 236.139 c 38.185 236.139 37.741 235.955 37.425 235.639 c 37.109 235.323 36.925 234.879 36.925 234.432 c 36.925 233.986 37.109 233.542 37.425 233.226 c 37.741 232.910 38.185 232.726 38.631 232.726 c 39.078 232.726 39.522 232.910 39.838 233.226 c 40.154 233.542 40.337 233.986 40.337 234.432 c f BT 45.750 231.465 Td /F1 9.8 Tf [(It may be appropriate to recheck the rapid ACTH stimulation test after 1 year, to establish continued full recovery of the )] TJ ET BT 45.750 219.560 Td /F1 9.8 Tf [(HPA axis.)] TJ ET BT 26.250 179.207 Td /F4 12.0 Tf [(Modification of above protocol:)] TJ ET 40.337 162.221 m 40.337 162.667 40.154 163.111 39.838 163.427 c 39.522 163.743 39.078 163.927 38.631 163.927 c 38.185 163.927 37.741 163.743 37.425 163.427 c 37.109 163.111 36.925 162.667 36.925 162.221 c 36.925 161.774 37.109 161.330 37.425 161.014 c 37.741 160.698 38.185 160.515 38.631 160.515 c 39.078 160.515 39.522 160.698 39.838 161.014 c 40.154 161.330 40.337 161.774 40.337 162.221 c f BT 45.750 159.253 Td /F1 9.8 Tf [(Omit monthly AM cortisol and ACTH and perform an ACTH stimulation test in 3 months after discontinuation of )] TJ ET BT 45.750 147.348 Td /F1 9.8 Tf [(corticosteroids)] TJ ET 40.337 134.661 m 40.337 135.108 40.154 135.552 39.838 135.868 c 39.522 136.184 39.078 136.368 38.631 136.368 c 38.185 136.368 37.741 136.184 37.425 135.868 c 37.109 135.552 36.925 135.108 36.925 134.661 c 36.925 134.215 37.109 133.771 37.425 133.455 c 37.741 133.139 38.185 132.955 38.631 132.955 c 39.078 132.955 39.522 133.139 39.838 133.455 c 40.154 133.771 40.337 134.215 40.337 134.661 c f BT 45.750 131.694 Td /F1 9.8 Tf [(During this time \(3 months before getting ACTH stimulation test\), patients will need to take stress dose at the time of stress)] TJ ET 40.337 119.006 m 40.337 119.453 40.154 119.897 39.838 120.213 c 39.522 120.529 39.078 120.713 38.631 120.713 c 38.185 120.713 37.741 120.529 37.425 120.213 c 37.109 119.897 36.925 119.453 36.925 119.006 c 36.925 118.560 37.109 118.116 37.425 117.800 c 37.741 117.484 38.185 117.300 38.631 117.300 c 39.078 117.300 39.522 117.484 39.838 117.800 c 40.154 118.116 40.337 118.560 40.337 119.006 c f BT 45.750 116.039 Td /F1 9.8 Tf [(If ACTH stimulation test result is abnormal \(peak cortisol <20\), patients will need to continue taking stress doses of )] TJ ET BT 45.750 104.134 Td /F1 9.8 Tf [(hydrocortisone at the time of stress. \(Patients should have a repeat ACTH stimulation test again in 1-2 months later and )] TJ ET BT 45.750 92.229 Td /F1 9.8 Tf [(families would need to have teaching on this with an endocrine nurse.\))] TJ ET BT 26.250 69.075 Td /F1 9.8 Tf [(Alternatively, when laboratory tests cannot be carried out:)] TJ ET 40.337 52.637 m 40.337 53.084 40.154 53.528 39.838 53.844 c 39.522 54.160 39.078 54.344 38.631 54.344 c 38.185 54.344 37.741 54.160 37.425 53.844 c 37.109 53.528 36.925 53.084 36.925 52.637 c 36.925 52.191 37.109 51.747 37.425 51.431 c 37.741 51.115 38.185 50.931 38.631 50.931 c 39.078 50.931 39.522 51.115 39.838 51.431 c 40.154 51.747 40.337 52.191 40.337 52.637 c f BT 45.750 49.670 Td /F1 9.8 Tf [(Patients who have used corticosteroids for prolonged periods can be considered as having suppression of the HPA axis up )] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(4)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular Dystrophy)] TJ ET 0.39 w 1 J 1 j Q endstream endobj 191 0 obj << /Type /Annot /Subtype /Link /A 192 0 R /Border [0 0 0] /H /I /Rect [ 119.9963 330.5034 129.6336 339.3218 ] >> endobj 192 0 obj << /Type /Action >> endobj 193 0 obj << /Type /Annot /Subtype /Link /A 194 0 R /Border [0 0 0] /H /I /Rect [ 119.9963 330.5034 129.6336 339.3218 ] >> endobj 194 0 obj << /Type /Action >> endobj 195 0 obj << /Type /Annot /Subtype /Link /A 196 0 R /Border [0 0 0] /H /I /Rect [ 119.9963 330.5034 129.6336 339.3218 ] >> endobj 196 0 obj << /Type /Action >> endobj 197 0 obj << /Type /Page /Parent 3 0 R /Annots [ 199 0 R 201 0 R 203 0 R 206 0 R 208 0 R 210 0 R 212 0 R 214 0 R 216 0 R ] /Contents 198 0 R >> endobj 198 0 obj << /Length 46825 >> stream 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG 0.39 w 1 J 1 j q 15.000 -94.535 577.500 871.535 re W n 0.271 0.267 0.267 rg BT 45.750 767.476 Td /F1 9.8 Tf [(to 1 year after discontinuation of corticosteroid therapy and therefore need hydrocortisone stress dose coverage during the )] TJ ET BT 45.750 755.571 Td /F1 9.8 Tf [(time of stress.)] TJ ET BT 26.250 732.417 Td /F1 9.8 Tf [(Risk factors for adrenal crisis include:)] TJ ET 0.267 0.267 0.267 rg BT 187.710 733.924 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG 40.337 715.980 m 40.337 716.426 40.154 716.870 39.838 717.186 c 39.522 717.502 39.078 717.686 38.631 717.686 c 38.185 717.686 37.741 717.502 37.425 717.186 c 37.109 716.870 36.925 716.426 36.925 715.980 c 36.925 715.533 37.109 715.089 37.425 714.773 c 37.741 714.457 38.185 714.273 38.631 714.273 c 39.078 714.273 39.522 714.457 39.838 714.773 c 40.154 715.089 40.337 715.533 40.337 715.980 c f BT 45.750 713.012 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 700.325 m 40.337 700.771 40.154 701.215 39.838 701.531 c 39.522 701.847 39.078 702.031 38.631 702.031 c 38.185 702.031 37.741 701.847 37.425 701.531 c 37.109 701.215 36.925 700.771 36.925 700.325 c 36.925 699.878 37.109 699.434 37.425 699.118 c 37.741 698.802 38.185 698.619 38.631 698.619 c 39.078 698.619 39.522 698.802 39.838 699.118 c 40.154 699.434 40.337 699.878 40.337 700.325 c f BT 45.750 697.357 Td /F1 9.8 Tf [(Infection and other physical illness)] TJ ET 40.337 684.670 m 40.337 685.117 40.154 685.561 39.838 685.877 c 39.522 686.192 39.078 686.376 38.631 686.376 c 38.185 686.376 37.741 686.192 37.425 685.877 c 37.109 685.561 36.925 685.117 36.925 684.670 c 36.925 684.223 37.109 683.779 37.425 683.463 c 37.741 683.148 38.185 682.964 38.631 682.964 c 39.078 682.964 39.522 683.148 39.838 683.463 c 40.154 683.779 40.337 684.223 40.337 684.670 c f BT 45.750 681.702 Td /F1 9.8 Tf [(Injury to the adrenal or pituitary gland)] TJ ET 40.337 669.015 m 40.337 669.462 40.154 669.906 39.838 670.222 c 39.522 670.538 39.078 670.721 38.631 670.721 c 38.185 670.721 37.741 670.538 37.425 670.222 c 37.109 669.906 36.925 669.462 36.925 669.015 c 36.925 668.569 37.109 668.125 37.425 667.809 c 37.741 667.493 38.185 667.309 38.631 667.309 c 39.078 667.309 39.522 667.493 39.838 667.809 c 40.154 668.125 40.337 668.569 40.337 669.015 c f BT 45.750 666.048 Td /F1 9.8 Tf [(Missing usual doses of corticosteroids)] TJ ET 40.337 653.361 m 40.337 653.807 40.154 654.251 39.838 654.567 c 39.522 654.883 39.078 655.067 38.631 655.067 c 38.185 655.067 37.741 654.883 37.425 654.567 c 37.109 654.251 36.925 653.807 36.925 653.361 c 36.925 652.914 37.109 652.470 37.425 652.154 c 37.741 651.838 38.185 651.654 38.631 651.654 c 39.078 651.654 39.522 651.838 39.838 652.154 c 40.154 652.470 40.337 652.914 40.337 653.361 c f BT 45.750 650.393 Td /F1 9.8 Tf [(Surgery)] TJ ET 40.337 637.706 m 40.337 638.152 40.154 638.596 39.838 638.912 c 39.522 639.228 39.078 639.412 38.631 639.412 c 38.185 639.412 37.741 639.228 37.425 638.912 c 37.109 638.596 36.925 638.152 36.925 637.706 c 36.925 637.259 37.109 636.815 37.425 636.499 c 37.741 636.183 38.185 636.000 38.631 636.000 c 39.078 636.000 39.522 636.183 39.838 636.499 c 40.154 636.815 40.337 637.259 40.337 637.706 c f BT 45.750 634.738 Td /F1 9.8 Tf [(Trauma)] TJ ET BT 26.250 611.583 Td /F1 9.8 Tf [(Symptoms of adrenal crisis can include any of the following:)] TJ ET 0.267 0.267 0.267 rg BT 284.186 613.091 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg 40.337 595.146 m 40.337 595.593 40.154 596.037 39.838 596.353 c 39.522 596.669 39.078 596.852 38.631 596.852 c 38.185 596.852 37.741 596.669 37.425 596.353 c 37.109 596.037 36.925 595.593 36.925 595.146 c 36.925 594.700 37.109 594.256 37.425 593.940 c 37.741 593.624 38.185 593.440 38.631 593.440 c 39.078 593.440 39.522 593.624 39.838 593.940 c 40.154 594.256 40.337 594.700 40.337 595.146 c f BT 45.750 592.179 Td /F1 9.8 Tf [(Abdominal pain)] TJ ET 40.337 579.491 m 40.337 579.938 40.154 580.382 39.838 580.698 c 39.522 581.014 39.078 581.198 38.631 581.198 c 38.185 581.198 37.741 581.014 37.425 580.698 c 37.109 580.382 36.925 579.938 36.925 579.491 c 36.925 579.045 37.109 578.601 37.425 578.285 c 37.741 577.969 38.185 577.785 38.631 577.785 c 39.078 577.785 39.522 577.969 39.838 578.285 c 40.154 578.601 40.337 579.045 40.337 579.491 c f BT 45.750 576.524 Td /F1 9.8 Tf [(Hypovolemic shock)] TJ ET 40.337 563.837 m 40.337 564.283 40.154 564.727 39.838 565.043 c 39.522 565.359 39.078 565.543 38.631 565.543 c 38.185 565.543 37.741 565.359 37.425 565.043 c 37.109 564.727 36.925 564.283 36.925 563.837 c 36.925 563.390 37.109 562.946 37.425 562.630 c 37.741 562.314 38.185 562.130 38.631 562.130 c 39.078 562.130 39.522 562.314 39.838 562.630 c 40.154 562.946 40.337 563.390 40.337 563.837 c f BT 45.750 560.869 Td /F1 9.8 Tf [(Confusion or coma)] TJ ET 40.337 548.182 m 40.337 548.629 40.154 549.073 39.838 549.389 c 39.522 549.704 39.078 549.888 38.631 549.888 c 38.185 549.888 37.741 549.704 37.425 549.389 c 37.109 549.073 36.925 548.629 36.925 548.182 c 36.925 547.735 37.109 547.291 37.425 546.975 c 37.741 546.660 38.185 546.476 38.631 546.476 c 39.078 546.476 39.522 546.660 39.838 546.975 c 40.154 547.291 40.337 547.735 40.337 548.182 c f BT 45.750 545.214 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 532.527 m 40.337 532.974 40.154 533.418 39.838 533.734 c 39.522 534.050 39.078 534.233 38.631 534.233 c 38.185 534.233 37.741 534.050 37.425 533.734 c 37.109 533.418 36.925 532.974 36.925 532.527 c 36.925 532.081 37.109 531.637 37.425 531.321 c 37.741 531.005 38.185 530.821 38.631 530.821 c 39.078 530.821 39.522 531.005 39.838 531.321 c 40.154 531.637 40.337 532.081 40.337 532.527 c f BT 45.750 529.560 Td /F1 9.8 Tf [(Dizziness or light-headedness)] TJ ET 40.337 516.872 m 40.337 517.319 40.154 517.763 39.838 518.079 c 39.522 518.395 39.078 518.579 38.631 518.579 c 38.185 518.579 37.741 518.395 37.425 518.079 c 37.109 517.763 36.925 517.319 36.925 516.872 c 36.925 516.426 37.109 515.982 37.425 515.666 c 37.741 515.350 38.185 515.166 38.631 515.166 c 39.078 515.166 39.522 515.350 39.838 515.666 c 40.154 515.982 40.337 516.426 40.337 516.872 c f BT 45.750 513.905 Td /F1 9.8 Tf [(Fatigue)] TJ ET 40.337 501.218 m 40.337 501.664 40.154 502.108 39.838 502.424 c 39.522 502.740 39.078 502.924 38.631 502.924 c 38.185 502.924 37.741 502.740 37.425 502.424 c 37.109 502.108 36.925 501.664 36.925 501.218 c 36.925 500.771 37.109 500.327 37.425 500.011 c 37.741 499.695 38.185 499.511 38.631 499.511 c 39.078 499.511 39.522 499.695 39.838 500.011 c 40.154 500.327 40.337 500.771 40.337 501.218 c f BT 45.750 498.250 Td /F1 9.8 Tf [(Flank pain)] TJ ET 40.337 485.563 m 40.337 486.010 40.154 486.454 39.838 486.770 c 39.522 487.085 39.078 487.269 38.631 487.269 c 38.185 487.269 37.741 487.085 37.425 486.770 c 37.109 486.454 36.925 486.010 36.925 485.563 c 36.925 485.116 37.109 484.672 37.425 484.356 c 37.741 484.041 38.185 483.857 38.631 483.857 c 39.078 483.857 39.522 484.041 39.838 484.356 c 40.154 484.672 40.337 485.116 40.337 485.563 c f BT 45.750 482.595 Td /F1 9.8 Tf [(Headache)] TJ ET 40.337 469.908 m 40.337 470.355 40.154 470.799 39.838 471.115 c 39.522 471.431 39.078 471.614 38.631 471.614 c 38.185 471.614 37.741 471.431 37.425 471.115 c 37.109 470.799 36.925 470.355 36.925 469.908 c 36.925 469.462 37.109 469.018 37.425 468.702 c 37.741 468.386 38.185 468.202 38.631 468.202 c 39.078 468.202 39.522 468.386 39.838 468.702 c 40.154 469.018 40.337 469.462 40.337 469.908 c f BT 45.750 466.941 Td /F1 9.8 Tf [(High fever)] TJ ET 40.337 454.253 m 40.337 454.700 40.154 455.144 39.838 455.460 c 39.522 455.776 39.078 455.960 38.631 455.960 c 38.185 455.960 37.741 455.776 37.425 455.460 c 37.109 455.144 36.925 454.700 36.925 454.253 c 36.925 453.807 37.109 453.363 37.425 453.047 c 37.741 452.731 38.185 452.547 38.631 452.547 c 39.078 452.547 39.522 452.731 39.838 453.047 c 40.154 453.363 40.337 453.807 40.337 454.253 c f BT 45.750 451.286 Td /F1 9.8 Tf [(Loss of appetite)] TJ ET 40.337 438.599 m 40.337 439.045 40.154 439.489 39.838 439.805 c 39.522 440.121 39.078 440.305 38.631 440.305 c 38.185 440.305 37.741 440.121 37.425 439.805 c 37.109 439.489 36.925 439.045 36.925 438.599 c 36.925 438.152 37.109 437.708 37.425 437.392 c 37.741 437.076 38.185 436.892 38.631 436.892 c 39.078 436.892 39.522 437.076 39.838 437.392 c 40.154 437.708 40.337 438.152 40.337 438.599 c f BT 45.750 435.631 Td /F1 9.8 Tf [(Loss of consciousness)] TJ ET 40.337 422.944 m 40.337 423.391 40.154 423.835 39.838 424.151 c 39.522 424.466 39.078 424.650 38.631 424.650 c 38.185 424.650 37.741 424.466 37.425 424.151 c 37.109 423.835 36.925 423.391 36.925 422.944 c 36.925 422.497 37.109 422.053 37.425 421.737 c 37.741 421.422 38.185 421.238 38.631 421.238 c 39.078 421.238 39.522 421.422 39.838 421.737 c 40.154 422.053 40.337 422.497 40.337 422.944 c f BT 45.750 419.976 Td /F1 9.8 Tf [(Severe hypotension)] TJ ET 40.337 407.289 m 40.337 407.736 40.154 408.180 39.838 408.496 c 39.522 408.812 39.078 408.995 38.631 408.995 c 38.185 408.995 37.741 408.812 37.425 408.496 c 37.109 408.180 36.925 407.736 36.925 407.289 c 36.925 406.843 37.109 406.399 37.425 406.083 c 37.741 405.767 38.185 405.583 38.631 405.583 c 39.078 405.583 39.522 405.767 39.838 406.083 c 40.154 406.399 40.337 406.843 40.337 407.289 c f BT 45.750 404.322 Td /F1 9.8 Tf [(Nausea)] TJ ET 40.337 391.634 m 40.337 392.081 40.154 392.525 39.838 392.841 c 39.522 393.157 39.078 393.341 38.631 393.341 c 38.185 393.341 37.741 393.157 37.425 392.841 c 37.109 392.525 36.925 392.081 36.925 391.634 c 36.925 391.188 37.109 390.744 37.425 390.428 c 37.741 390.112 38.185 389.928 38.631 389.928 c 39.078 389.928 39.522 390.112 39.838 390.428 c 40.154 390.744 40.337 391.188 40.337 391.634 c f BT 45.750 388.667 Td /F1 9.8 Tf [(Profound weakness)] TJ ET 40.337 375.980 m 40.337 376.426 40.154 376.870 39.838 377.186 c 39.522 377.502 39.078 377.686 38.631 377.686 c 38.185 377.686 37.741 377.502 37.425 377.186 c 37.109 376.870 36.925 376.426 36.925 375.980 c 36.925 375.533 37.109 375.089 37.425 374.773 c 37.741 374.457 38.185 374.273 38.631 374.273 c 39.078 374.273 39.522 374.457 39.838 374.773 c 40.154 375.089 40.337 375.533 40.337 375.980 c f BT 45.750 373.012 Td /F1 9.8 Tf [(Tachycardia)] TJ ET 40.337 360.325 m 40.337 360.772 40.154 361.216 39.838 361.532 c 39.522 361.847 39.078 362.031 38.631 362.031 c 38.185 362.031 37.741 361.847 37.425 361.532 c 37.109 361.216 36.925 360.772 36.925 360.325 c 36.925 359.878 37.109 359.434 37.425 359.118 c 37.741 358.803 38.185 358.619 38.631 358.619 c 39.078 358.619 39.522 358.803 39.838 359.118 c 40.154 359.434 40.337 359.878 40.337 360.325 c f BT 45.750 357.357 Td /F1 9.8 Tf [(Tachypnea)] TJ ET 40.337 344.670 m 40.337 345.117 40.154 345.561 39.838 345.877 c 39.522 346.193 39.078 346.376 38.631 346.376 c 38.185 346.376 37.741 346.193 37.425 345.877 c 37.109 345.561 36.925 345.117 36.925 344.670 c 36.925 344.224 37.109 343.780 37.425 343.464 c 37.741 343.148 38.185 342.964 38.631 342.964 c 39.078 342.964 39.522 343.148 39.838 343.464 c 40.154 343.780 40.337 344.224 40.337 344.670 c f BT 45.750 341.703 Td /F1 9.8 Tf [(Slow, sluggish movement)] TJ ET 40.337 329.015 m 40.337 329.462 40.154 329.906 39.838 330.222 c 39.522 330.538 39.078 330.722 38.631 330.722 c 38.185 330.722 37.741 330.538 37.425 330.222 c 37.109 329.906 36.925 329.462 36.925 329.015 c 36.925 328.569 37.109 328.125 37.425 327.809 c 37.741 327.493 38.185 327.309 38.631 327.309 c 39.078 327.309 39.522 327.493 39.838 327.809 c 40.154 328.125 40.337 328.569 40.337 329.015 c f BT 45.750 326.048 Td /F1 9.8 Tf [(Unusual and excessive sweating on face or palms)] TJ ET 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.654 38.631 311.654 c 39.078 311.654 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(Vomiting)] TJ ET BT 26.250 287.238 Td /F1 9.8 Tf [(Exams and Tests)] TJ ET BT 26.250 267.834 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress does of )] TJ ET BT 26.250 255.929 Td /F1 9.8 Tf [(hydrocortisone.)] TJ ET BT 26.250 236.524 Td /F1 9.8 Tf [(Tests that may be ordered to help diagnose acute adrenal crisis include:)] TJ ET 40.337 220.087 m 40.337 220.534 40.154 220.978 39.838 221.294 c 39.522 221.609 39.078 221.793 38.631 221.793 c 38.185 221.793 37.741 221.609 37.425 221.294 c 37.109 220.978 36.925 220.534 36.925 220.087 c 36.925 219.640 37.109 219.196 37.425 218.880 c 37.741 218.565 38.185 218.381 38.631 218.381 c 39.078 218.381 39.522 218.565 39.838 218.880 c 40.154 219.196 40.337 219.640 40.337 220.087 c f BT 45.750 217.119 Td /F1 9.8 Tf [(ACTH \(cosyntropin\) stimulation test)] TJ ET 40.337 204.432 m 40.337 204.879 40.154 205.323 39.838 205.639 c 39.522 205.955 39.078 206.138 38.631 206.138 c 38.185 206.138 37.741 205.955 37.425 205.639 c 37.109 205.323 36.925 204.879 36.925 204.432 c 36.925 203.986 37.109 203.542 37.425 203.226 c 37.741 202.910 38.185 202.726 38.631 202.726 c 39.078 202.726 39.522 202.910 39.838 203.226 c 40.154 203.542 40.337 203.986 40.337 204.432 c f BT 45.750 201.465 Td /F1 9.8 Tf [(Cortisol level)] TJ ET 40.337 188.777 m 40.337 189.224 40.154 189.668 39.838 189.984 c 39.522 190.300 39.078 190.484 38.631 190.484 c 38.185 190.484 37.741 190.300 37.425 189.984 c 37.109 189.668 36.925 189.224 36.925 188.777 c 36.925 188.331 37.109 187.887 37.425 187.571 c 37.741 187.255 38.185 187.071 38.631 187.071 c 39.078 187.071 39.522 187.255 39.838 187.571 c 40.154 187.887 40.337 188.331 40.337 188.777 c f BT 45.750 185.810 Td /F1 9.8 Tf [(Blood glucose)] TJ ET 40.337 173.123 m 40.337 173.569 40.154 174.013 39.838 174.329 c 39.522 174.645 39.078 174.829 38.631 174.829 c 38.185 174.829 37.741 174.645 37.425 174.329 c 37.109 174.013 36.925 173.569 36.925 173.123 c 36.925 172.676 37.109 172.232 37.425 171.916 c 37.741 171.600 38.185 171.416 38.631 171.416 c 39.078 171.416 39.522 171.600 39.838 171.916 c 40.154 172.232 40.337 172.676 40.337 173.123 c f BT 45.750 170.155 Td /F1 9.8 Tf [(Serum potassium)] TJ ET 40.337 157.468 m 40.337 157.915 40.154 158.359 39.838 158.675 c 39.522 158.990 39.078 159.174 38.631 159.174 c 38.185 159.174 37.741 158.990 37.425 158.675 c 37.109 158.359 36.925 157.915 36.925 157.468 c 36.925 157.021 37.109 156.577 37.425 156.261 c 37.741 155.946 38.185 155.762 38.631 155.762 c 39.078 155.762 39.522 155.946 39.838 156.261 c 40.154 156.577 40.337 157.021 40.337 157.468 c f BT 45.750 154.500 Td /F1 9.8 Tf [(Serum sodium)] TJ ET 40.337 141.813 m 40.337 142.260 40.154 142.704 39.838 143.020 c 39.522 143.336 39.078 143.519 38.631 143.519 c 38.185 143.519 37.741 143.336 37.425 143.020 c 37.109 142.704 36.925 142.260 36.925 141.813 c 36.925 141.367 37.109 140.923 37.425 140.607 c 37.741 140.291 38.185 140.107 38.631 140.107 c 39.078 140.107 39.522 140.291 39.838 140.607 c 40.154 140.923 40.337 141.367 40.337 141.813 c f BT 45.750 138.846 Td /F1 9.8 Tf [(Serum pH)] TJ ET 0.965 0.965 0.965 rg 26.250 -94.535 555.000 219.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 125.215 m 581.250 125.215 l 581.250 124.465 l 26.250 124.465 l f q 432.750 0 0 204.000 35.250 -88.535 cm /I5 Do Q q 35.250 -94.535 537.000 0.000 re W n Q Q q 15.000 -94.535 577.500 871.535 re W n 0.271 0.267 0.267 rg BT 45.750 767.476 Td /F1 9.8 Tf [(to 1 year after discontinuation of corticosteroid therapy and therefore need hydrocortisone stress dose coverage during the )] TJ ET BT 45.750 755.571 Td /F1 9.8 Tf [(time of stress.)] TJ ET BT 26.250 732.417 Td /F1 9.8 Tf [(Risk factors for adrenal crisis include:)] TJ ET 0.267 0.267 0.267 rg BT 187.710 733.924 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG 40.337 715.980 m 40.337 716.426 40.154 716.870 39.838 717.186 c 39.522 717.502 39.078 717.686 38.631 717.686 c 38.185 717.686 37.741 717.502 37.425 717.186 c 37.109 716.870 36.925 716.426 36.925 715.980 c 36.925 715.533 37.109 715.089 37.425 714.773 c 37.741 714.457 38.185 714.273 38.631 714.273 c 39.078 714.273 39.522 714.457 39.838 714.773 c 40.154 715.089 40.337 715.533 40.337 715.980 c f BT 45.750 713.012 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 700.325 m 40.337 700.771 40.154 701.215 39.838 701.531 c 39.522 701.847 39.078 702.031 38.631 702.031 c 38.185 702.031 37.741 701.847 37.425 701.531 c 37.109 701.215 36.925 700.771 36.925 700.325 c 36.925 699.878 37.109 699.434 37.425 699.118 c 37.741 698.802 38.185 698.619 38.631 698.619 c 39.078 698.619 39.522 698.802 39.838 699.118 c 40.154 699.434 40.337 699.878 40.337 700.325 c f BT 45.750 697.357 Td /F1 9.8 Tf [(Infection and other physical illness)] TJ ET 40.337 684.670 m 40.337 685.117 40.154 685.561 39.838 685.877 c 39.522 686.192 39.078 686.376 38.631 686.376 c 38.185 686.376 37.741 686.192 37.425 685.877 c 37.109 685.561 36.925 685.117 36.925 684.670 c 36.925 684.223 37.109 683.779 37.425 683.463 c 37.741 683.148 38.185 682.964 38.631 682.964 c 39.078 682.964 39.522 683.148 39.838 683.463 c 40.154 683.779 40.337 684.223 40.337 684.670 c f BT 45.750 681.702 Td /F1 9.8 Tf [(Injury to the adrenal or pituitary gland)] TJ ET 40.337 669.015 m 40.337 669.462 40.154 669.906 39.838 670.222 c 39.522 670.538 39.078 670.721 38.631 670.721 c 38.185 670.721 37.741 670.538 37.425 670.222 c 37.109 669.906 36.925 669.462 36.925 669.015 c 36.925 668.569 37.109 668.125 37.425 667.809 c 37.741 667.493 38.185 667.309 38.631 667.309 c 39.078 667.309 39.522 667.493 39.838 667.809 c 40.154 668.125 40.337 668.569 40.337 669.015 c f BT 45.750 666.048 Td /F1 9.8 Tf [(Missing usual doses of corticosteroids)] TJ ET 40.337 653.361 m 40.337 653.807 40.154 654.251 39.838 654.567 c 39.522 654.883 39.078 655.067 38.631 655.067 c 38.185 655.067 37.741 654.883 37.425 654.567 c 37.109 654.251 36.925 653.807 36.925 653.361 c 36.925 652.914 37.109 652.470 37.425 652.154 c 37.741 651.838 38.185 651.654 38.631 651.654 c 39.078 651.654 39.522 651.838 39.838 652.154 c 40.154 652.470 40.337 652.914 40.337 653.361 c f BT 45.750 650.393 Td /F1 9.8 Tf [(Surgery)] TJ ET 40.337 637.706 m 40.337 638.152 40.154 638.596 39.838 638.912 c 39.522 639.228 39.078 639.412 38.631 639.412 c 38.185 639.412 37.741 639.228 37.425 638.912 c 37.109 638.596 36.925 638.152 36.925 637.706 c 36.925 637.259 37.109 636.815 37.425 636.499 c 37.741 636.183 38.185 636.000 38.631 636.000 c 39.078 636.000 39.522 636.183 39.838 636.499 c 40.154 636.815 40.337 637.259 40.337 637.706 c f BT 45.750 634.738 Td /F1 9.8 Tf [(Trauma)] TJ ET BT 26.250 611.583 Td /F1 9.8 Tf [(Symptoms of adrenal crisis can include any of the following:)] TJ ET 0.267 0.267 0.267 rg BT 284.186 613.091 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg 40.337 595.146 m 40.337 595.593 40.154 596.037 39.838 596.353 c 39.522 596.669 39.078 596.852 38.631 596.852 c 38.185 596.852 37.741 596.669 37.425 596.353 c 37.109 596.037 36.925 595.593 36.925 595.146 c 36.925 594.700 37.109 594.256 37.425 593.940 c 37.741 593.624 38.185 593.440 38.631 593.440 c 39.078 593.440 39.522 593.624 39.838 593.940 c 40.154 594.256 40.337 594.700 40.337 595.146 c f BT 45.750 592.179 Td /F1 9.8 Tf [(Abdominal pain)] TJ ET 40.337 579.491 m 40.337 579.938 40.154 580.382 39.838 580.698 c 39.522 581.014 39.078 581.198 38.631 581.198 c 38.185 581.198 37.741 581.014 37.425 580.698 c 37.109 580.382 36.925 579.938 36.925 579.491 c 36.925 579.045 37.109 578.601 37.425 578.285 c 37.741 577.969 38.185 577.785 38.631 577.785 c 39.078 577.785 39.522 577.969 39.838 578.285 c 40.154 578.601 40.337 579.045 40.337 579.491 c f BT 45.750 576.524 Td /F1 9.8 Tf [(Hypovolemic shock)] TJ ET 40.337 563.837 m 40.337 564.283 40.154 564.727 39.838 565.043 c 39.522 565.359 39.078 565.543 38.631 565.543 c 38.185 565.543 37.741 565.359 37.425 565.043 c 37.109 564.727 36.925 564.283 36.925 563.837 c 36.925 563.390 37.109 562.946 37.425 562.630 c 37.741 562.314 38.185 562.130 38.631 562.130 c 39.078 562.130 39.522 562.314 39.838 562.630 c 40.154 562.946 40.337 563.390 40.337 563.837 c f BT 45.750 560.869 Td /F1 9.8 Tf [(Confusion or coma)] TJ ET 40.337 548.182 m 40.337 548.629 40.154 549.073 39.838 549.389 c 39.522 549.704 39.078 549.888 38.631 549.888 c 38.185 549.888 37.741 549.704 37.425 549.389 c 37.109 549.073 36.925 548.629 36.925 548.182 c 36.925 547.735 37.109 547.291 37.425 546.975 c 37.741 546.660 38.185 546.476 38.631 546.476 c 39.078 546.476 39.522 546.660 39.838 546.975 c 40.154 547.291 40.337 547.735 40.337 548.182 c f BT 45.750 545.214 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 532.527 m 40.337 532.974 40.154 533.418 39.838 533.734 c 39.522 534.050 39.078 534.233 38.631 534.233 c 38.185 534.233 37.741 534.050 37.425 533.734 c 37.109 533.418 36.925 532.974 36.925 532.527 c 36.925 532.081 37.109 531.637 37.425 531.321 c 37.741 531.005 38.185 530.821 38.631 530.821 c 39.078 530.821 39.522 531.005 39.838 531.321 c 40.154 531.637 40.337 532.081 40.337 532.527 c f BT 45.750 529.560 Td /F1 9.8 Tf [(Dizziness or light-headedness)] TJ ET 40.337 516.872 m 40.337 517.319 40.154 517.763 39.838 518.079 c 39.522 518.395 39.078 518.579 38.631 518.579 c 38.185 518.579 37.741 518.395 37.425 518.079 c 37.109 517.763 36.925 517.319 36.925 516.872 c 36.925 516.426 37.109 515.982 37.425 515.666 c 37.741 515.350 38.185 515.166 38.631 515.166 c 39.078 515.166 39.522 515.350 39.838 515.666 c 40.154 515.982 40.337 516.426 40.337 516.872 c f BT 45.750 513.905 Td /F1 9.8 Tf [(Fatigue)] TJ ET 40.337 501.218 m 40.337 501.664 40.154 502.108 39.838 502.424 c 39.522 502.740 39.078 502.924 38.631 502.924 c 38.185 502.924 37.741 502.740 37.425 502.424 c 37.109 502.108 36.925 501.664 36.925 501.218 c 36.925 500.771 37.109 500.327 37.425 500.011 c 37.741 499.695 38.185 499.511 38.631 499.511 c 39.078 499.511 39.522 499.695 39.838 500.011 c 40.154 500.327 40.337 500.771 40.337 501.218 c f BT 45.750 498.250 Td /F1 9.8 Tf [(Flank pain)] TJ ET 40.337 485.563 m 40.337 486.010 40.154 486.454 39.838 486.770 c 39.522 487.085 39.078 487.269 38.631 487.269 c 38.185 487.269 37.741 487.085 37.425 486.770 c 37.109 486.454 36.925 486.010 36.925 485.563 c 36.925 485.116 37.109 484.672 37.425 484.356 c 37.741 484.041 38.185 483.857 38.631 483.857 c 39.078 483.857 39.522 484.041 39.838 484.356 c 40.154 484.672 40.337 485.116 40.337 485.563 c f BT 45.750 482.595 Td /F1 9.8 Tf [(Headache)] TJ ET 40.337 469.908 m 40.337 470.355 40.154 470.799 39.838 471.115 c 39.522 471.431 39.078 471.614 38.631 471.614 c 38.185 471.614 37.741 471.431 37.425 471.115 c 37.109 470.799 36.925 470.355 36.925 469.908 c 36.925 469.462 37.109 469.018 37.425 468.702 c 37.741 468.386 38.185 468.202 38.631 468.202 c 39.078 468.202 39.522 468.386 39.838 468.702 c 40.154 469.018 40.337 469.462 40.337 469.908 c f BT 45.750 466.941 Td /F1 9.8 Tf [(High fever)] TJ ET 40.337 454.253 m 40.337 454.700 40.154 455.144 39.838 455.460 c 39.522 455.776 39.078 455.960 38.631 455.960 c 38.185 455.960 37.741 455.776 37.425 455.460 c 37.109 455.144 36.925 454.700 36.925 454.253 c 36.925 453.807 37.109 453.363 37.425 453.047 c 37.741 452.731 38.185 452.547 38.631 452.547 c 39.078 452.547 39.522 452.731 39.838 453.047 c 40.154 453.363 40.337 453.807 40.337 454.253 c f BT 45.750 451.286 Td /F1 9.8 Tf [(Loss of appetite)] TJ ET 40.337 438.599 m 40.337 439.045 40.154 439.489 39.838 439.805 c 39.522 440.121 39.078 440.305 38.631 440.305 c 38.185 440.305 37.741 440.121 37.425 439.805 c 37.109 439.489 36.925 439.045 36.925 438.599 c 36.925 438.152 37.109 437.708 37.425 437.392 c 37.741 437.076 38.185 436.892 38.631 436.892 c 39.078 436.892 39.522 437.076 39.838 437.392 c 40.154 437.708 40.337 438.152 40.337 438.599 c f BT 45.750 435.631 Td /F1 9.8 Tf [(Loss of consciousness)] TJ ET 40.337 422.944 m 40.337 423.391 40.154 423.835 39.838 424.151 c 39.522 424.466 39.078 424.650 38.631 424.650 c 38.185 424.650 37.741 424.466 37.425 424.151 c 37.109 423.835 36.925 423.391 36.925 422.944 c 36.925 422.497 37.109 422.053 37.425 421.737 c 37.741 421.422 38.185 421.238 38.631 421.238 c 39.078 421.238 39.522 421.422 39.838 421.737 c 40.154 422.053 40.337 422.497 40.337 422.944 c f BT 45.750 419.976 Td /F1 9.8 Tf [(Severe hypotension)] TJ ET 40.337 407.289 m 40.337 407.736 40.154 408.180 39.838 408.496 c 39.522 408.812 39.078 408.995 38.631 408.995 c 38.185 408.995 37.741 408.812 37.425 408.496 c 37.109 408.180 36.925 407.736 36.925 407.289 c 36.925 406.843 37.109 406.399 37.425 406.083 c 37.741 405.767 38.185 405.583 38.631 405.583 c 39.078 405.583 39.522 405.767 39.838 406.083 c 40.154 406.399 40.337 406.843 40.337 407.289 c f BT 45.750 404.322 Td /F1 9.8 Tf [(Nausea)] TJ ET 40.337 391.634 m 40.337 392.081 40.154 392.525 39.838 392.841 c 39.522 393.157 39.078 393.341 38.631 393.341 c 38.185 393.341 37.741 393.157 37.425 392.841 c 37.109 392.525 36.925 392.081 36.925 391.634 c 36.925 391.188 37.109 390.744 37.425 390.428 c 37.741 390.112 38.185 389.928 38.631 389.928 c 39.078 389.928 39.522 390.112 39.838 390.428 c 40.154 390.744 40.337 391.188 40.337 391.634 c f BT 45.750 388.667 Td /F1 9.8 Tf [(Profound weakness)] TJ ET 40.337 375.980 m 40.337 376.426 40.154 376.870 39.838 377.186 c 39.522 377.502 39.078 377.686 38.631 377.686 c 38.185 377.686 37.741 377.502 37.425 377.186 c 37.109 376.870 36.925 376.426 36.925 375.980 c 36.925 375.533 37.109 375.089 37.425 374.773 c 37.741 374.457 38.185 374.273 38.631 374.273 c 39.078 374.273 39.522 374.457 39.838 374.773 c 40.154 375.089 40.337 375.533 40.337 375.980 c f BT 45.750 373.012 Td /F1 9.8 Tf [(Tachycardia)] TJ ET 40.337 360.325 m 40.337 360.772 40.154 361.216 39.838 361.532 c 39.522 361.847 39.078 362.031 38.631 362.031 c 38.185 362.031 37.741 361.847 37.425 361.532 c 37.109 361.216 36.925 360.772 36.925 360.325 c 36.925 359.878 37.109 359.434 37.425 359.118 c 37.741 358.803 38.185 358.619 38.631 358.619 c 39.078 358.619 39.522 358.803 39.838 359.118 c 40.154 359.434 40.337 359.878 40.337 360.325 c f BT 45.750 357.357 Td /F1 9.8 Tf [(Tachypnea)] TJ ET 40.337 344.670 m 40.337 345.117 40.154 345.561 39.838 345.877 c 39.522 346.193 39.078 346.376 38.631 346.376 c 38.185 346.376 37.741 346.193 37.425 345.877 c 37.109 345.561 36.925 345.117 36.925 344.670 c 36.925 344.224 37.109 343.780 37.425 343.464 c 37.741 343.148 38.185 342.964 38.631 342.964 c 39.078 342.964 39.522 343.148 39.838 343.464 c 40.154 343.780 40.337 344.224 40.337 344.670 c f BT 45.750 341.703 Td /F1 9.8 Tf [(Slow, sluggish movement)] TJ ET 40.337 329.015 m 40.337 329.462 40.154 329.906 39.838 330.222 c 39.522 330.538 39.078 330.722 38.631 330.722 c 38.185 330.722 37.741 330.538 37.425 330.222 c 37.109 329.906 36.925 329.462 36.925 329.015 c 36.925 328.569 37.109 328.125 37.425 327.809 c 37.741 327.493 38.185 327.309 38.631 327.309 c 39.078 327.309 39.522 327.493 39.838 327.809 c 40.154 328.125 40.337 328.569 40.337 329.015 c f BT 45.750 326.048 Td /F1 9.8 Tf [(Unusual and excessive sweating on face or palms)] TJ ET 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.654 38.631 311.654 c 39.078 311.654 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(Vomiting)] TJ ET BT 26.250 287.238 Td /F1 9.8 Tf [(Exams and Tests)] TJ ET BT 26.250 267.834 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress does of )] TJ ET BT 26.250 255.929 Td /F1 9.8 Tf [(hydrocortisone.)] TJ ET BT 26.250 236.524 Td /F1 9.8 Tf [(Tests that may be ordered to help diagnose acute adrenal crisis include:)] TJ ET 40.337 220.087 m 40.337 220.534 40.154 220.978 39.838 221.294 c 39.522 221.609 39.078 221.793 38.631 221.793 c 38.185 221.793 37.741 221.609 37.425 221.294 c 37.109 220.978 36.925 220.534 36.925 220.087 c 36.925 219.640 37.109 219.196 37.425 218.880 c 37.741 218.565 38.185 218.381 38.631 218.381 c 39.078 218.381 39.522 218.565 39.838 218.880 c 40.154 219.196 40.337 219.640 40.337 220.087 c f BT 45.750 217.119 Td /F1 9.8 Tf [(ACTH \(cosyntropin\) stimulation test)] TJ ET 40.337 204.432 m 40.337 204.879 40.154 205.323 39.838 205.639 c 39.522 205.955 39.078 206.138 38.631 206.138 c 38.185 206.138 37.741 205.955 37.425 205.639 c 37.109 205.323 36.925 204.879 36.925 204.432 c 36.925 203.986 37.109 203.542 37.425 203.226 c 37.741 202.910 38.185 202.726 38.631 202.726 c 39.078 202.726 39.522 202.910 39.838 203.226 c 40.154 203.542 40.337 203.986 40.337 204.432 c f BT 45.750 201.465 Td /F1 9.8 Tf [(Cortisol level)] TJ ET 40.337 188.777 m 40.337 189.224 40.154 189.668 39.838 189.984 c 39.522 190.300 39.078 190.484 38.631 190.484 c 38.185 190.484 37.741 190.300 37.425 189.984 c 37.109 189.668 36.925 189.224 36.925 188.777 c 36.925 188.331 37.109 187.887 37.425 187.571 c 37.741 187.255 38.185 187.071 38.631 187.071 c 39.078 187.071 39.522 187.255 39.838 187.571 c 40.154 187.887 40.337 188.331 40.337 188.777 c f BT 45.750 185.810 Td /F1 9.8 Tf [(Blood glucose)] TJ ET 40.337 173.123 m 40.337 173.569 40.154 174.013 39.838 174.329 c 39.522 174.645 39.078 174.829 38.631 174.829 c 38.185 174.829 37.741 174.645 37.425 174.329 c 37.109 174.013 36.925 173.569 36.925 173.123 c 36.925 172.676 37.109 172.232 37.425 171.916 c 37.741 171.600 38.185 171.416 38.631 171.416 c 39.078 171.416 39.522 171.600 39.838 171.916 c 40.154 172.232 40.337 172.676 40.337 173.123 c f BT 45.750 170.155 Td /F1 9.8 Tf [(Serum potassium)] TJ ET 40.337 157.468 m 40.337 157.915 40.154 158.359 39.838 158.675 c 39.522 158.990 39.078 159.174 38.631 159.174 c 38.185 159.174 37.741 158.990 37.425 158.675 c 37.109 158.359 36.925 157.915 36.925 157.468 c 36.925 157.021 37.109 156.577 37.425 156.261 c 37.741 155.946 38.185 155.762 38.631 155.762 c 39.078 155.762 39.522 155.946 39.838 156.261 c 40.154 156.577 40.337 157.021 40.337 157.468 c f BT 45.750 154.500 Td /F1 9.8 Tf [(Serum sodium)] TJ ET 40.337 141.813 m 40.337 142.260 40.154 142.704 39.838 143.020 c 39.522 143.336 39.078 143.519 38.631 143.519 c 38.185 143.519 37.741 143.336 37.425 143.020 c 37.109 142.704 36.925 142.260 36.925 141.813 c 36.925 141.367 37.109 140.923 37.425 140.607 c 37.741 140.291 38.185 140.107 38.631 140.107 c 39.078 140.107 39.522 140.291 39.838 140.607 c 40.154 140.923 40.337 141.367 40.337 141.813 c f BT 45.750 138.846 Td /F1 9.8 Tf [(Serum pH)] TJ ET 0.965 0.965 0.965 rg 26.250 -94.535 555.000 219.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 125.215 m 581.250 125.215 l 581.250 124.465 l 26.250 124.465 l f q 432.750 0 0 204.000 35.250 -88.535 cm /I5 Do Q q 35.250 -94.535 537.000 0.000 re W n Q Q q 15.000 -94.535 577.500 871.535 re W n 0.271 0.267 0.267 rg BT 45.750 767.476 Td /F1 9.8 Tf [(to 1 year after discontinuation of corticosteroid therapy and therefore need hydrocortisone stress dose coverage during the )] TJ ET BT 45.750 755.571 Td /F1 9.8 Tf [(time of stress.)] TJ ET BT 26.250 732.417 Td /F1 9.8 Tf [(Risk factors for adrenal crisis include:)] TJ ET 0.267 0.267 0.267 rg BT 187.710 733.924 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG 40.337 715.980 m 40.337 716.426 40.154 716.870 39.838 717.186 c 39.522 717.502 39.078 717.686 38.631 717.686 c 38.185 717.686 37.741 717.502 37.425 717.186 c 37.109 716.870 36.925 716.426 36.925 715.980 c 36.925 715.533 37.109 715.089 37.425 714.773 c 37.741 714.457 38.185 714.273 38.631 714.273 c 39.078 714.273 39.522 714.457 39.838 714.773 c 40.154 715.089 40.337 715.533 40.337 715.980 c f BT 45.750 713.012 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 700.325 m 40.337 700.771 40.154 701.215 39.838 701.531 c 39.522 701.847 39.078 702.031 38.631 702.031 c 38.185 702.031 37.741 701.847 37.425 701.531 c 37.109 701.215 36.925 700.771 36.925 700.325 c 36.925 699.878 37.109 699.434 37.425 699.118 c 37.741 698.802 38.185 698.619 38.631 698.619 c 39.078 698.619 39.522 698.802 39.838 699.118 c 40.154 699.434 40.337 699.878 40.337 700.325 c f BT 45.750 697.357 Td /F1 9.8 Tf [(Infection and other physical illness)] TJ ET 40.337 684.670 m 40.337 685.117 40.154 685.561 39.838 685.877 c 39.522 686.192 39.078 686.376 38.631 686.376 c 38.185 686.376 37.741 686.192 37.425 685.877 c 37.109 685.561 36.925 685.117 36.925 684.670 c 36.925 684.223 37.109 683.779 37.425 683.463 c 37.741 683.148 38.185 682.964 38.631 682.964 c 39.078 682.964 39.522 683.148 39.838 683.463 c 40.154 683.779 40.337 684.223 40.337 684.670 c f BT 45.750 681.702 Td /F1 9.8 Tf [(Injury to the adrenal or pituitary gland)] TJ ET 40.337 669.015 m 40.337 669.462 40.154 669.906 39.838 670.222 c 39.522 670.538 39.078 670.721 38.631 670.721 c 38.185 670.721 37.741 670.538 37.425 670.222 c 37.109 669.906 36.925 669.462 36.925 669.015 c 36.925 668.569 37.109 668.125 37.425 667.809 c 37.741 667.493 38.185 667.309 38.631 667.309 c 39.078 667.309 39.522 667.493 39.838 667.809 c 40.154 668.125 40.337 668.569 40.337 669.015 c f BT 45.750 666.048 Td /F1 9.8 Tf [(Missing usual doses of corticosteroids)] TJ ET 40.337 653.361 m 40.337 653.807 40.154 654.251 39.838 654.567 c 39.522 654.883 39.078 655.067 38.631 655.067 c 38.185 655.067 37.741 654.883 37.425 654.567 c 37.109 654.251 36.925 653.807 36.925 653.361 c 36.925 652.914 37.109 652.470 37.425 652.154 c 37.741 651.838 38.185 651.654 38.631 651.654 c 39.078 651.654 39.522 651.838 39.838 652.154 c 40.154 652.470 40.337 652.914 40.337 653.361 c f BT 45.750 650.393 Td /F1 9.8 Tf [(Surgery)] TJ ET 40.337 637.706 m 40.337 638.152 40.154 638.596 39.838 638.912 c 39.522 639.228 39.078 639.412 38.631 639.412 c 38.185 639.412 37.741 639.228 37.425 638.912 c 37.109 638.596 36.925 638.152 36.925 637.706 c 36.925 637.259 37.109 636.815 37.425 636.499 c 37.741 636.183 38.185 636.000 38.631 636.000 c 39.078 636.000 39.522 636.183 39.838 636.499 c 40.154 636.815 40.337 637.259 40.337 637.706 c f BT 45.750 634.738 Td /F1 9.8 Tf [(Trauma)] TJ ET BT 26.250 611.583 Td /F1 9.8 Tf [(Symptoms of adrenal crisis can include any of the following:)] TJ ET 0.267 0.267 0.267 rg BT 284.186 613.091 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg 40.337 595.146 m 40.337 595.593 40.154 596.037 39.838 596.353 c 39.522 596.669 39.078 596.852 38.631 596.852 c 38.185 596.852 37.741 596.669 37.425 596.353 c 37.109 596.037 36.925 595.593 36.925 595.146 c 36.925 594.700 37.109 594.256 37.425 593.940 c 37.741 593.624 38.185 593.440 38.631 593.440 c 39.078 593.440 39.522 593.624 39.838 593.940 c 40.154 594.256 40.337 594.700 40.337 595.146 c f BT 45.750 592.179 Td /F1 9.8 Tf [(Abdominal pain)] TJ ET 40.337 579.491 m 40.337 579.938 40.154 580.382 39.838 580.698 c 39.522 581.014 39.078 581.198 38.631 581.198 c 38.185 581.198 37.741 581.014 37.425 580.698 c 37.109 580.382 36.925 579.938 36.925 579.491 c 36.925 579.045 37.109 578.601 37.425 578.285 c 37.741 577.969 38.185 577.785 38.631 577.785 c 39.078 577.785 39.522 577.969 39.838 578.285 c 40.154 578.601 40.337 579.045 40.337 579.491 c f BT 45.750 576.524 Td /F1 9.8 Tf [(Hypovolemic shock)] TJ ET 40.337 563.837 m 40.337 564.283 40.154 564.727 39.838 565.043 c 39.522 565.359 39.078 565.543 38.631 565.543 c 38.185 565.543 37.741 565.359 37.425 565.043 c 37.109 564.727 36.925 564.283 36.925 563.837 c 36.925 563.390 37.109 562.946 37.425 562.630 c 37.741 562.314 38.185 562.130 38.631 562.130 c 39.078 562.130 39.522 562.314 39.838 562.630 c 40.154 562.946 40.337 563.390 40.337 563.837 c f BT 45.750 560.869 Td /F1 9.8 Tf [(Confusion or coma)] TJ ET 40.337 548.182 m 40.337 548.629 40.154 549.073 39.838 549.389 c 39.522 549.704 39.078 549.888 38.631 549.888 c 38.185 549.888 37.741 549.704 37.425 549.389 c 37.109 549.073 36.925 548.629 36.925 548.182 c 36.925 547.735 37.109 547.291 37.425 546.975 c 37.741 546.660 38.185 546.476 38.631 546.476 c 39.078 546.476 39.522 546.660 39.838 546.975 c 40.154 547.291 40.337 547.735 40.337 548.182 c f BT 45.750 545.214 Td /F1 9.8 Tf [(Dehydration)] TJ ET 40.337 532.527 m 40.337 532.974 40.154 533.418 39.838 533.734 c 39.522 534.050 39.078 534.233 38.631 534.233 c 38.185 534.233 37.741 534.050 37.425 533.734 c 37.109 533.418 36.925 532.974 36.925 532.527 c 36.925 532.081 37.109 531.637 37.425 531.321 c 37.741 531.005 38.185 530.821 38.631 530.821 c 39.078 530.821 39.522 531.005 39.838 531.321 c 40.154 531.637 40.337 532.081 40.337 532.527 c f BT 45.750 529.560 Td /F1 9.8 Tf [(Dizziness or light-headedness)] TJ ET 40.337 516.872 m 40.337 517.319 40.154 517.763 39.838 518.079 c 39.522 518.395 39.078 518.579 38.631 518.579 c 38.185 518.579 37.741 518.395 37.425 518.079 c 37.109 517.763 36.925 517.319 36.925 516.872 c 36.925 516.426 37.109 515.982 37.425 515.666 c 37.741 515.350 38.185 515.166 38.631 515.166 c 39.078 515.166 39.522 515.350 39.838 515.666 c 40.154 515.982 40.337 516.426 40.337 516.872 c f BT 45.750 513.905 Td /F1 9.8 Tf [(Fatigue)] TJ ET 40.337 501.218 m 40.337 501.664 40.154 502.108 39.838 502.424 c 39.522 502.740 39.078 502.924 38.631 502.924 c 38.185 502.924 37.741 502.740 37.425 502.424 c 37.109 502.108 36.925 501.664 36.925 501.218 c 36.925 500.771 37.109 500.327 37.425 500.011 c 37.741 499.695 38.185 499.511 38.631 499.511 c 39.078 499.511 39.522 499.695 39.838 500.011 c 40.154 500.327 40.337 500.771 40.337 501.218 c f BT 45.750 498.250 Td /F1 9.8 Tf [(Flank pain)] TJ ET 40.337 485.563 m 40.337 486.010 40.154 486.454 39.838 486.770 c 39.522 487.085 39.078 487.269 38.631 487.269 c 38.185 487.269 37.741 487.085 37.425 486.770 c 37.109 486.454 36.925 486.010 36.925 485.563 c 36.925 485.116 37.109 484.672 37.425 484.356 c 37.741 484.041 38.185 483.857 38.631 483.857 c 39.078 483.857 39.522 484.041 39.838 484.356 c 40.154 484.672 40.337 485.116 40.337 485.563 c f BT 45.750 482.595 Td /F1 9.8 Tf [(Headache)] TJ ET 40.337 469.908 m 40.337 470.355 40.154 470.799 39.838 471.115 c 39.522 471.431 39.078 471.614 38.631 471.614 c 38.185 471.614 37.741 471.431 37.425 471.115 c 37.109 470.799 36.925 470.355 36.925 469.908 c 36.925 469.462 37.109 469.018 37.425 468.702 c 37.741 468.386 38.185 468.202 38.631 468.202 c 39.078 468.202 39.522 468.386 39.838 468.702 c 40.154 469.018 40.337 469.462 40.337 469.908 c f BT 45.750 466.941 Td /F1 9.8 Tf [(High fever)] TJ ET 40.337 454.253 m 40.337 454.700 40.154 455.144 39.838 455.460 c 39.522 455.776 39.078 455.960 38.631 455.960 c 38.185 455.960 37.741 455.776 37.425 455.460 c 37.109 455.144 36.925 454.700 36.925 454.253 c 36.925 453.807 37.109 453.363 37.425 453.047 c 37.741 452.731 38.185 452.547 38.631 452.547 c 39.078 452.547 39.522 452.731 39.838 453.047 c 40.154 453.363 40.337 453.807 40.337 454.253 c f BT 45.750 451.286 Td /F1 9.8 Tf [(Loss of appetite)] TJ ET 40.337 438.599 m 40.337 439.045 40.154 439.489 39.838 439.805 c 39.522 440.121 39.078 440.305 38.631 440.305 c 38.185 440.305 37.741 440.121 37.425 439.805 c 37.109 439.489 36.925 439.045 36.925 438.599 c 36.925 438.152 37.109 437.708 37.425 437.392 c 37.741 437.076 38.185 436.892 38.631 436.892 c 39.078 436.892 39.522 437.076 39.838 437.392 c 40.154 437.708 40.337 438.152 40.337 438.599 c f BT 45.750 435.631 Td /F1 9.8 Tf [(Loss of consciousness)] TJ ET 40.337 422.944 m 40.337 423.391 40.154 423.835 39.838 424.151 c 39.522 424.466 39.078 424.650 38.631 424.650 c 38.185 424.650 37.741 424.466 37.425 424.151 c 37.109 423.835 36.925 423.391 36.925 422.944 c 36.925 422.497 37.109 422.053 37.425 421.737 c 37.741 421.422 38.185 421.238 38.631 421.238 c 39.078 421.238 39.522 421.422 39.838 421.737 c 40.154 422.053 40.337 422.497 40.337 422.944 c f BT 45.750 419.976 Td /F1 9.8 Tf [(Severe hypotension)] TJ ET 40.337 407.289 m 40.337 407.736 40.154 408.180 39.838 408.496 c 39.522 408.812 39.078 408.995 38.631 408.995 c 38.185 408.995 37.741 408.812 37.425 408.496 c 37.109 408.180 36.925 407.736 36.925 407.289 c 36.925 406.843 37.109 406.399 37.425 406.083 c 37.741 405.767 38.185 405.583 38.631 405.583 c 39.078 405.583 39.522 405.767 39.838 406.083 c 40.154 406.399 40.337 406.843 40.337 407.289 c f BT 45.750 404.322 Td /F1 9.8 Tf [(Nausea)] TJ ET 40.337 391.634 m 40.337 392.081 40.154 392.525 39.838 392.841 c 39.522 393.157 39.078 393.341 38.631 393.341 c 38.185 393.341 37.741 393.157 37.425 392.841 c 37.109 392.525 36.925 392.081 36.925 391.634 c 36.925 391.188 37.109 390.744 37.425 390.428 c 37.741 390.112 38.185 389.928 38.631 389.928 c 39.078 389.928 39.522 390.112 39.838 390.428 c 40.154 390.744 40.337 391.188 40.337 391.634 c f BT 45.750 388.667 Td /F1 9.8 Tf [(Profound weakness)] TJ ET 40.337 375.980 m 40.337 376.426 40.154 376.870 39.838 377.186 c 39.522 377.502 39.078 377.686 38.631 377.686 c 38.185 377.686 37.741 377.502 37.425 377.186 c 37.109 376.870 36.925 376.426 36.925 375.980 c 36.925 375.533 37.109 375.089 37.425 374.773 c 37.741 374.457 38.185 374.273 38.631 374.273 c 39.078 374.273 39.522 374.457 39.838 374.773 c 40.154 375.089 40.337 375.533 40.337 375.980 c f BT 45.750 373.012 Td /F1 9.8 Tf [(Tachycardia)] TJ ET 40.337 360.325 m 40.337 360.772 40.154 361.216 39.838 361.532 c 39.522 361.847 39.078 362.031 38.631 362.031 c 38.185 362.031 37.741 361.847 37.425 361.532 c 37.109 361.216 36.925 360.772 36.925 360.325 c 36.925 359.878 37.109 359.434 37.425 359.118 c 37.741 358.803 38.185 358.619 38.631 358.619 c 39.078 358.619 39.522 358.803 39.838 359.118 c 40.154 359.434 40.337 359.878 40.337 360.325 c f BT 45.750 357.357 Td /F1 9.8 Tf [(Tachypnea)] TJ ET 40.337 344.670 m 40.337 345.117 40.154 345.561 39.838 345.877 c 39.522 346.193 39.078 346.376 38.631 346.376 c 38.185 346.376 37.741 346.193 37.425 345.877 c 37.109 345.561 36.925 345.117 36.925 344.670 c 36.925 344.224 37.109 343.780 37.425 343.464 c 37.741 343.148 38.185 342.964 38.631 342.964 c 39.078 342.964 39.522 343.148 39.838 343.464 c 40.154 343.780 40.337 344.224 40.337 344.670 c f BT 45.750 341.703 Td /F1 9.8 Tf [(Slow, sluggish movement)] TJ ET 40.337 329.015 m 40.337 329.462 40.154 329.906 39.838 330.222 c 39.522 330.538 39.078 330.722 38.631 330.722 c 38.185 330.722 37.741 330.538 37.425 330.222 c 37.109 329.906 36.925 329.462 36.925 329.015 c 36.925 328.569 37.109 328.125 37.425 327.809 c 37.741 327.493 38.185 327.309 38.631 327.309 c 39.078 327.309 39.522 327.493 39.838 327.809 c 40.154 328.125 40.337 328.569 40.337 329.015 c f BT 45.750 326.048 Td /F1 9.8 Tf [(Unusual and excessive sweating on face or palms)] TJ ET 40.337 313.361 m 40.337 313.807 40.154 314.251 39.838 314.567 c 39.522 314.883 39.078 315.067 38.631 315.067 c 38.185 315.067 37.741 314.883 37.425 314.567 c 37.109 314.251 36.925 313.807 36.925 313.361 c 36.925 312.914 37.109 312.470 37.425 312.154 c 37.741 311.838 38.185 311.654 38.631 311.654 c 39.078 311.654 39.522 311.838 39.838 312.154 c 40.154 312.470 40.337 312.914 40.337 313.361 c f BT 45.750 310.393 Td /F1 9.8 Tf [(Vomiting)] TJ ET BT 26.250 287.238 Td /F1 9.8 Tf [(Exams and Tests)] TJ ET BT 26.250 267.834 Td /F1 9.8 Tf [(While it is appropriate to assess for acute adrenal crisis, this assessment should never delay treatment with a stress does of )] TJ ET BT 26.250 255.929 Td /F1 9.8 Tf [(hydrocortisone.)] TJ ET BT 26.250 236.524 Td /F1 9.8 Tf [(Tests that may be ordered to help diagnose acute adrenal crisis include:)] TJ ET 40.337 220.087 m 40.337 220.534 40.154 220.978 39.838 221.294 c 39.522 221.609 39.078 221.793 38.631 221.793 c 38.185 221.793 37.741 221.609 37.425 221.294 c 37.109 220.978 36.925 220.534 36.925 220.087 c 36.925 219.640 37.109 219.196 37.425 218.880 c 37.741 218.565 38.185 218.381 38.631 218.381 c 39.078 218.381 39.522 218.565 39.838 218.880 c 40.154 219.196 40.337 219.640 40.337 220.087 c f BT 45.750 217.119 Td /F1 9.8 Tf [(ACTH \(cosyntropin\) stimulation test)] TJ ET 40.337 204.432 m 40.337 204.879 40.154 205.323 39.838 205.639 c 39.522 205.955 39.078 206.138 38.631 206.138 c 38.185 206.138 37.741 205.955 37.425 205.639 c 37.109 205.323 36.925 204.879 36.925 204.432 c 36.925 203.986 37.109 203.542 37.425 203.226 c 37.741 202.910 38.185 202.726 38.631 202.726 c 39.078 202.726 39.522 202.910 39.838 203.226 c 40.154 203.542 40.337 203.986 40.337 204.432 c f BT 45.750 201.465 Td /F1 9.8 Tf [(Cortisol level)] TJ ET 40.337 188.777 m 40.337 189.224 40.154 189.668 39.838 189.984 c 39.522 190.300 39.078 190.484 38.631 190.484 c 38.185 190.484 37.741 190.300 37.425 189.984 c 37.109 189.668 36.925 189.224 36.925 188.777 c 36.925 188.331 37.109 187.887 37.425 187.571 c 37.741 187.255 38.185 187.071 38.631 187.071 c 39.078 187.071 39.522 187.255 39.838 187.571 c 40.154 187.887 40.337 188.331 40.337 188.777 c f BT 45.750 185.810 Td /F1 9.8 Tf [(Blood glucose)] TJ ET 40.337 173.123 m 40.337 173.569 40.154 174.013 39.838 174.329 c 39.522 174.645 39.078 174.829 38.631 174.829 c 38.185 174.829 37.741 174.645 37.425 174.329 c 37.109 174.013 36.925 173.569 36.925 173.123 c 36.925 172.676 37.109 172.232 37.425 171.916 c 37.741 171.600 38.185 171.416 38.631 171.416 c 39.078 171.416 39.522 171.600 39.838 171.916 c 40.154 172.232 40.337 172.676 40.337 173.123 c f BT 45.750 170.155 Td /F1 9.8 Tf [(Serum potassium)] TJ ET 40.337 157.468 m 40.337 157.915 40.154 158.359 39.838 158.675 c 39.522 158.990 39.078 159.174 38.631 159.174 c 38.185 159.174 37.741 158.990 37.425 158.675 c 37.109 158.359 36.925 157.915 36.925 157.468 c 36.925 157.021 37.109 156.577 37.425 156.261 c 37.741 155.946 38.185 155.762 38.631 155.762 c 39.078 155.762 39.522 155.946 39.838 156.261 c 40.154 156.577 40.337 157.021 40.337 157.468 c f BT 45.750 154.500 Td /F1 9.8 Tf [(Serum sodium)] TJ ET 40.337 141.813 m 40.337 142.260 40.154 142.704 39.838 143.020 c 39.522 143.336 39.078 143.519 38.631 143.519 c 38.185 143.519 37.741 143.336 37.425 143.020 c 37.109 142.704 36.925 142.260 36.925 141.813 c 36.925 141.367 37.109 140.923 37.425 140.607 c 37.741 140.291 38.185 140.107 38.631 140.107 c 39.078 140.107 39.522 140.291 39.838 140.607 c 40.154 140.923 40.337 141.367 40.337 141.813 c f BT 45.750 138.846 Td /F1 9.8 Tf [(Serum pH)] TJ ET 0.965 0.965 0.965 rg 26.250 -94.535 555.000 219.750 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 125.215 m 581.250 125.215 l 581.250 124.465 l 26.250 124.465 l f q 432.750 0 0 204.000 35.250 -88.535 cm /I5 Do Q q 35.250 -94.535 537.000 0.000 re W n Q Q q 432.750 0 0 204.000 35.250 -88.535 cm /I5 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(5)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular 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Despite the tragic loss of PJs life, the PJ Nicholoff Steroid Protocol is a positive result that )] TJ ET BT 26.250 654.624 Td /F1 9.8 Tf [(will impact the lives of people living with Duchenne and using corticosteroids around the world. We thank PJ and his family for )] TJ ET BT 26.250 642.719 Td /F1 9.8 Tf [(encouraging the development of this resource.)] TJ ET BT 26.250 623.314 Td /F4 9.8 Tf [(A pdf of the PJ Nicholoff Protocol can be downloaded at: )] TJ ET BT 26.250 611.409 Td /F4 9.8 Tf [(http://www.parentprojectmd.org/site/DocServer/PJ_Nicholoff_Steroid_Protocol.pdf?docID=15843Acknowledgements )] TJ ET BT 26.250 599.505 Td /F4 9.8 Tf [(for the development of the PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 580.100 Td /F5 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community.)] TJ ET 0.271 0.267 0.267 RG 40.337 563.663 m 40.337 564.109 40.154 564.553 39.838 564.869 c 39.522 565.185 39.078 565.369 38.631 565.369 c 38.185 565.369 37.741 565.185 37.425 564.869 c 37.109 564.553 36.925 564.109 36.925 563.663 c 36.925 563.216 37.109 562.772 37.425 562.456 c 37.741 562.140 38.185 561.956 38.631 561.956 c 39.078 561.956 39.522 562.140 39.838 562.456 c 40.154 562.772 40.337 563.216 40.337 563.663 c f BT 45.750 560.695 Td /F1 9.8 Tf [(Vincents Hospital, Indianapolis, IN)] TJ ET 40.337 548.008 m 40.337 548.455 40.154 548.899 39.838 549.215 c 39.522 549.530 39.078 549.714 38.631 549.714 c 38.185 549.714 37.741 549.530 37.425 549.215 c 37.109 548.899 36.925 548.455 36.925 548.008 c 36.925 547.561 37.109 547.117 37.425 546.801 c 37.741 546.486 38.185 546.302 38.631 546.302 c 39.078 546.302 39.522 546.486 39.838 546.801 c 40.154 547.117 40.337 547.561 40.337 548.008 c f BT 45.750 545.040 Td /F1 9.8 Tf [(Philip Zeitler, Childrens Hospital Colorado, Aurora, CO)] TJ ET 40.337 532.353 m 40.337 532.800 40.154 533.244 39.838 533.560 c 39.522 533.876 39.078 534.059 38.631 534.059 c 38.185 534.059 37.741 533.876 37.425 533.560 c 37.109 533.244 36.925 532.800 36.925 532.353 c 36.925 531.907 37.109 531.463 37.425 531.147 c 37.741 530.831 38.185 530.647 38.631 530.647 c 39.078 530.647 39.522 530.831 39.838 531.147 c 40.154 531.463 40.337 531.907 40.337 532.353 c f BT 45.750 529.386 Td /F1 9.8 Tf [(Sasigarn Bowden, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 516.698 m 40.337 517.145 40.154 517.589 39.838 517.905 c 39.522 518.221 39.078 518.405 38.631 518.405 c 38.185 518.405 37.741 518.221 37.425 517.905 c 37.109 517.589 36.925 517.145 36.925 516.698 c 36.925 516.252 37.109 515.808 37.425 515.492 c 37.741 515.176 38.185 514.992 38.631 514.992 c 39.078 514.992 39.522 515.176 39.838 515.492 c 40.154 515.808 40.337 516.252 40.337 516.698 c f BT 45.750 513.731 Td /F1 9.8 Tf [(Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON)] TJ ET 40.337 501.044 m 40.337 501.490 40.154 501.934 39.838 502.250 c 39.522 502.566 39.078 502.750 38.631 502.750 c 38.185 502.750 37.741 502.566 37.425 502.250 c 37.109 501.934 36.925 501.490 36.925 501.044 c 36.925 500.597 37.109 500.153 37.425 499.837 c 37.741 499.521 38.185 499.337 38.631 499.337 c 39.078 499.337 39.522 499.521 39.838 499.837 c 40.154 500.153 40.337 500.597 40.337 501.044 c f BT 45.750 498.076 Td /F1 9.8 Tf [(Jerry R. Mendell, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 485.389 m 40.337 485.836 40.154 486.280 39.838 486.596 c 39.522 486.911 39.078 487.095 38.631 487.095 c 38.185 487.095 37.741 486.911 37.425 486.596 c 37.109 486.280 36.925 485.836 36.925 485.389 c 36.925 484.942 37.109 484.498 37.425 484.182 c 37.741 483.867 38.185 483.683 38.631 483.683 c 39.078 483.683 39.522 483.867 39.838 484.182 c 40.154 484.498 40.337 484.942 40.337 485.389 c f BT 45.750 482.421 Td /F1 9.8 Tf [(Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 459.267 Td /F4 9.8 Tf [(Supporting Organizations)] TJ ET BT 26.250 439.862 Td /F4 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD\))] TJ ET BT 26.250 420.457 Td /F1 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD, www.parentprojectmd.org\) is the largest nonprofit organization in the United States )] TJ ET BT 26.250 408.552 Td /F1 9.8 Tf [(focused entirely on Duchenne. Started in 1994 by Pat Furlong, PPMD takes a comprehensive approach in the fight against )] TJ ET BT 26.250 396.648 Td /F1 9.8 Tf [(Duchennefunding research, raising awareness, promoting advocacy, connecting the community, and broadening treatment )] TJ ET BT 26.250 384.743 Td /F1 9.8 Tf [(options. PPMDs care objectives are to identify gaps in care for people with Duchenne and work toward solutions, and to work )] TJ ET BT 26.250 372.838 Td /F1 9.8 Tf [(with clinicians and other health care professionals across the globe to ensure all Duchenne patients have access to optimal care.)] TJ ET BT 26.250 336.236 Td /F4 12.0 Tf [(Competing Interests Statement)] TJ ET BT 26.250 316.281 Td /F1 9.8 Tf [(The Authors have declared that no competing interests exist.)] TJ ET BT 26.250 279.679 Td /F4 12.0 Tf [(Corresponding Author)] TJ ET BT 26.250 259.725 Td /F1 9.8 Tf [(Kathi Kinnett \(kathi@parentprojectmd.org\))] TJ ET BT 26.250 223.122 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 203.168 Td /F1 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community. St. Vincents Hospital, )] TJ ET BT 26.250 191.263 Td /F1 9.8 Tf [(Indianapolis, IN Philip Zeitler, Childrens Hospital Colorado, Aurora, CO Sasigarn Bowden, Nationwide Childrens Hospital, )] TJ ET BT 26.250 179.358 Td /F1 9.8 Tf [(Columbus, OH Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON Jerry R. Mendell, Nationwide Childrens Hospital, )] TJ ET BT 26.250 167.454 Td /F1 9.8 Tf [(Columbus, OH Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 138.351 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 110.897 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 110.897 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, et al. Evidence Based Path to Newborn Screening for Duchenne Muscular Dystrophy. Ann )] TJ ET BT 26.250 98.992 Td /F1 9.8 Tf [(Neurol 2012;71:304313.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 90.506 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 71.956 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 71.956 Td /F1 9.8 Tf [(Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of )] TJ ET BT 26.250 60.051 Td /F1 9.8 Tf [(Duchenne and Becker muscular dystrophy. 2014;24:482491.)] TJ ET Q q 15.000 50.170 577.500 726.830 re W n 0.965 0.965 0.965 rg 26.250 744.514 555.000 32.486 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 744.514 m 581.250 744.514 l 581.250 745.264 l 26.250 745.264 l f q 35.250 755.764 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 766.011 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 68.849 766.011 Td /F1 9.8 Tf [(: Corticosteroid Conversion Table)] TJ ET Q BT 26.250 710.292 Td /F4 12.0 Tf [(Conclusion)] TJ ET BT 26.250 690.338 Td /F1 9.8 Tf [(This protocol, on how to manage patients with corticosteroid dependence, particularly during periods of stress and how to )] TJ ET BT 26.250 678.433 Td /F1 9.8 Tf [(recognize and prevent an acute adrenal crisis, was named in honor of the late Philip James PJ Nicholoff, for his contribution to )] TJ ET BT 26.250 666.528 Td /F1 9.8 Tf [(the global Duchenne community. Despite the tragic loss of PJs life, the PJ Nicholoff Steroid Protocol is a positive result that )] TJ ET BT 26.250 654.624 Td /F1 9.8 Tf [(will impact the lives of people living with Duchenne and using corticosteroids around the world. We thank PJ and his family for )] TJ ET BT 26.250 642.719 Td /F1 9.8 Tf [(encouraging the development of this resource.)] TJ ET BT 26.250 623.314 Td /F4 9.8 Tf [(A pdf of the PJ Nicholoff Protocol can be downloaded at: )] TJ ET BT 26.250 611.409 Td /F4 9.8 Tf [(http://www.parentprojectmd.org/site/DocServer/PJ_Nicholoff_Steroid_Protocol.pdf?docID=15843Acknowledgements )] TJ ET BT 26.250 599.505 Td /F4 9.8 Tf [(for the development of the PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 580.100 Td /F5 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community.)] TJ ET 0.271 0.267 0.267 RG 40.337 563.663 m 40.337 564.109 40.154 564.553 39.838 564.869 c 39.522 565.185 39.078 565.369 38.631 565.369 c 38.185 565.369 37.741 565.185 37.425 564.869 c 37.109 564.553 36.925 564.109 36.925 563.663 c 36.925 563.216 37.109 562.772 37.425 562.456 c 37.741 562.140 38.185 561.956 38.631 561.956 c 39.078 561.956 39.522 562.140 39.838 562.456 c 40.154 562.772 40.337 563.216 40.337 563.663 c f BT 45.750 560.695 Td /F1 9.8 Tf [(Vincents Hospital, Indianapolis, IN)] TJ ET 40.337 548.008 m 40.337 548.455 40.154 548.899 39.838 549.215 c 39.522 549.530 39.078 549.714 38.631 549.714 c 38.185 549.714 37.741 549.530 37.425 549.215 c 37.109 548.899 36.925 548.455 36.925 548.008 c 36.925 547.561 37.109 547.117 37.425 546.801 c 37.741 546.486 38.185 546.302 38.631 546.302 c 39.078 546.302 39.522 546.486 39.838 546.801 c 40.154 547.117 40.337 547.561 40.337 548.008 c f BT 45.750 545.040 Td /F1 9.8 Tf [(Philip Zeitler, Childrens Hospital Colorado, Aurora, CO)] TJ ET 40.337 532.353 m 40.337 532.800 40.154 533.244 39.838 533.560 c 39.522 533.876 39.078 534.059 38.631 534.059 c 38.185 534.059 37.741 533.876 37.425 533.560 c 37.109 533.244 36.925 532.800 36.925 532.353 c 36.925 531.907 37.109 531.463 37.425 531.147 c 37.741 530.831 38.185 530.647 38.631 530.647 c 39.078 530.647 39.522 530.831 39.838 531.147 c 40.154 531.463 40.337 531.907 40.337 532.353 c f BT 45.750 529.386 Td /F1 9.8 Tf [(Sasigarn Bowden, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 516.698 m 40.337 517.145 40.154 517.589 39.838 517.905 c 39.522 518.221 39.078 518.405 38.631 518.405 c 38.185 518.405 37.741 518.221 37.425 517.905 c 37.109 517.589 36.925 517.145 36.925 516.698 c 36.925 516.252 37.109 515.808 37.425 515.492 c 37.741 515.176 38.185 514.992 38.631 514.992 c 39.078 514.992 39.522 515.176 39.838 515.492 c 40.154 515.808 40.337 516.252 40.337 516.698 c f BT 45.750 513.731 Td /F1 9.8 Tf [(Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON)] TJ ET 40.337 501.044 m 40.337 501.490 40.154 501.934 39.838 502.250 c 39.522 502.566 39.078 502.750 38.631 502.750 c 38.185 502.750 37.741 502.566 37.425 502.250 c 37.109 501.934 36.925 501.490 36.925 501.044 c 36.925 500.597 37.109 500.153 37.425 499.837 c 37.741 499.521 38.185 499.337 38.631 499.337 c 39.078 499.337 39.522 499.521 39.838 499.837 c 40.154 500.153 40.337 500.597 40.337 501.044 c f BT 45.750 498.076 Td /F1 9.8 Tf [(Jerry R. Mendell, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 485.389 m 40.337 485.836 40.154 486.280 39.838 486.596 c 39.522 486.911 39.078 487.095 38.631 487.095 c 38.185 487.095 37.741 486.911 37.425 486.596 c 37.109 486.280 36.925 485.836 36.925 485.389 c 36.925 484.942 37.109 484.498 37.425 484.182 c 37.741 483.867 38.185 483.683 38.631 483.683 c 39.078 483.683 39.522 483.867 39.838 484.182 c 40.154 484.498 40.337 484.942 40.337 485.389 c f BT 45.750 482.421 Td /F1 9.8 Tf [(Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 459.267 Td /F4 9.8 Tf [(Supporting Organizations)] TJ ET BT 26.250 439.862 Td /F4 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD\))] TJ ET BT 26.250 420.457 Td /F1 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD, www.parentprojectmd.org\) is the largest nonprofit organization in the United States )] TJ ET BT 26.250 408.552 Td /F1 9.8 Tf [(focused entirely on Duchenne. Started in 1994 by Pat Furlong, PPMD takes a comprehensive approach in the fight against )] TJ ET BT 26.250 396.648 Td /F1 9.8 Tf [(Duchennefunding research, raising awareness, promoting advocacy, connecting the community, and broadening treatment )] TJ ET BT 26.250 384.743 Td /F1 9.8 Tf [(options. PPMDs care objectives are to identify gaps in care for people with Duchenne and work toward solutions, and to work )] TJ ET BT 26.250 372.838 Td /F1 9.8 Tf [(with clinicians and other health care professionals across the globe to ensure all Duchenne patients have access to optimal care.)] TJ ET BT 26.250 336.236 Td /F4 12.0 Tf [(Competing Interests Statement)] TJ ET BT 26.250 316.281 Td /F1 9.8 Tf [(The Authors have declared that no competing interests exist.)] TJ ET BT 26.250 279.679 Td /F4 12.0 Tf [(Corresponding Author)] TJ ET BT 26.250 259.725 Td /F1 9.8 Tf [(Kathi Kinnett \(kathi@parentprojectmd.org\))] TJ ET BT 26.250 223.122 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 203.168 Td /F1 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community. St. Vincents Hospital, )] TJ ET BT 26.250 191.263 Td /F1 9.8 Tf [(Indianapolis, IN Philip Zeitler, Childrens Hospital Colorado, Aurora, CO Sasigarn Bowden, Nationwide Childrens Hospital, )] TJ ET BT 26.250 179.358 Td /F1 9.8 Tf [(Columbus, OH Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON Jerry R. Mendell, Nationwide Childrens Hospital, )] TJ ET BT 26.250 167.454 Td /F1 9.8 Tf [(Columbus, OH Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 138.351 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 110.897 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 110.897 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, et al. Evidence Based Path to Newborn Screening for Duchenne Muscular Dystrophy. Ann )] TJ ET BT 26.250 98.992 Td /F1 9.8 Tf [(Neurol 2012;71:304313.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 90.506 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 71.956 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 71.956 Td /F1 9.8 Tf [(Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of )] TJ ET BT 26.250 60.051 Td /F1 9.8 Tf [(Duchenne and Becker muscular dystrophy. 2014;24:482491.)] TJ ET Q q 15.000 50.170 577.500 726.830 re W n 0.965 0.965 0.965 rg 26.250 744.514 555.000 32.486 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 744.514 m 581.250 744.514 l 581.250 745.264 l 26.250 745.264 l f q 35.250 755.764 537.000 21.236 re W n 0.271 0.267 0.267 rg BT 35.250 766.011 Td /F4 9.8 Tf [(Table 3)] TJ ET BT 68.849 766.011 Td /F1 9.8 Tf [(: Corticosteroid Conversion Table)] TJ ET Q BT 26.250 710.292 Td /F4 12.0 Tf [(Conclusion)] TJ ET BT 26.250 690.338 Td /F1 9.8 Tf [(This protocol, on how to manage patients with corticosteroid dependence, particularly during periods of stress and how to )] TJ ET BT 26.250 678.433 Td /F1 9.8 Tf [(recognize and prevent an acute adrenal crisis, was named in honor of the late Philip James PJ Nicholoff, for his contribution to )] TJ ET BT 26.250 666.528 Td /F1 9.8 Tf [(the global Duchenne community. Despite the tragic loss of PJs life, the PJ Nicholoff Steroid Protocol is a positive result that )] TJ ET BT 26.250 654.624 Td /F1 9.8 Tf [(will impact the lives of people living with Duchenne and using corticosteroids around the world. We thank PJ and his family for )] TJ ET BT 26.250 642.719 Td /F1 9.8 Tf [(encouraging the development of this resource.)] TJ ET BT 26.250 623.314 Td /F4 9.8 Tf [(A pdf of the PJ Nicholoff Protocol can be downloaded at: )] TJ ET BT 26.250 611.409 Td /F4 9.8 Tf [(http://www.parentprojectmd.org/site/DocServer/PJ_Nicholoff_Steroid_Protocol.pdf?docID=15843Acknowledgements )] TJ ET BT 26.250 599.505 Td /F4 9.8 Tf [(for the development of the PJ Nicholoff Steroid Protocol)] TJ ET BT 26.250 580.100 Td /F5 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community.)] TJ ET 0.271 0.267 0.267 RG 40.337 563.663 m 40.337 564.109 40.154 564.553 39.838 564.869 c 39.522 565.185 39.078 565.369 38.631 565.369 c 38.185 565.369 37.741 565.185 37.425 564.869 c 37.109 564.553 36.925 564.109 36.925 563.663 c 36.925 563.216 37.109 562.772 37.425 562.456 c 37.741 562.140 38.185 561.956 38.631 561.956 c 39.078 561.956 39.522 562.140 39.838 562.456 c 40.154 562.772 40.337 563.216 40.337 563.663 c f BT 45.750 560.695 Td /F1 9.8 Tf [(Vincents Hospital, Indianapolis, IN)] TJ ET 40.337 548.008 m 40.337 548.455 40.154 548.899 39.838 549.215 c 39.522 549.530 39.078 549.714 38.631 549.714 c 38.185 549.714 37.741 549.530 37.425 549.215 c 37.109 548.899 36.925 548.455 36.925 548.008 c 36.925 547.561 37.109 547.117 37.425 546.801 c 37.741 546.486 38.185 546.302 38.631 546.302 c 39.078 546.302 39.522 546.486 39.838 546.801 c 40.154 547.117 40.337 547.561 40.337 548.008 c f BT 45.750 545.040 Td /F1 9.8 Tf [(Philip Zeitler, Childrens Hospital Colorado, Aurora, CO)] TJ ET 40.337 532.353 m 40.337 532.800 40.154 533.244 39.838 533.560 c 39.522 533.876 39.078 534.059 38.631 534.059 c 38.185 534.059 37.741 533.876 37.425 533.560 c 37.109 533.244 36.925 532.800 36.925 532.353 c 36.925 531.907 37.109 531.463 37.425 531.147 c 37.741 530.831 38.185 530.647 38.631 530.647 c 39.078 530.647 39.522 530.831 39.838 531.147 c 40.154 531.463 40.337 531.907 40.337 532.353 c f BT 45.750 529.386 Td /F1 9.8 Tf [(Sasigarn Bowden, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 516.698 m 40.337 517.145 40.154 517.589 39.838 517.905 c 39.522 518.221 39.078 518.405 38.631 518.405 c 38.185 518.405 37.741 518.221 37.425 517.905 c 37.109 517.589 36.925 517.145 36.925 516.698 c 36.925 516.252 37.109 515.808 37.425 515.492 c 37.741 515.176 38.185 514.992 38.631 514.992 c 39.078 514.992 39.522 515.176 39.838 515.492 c 40.154 515.808 40.337 516.252 40.337 516.698 c f BT 45.750 513.731 Td /F1 9.8 Tf [(Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON)] TJ ET 40.337 501.044 m 40.337 501.490 40.154 501.934 39.838 502.250 c 39.522 502.566 39.078 502.750 38.631 502.750 c 38.185 502.750 37.741 502.566 37.425 502.250 c 37.109 501.934 36.925 501.490 36.925 501.044 c 36.925 500.597 37.109 500.153 37.425 499.837 c 37.741 499.521 38.185 499.337 38.631 499.337 c 39.078 499.337 39.522 499.521 39.838 499.837 c 40.154 500.153 40.337 500.597 40.337 501.044 c f BT 45.750 498.076 Td /F1 9.8 Tf [(Jerry R. Mendell, Nationwide Childrens Hospital, Columbus, OH)] TJ ET 40.337 485.389 m 40.337 485.836 40.154 486.280 39.838 486.596 c 39.522 486.911 39.078 487.095 38.631 487.095 c 38.185 487.095 37.741 486.911 37.425 486.596 c 37.109 486.280 36.925 485.836 36.925 485.389 c 36.925 484.942 37.109 484.498 37.425 484.182 c 37.741 483.867 38.185 483.683 38.631 483.683 c 39.078 483.683 39.522 483.867 39.838 484.182 c 40.154 484.498 40.337 484.942 40.337 485.389 c f BT 45.750 482.421 Td /F1 9.8 Tf [(Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 459.267 Td /F4 9.8 Tf [(Supporting Organizations)] TJ ET BT 26.250 439.862 Td /F4 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD\))] TJ ET BT 26.250 420.457 Td /F1 9.8 Tf [(Parent Project Muscular Dystrophy \(PPMD, www.parentprojectmd.org\) is the largest nonprofit organization in the United States )] TJ ET BT 26.250 408.552 Td /F1 9.8 Tf [(focused entirely on Duchenne. Started in 1994 by Pat Furlong, PPMD takes a comprehensive approach in the fight against )] TJ ET BT 26.250 396.648 Td /F1 9.8 Tf [(Duchennefunding research, raising awareness, promoting advocacy, connecting the community, and broadening treatment )] TJ ET BT 26.250 384.743 Td /F1 9.8 Tf [(options. PPMDs care objectives are to identify gaps in care for people with Duchenne and work toward solutions, and to work )] TJ ET BT 26.250 372.838 Td /F1 9.8 Tf [(with clinicians and other health care professionals across the globe to ensure all Duchenne patients have access to optimal care.)] TJ ET BT 26.250 336.236 Td /F4 12.0 Tf [(Competing Interests Statement)] TJ ET BT 26.250 316.281 Td /F1 9.8 Tf [(The Authors have declared that no competing interests exist.)] TJ ET BT 26.250 279.679 Td /F4 12.0 Tf [(Corresponding Author)] TJ ET BT 26.250 259.725 Td /F1 9.8 Tf [(Kathi Kinnett \(kathi@parentprojectmd.org\))] TJ ET BT 26.250 223.122 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 203.168 Td /F1 9.8 Tf [(In honor of the late Philip James PJ Nicholoff, for his contribution to the global Duchenne community. St. Vincents Hospital, )] TJ ET BT 26.250 191.263 Td /F1 9.8 Tf [(Indianapolis, IN Philip Zeitler, Childrens Hospital Colorado, Aurora, CO Sasigarn Bowden, Nationwide Childrens Hospital, )] TJ ET BT 26.250 179.358 Td /F1 9.8 Tf [(Columbus, OH Doug Biggar, Holland Bloorview Kids Rehab, Toronto, ON Jerry R. Mendell, Nationwide Childrens Hospital, )] TJ ET BT 26.250 167.454 Td /F1 9.8 Tf [(Columbus, OH Anne M. Connolly, St. Louis Childrens Hospital, St. Louis, MO)] TJ ET BT 26.250 138.351 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 110.897 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 110.897 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, et al. Evidence Based Path to Newborn Screening for Duchenne Muscular Dystrophy. Ann )] TJ ET BT 26.250 98.992 Td /F1 9.8 Tf [(Neurol 2012;71:304313.)] TJ ET 0.267 0.267 0.267 rg BT 26.250 90.506 Td /F1 7.5 Tf [(REFERENCE LINK)] TJ ET 0.271 0.267 0.267 rg BT 26.250 71.956 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 71.956 Td /F1 9.8 Tf [(Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of )] TJ ET BT 26.250 60.051 Td /F1 9.8 Tf [(Duchenne and Becker muscular dystrophy. 2014;24:482491.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(6)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular Dystrophy)] TJ ET 0.39 w 1 J 1 j Q endstream endobj 220 0 obj << /Type /Annot /Subtype /Link /A 221 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 89.8125 91.2600 97.4437 ] >> endobj 221 0 obj << /Type /Action /S /URI /URI (https://www.ncbi.nlm.nih.gov/pubmed/22451200) >> endobj 222 0 obj << /Type /Annot /Subtype /Link /A 223 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 89.8125 91.2600 97.4437 ] >> endobj 223 0 obj << /Type /Action /S /URI /URI (https://www.ncbi.nlm.nih.gov/pubmed/22451200) >> endobj 224 0 obj << /Type /Annot /Subtype /Link /A 225 0 R /Border [0 0 0] /H /I /Rect [ 26.2500 89.8125 91.2600 97.4437 ] >> endobj 225 0 obj << /Type /Action /S /URI /URI (https://www.ncbi.nlm.nih.gov/pubmed/22451200) >> endobj 226 0 obj << /Type /Page /Parent 3 0 R /Contents 227 0 R >> endobj 227 0 obj << /Length 18480 >> stream 0.271 0.267 0.267 rg 0.271 0.267 0.267 RG 0.39 w 1 J 1 j q 15.000 182.119 577.500 594.881 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, Kneile K, Dunn DM, Duval B, Aoyagi A, )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hamil C, Mahmoud M, Roush K, Bird L, Rankin C, Lilly H, Street N, Chandrasekar R, Weiss RB. Evidence-based path to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012 Mar;71\(3\):30413.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne Muscular Dystrophy: )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular Disorders )] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2002;12\(10\): 926929.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Bushby K1, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 649.738 Td /F1 9.8 Tf [(muscular dystrophy, part 2: Implementation of multidisciplinary care. Lancet Neurol 2010;9:17789.)] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 630.333 Td /F1 9.8 Tf [(Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, Cnaan A, McDonald CM; CINRG )] TJ ET BT 26.250 618.429 Td /F1 9.8 Tf [(Investigators. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. )] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(2015 Sep 22;85\(12\):104855.)] TJ ET BT 26.250 587.119 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 587.119 Td /F1 9.8 Tf [(Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurology 2010?9:7793.)] TJ ET BT 26.250 543.905 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 543.905 Td /F1 9.8 Tf [(Kinnett K, Rodger S, Vroom E, Furlong P, Aartsma-Rus A, Bushby K. Imperatives for DUCHENNE MD: a Simplified Guide to )] TJ ET BT 26.250 532.000 Td /F1 9.8 Tf [(Comprehensive Care for Duchenne Muscular Dystrophy. PLOS Currents Muscular Dystrophy. 2015 Aug 7. Edition 1.)] TJ ET BT 26.250 512.595 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 512.595 Td /F1 9.8 Tf [(Pender ES, Pollack CV Jr, Evans OB. Fat embolism syndrome in a child with muscular dystrophy. J Emerg Med. 1992 Nov-)] TJ ET BT 26.250 500.691 Td /F1 9.8 Tf [(Dec;10\(6\):70511.)] TJ ET BT 26.250 481.286 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 481.286 Td /F1 9.8 Tf [(Medeiros MO, Behrend C, King W, Sanders J, Kissel J, Ciafaloni E. Fat embolism syndrome in patients with Duchenne )] TJ ET BT 26.250 469.381 Td /F1 9.8 Tf [(muscular dystrophy. Neurology. 2013 Apr 2;80\(14\):13502.)] TJ ET BT 26.250 449.976 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 449.976 Td /F1 9.8 Tf [(Estegan NV, LoughlinT, Yergey A, et al. Saily cortisol production in man determined by stable isotope dilution/mass )] TJ ET BT 26.250 438.072 Td /F1 9.8 Tf [(spectrometry. J Clin Endocrinol Metab. 1991;72:3945.)] TJ ET BT 26.250 418.667 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 418.667 Td /F1 9.8 Tf [(Krasner AS. Glucocorticoid-Induced adrenal insufficiency. JAMA. 1999; 282:671676.)] TJ ET BT 26.250 399.262 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 399.262 Td /F1 9.8 Tf [(Orth DN, Kovacs WJ. In: WilsonJD, Foster DW, Kronenberg HM, Larsen RP, eds. Williams Textbook of Endocrinology. 9th )] TJ ET BT 26.250 387.357 Td /F1 9.8 Tf [(ed. Philadelphia, PA: WB Saunders Co; 1998:517665.)] TJ ET BT 26.250 367.953 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 367.953 Td /F1 9.8 Tf [(Lamberts SWJ, Bruining HA, DeJong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997;337:12851292.)] TJ ET BT 26.250 348.548 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 348.548 Td /F1 9.8 Tf [(Arlt W, Allolio B. Adrenal insufficiency. Comment in Lancet. 2003 May 31;361\(9372\):188193.)] TJ ET BT 26.250 329.143 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 329.143 Td /F1 9.8 Tf [(Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236240.)] TJ ET BT 26.250 309.738 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 309.738 Td /F1 9.8 Tf [(Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. )] TJ ET BT 26.250 297.834 Td /F1 9.8 Tf [(Comment in Arch Surg. 2008 Dec;143\(12\):12226.)] TJ ET BT 26.250 278.429 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 278.429 Td /F1 9.8 Tf [(Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, )] TJ ET BT 26.250 266.524 Td /F1 9.8 Tf [(Maghnie M, Rose SR, Soule SG, Tordjman K, Consortium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary Adrenal )] TJ ET BT 26.250 254.619 Td /F1 9.8 Tf [(Insufficiency: Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a meta-analysis. J Clin Endocrinol Metab. )] TJ ET BT 26.250 242.715 Td /F1 9.8 Tf [(2008, 93: 424553.)] TJ ET BT 26.250 223.310 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 223.310 Td /F1 9.8 Tf [(Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of )] TJ ET BT 26.250 211.405 Td /F1 9.8 Tf [(adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 )] TJ ET BT 26.250 199.500 Td /F1 9.8 Tf [(Mar;162\(3\):597602.)] TJ ET Q q 15.000 182.119 577.500 594.881 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, Kneile K, Dunn DM, Duval B, Aoyagi A, )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hamil C, Mahmoud M, Roush K, Bird L, Rankin C, Lilly H, Street N, Chandrasekar R, Weiss RB. Evidence-based path to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012 Mar;71\(3\):30413.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne Muscular Dystrophy: )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular Disorders )] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2002;12\(10\): 926929.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Bushby K1, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 649.738 Td /F1 9.8 Tf [(muscular dystrophy, part 2: Implementation of multidisciplinary care. Lancet Neurol 2010;9:17789.)] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 630.333 Td /F1 9.8 Tf [(Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, Cnaan A, McDonald CM; CINRG )] TJ ET BT 26.250 618.429 Td /F1 9.8 Tf [(Investigators. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. )] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(2015 Sep 22;85\(12\):104855.)] TJ ET BT 26.250 587.119 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 587.119 Td /F1 9.8 Tf [(Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurology 2010?9:7793.)] TJ ET BT 26.250 543.905 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 543.905 Td /F1 9.8 Tf [(Kinnett K, Rodger S, Vroom E, Furlong P, Aartsma-Rus A, Bushby K. Imperatives for DUCHENNE MD: a Simplified Guide to )] TJ ET BT 26.250 532.000 Td /F1 9.8 Tf [(Comprehensive Care for Duchenne Muscular Dystrophy. PLOS Currents Muscular Dystrophy. 2015 Aug 7. Edition 1.)] TJ ET BT 26.250 512.595 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 512.595 Td /F1 9.8 Tf [(Pender ES, Pollack CV Jr, Evans OB. Fat embolism syndrome in a child with muscular dystrophy. J Emerg Med. 1992 Nov-)] TJ ET BT 26.250 500.691 Td /F1 9.8 Tf [(Dec;10\(6\):70511.)] TJ ET BT 26.250 481.286 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 481.286 Td /F1 9.8 Tf [(Medeiros MO, Behrend C, King W, Sanders J, Kissel J, Ciafaloni E. Fat embolism syndrome in patients with Duchenne )] TJ ET BT 26.250 469.381 Td /F1 9.8 Tf [(muscular dystrophy. Neurology. 2013 Apr 2;80\(14\):13502.)] TJ ET BT 26.250 449.976 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 449.976 Td /F1 9.8 Tf [(Estegan NV, LoughlinT, Yergey A, et al. Saily cortisol production in man determined by stable isotope dilution/mass )] TJ ET BT 26.250 438.072 Td /F1 9.8 Tf [(spectrometry. J Clin Endocrinol Metab. 1991;72:3945.)] TJ ET BT 26.250 418.667 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 418.667 Td /F1 9.8 Tf [(Krasner AS. Glucocorticoid-Induced adrenal insufficiency. JAMA. 1999; 282:671676.)] TJ ET BT 26.250 399.262 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 399.262 Td /F1 9.8 Tf [(Orth DN, Kovacs WJ. In: WilsonJD, Foster DW, Kronenberg HM, Larsen RP, eds. Williams Textbook of Endocrinology. 9th )] TJ ET BT 26.250 387.357 Td /F1 9.8 Tf [(ed. Philadelphia, PA: WB Saunders Co; 1998:517665.)] TJ ET BT 26.250 367.953 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 367.953 Td /F1 9.8 Tf [(Lamberts SWJ, Bruining HA, DeJong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997;337:12851292.)] TJ ET BT 26.250 348.548 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 348.548 Td /F1 9.8 Tf [(Arlt W, Allolio B. Adrenal insufficiency. Comment in Lancet. 2003 May 31;361\(9372\):188193.)] TJ ET BT 26.250 329.143 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 329.143 Td /F1 9.8 Tf [(Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236240.)] TJ ET BT 26.250 309.738 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 309.738 Td /F1 9.8 Tf [(Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. )] TJ ET BT 26.250 297.834 Td /F1 9.8 Tf [(Comment in Arch Surg. 2008 Dec;143\(12\):12226.)] TJ ET BT 26.250 278.429 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 278.429 Td /F1 9.8 Tf [(Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, )] TJ ET BT 26.250 266.524 Td /F1 9.8 Tf [(Maghnie M, Rose SR, Soule SG, Tordjman K, Consortium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary Adrenal )] TJ ET BT 26.250 254.619 Td /F1 9.8 Tf [(Insufficiency: Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a meta-analysis. J Clin Endocrinol Metab. )] TJ ET BT 26.250 242.715 Td /F1 9.8 Tf [(2008, 93: 424553.)] TJ ET BT 26.250 223.310 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 223.310 Td /F1 9.8 Tf [(Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of )] TJ ET BT 26.250 211.405 Td /F1 9.8 Tf [(adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 )] TJ ET BT 26.250 199.500 Td /F1 9.8 Tf [(Mar;162\(3\):597602.)] TJ ET Q q 15.000 182.119 577.500 594.881 re W n 0.271 0.267 0.267 rg BT 26.250 759.976 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 759.976 Td /F1 9.8 Tf [(Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, Kneile K, Dunn DM, Duval B, Aoyagi A, )] TJ ET BT 26.250 748.071 Td /F1 9.8 Tf [(Hamil C, Mahmoud M, Roush K, Bird L, Rankin C, Lilly H, Street N, Chandrasekar R, Weiss RB. Evidence-based path to )] TJ ET BT 26.250 736.167 Td /F1 9.8 Tf [(newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012 Mar;71\(3\):30413.)] TJ ET BT 26.250 716.762 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 716.762 Td /F1 9.8 Tf [(Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne Muscular Dystrophy: )] TJ ET BT 26.250 704.857 Td /F1 9.8 Tf [(Improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular Disorders )] TJ ET BT 26.250 692.952 Td /F1 9.8 Tf [(2002;12\(10\): 926929.)] TJ ET BT 26.250 673.548 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 673.548 Td /F1 9.8 Tf [(Bushby K1, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 661.643 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 649.738 Td /F1 9.8 Tf [(muscular dystrophy, part 2: Implementation of multidisciplinary care. Lancet Neurol 2010;9:17789.)] TJ ET BT 26.250 630.333 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 630.333 Td /F1 9.8 Tf [(Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, Cnaan A, McDonald CM; CINRG )] TJ ET BT 26.250 618.429 Td /F1 9.8 Tf [(Investigators. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. )] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(2015 Sep 22;85\(12\):104855.)] TJ ET BT 26.250 587.119 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 587.119 Td /F1 9.8 Tf [(Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, )] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurology 2010?9:7793.)] TJ ET BT 26.250 543.905 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 543.905 Td /F1 9.8 Tf [(Kinnett K, Rodger S, Vroom E, Furlong P, Aartsma-Rus A, Bushby K. Imperatives for DUCHENNE MD: a Simplified Guide to )] TJ ET BT 26.250 532.000 Td /F1 9.8 Tf [(Comprehensive Care for Duchenne Muscular Dystrophy. PLOS Currents Muscular Dystrophy. 2015 Aug 7. Edition 1.)] TJ ET BT 26.250 512.595 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 512.595 Td /F1 9.8 Tf [(Pender ES, Pollack CV Jr, Evans OB. Fat embolism syndrome in a child with muscular dystrophy. J Emerg Med. 1992 Nov-)] TJ ET BT 26.250 500.691 Td /F1 9.8 Tf [(Dec;10\(6\):70511.)] TJ ET BT 26.250 481.286 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 481.286 Td /F1 9.8 Tf [(Medeiros MO, Behrend C, King W, Sanders J, Kissel J, Ciafaloni E. Fat embolism syndrome in patients with Duchenne )] TJ ET BT 26.250 469.381 Td /F1 9.8 Tf [(muscular dystrophy. Neurology. 2013 Apr 2;80\(14\):13502.)] TJ ET BT 26.250 449.976 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 449.976 Td /F1 9.8 Tf [(Estegan NV, LoughlinT, Yergey A, et al. Saily cortisol production in man determined by stable isotope dilution/mass )] TJ ET BT 26.250 438.072 Td /F1 9.8 Tf [(spectrometry. J Clin Endocrinol Metab. 1991;72:3945.)] TJ ET BT 26.250 418.667 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 418.667 Td /F1 9.8 Tf [(Krasner AS. Glucocorticoid-Induced adrenal insufficiency. JAMA. 1999; 282:671676.)] TJ ET BT 26.250 399.262 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 399.262 Td /F1 9.8 Tf [(Orth DN, Kovacs WJ. In: WilsonJD, Foster DW, Kronenberg HM, Larsen RP, eds. Williams Textbook of Endocrinology. 9th )] TJ ET BT 26.250 387.357 Td /F1 9.8 Tf [(ed. Philadelphia, PA: WB Saunders Co; 1998:517665.)] TJ ET BT 26.250 367.953 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 367.953 Td /F1 9.8 Tf [(Lamberts SWJ, Bruining HA, DeJong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997;337:12851292.)] TJ ET BT 26.250 348.548 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 348.548 Td /F1 9.8 Tf [(Arlt W, Allolio B. Adrenal insufficiency. Comment in Lancet. 2003 May 31;361\(9372\):188193.)] TJ ET BT 26.250 329.143 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 329.143 Td /F1 9.8 Tf [(Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236240.)] TJ ET BT 26.250 309.738 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 309.738 Td /F1 9.8 Tf [(Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. )] TJ ET BT 26.250 297.834 Td /F1 9.8 Tf [(Comment in Arch Surg. 2008 Dec;143\(12\):12226.)] TJ ET BT 26.250 278.429 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 278.429 Td /F1 9.8 Tf [(Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, )] TJ ET BT 26.250 266.524 Td /F1 9.8 Tf [(Maghnie M, Rose SR, Soule SG, Tordjman K, Consortium for Evaluation of Corticotropin Test in Hypothalamic-Pituitary Adrenal )] TJ ET BT 26.250 254.619 Td /F1 9.8 Tf [(Insufficiency: Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a meta-analysis. J Clin Endocrinol Metab. )] TJ ET BT 26.250 242.715 Td /F1 9.8 Tf [(2008, 93: 424553.)] TJ ET BT 26.250 223.310 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 223.310 Td /F1 9.8 Tf [(Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of )] TJ ET BT 26.250 211.405 Td /F1 9.8 Tf [(adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 )] TJ ET BT 26.250 199.500 Td /F1 9.8 Tf [(Mar;162\(3\):597602.)] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(7)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Muscular Dystrophy)] TJ ET 0.39 w 1 J 1 j Q endstream endobj xref 0 228 0000000000 65535 f 0000000008 00000 n 0000000073 00000 n 0000000119 00000 n 0000000437 00000 n 0000000474 00000 n 0000000733 00000 n 0000001039 00000 n 0000025978 00000 n 0000026085 00000 n 0000026193 00000 n 0000026304 00000 n 0000026417 00000 n 0000026533 00000 n 0000026921 00000 n 0000031278 00000 n 0000031405 00000 n 0000031594 00000 n 0000031721 00000 n 0000031910 00000 n 0000032037 00000 n 0000032170 00000 n 0000032296 00000 n 0000032393 00000 n 0000032520 00000 n 0000032643 00000 n 0000032771 00000 n 0000032807 00000 n 0000032935 00000 n 0000032971 00000 n 0000033099 00000 n 0000033135 00000 n 0000033263 00000 n 0000033299 00000 n 0000033427 00000 n 0000033463 00000 n 0000033589 00000 n 0000033625 00000 n 0000033752 00000 n 0000033941 00000 n 0000034068 00000 n 0000034257 00000 n 0000034384 00000 n 0000034517 00000 n 0000034643 00000 n 0000034740 00000 n 0000034867 00000 n 0000034990 00000 n 0000035118 00000 n 0000035154 00000 n 0000035282 00000 n 0000035318 00000 n 0000035446 00000 n 0000035482 00000 n 0000035610 00000 n 0000035646 00000 n 0000035774 00000 n 0000035810 00000 n 0000035936 00000 n 0000035972 00000 n 0000036099 00000 n 0000036288 00000 n 0000036415 00000 n 0000036604 00000 n 0000036731 00000 n 0000036864 00000 n 0000036990 00000 n 0000037087 00000 n 0000037214 00000 n 0000037337 00000 n 0000037465 00000 n 0000037501 00000 n 0000037629 00000 n 0000037665 00000 n 0000037793 00000 n 0000037829 00000 n 0000037957 00000 n 0000037993 00000 n 0000038121 00000 n 0000038157 00000 n 0000038283 00000 n 0000038319 00000 n 0000038651 00000 n 0000074165 00000 n 0000074293 00000 n 0000074329 00000 n 0000074457 00000 n 0000074493 00000 n 0000074621 00000 n 0000074657 00000 n 0000074785 00000 n 0000074821 00000 n 0000074949 00000 n 0000074985 00000 n 0000075111 00000 n 0000075147 00000 n 0000075273 00000 n 0000075309 00000 n 0000075437 00000 n 0000075473 00000 n 0000075602 00000 n 0000075639 00000 n 0000075769 00000 n 0000075806 00000 n 0000075936 00000 n 0000075973 00000 n 0000076103 00000 n 0000076140 00000 n 0000076270 00000 n 0000076307 00000 n 0000076437 00000 n 0000076474 00000 n 0000076604 00000 n 0000076641 00000 n 0000076771 00000 n 0000076808 00000 n 0000076936 00000 n 0000076973 00000 n 0000077101 00000 n 0000077138 00000 n 0000077268 00000 n 0000077305 00000 n 0000077435 00000 n 0000077472 00000 n 0000077602 00000 n 0000077639 00000 n 0000077769 00000 n 0000077806 00000 n 0000077936 00000 n 0000077973 00000 n 0000078103 00000 n 0000078140 00000 n 0000078270 00000 n 0000078307 00000 n 0000078437 00000 n 0000078474 00000 n 0000078604 00000 n 0000078641 00000 n 0000078769 00000 n 0000078806 00000 n 0000078934 00000 n 0000078971 00000 n 0000079101 00000 n 0000079138 00000 n 0000079268 00000 n 0000079305 00000 n 0000079435 00000 n 0000079472 00000 n 0000079602 00000 n 0000079639 00000 n 0000079862 00000 n 0000095921 00000 n 0000096051 00000 n 0000096088 00000 n 0000096218 00000 n 0000096255 00000 n 0000096384 00000 n 0000096490 00000 n 0000150891 00000 n 0000151021 00000 n 0000151058 00000 n 0000151188 00000 n 0000151225 00000 n 0000151354 00000 n 0000151460 00000 n 0000277653 00000 n 0000277783 00000 n 0000277820 00000 n 0000277950 00000 n 0000277987 00000 n 0000278116 00000 n 0000278222 00000 n 0000278352 00000 n 0000278389 00000 n 0000278519 00000 n 0000278556 00000 n 0000278685 00000 n 0000278791 00000 n 0000278921 00000 n 0000278958 00000 n 0000279088 00000 n 0000279125 00000 n 0000279254 00000 n 0000279360 00000 n 0000279490 00000 n 0000279527 00000 n 0000279657 00000 n 0000279694 00000 n 0000279823 00000 n 0000279929 00000 n 0000280032 00000 n 0000326536 00000 n 0000326666 00000 n 0000326703 00000 n 0000326833 00000 n 0000326870 00000 n 0000327000 00000 n 0000327037 00000 n 0000327188 00000 n 0000374068 00000 n 0000374198 00000 n 0000374235 00000 n 0000374365 00000 n 0000374402 00000 n 0000374531 00000 n 0000374639 00000 n 0000441231 00000 n 0000441361 00000 n 0000441398 00000 n 0000441528 00000 n 0000441565 00000 n 0000441694 00000 n 0000441802 00000 n 0000441932 00000 n 0000441969 00000 n 0000442099 00000 n 0000442136 00000 n 0000442265 00000 n 0000442373 00000 n 0000442476 00000 n 0000465148 00000 n 0000465274 00000 n 0000465371 00000 n 0000465497 00000 n 0000465594 00000 n 0000465720 00000 n 0000465817 00000 n 0000465884 00000 n trailer << /Size 228 /Root 1 0 R /Info 5 0 R >> startxref 484419 %%EOF