ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2018; 103(6):2336-2345

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol production in the adrenal cortex. Classic CAH represents the most common cause of primary adrenal insufficiency in childhood (10). Infant mortality in patients with CAH has decreased since the advent of neonatal screening (11), however, fatal adrenal crises still occur. Here, the authors characterized the rates and causes of glucocorticoid stress dosing and related consequences [emergency room (ER) visits, hospitalizations, adrenal crises] in a large cohort of CAH patients followed prospectively at the NIH Clinical Center for 23 years, who received patient education regarding glucocorticoid stress dosing at each visit. They investigated the association of these outcomes with phenotype, age, daily medication doses, and hormonal evaluations. They report a comprehensive evaluation of illness episodes, glucocorticoid stress dosing habits, and associated outcomes of this large cohort of patients with CAH. Intensive, frequent, and repeated glucocorticoid stress dose teaching allowed patients to often be successfully managed at home during illness episodes; however, adrenal crises requiring hospitalizations and hypoglycemia still occurred. Children had higher rates of illnesses and stress dosing than adults [OR=3.27 (95% CI: 1.74-6.15), P=0.002 OR=4.99 (95% CI: 3.35, 7.42), P<0.0001 respectively], while adults had more ER visits, hospitalizations, and adrenal crises, and were also more likely to stress dose for reasons contrary to the authors’ guidelines. Among children with classic CAH, the most robust predictors of glucocorticoid stress dosing and illnesses were young age and replacement doses (low glucocorticoid and high mineralocorticoid). Although the majority of patients stress-dosed appropriately with illnesses, hypoglycemia occurred in 11 children, with one patient having encephalopathy and probable long-term sequelae.

These findings indicate that patients with CAH are at risk for developing adrenal crises, despite receiving comprehensive preventative education and guidelines aimed at optimizing home management. Revised guidelines for the management of infectious illnesses in patients with CAH are needed and should include frequent glucocorticoid dosing, in addition to guidance regarding carbohydrate and fluid intake aimed at prevention of hypoglycemia, especially during early childhood. Furthermore, these aspects of care should be better communicated to our patients with CAH.

10. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101(2): 364-89.

11. Gidlöf S, Falhammar H, Thilén A, von Döbeln U, Ritzén M, Wedell A, Nordenström A. One hundred years of congenital adrenal hyperplasia in Sweden: a retrospective, population-based cohort study. Lancet Diabetes Endocrinol. 2013; 1(1): 35-42.