Invited Talk ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Congenital adrenal hyperplasia, paediatric to adult care     (#188)

David J. Torpy 1 2
  1. Faculty of Medicine , University of Adelaide, Adelaide, SA, Australia
  2. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia

 

The commonest form of congenital adrenal hyperplasia (CAH) is due to the homozygous presence of CYP21A2 gene variant(s), leading to deficiency of 21-hydroxylase steroidogenic enzyme, a condition affecting 1/15,000-1/18,000 individuals.  The resulting deficiency of cortisol, often deficient aldosterone, and excess androstenedione with consequent testosterone excess and androgenization underlie the clinical manifestations.  Clinical severity, sometimes classified as salt-losing, simple virilising and non-classical adult onset forms correspond to enzyme activities of 0%, 1-2% and 20-60% respectively.  Diagnostic confirmation often involves AM measurement of the steroidogenic precursor 17-hydroxyprogesterone, including neonatal screening, and confirmation with ACTH stimulation.  Endocrinological treatment involves glucocorticoid replacement /judicious ACTH suppression and often fludrocortisone replacement at replacement doses.  Endocrine monitoring requires measurement of androstenedione, 17 hydroxyprogesterone, renin and testosterone.  Clinical monitoring involves minimising the risks of Cushing's syndrome and adrenal crises.  Changes at puberty/adolescence alter management.  These include: a less severe androgenic profile as the 5-step "alternate" pathway 17-OHP to the potent androgen dihydrotestosterone is inhibited, particularly relevant in women; reported increased metabolism of glucocorticoid; reduced emphasis on linear growth and a new emphasis on fertiity; engagement especially among men; and long term risks of osteoporosis, metabolic syndrome and the variable neurocognitive effects of CAH.  Current management of CAH leads to glucocorticoid excess or androgen excess in most patients, with a varying degree of clinical effect.  New treatments are required and CRH antagonist therapy is showing promise.