Endocrine Abstracts

Introduction: Non-classical congenital adrenal hyperplasia (NCCAH) is a common autosomal recessive disorder characterized by androgen excess. It classically presents in later life with symptoms of acne, hirsutism, and premature adrenarche. This case illustrates a rare case presentation of NCCAH in early infancy.

Clinical case: An 18 day old term male infant was brought to the A&E for 9% weight loss. On review he was mottled, but otherwise examination was unremarkable; he had normal male external genitalia with bilaterally descended testes. Initial investigations revealed a severe salt losing crisis (sodium 121 nmol/l, potassium 8 mmol/l) and a mild metabolic acidosis. He was initially treated with IV fluids and antibiotics for suspected urosepsis. Following investigations intravenous hydrocortisone, sodium chloride supplements and fludrocortisone were commenced in view of suspected CAH. Initial random baseline cortisol and androgen profile was normal, with markedly raised aldosterone (18 900 pmol/l) and Renin (307.8 nmol/l per hour) concentration but a normal urine steroid profile (USP). A standard synacthen test (SST) showed baseline cortisol 707 nmol/l and stimulated 1046 nmol/l with normal androgens. Hydrocortisone, fludrocortisone and salt supplements were therefore stopped with a provisional diagnosis of pseudohypoaldosteronism. Surprisingly, 17-OHP results from the SST subsequently demonstrated a significant rise from a baseline of 15.1 to 203.0 nmol/l at 60 min. A repeat SST at age 1 month off all medications again confirmed an adequate cortisol response to 538 nmol/l but with abnormally raised 17-OHP. Pre- and post-synacthen USP were initially reported as normal. CYP21A2 Sanger sequencing subsequently revealed a compound heterozygous mutation for c.841G>T (p.V281L) and C.1357C>t (p.P453S), both known to be associated with NCCAH. Serial U&Es remained stable off treatment but ACTH concentrations were intermittently raised up to 314 ng/l, now normalized to 37 ng/l. Aldosterone levels have normalized (2740 pmol/l) but Renin remained raised (23.5 pmol/l per hour). Retrospective analysis of previous urine steroid profiles showed very mildly raised 11-oxopregnanetriol concentrations in keeping with the diagnosis.

Discussion: To our knowledge, this is the earliest reported presentation of salt-losing crisis in a patient with genetically proven non-classical CAH, most likely reflecting an additional diagnosis of transient pseudohypoaldosteronism