Endocrine Abstracts

Neonatal salt wasting can present in neonates with a life-threatening state of hyponatraemia, hyperkalaemia, dehydration and metabolic acidosis. The differential diagnosis of neonatal salt wasting includes congenital adrenal hyperplasia (CAH) most commonly due to 21-hydroxylase deficiency, pseudohypoaldosteronism (PHA), X-linked adrenal hypoplasia congenital (AHC) and aldosterone synthase defects. Diagnostic work up should include serum measurement of ACTH, Cortisol, 17OH-progesterone, androstenedione, aldosterone and renin. A term male neonate with a complex neonatal course including abdominal distention, meconium ilius, transient hypoglycaemia and vomiting episodes was found to be hyponatraemic and hyperkalaemic on day nine. NaCl supplements were administered. Electrolyte abnormalities persisted to D19 when a 10% weight loss from birth was reported. Further investigations showed a flat response to a short Synacthen test (Cortisol 138 to 137 nmol/l), after which the patient was commenced on NaCl, hydrocortisone and fludrocortisone. Serum androgen profile was suggestive of 11-beta-hydroxylase deficiency CAH (testosterone 16.4 nmol/l, androstenedione 9.1 nmol/l, 17OH progesterone 7.0 nmol/l, 11-deoxycortisol >53.5 nmol/l and 21-deoxycortisol <0.5 nmol/l). Elevated renin >550 mIU/l (<450) excluded PHA. ACTH and aldosterone were not available. A small dilute sample for urine steroid profile (USP) did not confirm a diagnosis of 11BOH deficiency. Further USP samples were consistent with hydrocortisone treatment but showed no evidence of 11BOH deficiency. No causative sequence variants in CYP11B1 were detected. Further genetic analysis of a 56 gene panel for disorders of sexual development identified a hemizygous pathogenic sequence variant c.106del p.(Asp36Ilefs*49) in NR0B1 gene. The patient was diagnosed with X-linked adrenal hypoplasia congenita, which can present with adrenal insufficiency and hypogonadotrophic hypogonadism. Raised 11-deoxycortisol in the first few weeks of life can lead to a misdiagnosis of 11BOH deficiency CAH. Increased 11-deoxycortisol is reported to return to normal levels in patients with AHC within a few months.