Endocrine Abstracts

A 1 month old baby boy presented at a local district general hospital with failure to thrive. He was born to non-consanguineous Eastern European parents, with an 18 month old healthy sister. The term birth was unremarkable, with nil of note from the antenatal history. Initial clinical examination revealed a slightly low but stable blood pressure for age, but was otherwise normal.

Investigations: Biochemistry results showed low plasma sodium (125 mmol/l) and elevated potassium (6.1 mmol/l) concentrations. Urine sodium was <10 mmol/l. Blood glucose was stable (3.5–4.2 mmol/l). The plasma cortisol response to synacthen was assessed; baseline: 65 nmol/l, 30 min: 286 nmol/l. Based on these results, CAH remained a potential diagnosis and hydrocortisone and sodium supplementation were commenced. Additional blood tests (17-OHP, ACTH, renin activity, aldosterone) were requested and a spot urine sent for urine steroid profile (USP) analysis.

The USP showed normal cortisol metabolite excretion, and no biomarkers associated with CAH. However, the corticosterone metabolites tetrahydro-11-dehydrocorticosterone (THA), hexahydro-11-dehydrocorticosterone, 6-hydroxyTHA and 18-hydroxy THA were comparatively abundant in the absence of detectable tetrahydroaldosterone. This pattern is indicative of an aldosterone synthase, specifically corticosterone methyl oxidase type II, deficiency. Subsequent plasma renin activity (185 nmol/L per h) and inappropriately low aldosterone (1040 pmol/l) measurements supported this diagnosis. Whole gene sequencing of CYP11B2 identified a known pathological change, c.554C>T (p.Thr185Ile), confirming aldosterone synthase deficiency.

Conclusion: The investigation of a young infant presenting with hyponatraemia is challenging, further complicated by the need to obtain sufficient blood samples and prioritise informative tests. Where a steroid disorder is suspected, a USP has great utility since the specimen is easily accessible and the test can identify/exclude a variety of disorders. Furthermore, where urgent samples are involved, analyses can be prioritised with a relatively rapid turnaround time. In this case, the USP diagnosis was made within 2 days of sample receipt, prompting fludrocortisone treatment and reduction of hydrocortisone.