Utility of urinary steroid profiling to distinguish causes of urinary salt loss in infancy: evidence for adaptive response of steroid biosynthetic pathways and of characteristic presence of urinary cholesterol in secondary pseudohypoaldosteronism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 358-380-Steroid Hormone Biosynthesis & Metabolism
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-362
Charles R Buchanan*1, Lea Ghataore1, Vimmi Abbot1, Pandina Kwong2, Jaco Pieterse1, Gill Rumsby3 and Norman F Taylor1
1King's College Hosp, London, United Kingdom, 2King George Hospital, Essex, United Kingdom, 3UCL Hospitals, London, England
Urinary salt wasting in infants presents a diagnostic challenge until full blood and urine biochemical analyses and renal tract imaging are complete. Molecular genetic studies may also be needed.

GC-MS steroid profiling of urine (USP), when the sample is collected before confounding treatments are initiated, can differentiate all causes related to impaired aldosterone production and renal response. These comprise congenital adrenal insufficiency due to deficiencies of cholesterol - pregnenolone conversion (P450 side chain cleavage – P450ssc; CYP11A1), 3β-(OH)steroid dehydrogenase (3β-HSD; HSD3β2), 21-hydroxylase (CYP21), and aldosterone synthase (CMOI/II;CYP11B2). The aldosterone resistance syndromes (pseudohypoaldosteronism, PHA), due to genetic mineralocorticoid receptor or sodium channel defects can be distinguished from secondary PHA due to urinary tract infection or anatomical defects. In the latter, cholesterol is almost invariably found at high concentration in the urine, probably arising from tubular cellular damage. USP will clearly distinguish congenital adrenal hypoplasia (CAHypo/NROB1 defects) and CYP21def.

A urine sample as small as 500 microL, or even just a urine-containing nappy/diaper is adequate for analysis, with results available within 2 days by present techniques.

A previously recognised feature of CAHypo is very low excretion of the 3β-hydroxy-5-ene (3βOH-5-ene) metabolites characteristic of newborns in the first few months of life. We now report that these very low 3βOH-5-ene metabolite levels are also a feature common to CMOI/II and PHA, but not to 3β-HSD or CYP21def. This seems to represent a metabolic adaptation to salt wasting, since in a case of CMOI def. it was not apparent on day 1 of life, but evident by day 8, when hyponatraemia had developed.

P450scc deficiency and CAHypo may both demonstrate reduced or absent urinary steroid metabolites but in CAHypo this is usually selective, notably in two cases due to NROB1 defects we present, which have shown cortisol metabolites only. 3βHSD shows reduced or absent cortisol metabolites but confirmation of the diagnosis requires demonstration of persistence of 3βOH-5-ene metabolites beyond 3 months. CMOI/II def. and PHA show increased corticosterone metabolites, with respectively reduced / absent or increased tetrahydroaldosterone.

We illustrate these observations with biochemical and molecular diagnostic details of recent clinical cases.

Nothing to Disclose: CRB, LG, VA, PK, JP, GR, NFT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm