Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P321

SFEBES2008 Poster Presentations Steroids (35 abstracts)

Partial 21-hydroxylase deficiency: diagnostic role of urinary steroid profiling

Adrian Heald 1 , Zubair Qureshi 1 , Azhar Khan 1 , Julian Waldron 1 , Marten Davies 1 , Norman Taylor 2 & John Kane 3


1Leighton Hospital, Crewe, Cheshire, UK; 2Kings College Hospital, London, UK; 3Salford Royal Hospitals Foundation Trust, Salford, UK.


Background: Virilising congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, and 90–95% of CAH cases are caused by 21-hydroxylase deficiency. Associated inefficient cortisol synthesis results in increased CRH and ACTH levels, leading to production of excess sex hormone precursors. These are further metabolized to active androgens and to a lesser extent oestrogens. We recently reported that one of these androgens, DHEA-S or its metabolites significantly interferes in the testosterone assay when at higher concentrations.

Case report: A 14-year-old girl presented with facial hirsutism and acne. Menarche was at the age of 10; she has had a 4–8 week menstrual cycle since. On examination she was of stocky build with central adiposity and was normotensive. Height was at the 91st centile for her age. There was no evidence of clitoromegaly.

Total serum testosterone by direct immunoassay was very high at 7.7 nmol/l (0–3.5) with 17-hydroxyprogesterone elevated at 58.0 nmol/l (normal range ≤12 nmol/l). Plasma electrolytes were normal. Twenty-four hour urinary free cortisol was normal.

Repeat serum testosterone measurement after ether extraction gave a slightly elevated level of 3.1 nmol/l (0–2.4). A urinary steroid profile (GLC) was performed. This showed excess 17-hydroxyprogesterone metabolites in a pattern characteristic of partial 21-hydroxylase deficiency. The presence of excess 11-oxopregnanetriol excluded the rare possibility of an ovarian tumour.

Urinary cortisol metabolites (34 865 ug/24 h) were higher than 17-hydroxyprogesterone metabolites (14 787 ug/24 h), indicative of partial 21-hydroxylase deficiency.

Comment: We propose that urinary steroid profiling is very helpful in characterizing the precise form of CAH. As seen here, partial 21-hydroxylase deficiency frequently associates with a paradoxical increase of cortisol metabolites, probably due to competition for the glucocorticoid receptor by 21-deoxycortisol.

The high levels of androgen metabolites, including DHEA and DHEA metabolites, could provide an explanation for the spuriously high direct testosterone result.

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