ESPE Abstracts

Background: An accurate and comprehensive assessment of steroid hormones is pivotal for differential diagnosis of disorders of sex development (DSD) 46,XY, a part of which may be due to defects of testosterone biosynthesis.

Objective and hypotheses: To describe and characterise a case of DSD 46,XY presented with unusual serum steroid profile.

Method: Serum steroid hormones were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). HSD17B3 and CYP21A2 genes were analysed by Sanger sequencing.

Results: An 18-year-old professional female athlete presented with primary amenorrhea. Physical examination showed increased muscle mass, no breast development, male pattern of hair distribution, clitoris enlargement and blind-ending pseudo-vagina. Ultrasound examination revealed bilateral inguinal gonads and no uterus. Karyotype analysis showed 46,XY. Profile of serum steroid hormones assayed by LC-MS/MS was abnormal and not compatible with any known disorder of steroid hormone biosynthesis: 17OHP, 35.6 nmol/l (1.5–7.2); 21-deoxycortisol, 9.9 nmol/l (0.5–3.4); cortisol, 353 nmol/l (150–650); androstenedione, 29.5 nmol/l (1.4–7.9); testosterone, 12.9 nmol/l (12–33). Combination of HSD17B3 and CYP21A2 deficiencies was suspected. Sequencing of HSD17B3 gene showed a known pathogenic homozygous splicing mutation c.277+4A>T, whereas analysis of CYP21A2 gene revealed a homozygous p.V281L mutation, a frequent finding in non-classical congenital adrenal hyperplasia (NC CAH).

Conclusion: To our knowledge, this is the first description of combined HSD17B3 and CYP21A2 deficiencies. Owing to the fact that NC CAH is frequent in certain populations, its contribution to observed peculiarities of phenotype and/or steroid profiles may be considered.