Endocrine Abstracts

17alpha hydroxylase deficiency accounts for less than 1% of all patients diagnosed with congenital adrenal hyperplasia. Almost 100 mutations in the CYP17A1 gene causing 17-hydroxylase/17,20-lyase deficiency (17OHD) have been described (OMIM 609300). CYP17A1 is expressed in both the adrenals and gonads. Hallmarks of 17OHD include hypertension, hypokalaemia, primary amenorrhoea and absence of secondary sexual characteristics. Most patients with 17OHD remain infertile.

Here we report the case of a 26 year old Afghan lady of consanguineous parents. Aged 14 she had investigations for primary amenorrhea. 17OHD was suspected, but not confirmed and she was lost to follow up. She underwent spontaneous menarche at the age of 18. Aged 24, she represented with primary infertility. She had otherwise been in good health and her menstrual cycle remained regular.

On initial examination she was normotensive with normal breast development but reduced body hair. Gonadotrophins were normal as was oestradiol. ACTH stimulation testing showed a peak cortisol of 139 nmol/L and no rise in 17-hydroxyprogesterone. DHEAS, testosterone and aldosterone were undetectable with normal renin activity. Imaging demonstrated normal pelvic viscera. 24 hour urinary steroid profile showed a decrease in cortisol metabolites, elevated corticosterone and progesterone but also some 17-hydroxyprogesterone metabolites suggesting reduced 17-hydroxylase and 17,20-lyase activities. Aldosterone metabolites were absent raising the added possibility of aldosterone synthase deficiency.

Genetic testing confirmed 17OHD with the variant, c.160_162del (g.Phe54del) known to have residual 17alpha-hydroxylase activity (37%) but more complete loss of 17,20-lyase activity (8%) (rs.121434319). Aldosterone synthase genetic testing results are pending.

She is currently undergoing IVF treatment and was commenced on 3 mg of prednisolone daily. There has been no symptomatic change since she was commenced on glucocorticoid replacement and the question arises whether she does require lifelong continuous steroid replacement or simply cover at times of stress.