Endocrine Abstracts

A 13 year old female presented with a two day history of abdominal pain and vomiting which responded to analgesia. Pelvic ultrasound showed complex ovarian cysts and a pre-pubertal uterus. Initial blood tests were consistent with hypergonadotrophic hypogonadism (LH 31.5 U/l, FSH 14.3 U/l and oestradiol <70 pmol/l) and karyotype was 46 XX. Bone age was slightly delayed (measured 12.4 years, chronological age 13.7 years). On referral to paediatric endocrinology, the patient reported primary amenorrhoea and on examination had some breast development, tanner stage B2. Blood tests showed undetectable androgens, testosterone <0.5 nmol/l, androstenedione <0.5 nmol/l, 17OH progesterone <0.5 nmol/l, DHEAS <0.5 nmol/l. Urine steroid profile showed elevated mineralocorticoid metabolites, undetectable cortisol metabolites and undetectable androgen metabolites consistent with a diagnosis of 17-alpha hydroxylase deficiency congenital adrenal hyperplasia (CAH). Genetic analysis using a 56 gene panel for disorders of sexual development detected an apparently homozygous likely pathogenic sequence variant in CYP17A1 gene (c.2T>C p.(Met1?)). Short Synacthen test showed a flat response, cortisol 38 nmol/l to 36 nmol/l with a significantly elevated ACTH 682 ng/l, consistent with adrenal insufficiency. Hydrocortisone therapy was commenced. Aldosterone was <130 pmol/l (130-600) and renin 8.5 mIU/l (<125). On review the patient had mild hypokalemia and intermittent hypertension. CAH due to 17-alpha hydroxylase deficiency is rare and can present with delayed puberty, hypertension, delayed bone age and the absence of secondary sexual characteristics. Adrenal crisis is unlikely due to the mild glucocorticoid activity from deoxycorticosterone. Treatment includes hydrocortisone and oestrogen replacement.