Endocrine Abstracts

A 17 year old girl was referred to us from the gynaecology department with history of primary amenorrhea. She was otherwise well and previous medical history included severe acne requiring referral to ENT, plastic surgery and dermatology services at age 13 and hirsutism for which she had privately funded laser treatment. On examination she had acanthosis nigricans and BMI of 22 but was virilised with clitoromegaly, hypertrophied labia majora and hirsuitism. Pelvic ultrasound revealed polycystic ovaries and she was also found to have a raised testosterone at 5.8 (0.2–2.9) and low sex hormone binding globulin at 23 nmol/L (30–100). She was referred to the endocrine department for management of PCOS. Investigations revealed normal pituitary profile and normal 17 hydroxy progesterone. Low dose dexamethasone suppression test revealed suppressed cortisol (25 nmol/L) but unsuppressed testosterone (4.3 nmol/L). CT scan of her adrenal glands was normal. Initial oral glucose tolerance showed normal fasting and postprandial glucose levels with raised fasting insulin levels at 276 pmol/L. We then repeated a prolonged oral glucose tolerance test that showed evidence of severe hypoglycaemia, with glucose dropping to 1.7 at 300 mins. Her peak insulin levels were significantly raised upto 13600 (0–60). On further questioning, the patients mother reported symptoms of reactive hypoglycaemia that was partially investigated in past. Her glucose dropped to 1.6 on prolonged glucose tolerance testing with markedly raised peak insulin levels of 2260. Based on the history and clinical findings a strong suspicion of a genetic defect in insulin receptor was raised. This has been confirmed by genetic testing which has revealed a Pro 1178 Leu variant in mother and daughter which is the commonest dominant negative tyrosine kinase mutation. As far as we are aware, this is the first case of a insulin receptor mutation that has presented with primary amenorrhea.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.