Endocrine Abstracts (2001) 2 P12

Severe hyperandrogenism with polycythaemia: use of metformin as a therapeutic and diagnostic tool

PA Senior1, SG Ball2, PH Baylis2 & R Quinton1,2

1Dept.of Endocrinology, Royal Victoria Infirmary, Newcastle, UK; 2Dept.of Endocrinology, Newcastle University, Newcastle, UK.

Polycystic ovarian syndrome (PCOS) is the commonest cause of hyperandrogenism in women. Severe hyperandrogenism or virilisation, however, suggest the need to consider rarer causes e.g. Cushing's, congenital adrenal hyperplasia and androgen-secreting tumours. Here we present a case of PCOS where the remarkable response of severe hyperandrogenism with polycythaemia to metformin excluded these rarer causes without the need for complex or invasive investigation.

A 31 year old female presented with secondary amennorrhoea, infertility, hirsutism and the suggestion of prognathism without significant clitoromegaly. She was obese (BMI 40 kilograms per metre2) with acanthosis nigricans and mild hypertension. A ten day course of medroxyprogesterone acetate failed to induce withdrawal bleeding.

Initial investigations revealed LH/FSH 11.3/6.1units per litre, prolactin 80 milliunits per litre, oestradiol 220 picomol per litre, testosterone 9.5, SHBG 20, androstenedione12.1, 17-hydroxyprogesterone 5.6 (all nanomol per litre), DHEAS 4.5 micromol per litre, 24hr urinary free cortisol 106 & 260 nanomol per 24 hours, glucose 4.4 millimol per litre, HbA1c 5.3%. Haemoglobin was17.2grams per decilitre and haematocrit 50.3%. Ultrasound examination showed multifollicular ovaries (left 10 millilitres, right 6 millilitres).

PCOS with insulin resistance was the presumptive diagnosis and metformin therapy commenced (3 grams daily). 3 months later, menstruation had resumed (x2) and weight decreased by 3 kilograms. Testosterone and androstenedione had fallen to 1.7 and 1.0 nanomol per litre, respectively, with resolution of polycythaemia and amelioration of hirsutes.

Although some features raised the possibility of an androgen-secreting tumour, acanthosis nigricans suggested marked insulin-resistance. The dramatic fall in testosterone levels after metformin supports the diagnosis of PCOS, and excludes more sinister pathology. Patients with markedly elevated serum testosterone levels usually undergo detailed investigation before a diagnosis of simple PCOS is made. In this case, the biochemical response to metformin therapy obviated the need for dynamic/suppressive testing and/or venous sampling of the ovaries & adrenal glands.

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