Diagnostic and therapeutic role of GnRH analogue in postmenopausal hyperandrogenism
Seong Keat Cheah, Anitha Mathews, Singhan Murali Krishnan, Hinchingbrooke Hospital, North West Anglia NHS Foundation Trust
A 48 years old lady with marked obesity had a CT abdomen due to non-specific abdominal discomfort. This revealed a 9mm lesion in right adrenal and a 18mm lesion in left adrenal, with fat content and appearance consistent with adenoma. Subsequent review at Endocrinology clinic unfolded a history of gradually worsening hirsuitism which required daily chin shaving, while virilisation was absent. Her period stopped 4 years ago when she was 45 years old with no post-menopausal symptoms such as flushing. There was no recent change in her weight (115kg).
Her hyperandrogenism was confirmed biochemically with testosterone elevated at 6.5nmol/L (0.0-1.8) and remained high on repeated samples. The marked elevation led to a pursuit of adrenal and ovarian source. However, her adrenal androgens were normal: Androstenedione 3.3 nmol/L (0.9-4.8), DHEAS 0.9 µmol/L (0.7-7.8), and 17-OH progesterone 3.4 nmol/L (0.0–5.0). Her FSH and LH were consistent with post-menopausal state. Thyroid function test, ACTH, 9am Cortisol, prolactin and CA125 were normal.
MRI adrenal showed right 19mm nodule with hyperplastic left adrenal. Signal drop on both adrenals again agrees with adenomatous nature. Technical limitation of ultrasound of pelvis due to body habitus had led to MRI pelvis showing ovaries of normal appearance with small follicles, not typical of hyperthecosis. A delineation between adrenal and ovarian aetiology was not clear at this stage while patient preference and body habitus limited the option for specific venous sampling.
An overnight dexamethasone suppression test had led to cortisol suppression to 38nmol/L excluding Cushing’s syndrome, while testosterone remained non-suppressed at 5.8nmol/L, suggesting an ovarian androgen source (1,2). A trial of GnRH analogue (subcutaneous Leuprorelin 3.75mg monthly) was initiated. Suppression and normalisation of testosterone (0.6nmol/L) was observed after 2 months, a typical finding described in ovarian hyperandrogenism in multiple case reports (3–5). Long term treatment options were explored between the patient, Endocrinology and Gynaecology team. Laparoscopic bilateral oophorectomy was preferred by the patient because of intolerance to GnRH analogue (flushing).
1. Buyalos RP, Geffner ME, Azziz R, Judd HL. Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome. Hum Reprod. Oxford University Press; 1997 Jun 1;12(6):1138–41.
2. Ambroziak U, Kepczynska-Nyk A, Nowak K, Morawska E, Kunicki M, Bednarczuk T. Overnight 1 mg dexamethasone androgen suppression test is useful diagnostic tool in hyperandrogenism. Endocr Abstr. BioScientifica; 2013 Apr 1