Endocrine Abstracts

Case history: An 18-year-old Caucasian female presented with primary amenorrhoea after her younger sister aged 16 years old started menstruating. She had a normal childhood and progressed through puberty normally, with no past medical history or family history. BMI was 22.6 with a normal examination including secondary sexual characteristics (Tanner Stage 5) and no signs of hyperandrogenism.

Investigations and Results: Bloods showed an elevated LH:FSH ratio, low oestradiol with borderline raised testosterone, similar to results found in polycystic ovarian syndrome (PCOS). Other pituitary function and pelvic ultrasound were normal and Karyotype was 46XX. DEXA scan showed a lumbar Z-score −1.0 and wrist X-ray fused bones. She had a withdrawal bleed post progesterone, indicating normal uterine function. A GnRH stimulation test confirmed normal pituitary gonadotroph functioning and 8-h blood sampling every 10 min for LH showed normal LH pulsatility but an elevated LH baseline and pulse amplitude. Hypothalamic GnRH function was tested by administering IV kisspeptin, a neuropeptide that stimulates GnRH neurons to secrete GnRH. She responded normally by raising gonadotrophins (surrogate for GnRH secretion). Therefore, with normal investigations and hypothalamic pituitary function but raised LH, the most likely diagnosis was of PCOS presenting with primary amenorrhoea.

Treatment: The oral contraceptive was given to provide oestrogen and progesterone replacement for regular withdrawal bleeds as well as to achieve peak bone mass.

Conclusions and points for discussion: PCOS has been shown to present with primary amenorrhoea. Although our patient is not the classical phenotype, a subset of patients are lean with little or no signs of hyperandrogenism and so should be considered in the differential diagnosis of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity. Interestingly the subgroup presenting with primary amenorrhoea display a higher incidence of metabolic dysfunction. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function. Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.