Gonadotrophin secretion may be a useful adjunct in the assessment of patients with Hyperprolactinaemia

S Clarke, A Abbara, A Nesbitt, S Ali, AN Comninos, E Hatfield, NM Martin, A Sam, WS Dhillo, Hammersmith Hospital.

Abstract: Hyperprolactinaemia accounts for up to 14% of patients presenting with amenorrhoea. Recent data suggests that prolactin acts upstream of kisspeptin neurons in the hypothalamus to reduce GnRH pulsatility. Conditions in which GnRH pulsatility is reduced such as hypothalamic amenorrhoea favour FSH secretion from the pituitary gland, however in contrast conditions in which GnRH pulsatility is increased such as polycystic ovarian syndrome favour LH secretion. Thus we hypothesised that causes of hyperprolactinaemia in which pituitary gonadotrophs are unaffected (E.g. drug-induced or microprolactinoma) would have relatively more FSH secreted than LH, when compared with hyperprolactinaemic conditions in which pituitary gonadotroph function may be attenuated (E.g. macroadenomas or hypopituitarism) in which both FSH and LH secretion may be impaired.

Methods: A retrospective analysis of gonadotrophin secretion in patients presenting to Imperial College Healthcare NHS Trust with hyperprolactinaemia from June 2012-October 2015 was performed. 

Results: 309 patients with hyperprolactinaemia were identified (212 female, 97 male). The most frequently encountered diagnoses were prolactinoma (n=144), non-functioning adenoma (n=121) and drug-induced hyperprolactinaemia (n=18). Patients with a serum prolactin <1000mU/L (n=138) were excluded from further analyses. Gonadotrophin secretion in drug induced hyperprolactinaemia (mean FSH 6.1iU/L, mean LH 3.5iU/L, mean FSH-LH 2.6iU/L) was similar to that observed in microprolactinomas (mean FSH 5.9iU/L, mean LH 4.2iU/L, mean FSH-LH 1.7iU/L). However in macroprolactinomas, FSH and LH secretion were both significantly reduced (mean FSH 3.0iU/L, mean LH 2.5iU/L) and there was a smaller difference between levels of FSH and LH secretion (mean FSH-LH 0.5iU/L) (P<0.05 vs microprolactinoma). In 52 patients with pituitary adenoma, serum LH levels were undetectable and 88% of such patients had macroadenomas. All patients with undetectable FSH secretion (n=30) had undetectable LH secretion, suggesting that LH secretion is often lost first in patients with pituitary gonadotroph hypofunction.

Conclusion: Assessment of gonadotrophin secretion may aid the assessment of patients presenting with hyperprolactinaemia, as reduced gonadotrophin secretion is often indicative of hypopituitarism, whilst FSH predominance is more consistent with hyperprolactinaemia due to drug causes or microprolactinomas.