Endocrine Abstracts

Background: Hyperprolactinaemia accounts for 1 in 7 patients presenting with amenorrhoea. Recent data suggests that prolactin acts at the hypothalamus to reduce GnRH-pulsatility. Conditions in which GnRH-pulsatility is reduced, such as hypothalamic amenorrhoea, favour FSH over LH secretion from the pituitary gland. We examined gonadotrophin secretion in hyperprolactinaemic patients as a surrogate marker of GnRH-pulsatility.

Methods: A retrospective analysis of gonadotrophin secretion in patients with hyperprolactinaemia over the gender-specific reference range during 2012–2015 was performed at Imperial College Healthcare NHS Trust.

Results: Of 470 patient-records reviewed, 275 (Female 210, Male 65) had raised serum monomeric prolactin levels concomitant with serum gonadotrophin (FSH/LH) levels. Frequent diagnoses included microprolactinoma (n=80), macroprolactinoma (n=46), non-functioning macroadenoma (NFA; n=72), drug-induced hyperprolactinaemia (DIH; n=22) and polycystic ovarian syndrome (PCOS; n=15).

In PCOS, LH-predominant secretion was observed consistent with increased GnRH-pulsatility (FSH 4.0iU/L, LH 7.2iU/L, FSH-LH -3.2iU/L). Conversely in DIH, FSH-predominant secretion was observed, consistent with reduced GnRH-pulsatility (FSH 5.5iU/L, LH 3.4iU/L, FSH-LH +2.1iU/L; FSH-LH P=0.0006 vs PCOS).

In patients with prolactinoma, there was a progressive increase in ‘FSH-LH’ differential with increasing serum prolactin level, consistent with a progressive fall in GnRH-pulsatility. However, both FSH and LH secretion were reduced in patients with prolactin levels >4000 mU/l, consistent with intrinsic pituitary gonadotroph hypofunction in larger prolactinomas.

In patients with macroadenomas, extremes of gonadotrophin secretion were more frequently observed in NFAs when compared with macroprolactinomas. This observation was not accounted for by the effect of prolactin on GnRH-pulsatility and was more consistent with autonomous intrinsic pituitary gonadotrophin secretion in NFA (100% of FSH+LH>15iU/L had NFA vs 47% with FSH+LH <5iU/L).

Conclusion: Raised prolactin acts at the hypothalamus to reduce GnRH pulsatility, resulting in FSH-predominant secretion. In larger prolactinomas, gonadotrophin secretion is reduced due to pituitary gonadotroph hypofunction. Thus, gonadotrophin levels are a useful adjunct in the diagnosis of patients with hyperprolactinaemia.