Endocrine Abstracts (2004) 7 P80

FSH-secreting pituitary gonadotroph adenoma producing ovarian hyperstimulation

AJ Norris1, C Hay1, M Wilding2, G McDowell3, I Laing3, JP Holland4, JR McNeilly5, AS McNeilly5 & JRE Davis1,2


1Department of Endocrinology, Manchester Royal Infirmary, Manchester, UK; 2Endocrine Sciences Research Group, University of Manchester, Manchester, UK; 3Department of Biochemistry , Manchester Royal Infirmary, Manchester, UK; 4Department of Neurosurgery, Manchester Royal Infirmary, Manchester, UK; 5MRC Human Reproductive Sciences Research Group, University of Edinburgh, Edinburgh, UK.


A 28-year-old Asian female presented with a 2 year history of abdominal pain and bloating and irregular heavy periods. She had a normal menarche and had 3 uncomplicated pregnancies after conceiving naturally, the last 4 years before presentation. Investigations showed LH 0.7 IU/l (normal range 2-14 IU/l), FSH 8.6 IU/l (2-14 IU/l), oestradiol 2030 pmol/l (80-300 pmol/l), prolactin 346 mU/l, and normal alpha GSU (0.3mcg/l). Ultrasound scanning revealed enlarged multicystic ovaries. MR imaging showed an 8mm hyperintense pituitary adenoma. While awaiting surgery she experienced further episodes of abdominal bloating with persistently high oestradiol levels (1120-3100 pmol/l). Inhibin-B levels were low and inhibin-A high, suggesting the presence of luteinised, rather than typical follicular phase ovarian follicles. GnRH antagonist (ganirelix) treatment for 7 days failed to suppress oestradiol. The adenoma, removed by transsphenoidal surgery, showed intense immunostaining for FSH with very few LH cells. Tumour cells in culture secreted mainly FSH (46 U/105 cells/24h) with little LH (5.8 U/105 cells/24h), that was unaffected by 24h incubation with 10nM oestradiol, 500ng/ml inhibin A, or both in combination. 4 weeks postoperatively, serum FSH and oestradiol fell to 4.6 IU/l and 187 pmol/l respectively, LH remained suppressed, and she noted transient fatigue and flushing. Residual anterior pituitary function was normal, and biochemical and ultrasound tracking, 3 months after surgery, confirmed resumption of regular ovulatory cycles.

Ovarian hyperstimulation due to overproduction of intact gonadotrophins is rare. Gonadotrophinomas generally express low levels of LHbeta and/or FSHbeta subunits, and therefore do not normally cause gonadal stimulation and are 'non-functioning adenomas'. This tumour was composed mainly of FSH-only cells with negligible LH production in vivo or in vitro. Normal adult gonadotroph cells are bihormonal, whereas FSH-only cells are seen in the fetal pituitary. This tumour may therefore have arisen from expansion of fetal FSH-gonadotroph precursor cells.

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