Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma

We report a unique case of a 28-yr-old woman with a gonadotroph adenoma sec reting FSH, presented with ovarian hyperstimulation, without elevation of s erum estradiol. She presented with abdominal pain and large ovaries (both 1 0 cm in diameter) with multiple follicular cysts shortly after discontinuin g oral contraceptive pills. She had a supranormal PRL level of 71 mug/liter (normal, < 20), FSH of 8.4-9.2 IU/liter (normal for follicular phase, 2.4- 10), LH of 0.01 IU/liter (normal, 1.6-9.3), estradiol of 108 pmol/liter (no rmal for follicular phase, 80-790), and free alpha -subunit level of 0.11 m ug/liter (normal, <1.8). A nuclear magnetic resonance study revealed invasi ve pituitary macroadenoma, 30 mm in diameter. Dopamine agonist (cabergoline ) treatment normalized serum PRL but had no affect on FSH levels. A transsp henoidal surgery was performed, and most of the adenoma was resected. One m onth after surgery the patient resumed menstruation, and the hormonal profi le included serum FSH of 6.3 IU/Iiter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, and PRL of 10 mug/liter. The excised adenoma tissue exhibited intense immunostaining for FSH and secreted this hormone to culture medium. Stimulation with TRH (both in vivo preoperatively and in vitro study of th e excised tumor) had no effect on FSH secretion from the adenoma. Estradiol did not suppress FSH release from cultured adenoma cells. Patient serum sa mples showed significant FSH bioactivity when tested in a human granulosa c ell line. This case is remarkable because the ovarian hyperstimulation related to the FSH-secreting adenoma was not associated with high levels of serum estradi ol, probably due to insufficient LH production by the normal pituitary. Thu s, it supports the two-cell, two-gonadotropin theory, that both FSH and LH are necessary for normal ovarian estrogen production.