Ovarian Hyperstimulation without Elevated Serum Estradiol Associated with Pure Follicle-Stimulating Hormone-Secreting Pituitary Adenoma

Abstract

We report a unique case of a 28-yr-old woman with a gonadotroph adenoma secreting FSH, presented with ovarian hyperstimulation, without elevation of serum estradiol. She presented with abdominal pain and large ovaries (both 10 cm in diameter) with multiple follicular cysts shortly after discontinuing oral contraceptive pills. She had a supranormal PRL level of 71 microg/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 (normal for follicular phase, 80-790), and free alpha-subunit level of 0.11 microg/liter (normal, <1.8). A nuclear magnetic resonance study revealed invasive pituitary macroadenoma, 30 mm in diameter. Dopamine agonist (cabergoline) treatment normalized serum PRL but had no affect on FSH levels. A transsphenoidal surgery was performed, and most of the adenoma was resected. One month after surgery the patient resumed menstruation, and the hormonal profile included serum FSH of 6.3 IU/liter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, and PRL of 10 microg/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 the excised tumor) had no effect on FSH secretion from the adenoma. Estradiol did not suppress FSH release from cultured adenoma cells. Patient serum samples showed significant FSH bioactivity when tested in a human granulosa cell line. This case is remarkable because the ovarian hyperstimulation related to the FSH-secreting adenoma was not associated with high levels of serum estradiol, probably due to insufficient LH production by the normal pituitary. Thus, it supports the two-cell, two-gonadotropin theory, that both FSH and LH are necessary for normal ovarian estrogen production.

A Case of Acquired Deficiency of Pituitary GH, PRL and TSH, Associated with Type 1 Diabetes Mellitus

“…In addition, some reports showed female cases who showed high levels of FSH and estradiol [11][12][13]. Moreover, Shimon et al reported a case of a 28-year-old female with a high concentration of FSH and a normal level of estradiol [14]. These case reports indicate that high plasma levels of FSH induce hyper-or normal secretion of sex hormones.…”

Follicle stimulating hormone secreting pituitary adenoma: a challenging diagnosis

“…Serum LH level is also significantly reduced to below the lower limit of the normal range, probably due to the negative feedback mechanism or compression of the normal pituitary gland by the tumor. 4,8,12 Apparent normal FSH, suppressed LH, and high estradiol levels can be considered as the characteristic endocrinological profile of this FSH-secreting gonadotroph cell adenoma. Serum prolactin concentration was elevated in most cases, probably due to pituitary stalk compression by the sellar tumor, the so-called stalk effect.…”

“…2,8 Age is the most fundamental characteristic for the diagnosis of this entity, because the response of the ovary to FSH stimuli is important for the onset of ovarian hyperstimulation. In postmenopausal women, FSH over secretion cannot be recognized unless a very low LH level is noticed, so that all reported patients with ovarian hyperstimulation are of reproductive age.…”

“…To determine sure nature of pituitary tumour, other pituitary hormonal assays were done -Serum ACTH -38 pg/ml (0-46), Serum cortisol -1.3 mcg/ml (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). It confirmed the nature of tumour as 'mixed pituitary adenoma' secreting FSH and prolactin.…”

Reproductive disturbances in multiple neuroendocrine tumor syndromes

“…However, in cases with essentially absent LH, the ovarian hyperstimulation profile associated with a FSH-secreting adenoma is not accompanied by high estrogen levels and endometrial hyperplasia. As an example, in a 28-year-old woman with abdominal pain and large ovaries with multiple follicular cysts, a FSH-secreting pituitary macroadenoma (not in the context of a MEN1 phenotype) was not accompanied by high levels of serum E 2 , probably due to insufficient LH production (Shimon et al 2001).…”