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

Institutes of Endocrinology (I.S., T.R.) and Pathology (D.N.), and Department of Neurosurgery (M.H.), Sheba Medical Center, Tel-Hashomer 52621; Fertility Unit (I.B.-H.) and Endocrinology Service (G.H.), Rabin Medical Center, Golda Campus, Petah Tikva 49372; and Department of Molecular Cell Biology (A.A.), The Weizmann Institute of Science, Rehovot 76100, Israel

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 µg/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 -subunit level of 0.11 µg/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 µg/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.

APPROXIMATELY 40% OF all pituitary macroadenomas are nonfunctional monoclonal gonadotroph-cell tumors (1). These tumors may secrete intact gonadotropins or -subunits, ß-FSH, and ß-LH. Gonadotroph-cell tumors usually secrete their products inefficiently and in low concentrations and, thus, very rarely cause any clinical syndrome other than sellar mass effects (2, 3). Several cases of men with FSH-secreting pituitary macroadenomas have been reported (4, 5, 6). These patients may present with visual disturbances and hypogonadism due to destruction of normal pituitary gonadotrophs by the macroadenoma, or because of simultaneous hypersecretion of PRL by the pituitary adenoma. Postmenopausal women with FSH-secreting pituitary adenomas do not present with any characteristic hormonal hypersecretion signs (7). Thus, gonadotropin overproduction by pituitary adenomas usually does not result in a clinically recognizable syndrome.

We report a unique case of a 28-yr-old female with a large pituitary macroadenoma secreting intact FSH, who presented with bilateral multicystic enlarged ovaries without elevated serum estradiol levels.

Materials and Methods

Hormone assays

Serum FSH and PRL were quantified with the Immulite two-site chemiluminescent immunometric assay from Diagnostic Products (Los Angeles, CA; detection limit of FSH, 0.6 IU/liter). Serum LH was quantified preoperatively and postoperatively with a Delfia fluoroimmunoassay LH kit (detection limit, 0.05 IU/liter), but during the immediate postoperative period with the Immulite competitive immunoassay (Diagnostic Products; detection limit, 0.7 IU/liter). 17ß-Estradiol was measured with Immulite competitive immunoassay and -subunit with double antibody RIA kit from Biomerica (Newport Beach, CA). Human FSH in cell culture medium was measured using FSH immunoradiometric assay from Diagnostic Products (Coat-A-Count).

Histological studies

The transsphenoidal specimen of the pituitary tumor was fixed in formalin, paraffin-embedded sections were stained with hematoxylin-eosin, and histochemical staining for reticulin was performed. Immunohistochemistry studies included staining for FSH, LH, PRL, GH, ACTH, and TSH. Monoclonal mouse antihuman FSH and LH antibodies were purchased from Zymed Laboratories, Inc. (South San Francisco, CA). Cross-reactivity of these antibodies with human TSH is 0.05–0.1%, the anti-FSH with human LH is 0.1%, and the anti-LH with FSH is 0.02%.

FSH bioactivity

Human granulosa cell line expressing human FSH receptor and secreting progesterone in response to human FSH in cell culture medium was used for measuring FSH bioactivity in the patient serum. This cell line was prepared using a similar methodology as previously reported (8). Cells were incubated in 24-well tissue cultures plates for 24 h with serum samples of the patient (25–100 µl added to 0.5 ml culture medium; in triplicates) or with known concentrations of human recombinant FSH (standard curve). Medium was collected after treatment for later progesterone measurements (RIA, using materials supplied by the NIDDK, NIH).

Pituitary cell culture

A specimen of the pituitary adenoma was minced and enzymatically dissociated using 0.35% collagenase and 0.1% hyaluronidase (both from Sigma, St. Louis, MO) for 45–60 min. Cell suspensions were filtered and resuspended in low glucose DMEM supplemented with 10% fetal bovine serum, 2 mM glutamine, and antibiotics. For primary cultures, 5 x 10⁴ cells were seeded in 48-well tissue culture plates (Costar, Cambridge, MA) in 0.5 ml medium and incubated for 72 h in a humidified atmosphere of 95% air/5% CO₂, at 37 C. The medium was then changed to serum-free defined low glucose DMEM containing 0.2% BSA, 120 nM transferrin, 100 nM hydrocortisone, 0.6 nM triiodothyronine, 5 U/liter insulin, 3 nM glucagon, 50 nM PTH, 2 mM glutamine, 15 nM epidermal growth factor, and antibiotics. The cells were treated for 4 h with either 17ß-estradiol (100 nM), TRH (10 nM), or GnRH (100 nM) (all from Sigma), whereas control cell cultures were treated with vehicle solution. Medium was collected after treatment and stored at -20 C for later FSH measurements.

Case report

A 28-yr-old woman presented to the Department of Obstetrics and Gynecology in August 1999 with right lower quadrant abdominal pain and tenderness. Her past medical history was unremarkable. She had regular menses before she started taking contraceptive pills 10 yr ago and while taking the pills, and had never been pregnant. She had no galactorrhea or headache. Three weeks before admission she stopped oral contraceptives containing 20 µg ethinyl estradiol and 150 µg desorgestel (Mercilon; Organon, Oss, Holland). The abdominal pain was combined with nausea that gradually increased during the preceding week. She mentioned one episode of vomiting on the same day. Her vital signs were normal. Abdominal examination revealed general tenderness with no sign of peritoneal irritation. On bimanual examination the uterus was found to be of normal size and not tender. Transvaginal ultrasound examination (Fig. 1) revealed bilateral enlarged ovaries (both 10 cm in diameter) with a sonographic picture resembling ovarian hyperstimulation, demonstrating multiple (>20) ovarian cysts ("expanded follicles") on both ovaries. There was no free fluid in the peritoneal cavity, and a thin (6 mm) endometrium was demonstrated. Due to the clinical picture (pain, nausea, vomiting, abdominal tenderness especially on the right side, and enlarged ovaries), subtorsion of the right adnexa was suspected. Therefore, a laparoscopy was conducted. During the laparoscopy bilateral enlarged ovaries (10 cm each) with smooth surface were seen. There were no signs of torsion, pelvic inflammatory disease, hydrosalpinges, endometriosis, or pelvic adhesions. A biopsy was taken from the right ovary, later found to be consistent with a follicular cyst. The postoperative course was unremarkable. After the procedure oral contraceptives were restarted and stopped 3 months later when repeated ultrasound did not show significant ovarian changes.

View larger version (114K): [in this window] [in a new window]   Figure 1. Transvaginal ultrasound examination of the ovaries demonstrating bilateral enlarged ovaries with multiple large ovarian cysts.

Magnetic resonance imaging (MRI) of the pituitary was performed due the hyperprolactinemia and showed invasive pituitary macroadenoma, 30 mm in diameter, with parasellar extension, and invasion of the right cavernous sinus and the sphenoid sinus (Fig. 2). Visual field examination was normal. A 3-week therapeutic trial of cabergoline (0.5 mg; Pharmacia & Upjohn, Inc., s.p.A., Italy), twice a week, without contraceptives normalized PRL, but had no influence on FSH or LH levels. Stimulation with 400 µg TRH had no effect on serum FSH and LH levels (Table 1). Transsphenoidal pituitary surgery was performed with successful removal of the intrasellar adenoma. Postoperatively the patient developed severe hot flashes together with decrease of her serum estradiol levels (Table 2). The hot flashes gradually disappeared in a week, whereas LH and estradiol levels became detectable (Table 2). A month after operation the patient resumed menstrual bleeding, and her hormonal profile included FSH of 6.3 IU/liter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, PRL of 10 µg/liter, and normal thyroid hormones. Four months after the operation her midcycle serum FSH measured 3.3 IU/liter, LH measured 0.08 IU/liter, and estradiol was 481 pmol/liter (Table 2). Ultrasound evaluation 4 months after the operation disclosed a decrease in ovarian size to less than 5 cm each and gradual disappearance of the cysts. MRI done 6 months after the operation revealed residual tumor mass in the right cavernous sinus.

View larger version (104K): [in this window] [in a new window]   Figure 2. Gadolinium-enhanced MRI of the pituitary (A, Coronal; B, sagittal) showing an invasive sellar mass, 30 mm in diameter, with parasellar extension, and invasion of the right cavernous sinus and the sphenoid sinus. Importantly, the normal pituitary is seen overriding the macroadenoma.

In vitro studies

Histology.Histological examination of the pituitary tissue resected showed the characteristic disruption of reticulin fiber network as seen in pituitary adenomas stained for reticulin (Fig. 3A). Immunohistochemical studies for anterior pituitary hormones revealed diffuse and intense cytoplasmic staining for intact FSH in pituicytes all over the adenoma (Fig. 3B), whereas LH, PRL, GH, ACTH, and TSH were not detected.

View larger version (167K): [in this window] [in a new window]   Figure 3. Photo-micrographs of the resected pituitary tumor. Staining for reticulin (A) shows disruption of the characteristic reticulin network of the pituitary adenoma. Immunostaining for human intact FSH (B) reveals intense and diffuse staining for FSH, whereas LH was not detected in the adenoma (data not shown).

Tissue culture. Tumor tissue obtained from the surgical specimen was kept for 8 h in low glucose DME supplemented with 0.3% BSA and antibiotics, and the concentrations of FSH, LH, and PRL in the medium were analyzed. The FSH level was 60.7 IU/liter, LH was undetectable, and PRL was 1.2 µg/liter. Then, the tumor specimen was cultured for 72 h before a 4-h treatment with 17ß-estradiol, TRH, or GnRH. Estradiol did not suppress in vitro FSH secretion from the adenoma cells, and TRH and GnRH failed to stimulate FSH release to the medium.

Discussion

The patient presented had ovarian hyperstimulation with bilateral enlarged multicystic ovaries associated with an FSH-secreting pituitary macroadenoma. The full-blown ovarian hyperstimulation syndrome is characterized by massive ovarian enlargement with multiple cysts and by an increase in capillary permeability, which may cause ascites or edema. This syndrome is usually associated with extremely high serum estradiol levels after gonadotropin therapy for ovulation induction or for controlled ovarian stimulation for harvesting ova for in vitro fertilization (9). Rare cases of ovarian hyperstimulation were reported associated with severe primary hypothyroidism (10), bilateral granulosa cell tumors (11), and during spontaneous pregnancy in a woman with polycystic ovary disease (12).

Gonadotroph adenomas rarely present with hormonal hypersecretion. Excessive secretion of FSH is more commonly reported in men with gonadotroph adenomas, but it does not cause any symptoms. FSH-secreting tumors are rare in postmenopausal women. The tumor is not associated with any recognizable hormonal syndrome, and it is difficult to distinguish between FSH hypersecretion from normal postmenopausal gonadotrophs or from adenoma cells, unless LH levels are extremely low (7). Our premenopausal patient had pure FSH-secreting pituitary adenoma. The resected tumor secreted intact FSH to the culture medium but not LH and was immunostained for FSH only. Preoperatively the patient had serum FSH levels in the upper normal range, LH was very low (also after stimulation with TRH; Table 1), and free -subunits were also very low. Estradiol was within low-normal follicular phase levels, and pituitary imaging was performed because of hyperprolactinemia (caused probably by stalk compression). LH was very low, probably as the result of tumor pressure and destruction of normal pituitary tissue and gonadotrophs. After transsphenoidal removal of a large part of the adenoma, this mass effect resolved, and several days later LH secretion from normal gonadotrophs was increased (Table 2). FSH decreased immediately after tumor removal (Table 2), together with a rapid decline of estradiol, which was associated with transient hot flashes. FSH mildly increased later with the expected recovery of normal pituitary FSH secretion. However, it is clear that some FSH was still released from the adenoma tissue left in the cavernous sinus postoperatively. Importantly, the postoperative decrease of ovarian size confirms the critical role of FSH secreted from the adenoma in ovarian hyperstimulation development in this patient.

Three premenopausal women (13, 14, 15) and one prepubertal girl with ovarian hyperstimulation (16) caused by gonadotroph adenomas have been described before the current case. In two of these cases FSH was within the normal range (14, 15), and in two others (13, 16) FSH was elevated (Table 3). Serum FSH in our patient was in the normal range, but its bioactivity was enhanced, thus enough to stimulate ovarian enlargement. FSH-secreting adenomas are known to produce intact and biologically active FSH, and the bioactivity to immunoreactivity ratio of secreted FSH may be increased (17). LH was normal in one woman with ovarian hyperstimulation (14) and suppressed but detected in all other reported cases (13, 15, 16). However, unlike the other patients described who had high estrogen levels and endometrial hyperplasia (13, 14), our patient did not have elevated estradiol or thick endometrium (Table 3). This difference may be explained by the very low LH levels measured in our reported patient. FSH alone can induce follicular growth and ovarian enlargement without stimulating the release of estrogen (18). However, minute LH is required for steroidogenesis and estrogen production in the ovary. In women with hypogonadotrophic hypogonadism, treatment with purified or recombinant FSH to induce ovulation was associated with inappropriately low serum estradiol, compared with human menopausal gonadotropin (FSH with LH) treatment that induced very high estrogen concentrations and endometrial hyperplasia (19, 20). This phenomenon supports the two-cell, two-gonadotropin hypothesis of ovarian steroid synthesis (21), confirming that LH enhances androgen production in theca cells, which are then aromatized by granulosa cells to estrogens under the control of FSH. In primates, FSH alone can induce follicular growth and maturation without the presence of LH (22), whereas LH supports and augments the regulatory function of FSH during ovarian steroidogenesis. However, as in our patient, some estradiol may be secreted despite deficient LH action. This phenomenon is also found in female patients with ovarian resistance to LH due to mutation in the LH receptor gene (23), who have estradiol levels that are low or normal for follicular phase due to impaired LH effect. The patient reported here is unique because, unlike the other four reported females with FSH-secreting adenomas and ovarian hyperstimulation (13, 14, 15, 16) who had at least minute LH secretion enough to stimulate estradiol hypersecretion, her large tumor abolished LH secretion and prevented estrogen overproduction.

Our patient, similarly to the patient reported by Valimaki et al. (15), developed symptoms of ovarian enlargement shortly after discontinuing the use of contraceptive pills containing 20 µg ethinyl estradiol in combination with progestin. We tested in vitro the feasibility of estradiol to suppress FSH production by the tumor, but were unable to show any effect. Moreover, restarting oral contraceptives was inefficient in suppressing FSH and ovarian enlargement in our patient, confirming the gonadotroph adenoma cell autonomy.

In conclusion, FSH-secreting pituitary adenomas should be considered in the differential diagnosis of ovarian hyperstimulation, when normal estradiol concentration is associated with very low LH levels. These cases may be difficult to diagnose, but the finding of high PRL levels (Table 3) may help, indicating the need for pituitary imaging to detect a gonadotroph adenoma.

Acknowledgments

Received June 7, 2000. Accepted April 25, 2001.

Address all correspondence and requests for reprints to: Ilan Shimon, M.D., Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel. E-mail: i_shimon@netvision.net.il.

Footnotes

Abbreviation: MRI, Magnetic resonance imaging.

References

1. Snyder PJ 1985 Gonadotroph cell adenomas of the pituitary. Endocr Rev 6:552–563[Abstract]
2. Daneshdoost L, Gennarelli TA, Bashey HM, et al. 1993 Identification of gonadotroph adenomas in men with clinically nonfunctioning adenomas by the luteinizing hormone ß subunit response to thyrotropin-releasing hormone. J Clin Endocrinol Metab 77:1352–1355[Abstract]
3. Klibansky A, Ridgway EC, Zervas NT 1983 Pure subunit-secreting pituitary tumors. J Neurosurg 59:585–589[CrossRef][Medline]
4. Kovacs K, Horvath E, Van Loon GR, Rewcastle NR, Ezrin C, Rosenbloom AA 1978 Pituitary adenomas associated with elevated blood follicle-stimulating hormone levels: a histologic, immunocytologic, and electron microscopic study of two cases. Fertil Steril 29:622–628[Medline]
5. Berezin M, Olchovsky D, Pines A, Tadmor R, Lunenfeld B 1984 Reduction of follicle-stimulating hormone (FSH) secretion in FSH-producing pituitary adenoma by bromocriptine. J Clin Endocrinol Metab 59:1220–1223[Abstract]
6. Vance ML, Ridgway EC, Thorner MO 1985 Follicle-stimulating hormone- and -subunit-secreting pituitary tumor treated with bromocrptine. J Clin Endocrinol Metab 61:580–584[Abstract]
7. Wide L, Lundberg PO 1981 Hypersecretion of an abnormal form of follicle-stimulating hormone associated with suppressed luteinizing hormone secretion in a woman with a pituitary adenoma. J Clin Endocrinol Metab 53:923–930[Abstract]
8. Keren-Tal I, Dantes A, Sprengel R, Amsterdam A 1993 Establishment of steroidogenic granulosa cell lines expressing follicle stimulating hormone receptors. Mol Cell Endocrinol 95:R1–R10
9. Navot D, Bergh PA, Laufer N 1992 Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril 58:249–261[Medline]
10. Rotmensch S, Scommegna A 1989 Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol 160:1220–1222[Medline]
11. Segal R, DePetrillo D, Thomas G 1995 Clinical review of adult granulosa cell tumors of the ovary. Gynecol Oncol 56:338–344[CrossRef][Medline]
12. Zalel Y, Katz Z, Caspi B, Ben-Hur H, Dgani R, Insler V 1992 Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease. Am J Obstet Gynecol 167:122–124[Medline]
13. Djerassi A, Coutifaris C, West VA, et al. 1995 Gonadotroph adenoma in a premenopausal woman secreting follicle-stimulating hormone and causing ovarian hyperstimulation. J Clin Endocrinol Metab 80:591–594[Abstract]
14. Christin-Maitre S, Rongieres-Bertrand C, Kottler M-L, et al. 1998 A spontaneous and severe hyperstimulation of the ovaries revealing a gonadotroph adenoma. J Clin Endocrinol Metab 83:3450–3453[Abstract/Free Full Text]
15. Valimaki MJ, Tiitinen A, Alfthan H, et al. 1999 Ovarian hyperstimulation caused by gonadotroph adenoma secreting follicle-stimulating hormone in 28-year-old woman. J Clin Endocrinol Metab 84:4204–4208[Abstract/Free Full Text]
16. Tashiro H, Katabuchi H, Ohtake H, Kaku T, Ushio Y, Okamura H 1999 A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement in a 10-year-old girl. Fertil Steril 72:158–160[CrossRef][Medline]
17. Galway AB, Hsueh AJW, Daneshdoost L, Zhou M-H, Pavlov SN, Snyder PJ 1990 Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone. J Clin Endocrinol Metab 71:907–912[Abstract]
18. Fevold HL 1941 Synergism of follicle stimulating and luteinizing hormones in producing estrogen secretion. Endocrinology 28:33–36
19. Shoham Z, Balen A, Patel A, Jacobs HS 1991 Results of ovulation induction using human menopausal gonadotropin or purifird follicle-stimulating hormone in hypogonadotrophic hypogonadism patients. Fertil Steril 56:1048–1053[Medline]
20. Shoham Z, Mannaerts B, Insler V, Coelingh-Bennink H 1993 Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotrophic hypogonadism. Fertil Steril 59:738–742[Medline]
21. Ryan KJ, Petro Z, Kaiser J 1968 Steroid formation by isolated and recombined ovarian granulosa and theca cells. J Clin Endocrinol Metab 28:355–358[Medline]
22. Zelinski-Wooten MB, Hutchinson JS, Hess DL, Wolf DP, Stouffer RL 1995 Follicle-stimulating hormone alone supports follicle growth and oocyte development in gonadotropin-releasing hormone antagonist-treated monkeys. Hum Reprod 10:1658–1666[Abstract/Free Full Text]
23. Arnold IJP, Latronico AC, Batista MC, Izzo CR, Mendonca BB 1999 Clinical features of women with resistance to luteinizing hormone. Clin Endocrinol 51:701–707[CrossRef][Medline]
24. Amstrong DG, Webb R 1997 Ovarian follicular dominance: the role of intraovarian growth factors and novel proteins. Rev Reprod 2:139–146[Abstract]
25. Adashi EY 1998 The IGF family and folliculogenesis. J Reprod Immunol 39:13–19[CrossRef][Medline]

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