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Ovarian Hyperstimulation Caused by Gonadotroph Adenoma Secreting Follicle-Stimulating Hormone in 28-Year-Old Woman

Division of Endocrinology, Departments of Medicine (M.J.V., T.S.), Obstetrics and Gynecology (A.T.), Clinical Chemistry (H.A., U.-H.S.), Pathology (A.Pa.), and Neurosurgery (A.Po.), Helsinki University Central Hospital, FIN-00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. Matti J. Välimäki, M.D., Ph.D., Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland. E-mail: matti.valimaki{at}huch.fi

	Abstract

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Ovarian hyperstimulation caused by a gonadotroph adenoma in premenopausal women has been described only twice before this report. A 28-yr-old woman presented with menstrual disturbances and pelvic pains that began after stopping the use of contraceptive pills. Transvaginal ultrasound revealed enlarged ovaries with multiple cysts. The patient had elevated serum estradiol (up to 2900 pmol/L; normal, 80–300 pmol/L in the follicular phase) and inhibin (6.4 kU/L; normal, 0.5–2.5 kU/L) levels. Serum LH was appropriately suppressed (0.6 IU/L), but serum FSH varied from 4.9–8.1 IU/L. Both gonadotropins as well as the free -subunit showed a paradoxical response to the stimulus by TRH. A nuclear magnetic resonance study unraveled a pituitary tumor, 12–14 mm in diameter, extending up to the suprasellar cistern. After pituitary surgery, all hormone values normalized, and the patient resumed regular ovulatory cycles. In immunostaining, 20–30% of the cells of the tumor stained positively for FSHß. We conclude that a gonadotropin-producing adenoma must be considered in the differential diagnosis of a patient presenting with large multicystic ovaries and high estradiol levels in the absence of exogenous gonadotropins.

	Introduction

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OVARIAN hyperstimulation with enlargement of the ovaries and multiple ovarian cysts occurs in adult women under the influence of excessive gonadotropin stimulation. Gonadotropin therapy for conventional ovulation induction or for controlled ovarian stimulation for assisted reproductive techniques, often in combination with pregnancy, can lead to a full-blown ovarian hyperstimulation syndrome (1). This is characterized by a fluid shift from the intravascular to the third space after increased capillary permeability, presenting with ascites. In the absence of exogenous gonadotropin stimulation, rare cases of ovarian hyperstimulation have been encountered in association with severe primary hypothyroidism (2, 3, 4, 5), polycystic ovary syndrome (PCOS) concomitant with spontaneous pregnancy (6), and bilateral granulosa cell tumors (7). To our best knowledge, ovarian hyperstimulation caused by a FSH- or FSH- plus LH-producing pituitary adenoma has been described only twice before this report (8, 9).

	Materials and Methods

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LH and FSH were quantitated with time-resolved immunofluorometric assays (DELFIAÆ, Wallac, Inc., Turku, Finland). Two assays with different specificities were used for LH. The DELFIA hLH uses two monoclonal antibodies (MAbs). The solid phase antibody is directed to the ß-subunit, and the europium-labeled antibody is directed to the -subunit. This assay only detects the intact heterodimer of LH. In the DELFIA hLH Spec assay, the solid phase antibody is directed to the ß-subunit, and the europium-labeled antibody is directed to another epitope on the ß-subunit. This assay detects intact LH, the free ß-subunit of LH, as well as its fragments. Free LHß was estimated as a difference between the results by DELFIA hLH Spec and DELFIA hLH. Cross-reaction of hCG in the DELFIA hLH assay is 100%, and that in the DELFIA hLH Spec assay is less than 2%. Cross-reaction by FSH and TSH are less than 4% in both assays. The detection limit of the DELFIA hLH assay is 0.2 IU/L, and the interassay precision is less than 12% in the concentration range 1–250 IU/L. In the DELFIA hLH Spec assay, the detection limit is 0.05 IU/L, and the interassay precision is less than 4% in the concentration range 0.6–250 IU/L. Both assays have been calibrated against the WHO Second International Standard for pituitary LH for immunoassay (coded 80/552). The assay design of the DELFIA hFSH assay is similar to that of the hLH assay, with the solid phase antibody directed to the ß-subunit, and the europium-labeled antibody directed to the -subunit. Cross-reaction of hCG, LH, and TSH is less than 0.1%. The detection limit is 0.05 IU/L, and the interassay precision is less than 5% in the concentration range 1–250 IU/L. The assay is calibrated against the Second International Reference Preparation of Pituitary FSH/LH (ICSH) human for bioassay (coded 78/549).The free -subunit of the glycoprotein hormones was measured with a sandwich-type immunofluorometric assay developed in-house. It uses two different MAbs, both directed to the free -subunit, one immobilized onto a microtiter strip well and the other one labeled with a europium chelate. The detection limit is 1 pmol/L, and interassay precision is less than 12%. Cross-reaction of LH and FSH in the assay for the free -subunit is less than 1% on a molar basis, i.e. 10 IU/L LH in the free -subunit assay gives an apparent result of less than 0.5 pmol/L.

Inhibin was assayed with a solid phase sandwich enzyme-linked immunosorbent assay (Inhibin-EASIA, Medgenix Diagnostics, Fleuris, Belgium). The solid phase and the labeled antibodies are both directed to the -subunit of inhibin. The assay detects the free -subunit, its precursors, and 32- and 57-kDa inhibin. The detection limit of the assay is 0.1 kU/L, and the interassay precision is less than 9%. Estradiol was quantitated by RIA (Estradiol-2, Sorin Diagnostics, Milan, Italy). The serum samples were extracted with diethyl ether, the ether fraction was evaporated to dryness, and the residue was dissolved in buffer. The detection limit of the assay is 18 pmol/L, and the interassay variation in the range 290-1710 pmol/L is less than 0.9%. Cross-reaction with estrone is 0.6%, and that with estriol is 0.7%.

The transsphenoidal specimen of the pituitary tumor was fixed in formalin, and paraffin-embedded sections were stained with hematoxylin-eosin and periodic acid-Schiff and by FSH/LH immunohistochemistry. The latter procedure was performed with monoclonal primary antibodies to human FSH (ß-subunit) and LH (clone C10/M3504 for FSH, clone C93/M3502 for LH; DAKO Corp., Carpinteria, CA) diluted 1:500. Microwave pretreatment was used, and primary antibodies were incubated overnight at room temperature. Detection was performed with Vectastain Elite ABC mono kit (Vector Laboratories, Inc., Burlingame, CA) and 3-amino-9-ethylcarbazol as chromogen.

	Case Report

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A 28-yr-old woman presented to the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, with menstrual disturbances and pelvic pains. She had been taking contraceptive pills containing 30 µg ethinyl estradiol and 75 µg gestoden (Femoden, Schering AG, Helsinki, Finland) for 6 yr. Pelvic pains had developed soon after cessation of their use in September 1996. Her menstrual periods, which had been regular while taking the pills, had become irregular. The duration of the cycle had lengthened up to 60 days, and that of bleeding had lengthened to 2 weeks. The patient had spotting. The patient was primarily examined at another hospital in October 1996. Transvaginal ultrasound revealed enlarged ovaries, measuring 65 and 45 mm in the diameter, with multiple cysts. The patient underwent laparoscopy, in which the biggest cyst of the left ovary, 4 cm in the diameter, and three smaller ones were enucleated. Histology showed benign follicular cysts. Her serum estradiol level was 1900 pmol/L (reference range in the follicular phase, 80–300 pmol/L; in the midcycle, 150-1100 pmol/L). Serum LH was low 0.3 IU/L (reference range in the follicular phase, 2–10 IU/L), but serum FSH was within the normal range (4.9 IU/L; reference range, 4–12 IU/L). No signs of hyperandrogenism were found, and the serum testosterone level was normal (1.3 nmol/L; reference range, 0.5–3.0 nmol/L).

In the control examination in May 1997 serum estradiol had increased to 2600 pmol/L, serum FSH was 5.9 IU/L, and LH was 0.3 IU/L. Serum free T₄ was low (8.8 pmol/L; reference range, 10–20 pmol/L), but serum TSH was normal (1.6 mIU/L; reference range, 0.4–4.5 mIU/L). Serum thyroid peroxidase antibodies were negative. The patient underwent a TRH test, in which the basal value for TSH was slightly elevated (6.5 mIU/L) and rose to 48 mIU/L 20 min after TRH. T₄ supplementation was started, but had no effect on either the symptoms or serum gonadotropin or estradiol values. After 6 months of T₄ treatment, the ovaries at repeat ultrasound in November 1997 measured 90 and 86 mm, respectively, and showed multicystic structure; the endometrial thickness was normal (8 mm). Thereafter, cyclic progestin treatment with norethisterone acetate (10 mg daily for 10 days) was started, and regular menstrual cycles were achieved.

In the first evaluation at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, in February 1998 the estradiol level of the patient was further elevated to 2900 pmol/L; serum LH was still low at 0.6 UI/L, but serum FSH was inappropriately high at 8.1 UI/L. Transvaginal ultrasound revealed ovaries measuring 38 x 23 mm and 69 x 43 mm, respectively, with the biggest cyst being 35 mm in diameter (Fig. 1a). The endometrial thickness was 8.5 mm (Fig. 1b). Magnetic resonance imaging of the pituitary was performed due to mixed-type hypothyroidism and the FSH level, which was inappropriately high in relation to the very high estradiol. The examination unraveled a pituitary tumor, 12–14 mm in diameter, extending up to the suprasellar cistern (Fig. 2). The patient did not have headache or visual disturbances; confrontational screening of visual fields by finger counting was normal. A TRH test for intact gonadotropins and their subunits was performed by administering an iv bolus of 200 µg TRH (Relefact, Hoechst Fennica Ag, Frankfurt Am Main, Germany) and sampling blood before and 20 and 60 min after the injection. As shown in Table 1, serum FSH nearly doubled, and a paradoxical response to TRH was also obtained for intact LH, the free -subunit, and LHß. Serum inhibin level was elevated 6.4 kU/L (reference range, 0.5–2.5 kU/L). Transvaginal ultrasound was still repeated, and now the ovaries were 79 x 39 mm and 57 x 36 mm in size, and the endometrium was 6 mm thick.

View larger version (65K): [in this window] [in a new window]   Figure 1. Transvaginal ultrasound examination of the ovary and endometrium of a 28-yr-old woman with a pituitary adenoma secreting FSH. a and b, Before operation: multicystic ovary (69 x 43 mm) and normal endometrium (thickness, 8.5 mm).

View larger version (66K): [in this window] [in a new window]   Figure 2. T1-weighted coronal (a) and sagittal (b) nuclear magnetic resonance scan showing an intra- and suprasellar tumor, measuring 12 x 14 mm. A T1-weighted coronal (c) nuclear magnetic resonance scanning was performed 3 months after surgery.

View larger version (138K): [in this window] [in a new window]   Figure 3. Histology of the pituitary adenoma. The pattern is one of anastomosing ribbons of quite sparsely granulated, mainly chromophobic cells. Some tiny rosettes, slender capillaries, and proteinaceous droplets can be seen. In FSH immunostaining, 20–30% of the cells were clearly stained, with especially highlighted peripheral/luminal parts of the cytoplasms (inset). Hematoxylin-eosin staining, FSH immunostaining (inset). Original magnification, x160.

View larger version (67K): [in this window] [in a new window]   Figure 4. Transvaginal ultrasound examination of the ovary and endometrium of a 28-yr-old woman with a pituitary adenoma secreting FSH. a and b, After operation: normal ovary with preovulatory follicle (14 x 17 mm) and normal endometrium (thickness, 9.5 mm).

	Discussion

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Gonadotroph adenomas are relatively common among pituitary adenomas, accounting for approximately 40% of all macroadenomas recognized clinically (10, 11, 12) and approximately 80% of surgically excised clinically nonfunctioning adenomas when examined in vitro by measurements of hormonal secretion from cultured adenoma cells, immunospecific staining for pituitary hormones, or tests for the presence of the messenger ribonucleic acids for hormones (13, 14, 15). The in vitro evidence suggests that gonadotroph adenomas are equally common in women and men (13, 15, 16, 17), but clinically most of them are recognized in men who are more than 50 yr old, on the basis of headache, visual disturbance, and acquired hypogonadism (10). The clinical recognition of gonadotroph adenomas is relatively difficult, as they secrete inefficiently, and their secretory products, intact gonadotropins and their subunits, generally do not cause a recognizable clinical syndrome. In postmenopausal women, the diagnosis of a pituitary adenoma secreting intact FSH or LH is rendered even more difficult, because high serum concentrations of FSH and LH can be considered appropriately elevated and because the ovaries have lost their capability of responding to the stimulus by gonadotropins (11, 18, 19).

The diagnosis of the present patient was delayed by the fact that a FSH-producing adenoma did not appear on the lists of causes of ovarian hyperstimulation in textbooks at the time of the investigations when only one similar case had been published in the literature (8). Another reproductive-aged woman with a FSH- plus LH-producing adenoma was described when this article was under preparation (9). In the first paper Djerassi et al. (8) described a 39-yr-old woman who initially presented because of amenorrhea and who before the final diagnosis had had transsphenoidal surgery twice due to recurrent pituitary adenoma. As in our patient, transvaginal ultrasound showed multiple ovarian cysts, but in contrast to our case, it also showed endometrial thickening. The patient had markedly supranormal estradiol and free -subunit levels and a mildly supranormal FSH level, but serum LH level was clearly low. Immunocytochemical examination showed intense reactivity for -subunit in the majority of adenoma cells and focal positivity for FSHß in some cells. No reactivity for LHß was detected (8). In the second paper Christin-Maitre et al. (9) reported a 34-yr-old woman with very high estradiol level, elevated testosterone, but normal FSH and LH levels. Their patient presented with massive uterine bleeding, and she had multicystic ovaries with endometrial hyperplasia. Immunostaining of the tumor tissue was positive for FSHß (10%), LHß (50%), and -subunit (50%).

The majority of pituitary adenomas can be clinically recognized, even in postmenopausal women, by the responses of intact gonadotropins, the ß-subunit of LH, and -subunit to TRH stimulation (11). In a series of 16 women with apparently nonsecreting pituitary adenomas, 11 had significant increases in serum LHß in response to TRH, three had FSH responses, four had LH responses, and four also had -subunit responses (11). Before pituitary surgery, our patient showed paradoxical responses to TRH not only of intact FSH, but also of intact LH, LHß, as well as free -subunit, which all normalized after successful surgery. In the previous case reported by Djerassi et al. (8), only LHß increased in response to TRH; a TRH test was not performed in the patient reported by Christin-Maitre et al. (9). In our patient, TRH tests both before and after the operation were performed during T₄ treatment. Thus, rather than from normal thyrotropes, a brisk rise in the free -subunit level before the operation originated from tumor cells. This view was supported by the disappearance of the rise after the surgery.

Our patient developed her symptoms after cessation of the use of contraceptive pills containing ethinyl estradiol and gestoden. It is feasible to consider that ethinyl estradiol in combination with progestin was more potent than natural estrogens to suppress the production of FSH by the pituitary tumor, thus preventing the disease from becoming symptomatic. Chapman et al. described a 51-yr-old woman with a large FSH- and -subunit-producing pituitary adenoma who showed a clear-cut suppression of serum FSH by treatment with ethinyl estradiol (0.03 mg daily for 3 weeks); the effect of estradiol was not tested (19). A peculiar finding in our patient was the absence of apparent endometrial thickening despite the highly elevated estradiol levels; endometrial hyperplasia was observed in the patients described by Djerassi et al. (8) and Christin-Maitre et al. (9). In our patient, endometrial hyperplasia was possibly prevented by cyclic progestin treatment, which induced regular withdrawal bleeding, and was started quite soon after the disease became symptomatic. In the case of Djerassi et al. (8) and Christin-Maitre et al. (9), the patients had had unopposed estrogen effect on the endometrium for several years.

Ovarian hyperstimulation has been described as a consequence of severe primary hypothyroidism (2, 3, 4, 5); in these cases, serum TSH levels have been more than 50 mIU/L. Rotmensch et al. (2) reported a case of severe spontaneous ovarian hyperstimulation syndrome, where the hypothyroid patient had multicystic ovaries with ascites. Ovulatory dysfunction in primary hypothyroidism may be due to a number of mechanisms, including altered metabolism of estrogens, hypothalamic pituitary dysfunction, a direct effect of highly elevated TSH levels on the ovary, and altered PRL metabolism (4, 20). In our patient the primary findings indicated secondary hypothyroidism, but later slightly elevated TSH levels and its response to TRH were compatible with primary hypothyroidism. However, contrary to previous cases, the TSH levels were never highly elevated (2, 3, 4, 5). Furthermore, T₄ supplementation did not have any effect on the symptoms or clinical findings of the patient. Despite negative thyroid antibodies, the patient probably had primary hypothyroidism combined with impaired TSH secretion due to a pituitary mass. This view was supported by low normal free T₄ and high normal TSH after the surgery.

A constellation of menstrual irregularities, hyperandrogenic anovulation, hyperestrogenism, and enlarged ovaries with multiple follicles most commonly means PCOS. In ultrasound scanning, PCO is defined as ovaries containing 10 or more follicles 2–8 mm in diameter, usually subcapsular, with thickened ovarian stroma. Our patient, in contrast, had multiple ovarian cysts; the largest was 35 mm in diameter. In PCOS, pregnancy can be achieved with ovulation induction, and it is well established that ovarian hyperstimulation syndrome is more frequent in these patients. Ovarian hyperstimulation concomitant with spontaneous pregnancy has also been reported previously in PCOS patient (6). PCOS patients will usually have supranormal LH and normal to subnormal FSH levels. An estrogen-producing ovarian neoplasm, granulosa cell tumor presents with enlarged ovaries, signs of hyperestrogenism, and elevated inhibin, but suppressed gonadotropin levels in contrast to gonadotropin-producing pituitary adenomas and PCOS in which the level of at least one of the gonadotropins is nonsuppressed (7).

In conclusion, gonadotropin-producing pituitary adenoma should be considered in the differential diagnosis of ovarian hyperstimulation when pregnancy is ruled out. The nonsuppressed gonadotropin levels distinguish these adenomas from steroid-producing ovarian neoplasms, and a high FSH/LH ratio distinguishes the FSH-producing pituitary adenoma from PCOS.

Received February 19, 1999.

Revised June 17, 1999.

Accepted July 22, 1999.

	References

Top Abstract Introduction Materials and Methods Case Report Discussion References

 

1. Navot D, Bergh PA, Laufer N. 1992 Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril. 58:249–261.[Medline]
2. Rotmensch S, Scommegna A. 1989 Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol. 160:1220–1222.[Medline]
3. Van Voorhis BJ, Neff TW, Syrop CH, Chapler FK. 1994 Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in an adult. Obstet Gynecol. 83:885–887.[Medline]
4. Hansen KA, Tho SPT, Hanly M, Moretuzzo RW, McDonough PG. 1997 Massive ovarian enlargement in primary hypothyroidism. Fertil Steril. 67:169–171.[CrossRef][Medline]
5. Nappi R, Di Naro E, D’Aries AP, Nappi L. 1998 Natural pregnancy in hypothyroid woman complicated by spontaneous ovarian hyperstimulation syndrome. Am J Obstet Gynecol. 178:610–611.[CrossRef][Medline]
6. 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]
7. Segal R, DePetrillo D, Thomas G. 1995 Clinical review of adult granulosa cell tumors of the ovary. Gynecol Oncol. 56:338–344.[CrossRef][Medline]
8. 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]
9. 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]
10. Snyder PJ. 1985 Gonadotroph cell adenomas of the pituitary. Endocr Rev. 6:552–563.[Abstract/Free Full Text]
11. Daneshdoost L, Gennarelli TA, Bashey HM, et al. 1991 Recognition of gonatroph adenomas in women. N Engl J Med. 324:589–594.[Abstract]
12. 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]
13. Mashiter K, Adams E, Van Noorden S. 1981 Secretion of LH, FSH, and PRL shown by cell culture and immunocytochemistry of human functionless pituitary adenomas. Clin Endocrinol (Oxf). 15:103–112.[CrossRef][Medline]
14. Asa SL, Gerrie BM, Singer W, Horvath E, Kovacs K, Smyth HS. 1986 Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas. J Clin Endocrinol Metab. 62:1011–1019.[Abstract/Free Full Text]
15. Black PM, Hsu DW, Klibanski A, et al. 1987 Hormone production in clinically nonfunctioning pituitary adenomas. J Neurosurg. 66:244–250.[Medline]
16. Kwekkeboom DJ, de Jong FH, Lamberts SWJ. 1989 Gonadotropin release by clinically nonfunctioning and gonadotroph pituitary adenomas in vivo and in vitro: relation to sex and effects of thyrotropin-releasing hormone, gonadotropin-releasing hormone, and bromocriptine: J Clin Endocrinol Metab. 68:1128–1135.[Abstract/Free Full Text]
17. Jameson JL, Klibanski A, Black PM, et al. 1987 Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. J Clin Invest. 80:1472–1478.
18. 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/Free Full Text]
19. Chapman AJ, Macfarlane IA, Shalet SM, Beardwell CG, Dutton J, Sutton ML. 1984 Discordant serum -subunit and FSH concentrations in a woman with a pituitary tumour. Clin Endocrinol (Oxf). 21:123–129.[CrossRef][Medline]
20. Fishman J, Hellman L, Zumoff B. 1962 Influence of thyroid hormone on estrogen metabolism in man. J Clin Endocrinol Metab. 22:389–392.

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Välimäki, M. J. Articles by Stenman, U.-H. Search for Related Content PubMed PubMed Citation Articles by Välimäki, M. J. Articles by Stenman, U.-H.