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Serum FSH bioactivity and inhibin levels in patients with gonadotropin secreting and nonfunctioning pituitary adenomas

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Abstract

It has been reported that serum FSH bioactivity and inhibin levels can be used as markers of the presence of true gonadotropin-secreting pituitary adenoma (Gn-oma). To verify this hypothesis, we have investigated the bioactivity of FSH and serum inhibin α-α and α-βA levels in a series of patients with either Gn-oma or nonfunctioning pituitary adenoma (NFPA). Nine patients with Gn-oma (6 men and 3 women), 21 with NFPA (9 men and 12 women) and 30 normal subjects were included in the study. We studied FSH biological activity (FSH-B) by using Sertoli cell aromatase bioassay (SAB) and α-α and α-βA inhibin levels by two noncompetitive immunometric assays (IEMA). In male patients with Gn-oma, serum immunoreactive FSH (FSH-I) and FSH-B levels ranged from 5.1 to 35.5 U/L and from 8.3 to 48 U/L, respectively, FSH B/l ratio being elevated in 2 (2.5 and 4.1; normal male range: 0.3–1.5), while female patients with Gn-oma had serum FSH-I and FSH-B levels ranging from 43.2 to 162 U/L and from 41.2 to 112.8 U/l, respectively, with a normal FSH B/l ratio. In male patients with NFPA, FSH-I and FSH-B levels ranged from 2.7 to 10.7 U/l and from 2.4 to 11.4 U/l while in females they ranged from 3.4 to 67.9 and from 4.6 to 60.8 U/l, respectively. FSH B/l ratio was elevated in 1 male (3.3) and normal in the remaining patients with NFPA. Serum α-α inhibin levels were normal or low in patients with Gn-oma and NFPA, while α-βA inhibin concentrations were slightly elevated in 1 of 6 postmenopausal women (0.9; normal range <0.7 U/ml). The present study confirms and extends previous reports indicating that male patients with Gn-oma may secrete FSH molecules with increased bioactivity. However, this abnormality was also observed in one male patient with NFPA. Moreover, the measurement of inhibin levels does not appear to be a reliable in vivo marker of pituitary tumors of gonadotroph origin, as it was normal or low in almost all patients with either Gn-oma or NFPA.

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References

  1. Snyder P.J. Gonadotroph cell adenomas of the pituitary. Endocr. Rev. 6: 552, 1985.

    Article  PubMed  CAS  Google Scholar 

  2. Asa S.L., Gerrie B.M., Singer W., Horvath E., Kovacs K., Smyth H.S. Gonadotrophin secretion in vitro by human pituitary null cell adenomas and oncocytomas. J. Clin. Endocrinol. Metab. 62: 1011, 1986.

    Article  PubMed  CAS  Google Scholar 

  3. Snyder P.J., Bashey H.M., Kim S.U., Chappel S.C. Secretion of uncombined subunits of luteinizing hormone by gonadotroph cell adenomas. J. Clin. Endocrinol. Metab. 59: 1169, 1984.

    Article  PubMed  CAS  Google Scholar 

  4. Borges J.L., Ridgway E.C., Kovacs K., Rogolol A.D., Thorner M.O. Follicle-stimulating hormone-secreting pituitary tumor with concomitant elevation of serum α-subunit levels. J. Clin. Endocrinol. Metab. 58: 937, 1984.

    Article  PubMed  CAS  Google Scholar 

  5. Demura R., Jibiki K., Kubo O., Odagiri E., Demura H., Kitamura K., Shizume K. The significance of α-subunit as a tumor marker for gonadotropin-producing pituitary adenomas. J. Clin. Endocrinol. Metab. 63: 564, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Kwekkeboom D.J., De Jong F.H., Lamberts S.W.J. Gonadotropin release by nonfunctining 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, 1989.

    Article  PubMed  CAS  Google Scholar 

  7. Beck-Peccoz P., Persani L., Faglia G. Glycoprotein hormone α-subunit in pituitary adenomas. Trends Endocrinol. Metab. 3: 41, 1992.

    Article  PubMed  CAS  Google Scholar 

  8. Saccomanno K., Spada A., Bassetti M., Gil-del-Alamo P., Faglia G. Immunodetection of chorionic gonadotropin and its subunits in human nonfunctioning pituitary adenomas. J. Clin. Endocrinol. Metab. 78: 1103, 1994.

    PubMed  CAS  Google Scholar 

  9. Gil-del-Alamo P., Petterson K.S.I., Saccomanno K., Spada A., Faglia G., Beck-Peccoz P. Abnormal response of luteinizing hormone beta subunit to thyrotropin-releasing hormone in patients with non-functioning pituitary adenomas. Clin. Endocrinol. (Oxf.) 41: 661, 1994.

    Article  CAS  Google Scholar 

  10. Gil-del-Alamo P., Saccomanno K., Lania A., Pettersson K.S.I., Beck-Peccoz P., Spada A. Serum levels of β-subunit of chorionic gonadotropin in patients with pituitary tumors. Eur. J. Endocrinol. 133: 33, 1995.

    Article  PubMed  CAS  Google Scholar 

  11. Beck-Peccoz P., Persani L. Variable biological activity of thyroid-stimulating hormone. Eur. J. Endocrinol. 131: 331, 1994.

    Article  PubMed  CAS  Google Scholar 

  12. Galway A.B., Hsueh A.J.W., Daneshdoost L., Zhou M.H., Pavlou S.N., Snyder P.J. Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone. J. Clin. Endocrinol. Metab. 71: 907, 1990.

    Article  PubMed  CAS  Google Scholar 

  13. Snyder P.J., Muzyka R., Johnson J., Utiger R.D. Thyrotropin-releasing hormone provokes abnormal follicle-stimulating hormone (FSH) and luteinizing hormone responses in men who have pituitary adenomas and FSH hypersecretion. J. Clin. Endocrinol. Metab. 51: 744, 1980.

    Article  PubMed  CAS  Google Scholar 

  14. Lamberts S.W.J., Verleun T., Oosterom R., Hofland L., Van Ginkel L.A., Loeber J.G., Van Vroonhoven C.C., Stefanko S.Z., De Jong F.H. The effect of bromocriptine, tyrotropin-releasing hormone, and gonadotropin-releasing hormone on hormone secretion by gonadotropin-secreting pituitary adenomas in vivo and in vitro. J. Clin. Endocrinol. Metab. 64: 524, 1987.

    Article  PubMed  CAS  Google Scholar 

  15. Travaglini P., Bassetti M., Spada A., Togni M., Faglia G. Mixed LH, FSH and GH pituitary microadenoma, clinical and morphological studies. In: Landolt A.M., Heitz P.U., Zapf J., Girard J., Del Pozo E. (Eds), Adv. Biosciences 69: 435, 1988.

  16. Daneshdoost L., Gennarelli T.A., Bashey H.M., Savino P.J., Sergott R.C., Bosley T.M., Snyder P.J. Recognition of gonadotroph adenomas in woman. N. Engl. J. Med. 324: 589, 1991.

    Article  PubMed  CAS  Google Scholar 

  17. Daneshdoost L., Gennarelli T.A., Bashey H.M., Savino P.J., Sergott R.C., Bosley T.M., Snyder P.J. Identification of gonadotroph adenomas in men with clinically non-functioning adenomas by the luteinizing hormone β-subunit response to thyrotropin-releasing hormone. J. Clin. Endocrinol. Metab. 77: 1352, 1993.

    PubMed  CAS  Google Scholar 

  18. Lahlou N., Le Nestour E., Chanson P., Seret-Bégué D., Bouchard P., Roger M., Warnet A. Inhibin and follicle-stimulating hormone levels in gonadotroph adenomas: evidence of a positive correlation with tumor volume in men. Clin. Endocrinol. (Oxf.) 38: 301, 1993

    Article  CAS  Google Scholar 

  19. Ambrosi B., Bassetti M., Ferrario R., Medri G., Giannatasio G., Faglia G. Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumor: hormonal and immunocytochemical studies. Acta Endocrinol. (Copenh.). 122: 569, 1990.

    CAS  Google Scholar 

  20. Saccomanno K., Bassetti M., Lania A., Losa M., Faglia G., Spada A. Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas. J. Endocrinol. Invest. 20: 59, 1997.

    Article  PubMed  CAS  Google Scholar 

  21. Van Damme M.P., Robertson D.M., Marana R., Ritzen E., Diczfalusy E. A sensitive and specific in vitro bioassay method for the measurement of FSH activity. Acta Endocrinol. (Copenh.). 91: 224, 1979.

    Google Scholar 

  22. Padmanabhan V., Chappel S.C., Beitins I.Z. An improved in vitro bioassay for follicle-stimulating hormone (FSH): suitable for measurement of FSH in unextracted human serum. Endocrinology 121: 1089, 1987.

    Article  PubMed  CAS  Google Scholar 

  23. Beck-Peccoz P., Padbanabhan V., Baggiani M., Cortelazzi D., Buscaglia M., Medri G., Marconi A.M., Pardi G., Beitins I.Z. Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common α-subunit and free testosterone and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone. J. Clin. Endocrinol. Metab. 73: 525, 1991.

    Article  PubMed  CAS  Google Scholar 

  24. Padmanabhan V., Sonstein J., Olton P.L., Nippoldt O.T., Menon K.M.J., Marshall J.C., Kelch R.P., Beitins I.Z. Serum bioactive follicle-stimulating hormone activity increased during pregnancy. J. Clin. Endocrinol. Metab. 69: 968, 1989.

    Article  PubMed  CAS  Google Scholar 

  25. Robertson D., Burger H.G., Sullivan J., Cahir N., Groome N., Poncelet E., Franchimont P., Woodruff T., Mather J.P. Biological and immunological characterization of inhibin forms in human plasma. J. Clin. Endocrinol. Metab. 81: 669, 1996.

    PubMed  CAS  Google Scholar 

  26. Padmanabhan V., Lang L.L., Sonstein J., Kelch R.P., Beitins I.Z. Modulation of serum follicle-stimulating hormone bioactivity and isoform distribution by estrogenic steroid in normal women and in gonadal dysgenesis. J. Clin. Endocrinol. Metab. 67: 465, 1988.

    Article  PubMed  CAS  Google Scholar 

  27. Beitins I.Z, Padmanabhan V. Bioactivity of gonadotropin. Endocrinol. Metab. Clin. North Am. 20: 85, 1991.

    PubMed  CAS  Google Scholar 

  28. Papandreu M.J., Asteria C., Pettersson K., Ronin C., Beck-Peccoz P. Concanavalin A affinity chromatography of human serum gonadotropins: evidence for changes of carbohydrate structure in different clinical conditions. J. Clin. Endocrinol. Metab. 76: 1008, 1993.

    Google Scholar 

  29. Ying S.Y., Czvik J., Becker A., Ling N., Ueno N., Guillemin R. Secretion of follicle-stimulating hormone and production of inhibin are reciprocally related. Proc. Natl. Acad. Sci. USA 84: 4631, 1987.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Ying S.Y. Inhibins, activins and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev. 9: 267, 1988.

    Article  PubMed  CAS  Google Scholar 

  31. Groome N.P., Illingworth P.J., O’Brien M., Pai R., Rodger F.E., Mather J.P., McNeilly A.S. Measurement of dimeric inhibin-B throughout the human menstrual cycle. J. Clin. Endocrinol. Metab. 81: 1401, 1996.

    PubMed  CAS  Google Scholar 

  32. Illingworth P.J., Groome N.P., Byrd W., Rainey W.E., McNeilly A.S., Mather J.P., Bremner W.J. Inhibin-B: a likely candidate for the physiologically important form of inhibin in men. J. Clin. Endocrinol. Metab. 81: 1321, 1996.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto di Scienze Endocrine, Università di Milano, Ospedale Maggiore IRCCS (S.B., R.R., D.C., A.S.), Rozzano, Milano, Italy

    S. Borgato, R. Romoli, D. Cortelazzi & A. Spada

  2. Istituto di Scienze Endocrine, Università di Milano, Istituto Auxologico Italiano IRCCS (L.P.), Rozzano, Milano, Italy

    L. Persani

  3. Istituto di Scienze Endocrine, Università di Milano, Istituto Clinico Humanitas (P.B.-P.), Via Manzoni 56, 20089, Rozzano, Milano, Italy

    Paolo Beck-Peccoz M.D. (Professor of Endocrinology)

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  1. S. Borgato
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  2. L. Persani
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  3. R. Romoli
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  4. D. Cortelazzi
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  5. A. Spada
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  6. Paolo Beck-Peccoz M.D.
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Borgato, S., Persani, L., Romoli, R. et al. Serum FSH bioactivity and inhibin levels in patients with gonadotropin secreting and nonfunctioning pituitary adenomas. J Endocrinol Invest 21, 372–379 (1998). https://doi.org/10.1007/BF03350773

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