Skip to main content
Log in

Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4±15.4 IU/I to a nadir of 20.3+11.9 IU/I (−17%, p<0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas. D-Trp6-GnRH administration to patients with FSH-secreting adenomas produced a sharp increase in FSH (+115%) and alpha-subunit levels on the second day after the injection, and high values persisted for two weeks. Serum LH and testosterone concentrations declined to hypogonadal values following the initial increase. We conclude that the combined use of these tests may be of value in determining the potential gonadotroph nature of adenomas. However the great heterogeneity observed in the individual responses limits the use of these provocative tests in a given patient suspected of harboring gonadotroph adenoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Snyder P.J. Gonadotroph cell pituitary adenomas. Endocrinol. Metab. Clin. North. Am. 16: 755, 1987.

    CAS  PubMed  Google Scholar 

  3. Beckers A., Stevenaert A., Mashiter W., Hennen G. Follicle-stimulating hormone-secreting adenomas. J. Clin. Endocrinol. Metab. 61: 525, 1985.

    Article  CAS  PubMed  Google Scholar 

  4. 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  CAS  PubMed  Google Scholar 

  5. Lamberts S.W.J., Verleun T., Oosterom L., Hofland L., Van Ginkel L.A., Van Vroonhoven C.C.J., Stefanko S.Z., de Jong F.H. The effects of bromocriptine, thyrotropin-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  CAS  PubMed  Google Scholar 

  6. 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 women. N. Engl. J. Med. 324: 589, 1991.

    Article  CAS  PubMed  Google Scholar 

  7. Warnet A., Duet M., Seret D., Chanson P., Lajeunie E., Roche D., Mikol J. Les adénomes gonadotropes. Caractères sécrétaires in vivo. Immunoanal. Biol. Spec. 22: 29, 1990.

    Google Scholar 

  8. Roman S.H., Goldstein M., Kourides I.A., Comite F., Bardin C.W., Krieger D.T. The luteinizing hormone-releasing hormone (LHRH) agonist (DTrp 6 — Pro 9 — N — Et) LHRH increased rather than lowered LH and alpha-subunit levels in a patient with an LH-secreting pituitary tumor. J. Clin. Endocrinol. Metab, 58: 313, 1984.

    Article  CAS  PubMed  Google Scholar 

  9. Chapman A.J., MacFarlane A., Shalet S.M., Breardwell C.G., Dutton J., Sutton M.L. Discordant serum alpha-subunit and FSH concentrations in a woman with a pituitary tumour. Clin. Endocrinol. (Oxf.) 21: 123, 1984.

    Article  CAS  Google Scholar 

  10. Sassolas G., Lejeune H., Trouillas J., Forest M.G., Claustrat B., Lahlou N., Loras B. Gonadotropin-releasing hormone agonists are unsuccessful in reducing tumoral gonadotropin secretion in two patients with gonadotropin-secreting pituitary adenomas. J. Clin. Endocrinol. Metab. 67: 180, 1988.

    Article  CAS  PubMed  Google Scholar 

  11. Klibanski A., Jameson J.L., Biller B.M.K., Crowley W.F., Zervas N.T., Rivier J.E., Vale W., Bikkal H. Gonadotropin and alpha-subunit responses to chronic gonadotropin-releasing hormone analog administration in patients with glycoprotein hormone-secreting pituitary tumors. J. Clin. Endocrinol. Metab. 68: 81, 1989.

    Article  CAS  PubMed  Google Scholar 

  12. Daneshdoost L., Pavlou S.N., Molitch M.E., Gennarelli T.A., Savino P.J., Sergott R.C., Bosley T.M., Rivier J.E., Vale W.W., Snyder P. Inhibition of follicle-stimulating hormone secretion from gonadotroph adenomas by repetitive administration of a gonadotropin-releasing hormone antagonist. J. Clin. Endocrinol. Metab. 71: 92, 1990.

    Article  CAS  PubMed  Google Scholar 

  13. Pavlou S.N., Wakefield G., Schlechter N.L, Lindner J., Souza K.H., Kamilaris T.C., Konidaris S., Rivier J.E., Vale W.W., Toglia M. Mode of suppression of pituitary and gonadal function after acute or prolonged administration of a luteinizing hormone-releasing hormone antagonist in normal men. J. Clin. Endocrinol. Metab. 69: 43, 1989.

    Article  Google Scholar 

  14. Lahlou N., Delivet S., Bardin C.W., Roger M., Spitz I.M., Bouchard P. Changes in gonadotropin and alpha-subunit secretion after a single administration of gonadotropin-releasing hormone (GnRH) antagonist in adult males. Fertil. Steril. 53: 898, 1990.

    CAS  PubMed  Google Scholar 

  15. Coy D.H., Vilchez-Martinez J.A., Coy E.J., Schally A.V. Analogs of luteinizing hormone releasing hormone with increased biological activity produced by D-amino acid sustitutions in position 6. J. Med. Chem. 19: 423, 1976.

    Article  CAS  PubMed  Google Scholar 

  16. Rivier J., Porter J., Rivier C.L., Perrin M., Corrigan A., Hook W.A., Siraganian R.P., Vale W.W. New gonadotropin-releasing hormone antagonists with minimal potency for histamine release in vitro. J. Med. Chem. 29: 1846, 1986.

    Article  CAS  PubMed  Google Scholar 

  17. Lahlou N., Roger M., Chaussain J., Feinstein M.C., Sultan C., Toublanc J.E., Schally A.V., Scholler R. Gonadotropin and alpha-subunit secretion during long term pituitary suppression by DTrp 6 — luteinizing hormone-releasing hormone microcapsules as treatment of precocious puberty. J. Clin. Endocrinol. Metab. 65: 946, 1987.

    Article  CAS  PubMed  Google Scholar 

  18. Nahoul K., Rao L.V., Scholler R. Saliva testosterone time-course response to hCG in adult normal men. Comparison with plasma levels. J. Steroid. Biochem. 24: 1011, 1986.

    Article  CAS  Google Scholar 

  19. 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  CAS  PubMed  Google Scholar 

  20. Kwekkeboom D.J., De Jong F.H., Lamberts S.W.J. Gonadotropin release by clinically non functioning 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  CAS  PubMed  Google Scholar 

  21. Klibanski A., Deutsch P.J., Jameson J.L., Ridgway E.C., Crowley W.F., Hsu D.W., Habener J.F., Black P.M. Luteinizing hormone-secreting pituitary tumor: biosynthetic characterization and clinical studies. J. Clin. Endocrinol. Metab. 64: 536, 1987.

    Article  CAS  PubMed  Google Scholar 

  22. McDowell I.F.W., Morris J.F., Charlton H.M. The effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal mice. J. Endocrinol. 95: 331, 1982.

    Article  CAS  PubMed  Google Scholar 

  23. Tenover J.S., Dahl K.D., Vale W.W., Rivier J.E., Brenner W.J. Hormonal responses to a potent gonadotropin hormone-releasing hormone antagonist in normal elderly men. J. Clin. Endocrinol. Metab. 71: 881, 1990.

    Article  CAS  PubMed  Google Scholar 

  24. Couzinet B., Lahlou N., Thomas G., Thalabard J.C., Bouchard P., Roger M., Schaison G. Effects of gonadotropin releasing-hormone antagonist and agonist on the pulsatile release of gonadotropins and alpha-subunit in post-menopausal women. Clin. Endocrinol. (Oxf.) 34: 477, 1991.

    Article  CAS  Google Scholar 

  25. Meldrum D.R., Tsao Z., Monroe S.E., Braunstein G.D., Sladek J., Lu J.K.H., Vale W.W., Rivier J.E., Judd H.L., Chang R.J. Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women. J. Clin. Endocrinol. Metab. 56: 55, 1983.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chanson, P., Lahlou, N., Warnet, A. et al. Responses to gonadotropin releasing hormone agonist and antagonist administration in patients with gonadotroph cell adenomas. J Endocrinol Invest 17, 91–98 (1994). https://doi.org/10.1007/BF03347692

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347692

Key-words

Navigation