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Semin Reprod Med 2002; 20(4): 339-348
DOI: 10.1055/s-2002-36708
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Gonadotropinomas

Sushela S. Chaidarun1 , Anne  Klibanski2
  • 1Department of Medicine-Endocrine Division, The University of Virginia Health System, Charlottesville, Virginia
  • 2Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Further Information

Publication History

Publication Date:
21 January 2003 (online)

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ABSTRACT

Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty. The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their subunits; and nonfunctioning gonadotropinomas or null cell tumors with negative immunostaining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadenomas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation.

KEYWORD

Gonadotrope adenoma - gonadotropins - clinically nonfunctioning tumor - null cell adenoma

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