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
