NONFUNCTIONING ADENOMAS OF THE PITUITARY

The term ''nonfunctioning'' pituitary adenomas (NFPA) implies heteroge neity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual functi on, and despite the secretion of gonadotropins, hypogonadism is freque nt. NFPA must be differentiated from prolactinomas, because of the the rapeutic implications, but although prolactin (PRL) levels greater tha n 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-rele asing hormone (GnRH) is of no use, but the thyrotropin-releasing hormo ne (TRH) test is invaluable. NFPA are monoclonal in origin, but geneti c mutations data have not clarified their etiology, which remains larg ely unknown. Proliferating cell nuclear antigen expression is increase d in recurrent adenomas, as is abnormality and overexpression of the p rotein kinase C family in aggressive tumors. Mutations of tumor-suppre ssor genes, such as the p53 and Rb genes, and of the metastasizing sup pressor gene nm23, have been found in invasive tumors. Immunohistochem istry data confirm that most NFPA originate from gonadotroph cells; ma ny NFPA are negative for ail anterior pituitary hormone; tested, altho ugh isolated or clustered cells are often positive for glycoprotein ho rmones or their subunits. Silent gonadotroph and also silent growth ho rmone (GH) or corticotroph tumors can constitute the anatomical basis for clinical NFPA. The heterogeneity of the immunohistochemistry data is reflected in the receptor complex of these tumors. Dopaminergic rec eptors have recently been visualized in vivo and there are also recept ors for TRH or GnRH, since levels of alpha or beta subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, th ree second line pharmacological approaches have been tried: dopamine a gonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first . Copyright (C) 1996 by W.B. Saunders Company