Nonfunctioning adenomas of the pituitary

The term "nonfunctioning" pituitary adenomas (NFPA) implies heterogeneity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual function, and despite the secretion of gonadotropins, hypogonadism is frequent. NFPA must be differentiated from prolactinomas, because of the therapeutic implications, but although prolactin (PRL) levels greater than 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-releasing hormone (GnRH) is of no use, but the thyrotropin-releasing hormone (TRH) test is invaluable. NFPA are monoclonal in origin, but genetic mutations data have not clarified their etiology, which remains largely unknown. Proliferating cell nuclear antigen expression is increased in recurrent adenomas, as is abnormality and overexpression of the protein kinase C family in aggressive tumors. Mutations of tumor-suppressor genes, such as the p53 and Rb genes, and of the metastasizing suppressor gene nm23, have been found in invasive tumors. Immunohistochemistry data confirm that most NFPA originate from gonadotroph cells; many NFPA are negative for all anterior pituitary hormones tested, although isolated or clustered cells are often positive for glycoprotein hormones or their subunits. Silent gonadotroph and also silent growth hormone (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 receptors have recently been visualized in vivo and there are also receptors for TRH or GnRH, since levels of alpha or beta subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, three second-line pharmacological approaches have been tried: dopamine agonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first.