Mono- and plurihormonal thyrotropic pituitary adenomas: pathological, hormonal and clinical studies in 12 patients

In a series of 12 patients (eight women and four men, aged between 20 and 62 years), operated on for a pituitary adenoma shown to be thyrotropic by immunocytochemistry, we performed a retrospective and comparative analysis of clinical and biological data, tumor studies including immunocytochemistry with double labeling, and proliferation marker (proliferative cell nuclear antigen (PCNA) and Ki-67) detection, electron microscopy and culture. Our study leads us to confirm that thyrotropic tumors are rare (12 of 1174 pituitary adenomas: 1%). The main points arising were that: (1) high or normal plasma TSH associated with an increase in plasma alpha-subunit and high thyroid hormone levels is the best criterion for diagnosis; (2) the failure of TSH to respond to TRH or Werner's test is not a reliable criterion for diagnosis; (3) thyrotropic adenomas may be 'silent', without clinical signs of hyperthyroidism and with only slight increase in TSH, tri-iodothyronine and thyroxine concentrations; (4) mitoses and nuclear atypies are frequently detected in large tumors, which are invasive in more than 50% of cases - the first analysis of two proliferation markers (PCNA and Ki-67) bears out the relative aggressiveness of thyrotropic adenomas; (5) thyrotropic adenomas are frequently plurihormonal. Immunocytochemical double labeling, complemented by in vitro study, showed that thyrotropic tumor cells sometimes can or sometimes cannot cosecrete TSH, GH or prolactin. The pathological identification of monohormonal and plurihormonal adenomas seems to be supported by clinical and biological differences.