Clinical and immunohistochemical studies on TSH-secreting pituitary adenoma: its multihormonality and expression of Pit-1.

Eight patients with thyrotropin (TSH)-secreting pituitary adenoma are described. Serum TSH levels were inappropriately elevated in spite of elevated thyroid hormones. The serum-free glycoprotein alpha-subunit level was elevated in all the patients. The alpha-subunit to TSH molar ratio, a "tumor marker" for TSH-secreting adenoma, ranged from 1.06 to 6.16. All patients had macroadenoma and underwent transsphenoidal surgery. Light-microscopic indirect immunoperoxidase method applied on formalin-fixed paraffin-embedded specimens revealed alpha-subunit and TSH beta immunoreactivity in all adenomas. The proportion of TSH beta-positive cells ranged from 20% to 75% of adenoma cells. Six adenomas (75%) were associated with growth hormone (GH) and/or prolactine (PRL) immunoreactivity. By the double staining method, TSH beta and the alpha-subunit were frequently colocalized in the same cells, but some cells were found to contain either alpha-subunit or TSH beta. We also analyzed the localization of a pituitary-specific transcriptional factor, Pit-1, which has been suggested to play a role in functional differentiation toward growth hormone, prolactine, and TSH. All cases were positive for Pit-1 product using antibody against human Pit-1 synthesized peptide. Pit-1 product was localized in the nuclei of many adenoma cells and was frequently identified in cells that were positive for both TSH beta and growth hormone or prolactine. From our investigations, the role of Pit-1 in multidirectional differentiation during the development of TSH-secreting adenoma was suggested.