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.