Endocrine and Immunohistochemical Studies on Thyrotropin (TSH)-Secreting Pituitary Adenomas: Responses of TSH,α-Subunit, and Growth Hormone to Hypothalamic Releasing Hormones and Their Distribution in Adenoma Cells

Abstract

Endocrine and immunohistochemical studies were performed in two cases of TSH-secreting pituitary adenomas. The patients had elevated serum TSH and alpha-subunit concentrations despite high serum thyroid hormone levels. In addition, one patient (no. 1) had elevated serum GH levels with clinical evidence of acromegaly. GH-releasing hormone infusion increased serum levels of TSH, alpha-subunit and GH in the two patients. TRH injection increased serum TSH levels in both patients and, concomitantly, serum alpha-subunit and GH levels in patient 1. Basal TSH levels and their responses to TRH changed reciprocally to changes in serum thyroid hormone levels, although TRH-induced GH release did not. The administration of GnRH also increased serum TSH, alpha-subunit, and GH levels in patient 1. In accordance with these in vivo results, pituitary adenoma cells in culture obtained from patient 1 responded to GH-releasing hormone, TRH, or GnRH to secrete TSH, alpha-subunit, and GH. Incubation of cells with dexamethasone resulted in inhibition of TSH and stimulation of GH secretion without a significant change in alpha-subunit secretion. On the basis of light microscopic and electron microscopic double gold immunohistochemistry, the tumor from patient 1 was a bimorphous adenoma composed of two separate cell types: cells with TSH beta-subunit (TSH beta) and alpha-subunit, and those with GH and alpha-subunit. The remainder consisted mainly of cells with TSH beta and alpha-subunit. The coproduction of the unusual combination of two hormones such as GH and alpha-subunit in a single-type of adenoma cell and the coexistence of thyrotrophs and somatotrophs in one pituitary adenoma along with the aberrant responses of TSH beta, alpha-subunit, and GH to multiple hypothalamic hormones suggest the dedifferentiation of pituitary cells to multipotential progenitor cells by neoplastic transformation.