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.