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Endocrine and immunohistochemical studies on thyrotropin (TSH)-secreting pituitary adenomas: responses of TSH, alpha-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.
AuthorsN Kuzuya, K Inoue, M Ishibashi, Y Murayama, Y Koide, K Ito, T Yamaji, K Yamashita
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 71 Issue 5 Pg. 1103-11 (Nov 1990) ISSN: 0021-972X [Print] United States
PMID1699960 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Glycoprotein Hormones, alpha Subunit
  • Thyroid Hormones
  • Thyrotropin-Releasing Hormone
  • Dexamethasone
  • Thyrotropin
  • Growth Hormone
  • Growth Hormone-Releasing Hormone
Topics
  • Adenoma (metabolism, pathology)
  • Adult
  • Dexamethasone (pharmacology)
  • Glycoprotein Hormones, alpha Subunit (blood, metabolism)
  • Growth Hormone (metabolism)
  • Growth Hormone-Releasing Hormone
  • Humans
  • Immunohistochemistry
  • Male
  • Paraneoplastic Endocrine Syndromes
  • Pituitary Neoplasms (metabolism, pathology)
  • Thyroid Hormones (blood)
  • Thyrotropin (blood, metabolism)
  • Thyrotropin-Releasing Hormone (pharmacokinetics, pharmacology)
  • Tumor Cells, Cultured (drug effects)

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