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Clinical and molecular studies of a thyrotropin-secreting pituitary adenoma.

AbstractA 40-year-old woman, who had previously received radioactive iodine for hyperthyroidism, presumably due to Graves' disease, subsequently was found to have inappropriately elevated serum TSH and alpha-subunit levels and a pituitary adenoma. Detailed clinical studies revealed marked serum TSH elevations (approximately 100 mU/L) with no circadian variation, but with 7 pulses/24 h. Serum alpha-subunit levels averaged 2.5 micrograms/L, with 13 pulses/24 h. Neither serum TSH nor alpha-subunit responded to TRH stimulation, nor did serum TSH change during dopamine infusion, but alpha-subunit levels did decline slightly. In contrast, during somatostatin infusion, serum TSH declined to 30% of baseline levels, while alpha-subunit levels did not change. Pituitary adenoma tissue obtained at the time of transsphenoidal surgery immunostained weakly with anti-TSH beta serum and strongly with anti-alpha-subunit serum. Northern blot analysis of RNA isolated from the tumor revealed TSH beta and alpha-subunit mRNA levels of normal length, while primer extension analysis showed a major initiation site for the TSH beta gene that appeared to be identical in the tumor and normal pituitary tissue. A second minor upstream start site was detected in the tumor, but it represented less than 1% of transcription compared to the major downstream start site. We conclude that the tumor secreted TSH and alpha-subunit in an abnormal and discordant fashion, but that the TSH gene initiation site appeared to be normal and, therefore, did not explain the observed secretory abnormalities.
AuthorsM H Samuels, W M Wood, D F Gordon, B K Kleinschmidt-DeMasters, K Lillehei, E C Ridgway (Affiliation: Department of Medicine (Endocrinology), University of Colorado Health Sciences Center, Denver 80262.)
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 68 Issue 6 Pg. 1211-5 (Jun 1989) ISSN: 0021-972X UNITED STATES
PMID2723029 (Publication Type: Case Reports, In Vitro, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • RNA, Messenger
  • Thyrotropin
Topics
  • Adenoma (blood, secretion)
  • Adult
  • Autoradiography
  • Female
  • Gene Expression Regulation
  • Histocytochemistry
  • Humans
  • Hyperthyroidism (diagnosis, etiology)
  • Immunochemistry
  • Pituitary Neoplasms (blood, secretion)
  • RNA, Messenger (blood)
  • Thyrotropin (blood, genetics, secretion)
  • Transcription, Genetic