Clinical and molecular studies of a thyrotropin-secreting pituitary adenoma.
A 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.
Samuels
M H
MH
Department of Medicine (Endocrinology), University of Colorado Health Sciences Center, Denver 80262.
Wood
W M
WM
Gordon
D F
DF
Kleinschmidt-DeMasters
B K
BK
Lillehei
K
K
Ridgway
E C
EC
D000236:Adenoma / Q000097:blood / Q000378:metabolism*; D000328:Adult; D001345:Autoradiography; D005260:Female; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D006801:Humans; D006980:Hyperthyroidism / Q000175:diagnosis / Q000209:etiology; D007120:Immunochemistry; D066298:In Vitro Techniques; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000097:blood; D013972:Thyrotropin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013972:Thyrotropin