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 α-subunit levels and a pituitary adenoma. Detailed clinical studies revealed marked serum TSH elevations (~100 mU/L) with no circadian variation, but with 7 pulses/24 h. Serum α-subunit levels averaged 2.5 μg/L, with 13 pulses/24 h. Neither serum TSH nor α-subunit responded to TRH stimulation, nor did serum TSH change during dopamine infusion, but α-subunit levels did decline slightly. In contrast, during somatostatin infusion, serum TSH declined to 30% of baseline levels, while α-subunit levels did not change. Pituitary adenoma tissue obtained at the time of transsphenoidal surgery immunostained weakly with anti-TSHβ serum and strongly with anti-α-subunit serum. Northern blot analysis of RNA isolated from the tumor revealed TSHβ and α-subunit mRNA levels of normal length, while primer extension analysis showed a major initiation site for the TSHβ gene that appeared to be identical in the tumor and normal pituitary tissue. A second minor up-stream 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 α-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.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Clinical Endocrinology and Metabolism|
|Publication status||Published - 1989|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism