Effects of Thyroid-Stimulating Hormone on Human Thyroid Carcinoma and Adjacent Normal Tissue*

Abstract

Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered.

Thyrotrophin stimulation of adenylate cyclase and iodine uptake in human differentiated thyroid cancer

“…In cold thyroid adenoma, an intact TSH-responsive AC associated with defective iodine metabolism has been observed (De Rubertis et al 1972). In thyroid carcinoma, a marked variability from tumour to tumour was reported by Field et al (1978), despite similar morphological appearances.…”

“…Varying degrees of impairment of iodine meta¬ bolism have been found in human differentiated thyroid carcinomas (Triantaphyllidis & Tubiana 1956;Valenta et al 1968; Lemarchand-Béraud et al 1969;Pochin 1969; Thomas (Ichikawa et al 1976;Takahashi et al 1978;Clark & Castner 1979), in TSH stimulation of adenylate cyclase (Sand et al 1976;Field et al 1978; Thomas-Morvan 1978), or in both (Carayon etal. 1978(Carayon etal.…”

Modification of the amounts of G proteins and of the activity of adenylyl cyclase in human benign thyroid tumours

“…In thyroid carci¬ noma the response to TSH was greater than that of normal tissue (Orgiazzi, Munari, Rostagnat et al 1977;Clark et al 1981;Clark, Gerend, Goretzki & Nissenson, 1983;Clark et al 1984;Clark & Gerend, 1985), qualitatively similar to that of normal tissue (Field, Bloom, Chou et al 1978) or absent in undifferentiated thyroid carcinoma (Abe et al 1981) or in papillary carcinoma (Chang et al 1988). It is also well established that the TSH-stimulated adenylyl cyclase activity was generally lower in or absent from thyroid toxic adenoma compared with normal tissue sur¬ rounding the nodule (Tocafondi, Rotella, Tanini et al 1979;Van Sande, Mockel, Boeymans et al, 1980;Thomas et al 1984;Van Sande, Lamy, Lecocq et al 1988).…”

Prolonged Chronic Graft-versus-Host Disease is a Risk Factor for Thyroid Failure in Long-Term Survivors After Matched Sibling Donor Stem Cell Transplantation for Hematologic Malignancies

“…6;17;18 Initially we and others 6 did not treat subclinical hypothyroidism, in contrast to other investigators. 18 An important reason to treat subclinical hypothyroidism is to diminish the risk of thyroid adenoma and carcinoma 19;20 and in young patients to prevent growth failure and delayed development. Stem cell transplant recipients are at increased risk of developing second malignancies 21;22 An EBMT study showed thyroid cancer was the most common secondary cancer with a standardized incidence ratio (SIR) approaching 50 among long term survivors after SCT.…”