During the initial phase of recovery from a chronic overexposure to thyroid hormones, plasma TSH does not increase after the injection of TRH despite normal or low circulating level of T4 and/or T3. To study the possible causes underlying this observation, rats were treated for weeks with very high doses of T4 plus T3, at the end of which age-paired controls and hyperthyroid rats were stimulated with TRH. This test was carried out at different intervals up to 7 days after administration of the last high dose of T4 plus T3. Plasma and pituitary TSH, T4, and T3 were measured by specific RIAs. Chronic treatment with high doses of thyroid hormone resulted in a marked depletion of pituitary TSH stores to less than 1% of the control value. TSH stores did not increase until 4-5 days after withdrawal of the thyroid hormone treatment, though circulating T4 and T3 levels generally had become undetectable by day 3. An increase in circulating TSH and a response to TRH were also not observed until days 4-5 after interruption of the chronic tretment. Present data show that the lack of response to TRH is not due to a persistence of high intrapituitary T4 and/or T3 content. Changes in pituitary T4 and T3 followed a pattern which was similar to, but not identical with, the changes observed in circulating T4 and T3, the concentrations of these iodothyronines decreased very rapidly after interruption of treatment, reaching very low levels on withdrawal days 3 and 4. Levels had not incresed to normal values by the seventh day of the withdrawal period. The phase of low plasma T4 and T3 concentrations which follows interruption of chronic overexposure to thyroid hormones is not due to unresponsiveness of the thyroid to TSH; thyroidal secretion resumes as soon as plasma TSH levels increase to normal. Chronic overexposure appears to have activated excretory and degradative mechanisms which contribute to the ensuing phase of thyroid hormone depletion.

Peer Reviewed