Hypo- and Hyperthyroidism Caused by Mutations of the TSH Receptor

Abstract

The main function of the thyroid gland is to synthesize, store, and secrete the thyroid hormones T3 and T4. Regulation of this function is achieved primarily through a positive control exerted by the pituitary hormone thyroid stimulating hormone (TSH) and a negative control exerted by iodine. In most physiological circumstances the maintenance of eumetabolism requires steady concentrations of circulating thyroid hormones. This is achieved by a classical chemostat that involves the feedback of thyroid hormones on TSH production. Compared with other endocrine organs, the control of thyroid function is subject to relatively slow changes. The main roles of the regulatory mechanisms are to ensure adequate use of the available iodine in the diet to maintain steady levels of circulating hormones and to protect the thyroid gland and the organism from the toxicity that can result from excessive availability of iodine. Regulation of thyroid function is thus mainly of a “tonic” nature, with virtually no physiological circumstances in which the gland should be put completely at rest. This chapter concentrates on the regulatory actions of thyrotropin via its receptor.