Defective Thyroid Hormone Feedback Regulation in the Syndrome of Peripheral Resistance to Thyroid Hormone*

We have previously described an inherited syndrome best explained as peripheral resistance to the action of thyroid hormone. So far, studies were carried out principally in two affected siblings, the third being too young. These studies concentrated on the demonstration of authenticity of the circulating thyroid hormones, their metabolism, the lack of metabolic response to the administration of supraphysiological doses of thyroid hormones and their analogs, and the abnormalities of the T3 nuclear receptors. The present communication deals with the youngest sibling and the T3 feedback regulation of his pituitary, which is not previously assessed. The complete syndrome, including all somatic defects, developed in the youngest sibling, who was suspected of being affected at birth. TSH responded normally to the administration of TRH despite the presence in serum of T4, free T4, and T3 in concentrations 3-fold above the mean normal range. The administration of T3, producing a further rise in the serum T3 conce...