Altered Interaction Between Triiodothyronine and its Nuclear Receptors in Absence of Cortisol - a Proposed Mechanism for Increased Thyrotropin Secretion in Corticosteroid Deficiency States

. Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism, and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison's disease. In the latter condition, thyrotropin secretion is increased: this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits. Therefore, a possible role of Cortisol in interaction between triiodothyronine and its nuclear receptors was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure. The affinity of these receptors was found to be decreased, by more than 50% on average, in the absence of Cortisol treatments. This change was promptly corrected upon resumption of therapy. The number of binding sites was not significantly modified. The influence of Cortisol on thyroid hormone receptors discussed here might account for the clinical observations mentioned above.