Thyroid hormone resistance without mutations in thyroid hormone receptor beta

Abstract

Resistance to thyroid hormone (RTH) is a rare autosomal dominant disorder that leads to elevated free thyroid hormone levels in the presence of normal or increased serum thyroid-stimulating hormone (TSH) concentrations if it is generalized because both the pituitary and peripheral tissues are then partially resistant. In approximately 85% of patients with RTH, mutations in the thyroid hormone receptor beta (TR beta) gene can be identified. A 68-year-old German man presented for surgical hernia repair. He was found to have elevated free T3 and T4 plasma concentrations in coexistence with goiter, unsuppressed TSH, arterial hypertension, and arthritis urica/gout. An electrocardiogram showed a normal sinus rhythm with 69 beats per minute. There were neither signs or symptoms of hyper- or hypothyroidism nor psychological abnormalities. Generalized RTH was suspected. Generalized RTH should be considered in patients presenting with elevated free thyroid hormone levels and normal or increased TSH concentrations, especially if these patients appear clinically euthyroid. Signs and symptoms of hyper- and hypothyroidism should be evaluated to assure that these patients are candidates for surgical procedures such as hernia repair. Subsequent mutation analysis of the TR beta gene should be conducted to help identify family members. In approximately 15% of patients, mutations in the TR beta gene cannot be identified and raise the possibility of mosaicism.