Partial peripheral resistance to thyroid hormone

Abstract

A 33 year old partially thyroidectomized woman was euthyroid when ingesting 500 μg of L-triiodothyronine (T 3) daily. Her condition was evaluated during therapy with daily T 3 doses between 50 and 500 μg. She was hypothyroid and had a markedly subnormal oxygen consumption rate when taking 50 to 100 μg T 3 daily, and oxygen consumption did not increase greatly above predicted normal values despite serum T 3 concentrations up to 3,200 ng/dl. Her pulse rate, blood pressure, systolic time intervals and exercise tolerance changed minimally and remained within the normal range during the different dosage schedules. Urinary creatine and hydroxyproline, indices of muscle and skeletal protein catabolism, increased normally with higher T 3 doses, but serum cholesterol, creatine phosphokinase, calcium and alkaline phosphatase did not change substantially. Basal and thyrotropin-releasing hormone (TRH) stimulated thyrotropin secretion were suppressed during all T 3 doses. The prolactin response to TRH was normal at 50 μg T 3/day and was reduced by higher doses of T 3. Absorption of T 3, serum T 3 protein binding and T 3 metabolic clearance rates were all within normal limits. The findings in this patient are compared to clinical and biochemical findings in 17 previously described patients. The manifestations of peripheral thyroid hormone resistance are quite variable in the organ systems involved and in the degree of involvement. The molecular basis of the abnormality in our patient remains undefined.