Insulin action is altered in hyperthyroidism

We have assessed insulin action in five hyperthyroid patients, pre- and post-radioactive iodine therapy using oral glucose tolerance tests, monocyte insulin binding and dose response curves generated with the euglycemic clamp technique. All patients had become euthyroid after radioactive iodine therapy with a decline in the plasma free T4 index level from 278 +/- 43 to 105 +/- 9. Fasting glucose was modestly, but significantly elevated in the thyrotoxic patients compared to when they were rendered euthyroid (p less than 0.05). Oral glucose tolerance tests showed no difference in either glucose or insulin values after the glucose load. Insulin receptor binding and affinity were similar regardless of their thyroid status. Hepatic glucose production in the basal state was elevated in the thyrotoxic patients, 61 +/- 5 mg/M2/min vs 49 +/- 3 mg/M2/min (p less than 0.05). At the lowest level of insulin infusion no difference in glucose disposal was found. At maximum insulin concentrations the glucose disposal rate was enhanced in the thyrotoxic patients, 686 +/- 19 vs 567 +/- 26 mg/M2/min (p less than 0.01). These results indicate that higher fasting glucose levels may result from increased hepatic glucose production in thyrotoxicosis, but as indicated by the oral glucose tolerance tests, this defect in insulin action is usually of minor significance. However, insulin responsiveness measured at pharmacological insulin levels is augmented in thyrotoxicosis.