Insulin metabolism in hypothyroidism

Insulin resistance has been invoked to explain the glucose intolerance observed in hypothyroid patients. This possibility was studied by determining fractional and metabolic clearances of intravenously administered porcine crystalline insulin (0.1 U./kg.) and its effect on plasma glucose concentration in ten hypothyroid patients, ten normal subjects, and six treated euthyroid patients. Following administration of porcine insulin, serum immunoreactive insulin concentrations during the period of observation were similar in hypothyroid patients, in normal control subjects, and in treated euthyroid patients. Similarly, no significant differences in the mean half-life, distribution space, or fractional and metabolic clearances of insulin were observed among any of the three groups. In response to insulin administration, plasma glucose concentrations declined to the nadir of 36 +/- 4, 43 +/- 3, and 38 +/- 4 mg. per 100 ml. in hypothyroid patients, normal control subjects, and treated euthyroid patients, respectively. Thereafter, plasma glucose steadily increased and approached the baseline value at ninety minutes in normal subjects and treated euthyroid patients. In contrast, the plasma glucose values remained significantly lower than the baseline for the rest of the procedure in hypothyroid patients. The present study demonstrates that there is no evidence of resistance to the action of insulin in hypothyroid patients. The observation of prolonged hypoglycemic action of exogenously administered insulin in hypothyroid patients might in fact suggest increased sensitivity to insulin action. These findings indicate that glucose intolerance of the hypothyroid state is not characterized by insulin resistance.