Mechanism of hyperglycemia and response to treatment with an inhibitor of fatty acid oxidation in a patient with insulin resistance due to antiinsulin receptor antibodies.

Severe hyperglycemia and insulin resistance due to antiinsulin receptor antibodies developed over a period of 3 months in a 50-yr-old insulin-requiring diabetic patient. The hyperglycemia resulted from overproduction of glucose due to excessive rates of glycogenolysis and gluconeogenesis rather than decreased glucose utilization. Treatment with methyl-2-tetradecylglycidate, an inhibitor of fatty acid oxidation, resulted in a decrease in plasma glucose concentration. This was associated with a decrease in the rate of glucose production due to decreases in both gluconeogenesis and glycogenolysis rates, as well as an increase in the respiratory quotient. Plasma glucose concentrations continued to respond to the drug for the next 2 months until the sudden development of terminal hypoglycemia. The hypoglycemic action of the drug is consistent with the existence of an insulin-independent effect of fatty acid oxidation on glucose metabolism in man.

Pituitary-thyroid regulation in euthyroid patients with Graves' disease previously treated with antithyroid drugs.

To understand why some patients with hyperthyroidism due to Graves' disease remain euthyroid after a course of antithyroid drug therapy, pituitary-thyroid regulation was studied in 20 such patients who had remained well for six months or longer after the withdrawal of antithyroid drugs. Only patients who were clinically euthyroid and had normal serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were studied. Serum TSH responses to thyrotropin-releasing hormone (TRH) and thyroid suppression were determined in all patients. Seven patients had normal responses to both tests. Six patients had a subnormal response to TRH and abnormal suppression. Five patients had a subnormal response to TRH and normal suppression, and two patients had a normal TSH response to TRH and abnormal suppression. There were no differences in the mean serum T4, T3 or TSH concentrations between any of the groups. The mean duration of time after antithyroid drug withdrawal was 19 months in the patients in whom both tests were abnormal, whereas it was 58 months in those in whom both tests were normal and 45 months in those with a subnormal TSH response to TRH and a normal suppression test. Thus, in 13 of the 20 patients studied, various degrees of abnormality of pituitary-thyroid regulation were demonstrable. These results suggest that, in most patients with Graves' disease who remain clinically and biochemically euthyroid after a course of antithyroid drug therapy, the disease persists in a mild or subclinical form.