Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall's syndrome

Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the alpha-subunit of the insulin receptor. The associated insulin-resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1.0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.