Prolonged, hypoglycemia induced by acetohexamide (AH) in a patient with non-insulin dependent diabetes mellitus accompanied by primary hypothyroidism was presented.
A 74-year-old man who had been treated with AH (500mg, daily) for diabetes mellitus since 1973 was admitted to our hospital in Oct. 1988 because of hypoglycemic coma. On admission, the level of blood glucose was 20mg/dl. Continuous intravenous administration of 10 per cent glucose solution led to improvement in the mental state on the second day. However, the level of blood glucose remained between 30 to 45mg/dl for four days after admission. On the fifth day, a fasting blood glucose level finally reached 75mg/dl. In a thyroid function test, the serum levels of thyroid hormone showed the following decreases: T3 68ng/dl, T4 2.8μg/dl, free T4 0.3ng/dl, while basal TSH levels increased to 50.3μU/ml. Since anti-thyroid microsomal antibody was positive and thyroid ^99mTc-pertechnetate uptake was slightly elevated, the hypothyroidism in this patient was considered to be caused by chronic thyroiditis. Urinalysis was positive for protein. In a renal function test, the blood urea nitrogen was 26.7mg/dl and creatinine 1.7mg/dl, and creatinine clearance decreased to 22ml/min. After thyroid function returned to euthyroid, creatinine clearance improved (41ml/min).
To clarify the relationship between hypothyroidism and the metabolism of AH, the serum levels of AH and its metabolite hydroxyhexamide (HI) following oral administration of AH (500mg) were evaluated before and after thyroxine replacement therapy. The blood glucose level before therapy was lower than that after therapy, and hypoglycemic symptoms were observed early in the second and third morning after AH administration. There were no changes in the serum levels of AH between the pre-and post-replacement treatment. In contrast, the biological half time of HH before and after treatment was 16 hrs and 13 hrs, respectively. The serum levels of HH decreased more slowly before treatment than after treatment. However, compared to normal subjects, the biological half time of HH in this patient was exceedingly long in both conditions which seemed to arise from renal dysfunction caused by diabetic nephropathy.
These findings suggest that prolonged hypoglycemia in this patient was related to the delayed clearance of HH caused by renal insufficiency associated with hypothyroidism.