Endocrine Abstracts

Background

Although rare, hypoglycaemia in patients without history of diabetes should be recognized and studied, in order to reduce associated morbidity. Cotrimoxazole (TMP/SMX) is commonly used in clinical practice and hypoglycaemia is a rare side effect associated with its use. Literature advocates that this effect is due to the fact that SMX has the same sulphanilamide structural group of sulfonylurea, mimicking the hypoglycaemic effect by stimulating pancreatic insulin secretion.

Clinical case

A 62-year-old black woman, admitted in infectious diseases ward, with a diagnosis of cerebral toxoplasmosis. Previous history of bilateral nephrectomy and kidney transplantation 8 years ago, under treatment with tacrolimus 4 mg id and prednisolone 5 mg id, with 25.4 ml/min/1.73 m² eGFR. She started pyrimethamine 75 mg od and sulfadiazine 1500 mg 4 times a day, which were discontinued due to vomiting at day 21. A switch to TMP/SMX (1920 mg 3/day) was performed, with good tolerance. On 6^th day after starting this drug, the patient showed generalized tonic-clonic seizure and a blood glucose level of 21 mg/dl. Evaluation by endocrinology was requested for severe hypoglycaemia in a patient without diabetes. A 10% glucose infusion was initiated, but the patient maintained hypoglycaemia (capillary blood glucose ~ 30–41 mg/dl), requiring administration of an intravenous bolus of hypertonic glucose solution and also glucagon. The hypothesis of acute adrenal insufficiency and pituitary apoplexy were excluded. Retrospectively, an episode of hypoglycaemia was detected in routine analytical study, on the 3rd day after the beginning of TMP/SMX. Insulin and C-peptide levels were measured, with values of 99 uUI/ml (< 30) and 20 ng/ml (1–7.6), respectively, which were compatible with endogenous hyperinsulinism. TMP/SMX was suspended by the suspicion of iatrogenic hypoglycaemia. Glucose infusion was maintained for 2 days, without any further hypoglycaemic episodes. Ten days after the suspension of TMP/SMX, insulin (8.5 uUI/ml) and C-peptide (5.8 ng/ml) levels were back to normal.

Conclusion

High levels of C-peptide during the episode of hypoglycaemia confirm endogenous insulin secretion. TMP/SMX associated hypoglycaemia can occur in the presence of risk factors, such as high dosage and compromised renal function. Renal dysfunction can lead to decreased drug clearance, leading to gradual accumulation and manifestation of symptoms after a few days. After suspension, difficulty in reversing the hypoglycaemia was not only due to the half-life extension but also because of dose-dependent side effect.