Endocrine Abstracts

Introduction: Hypoglycaemia is a rare side-effect of 6-mercaptopurine (6MP) with unclear mechanism(s). The occurrence of hyperinsulinism accompanying the hypoglycaemia is reported here for the first time in children on 6MP for acute lymphoblastic leukaemia (ALL).

Case1: Caucasian female, diagnosed with ALL aged 4 years, was treated under UKALL2003 regime A. During an admission for neutropaenic sepsis, asymptomatic hypoglycaemia was noted pre-breakfast for 3 days. Laboratory glucose was 2.1 mmol/l with raised insulin 33.5 mIU/l on day 1. Full hypoglycaemic screen on day 3 showed glucose 2.3 mmol/l, insulin 36.7 mIU/l, and C-peptide 1087 pmol/l. Remainder of investigations (GH, cortisol, ammonia, lactate, acylcarnitine, free fatty acid, and 3-β-hydroxybutyrate) were normal. Synacthen stimulation test excluded primary adrenal disorders (peak cortisol 1124 mmol/l). Hypoglycaemia resolved after 6MP was discontinued. Two pre-breakfast hypoglycaemia (both 2.3 mmol/l), associated with reduced oral intake during illnesses, were recorded the following month while she was back on 6MP.

Case 2: Female of Bangladeshi origin, diagnosed with ALL, aged 4 years was treated under UKALL2003 regime A, modified to prednisolone due to dexamethasone toxicity. One year into treatment, she presented with symptomatic hypoglycaemia (dizziness, vomiting, and glucose 2.6 mmol/l) while fasted for a procedure under general anaesthesia. Continuous glucose monitoring revealed nocturnal hypoglycaemia (BM <2.6 mmol/l) which continued despite larger evening meals and slow release carbohydrate snacks pre-bed. Hypoglycaemic investigations showed glucose 2.6 mmol/l, insulin 11.5 mIU/l, and C-peptide 520 pmol/l. Remainder of investigations (as per case 1) were normal. Blood glucose levels normalised after switching 6MP administration to the morning. Five months later, she represented with hypoglycaemia after 6MP dosage increase, which resolved after reduction.

Discussion: Hyperinsulinism is a possible mechanism of 6MP associated hypoglycaemia. Paediatricians need to be aware of hypoglycaemic risk in young ALL patients on 6MP treatment. Glucose levels should be actively monitored during periods of fast or reduced oral intake.