Endocrine Abstracts

Background: Recent studies have linked both PEG -asparaginase and 6 mercaptopurine [6MP] with hypoglycemia, However, the risk of hypoglycemia associated with ALL therapy is not well understood, despite its potential to cause adverse events in children. We report three cases in Wales.

Case 1: An 18-month-old female with pre-B ALL presented with hypoglycemia during the induction phase of chemotherapy [PEG-asparaginase and high-dose dexamethasone] Hypoglycemic screen [HOG] showed hypoglycemia [2.3 mmol/l], inappropriately borderline insulin [3.0 mU/l], high C peptide [413 pmol/l] inappropriately low beta hydroxybutyrate [<0.01], high non esterified fatty acid [3.66 mmol/l] and markedly low Cortisol [<28 nmol/l]. Short Synacthen test not done as she still on induction phase but hypoglycemia resolved after initiating hydrocortisone.

Case 2: A 12 yr old male with T -cell Lymphoblastic Lymphoma presented with hypoglycemia during his maintenance chemotherapy [ daily 6mp, weekly methotrexate and monthly steroids] when he was fasting. HOG screen showed Hypoglycemia [2.1 mmol/l], inappropriately high insulin [5.4 mU/l] and high C peptide [511 pmol/l], appropriately high beta hydroxybutyrate [0.75 mmol] and high non esterified fatty acid [1.59 mmol/l]. Blood results returned to normal once maintenance chemotherapy was stopped.

Case 3: An 8 years male with B-cell ALL presented with hypoglycemia during his maintenance chemotherapy when he was fasting. HOG screen showed hypoglycaemia [1.2 mmol/l], appropriately low insulin [<3mU/l] and low C peptide [85 pmol/l]. High beta hydroxybutyrate [0.83 mmol/l] and high non esterified fatty acid [3.39 mmol/l]. Still on maintenance chemotherapy.

Conclusion: Case reports in the literature suggest that hypoglycemia associated with PEG-asparaginase is hypoketotic and likely secondary to hyperinsulinism. The mechanism of action of asparaginase is to convert asparagine to aspartic acid. However, asparaginase is also shown to convert glutamine to glutamic acid. Glutamate is a known stimulator of insulin secretion. Ketotic hypoglycaemia is associated with 6-MP without a clear aetiology. It is unclear from our case the cause of low cortisol this required further investigations/study. These findings highlight the importance of counselling about the risk of, and monitoring for, hypoglycemia, particularly in young children.