Endocrine Abstracts

Introduction: α 19-year-old female patient with no past medical history presented with multiple collapses following exercise due to hypoglycaemia. From the history it transpired that she had had previous symptoms consistent with hypoglycaemia on multiple occasions, with no relation to fasting or food or a specific diurnal or nocturnal pattern. The two most severe episodes (requiring paramedic treatment) were in the recovery period from anaerobic exercise. Her body mass index (BMI) is 23.4 kg/m2. She does not drink alcohol or take any illicit medications. Her half-brother has type 1 diabetes (T1DM) but lives away; no other family member has diabetes or known hypoglycaemia-related disease.

Investigations: Her pituitary screen, fasting gut peptides and prolonged oral glucose test (OGTT) were normal. Her 72-hr fast achieved hypoglycaemia with low insulin and C-peptide levels, excluding insulinoma. She had amino acids sent off for organic acids and this was reported as normal excluding aminoacidopathy, with a normal IgF1/IgF2 ratio and normal zinc 8 transporter, GAD and IA2 antibodies, too. Finally, genetic causes of hyperinsulinaemia (ABCC8, AKT2, CACNA1D, CREBBP, EP300, FOXA2, GCK, GLUD1, GPC3, HADH, HK1, HNF1A, HNF4A, INSR, KCNJ11, KDM6A, KMT2D, MAFA, NSD1, PHOX2B, PMM2, SLC16A1 and TRMT10A genes) were also negative. An ultrasound of her liver was of normal echogenicity and appearance. A repeat 72-hr fast to check insulin, C-peptide, insulin analogues, sulphonyluria screen, pH, lactate, pyruvate/lactate ratio when plasma glucose <2.5 mmol/lwas abandoned due to influenza A within 12 hours of admission. A further 72-hr fast is planned. At this point, it was theorised her symptoms could be explained by exercise-induced hyperinsulinaemia or a genetic defect in various metabolic pathways (gluconeogenesis, ketogenesis, or fatty acid oxidation disorder). To that end, an exercise test was organised with pH, lactate, pyruvate and glucose measurements; however, the patient did not develop hypoglycaemia. A continuous glucose monitoring system with an integrated low glucose alarm (Dexcom) has shown considerable variability with some days without hypoglycaemia, and others regularly <3 mmol/ldespite regular carbohydrate and sugar intake. The patient avoids anaerobic exercise for fear of hypoglycaemia, which means she cannot do lifeguarding, her main hobby.

Conclusion: This is a rare case of disabling hypoglycaemia without a confirmed cause. It highlights the merits of continuous glucose monitoring outside of diabetes and places emphasis on the need to consider additional metabolic causes; a pragmatic approach to treatment is likely to be needed.