Endocrine Abstracts

Case history: A 23-year-old Caucasian nurse presented with six months of frequent recurrent symptomatic hypoglycaemic episodes with capillary blood glucose ranging between 1.2 and 3.5 mmol/l and symptoms improving after a carbohydrate snack or a drink. The episodes were more likely to occur during fasting state and after excess physical activities. A careful history excluded intake of any off-prescription medications, dfrugs or psychosocial problem.

Investigations: FBC, U&E, LFTs, bone profile, prolactin, IGF-1, LH, FSH, free T4, TSH, random and 0900 h cortisol, short synacthen test, 72-hour fasting, 5 hour OGTT, mixed meal test, coeliac screening, plasm metanephrines, IGF1:IGF2 ratio, insulin antibodies, fasting gut peptides, amino acids carnitines, ammonia, lactate, glycogen storage disorder genetic testing. Urine metabolic and organic acid screening, 24-hour urine 5HIAA, sulphonylureas screening. MRI pancreas, small bowel, abdomen, neck. CT thorax.

Results and treatment: All above routine and other investigations, urine tests, pituitary hormone profile and radiological investigations were normal. During the first 72-hour fasting, she developed symptomatic hypoglycaemia (plasma glucose 1.8 mmol/l) and concomitant levels of insulin (10 mmol/l) and C-peptide (<94 pmol/l) were appropriately suppressed. Blood sulphonylurea screen during hypoglycaemia was negative. During the second 72-hour fasting, her lowest plasma glucose level was 2.3 mmol/l, and concomitant levels of insulin (11 mmo/l) and C-peptide (125 pmol/l) were appropriately supressed. Corresponding hydroxybutyrate levels were high >3000. IGF-2: IGF-1 ratio (4.0) and insulin antibodies (4.8 Mg/l (<5)) were normal. During the mixed meal test, her blood glucose was at its lowest (3.3 mmol/l) at 150 minutes post meal without any symptoms. A diagnosis of idiopathic hyperketotic hypoglycaemia resulting from some rare yet unidentified enzymatic defects in her glucose metabolism pathway was made. She has been enrolled in the 100,000-genome project. Despite a trial of dietary interventions she continued to suffer from hypoglycaemic episodes significantly affecting her work and quality of life. Therefore, oral hydrocortisone (total 20 mg a day) was initiated on a trial basis on which she showed a significant improvement.

Conclusions and points for discussion: Hypoglycaemic disorders are common especially in young women, where a common diagnosis is reactive hypoglycaemia. However, this case highlights the challenges in investigating and managing hypoglycaemia where a cause is not obvious after extensive investigations. When faced with any rare insulin-independent cause of hypoglycaemia a pragmatic approach to management with diet and, if necessary, pharmacotherapy is crucial in improving symptoms and quality of life.