Endocrine Abstracts

Introduction: Non-islet cell tumour hypoglycaemia (NICTH) is an uncommon but serious complication of disseminated malignancy. The underlying aetiology of hypoglycaemia is tumoral overproduction of IGF2, which results in stimulation of insulin receptors and increased glucose utilization. Extensive tumour burden involving the liver and adrenal glands can also cause severe hypoglycaemia.

Case report: An 80-year-old man presented acutely in an unresponsive state. Capillary glucose was recorded as 1.1 mmol/l. He had no history of diabetes and had no access to oral hypoglycaemic agents. Marked hepatomegaly, deranged liver functions (ALT 48 U/l, ALP 894 U/l, GGT 1262 U/l) and coagulopathy (prothrombin time 15.8 s) were noted. Abdominal ultrasound showed hepatic metastases and subsequent staging CT scan confirmed a primary colorectal malignancy with extensive hepatic metastases.

Severe hypoglycaemia was initially managed with a continuous 20% dextrose infusion. Diazoxide 200 mg BD was initiated but despite this and concurrent dextrose, capillary glucose remained low (<4 mmol/l). Prednisolone 60 mg once daily and subcutaneous octreotide 50 μg three times a day were subsequently initiated but despite this hypoglycaemia proved difficult to control. Serum C-peptide (<0.10 nmol/l) and Insulin (<1.0) were appropriately suppressed in keeping with NICTH. Adrenal insufficiency was excluded as a potential cause of hypoglycaemia. Despite maximal combined therapy, hypoglycaemia proved refractory and the patient succumbed to his illness.

Conclusion: NICTH is a major complication of malignancy particularly if associated with hepatic metastases. The aetiology is multi-factorial and includes reduced hepatic glycogen reserves, nutritional deficiency due to tumour induced cachexia and ectopic production of IGF2 which activates insulin receptors and promotes glucose utilization. Refractory hypoglycaemia in this context necessitates combination drug therapy but is a significant therapeutic challenge with a poor prognosis.