Case History: An 81-year-old gentleman was brought to A&E by ambulance after being found to be hypoglycaemic at home by paramedics. His wife reported that he experienced unsteadiness and slurred speech after waking up in the morning and she called the emergency number. On arrival of paramedics, his capillary blood glucose was found to be 1.2 mmol/l and he was administered intravenous dextrose. He also had a couple of similar episodes which were resolved with food. He is not known to have diabetes or alcohol abuse. He had a past medical history of right lung fibrous mesothelioma for which he underwent radiotherapy in 2016 and had been under surveillance. He had several comorbidities including atrial fibrillation, heart failure and hypertension. His medications included Amiodarone, Bisoprolol, furosemide, Spironolactone, Ramipril and Edoxaban.
Investigations: As part of an initial work-up, a CT scan of the chest revealed a right hemi-thoracic neoplasm which had marginally increased in size, when compared to imaging organised 6 months earlier. Further laboratory investigations revealed a normal response to short SynActhen test and normal thyroid function. His prolonged supervised fasting test, confirmed spontaneous hypoglycaemia with concomitant undetectable insulin, C-peptide and pro- insulin. Having excluded islet cell tumour as a cause of hypoglycaemia, we requested IGF-2/IGF-1 ratio, which was elevated at 12.7, consistent with the diagnosis of non-islet cell tumour.
Treatment: He was prescribed Prednisolone 10 mg OD at bedtime, and he was asked to carry out pre-meal and mid night capillary glucose testing to establish the dose of steroids. He responded well and his hypoglycaemic episodes were abolished with steroid treatment.
Discussion: Non-islet cell tumour hypoglycaemia (NICTH) is a rare cause of hypoglycaemia which is due to excessive secretion of insulin-like growth factor (IGF)-2 or pro IGF-2. These molecules can activate the insulin receptor and can cause hypoglycaemia. NICTH is mostly seen in epithelial and mesenchymal tumours. Complete tumour resection is curative but is often delayed or unfeasible. For patients with advanced disease, radiation, and/or chemotherapy have been shown to reduce hypoglycaemia, although to a lesser degree. If patients are not suitable for surgery or when hypoglycaemia persists after surgery, radiation, chemotherapy, medical therapy with glucocorticoids or recombinant GH have been utilized. Glucocorticoids act by promoting hepatic gluconeogenesis, lipolysis, and reducing peripheral glucose uptake. Glucocorticoids also help to decrease the levels of pro-IGF-2 either by decreased tumour production or by clearance.