Recurrent hypoglycaemia and a slowly rising hemidiaphragm: A case report.

A 92-year-old man presented to the hospital with recurrent hypoglycemia with a chronically raised right hemidiaphragm. A CT thorax-abdomen-pelvis showed a large abdominal mass. A ‘big’ IGF-2 secreting non-islet cell tumour was suspected and confirmed. The patient was treated with low dose prednisolone.

Hypoglycaemic crisis induced by non-islet cell tumours in two dogs

Two dogs were admitted for the diagnosis and treatment of neoplasia (a hepatic and a mammary tumour, respectively), lethargy, quadriparesis and abnormal mentation with hypoglycaemia. The blood analyses showed severe hypoglycaemia (1.32 and 1.60 mmol/l, respectively). Although prompt treatment, including intravenous administration of dextrose, was initiated, the blood glucose concentrations were not restored to a normal range. After the diagnostic procedures, no aetiology other than the hepatic tumour identified by the abdominal radiography and ultrasonography, and a mammary tumour that might have caused the hypoglycaemia, were identified. Because there was a high suspicion of non-islet cell tumour-induced hypoglycaemia as a paraneoplastic syndrome, the dogs underwent a hepatic lobectomy and total mastectomy with an ovariohysterectomy, respectively. Within 12 hours after surgery, the blood glucose concentrations of both cases had normalised, even without the administration of dextrose. The histopathological examinations identified a hepatocellular adenoma and a mammary carcinoma, respectively. The endocrine analysis of the serum at admission revealed low serum insulin concentrations (< 1.44 pmol/l) and high serum concentrations of insulin-like growth factor 2 in both dogs. Therefore, the diagnosis in both dogs was confirmed to be non-islet cell tumour-induced hypoglycaemia. Both dogs remained alive without the recurrence of hypoglycaemia 24 months later. Previously, the administration of intravenous dextrose has been considered as the initial treatment in dogs with hypoglycaemia; however, this can temporarily ameliorate the clinical signs related to the non-islet cell tumour-induced hypoglycaemia and help the anaesthesia for the surgical tumour resection as an emergency. Therefore, the definitive treatment of non-islet cell tumour-induced hypoglycaemia might be rapid surgical intervention, which can be associated with good prognosis in dogs with severe non-islet cell tumour-induced hypoglycaemia.

Non-islet cell tumour hypoglycaemia in a patient with a well-differentiated gastric neuroendocrine tumour

A 61-year-old man, without noteworthy medical history, presented with complaints of progressive fatigue and flushes. Diagnostic imaging revealed a large tumour in the stomach with liver metastases, and histopathological examination showed a well-differentiated gastric neuroendocrine tumour (NET). After chemotherapy, everolimus was administered, and upon progression, PD-1 inhibitor PDR001 was started. Two weeks after the first gift, he was admitted with loss of consciousness and a blood glucose level of 1.6 mmol/L. Plasma insulin was below 0.5 mU/L, C-peptide level was 250 pmol/L, insulin-like growth factor (IGF)-II was 804 ng/mL, and pro-IGF-IIE level was 80 µg/L. Based on the clinical findings, the patient was diagnosed with non-islet cell tumour hypoglycaemia (NICTH) with an overproduction of pro-IGF-IIE and eventually IGF-II due to progressive metastatic well-differentiated gastric NET. NICTH is a very rare condition. It has been reported in several tumour types but has never been described as a consequence of NET.

Non-islet-cell tumour hypoglycaemia in a cat with hepatocellular carcinoma

Case summary An 11-year-old male neutered domestic shorthair cat presented with behavioural changes. Physical examination revealed bradycardia and a cranial abdominal mass. The cat was persistently hypoglycaemic (1.2 mmol/l; reference interval [RI] 3.5–5.5 mmol/l) with decreased fructosamine concentration suggesting chronic hypoglycaemia, and decreased insulin concentration excluding insulinoma. Alanine aminotransferase activity was markedly increased (1219.31 U/l; RI 15–60 U/l). On staging CT a large, multilobulated hepatic mass was identified, with no evidence of metastatic disease. After surgical removal serum glucose concentration and heart rate quickly returned to within the RIs. Histopathology was consistent with a solid-to-trabecular, well-differentiated, hepatocellular carcinoma. There was no recurrence of signs or mass during 8 months of follow-up, and the cat was still alive 20 months after surgery. Relevance and novel information Non-islet-cell tumour hypoglycaemia (NICTH) is a rare but life-threatening paraneoplastic syndrome. In humans, hepatocellular carcinoma is the most common epithelial tumour causing NICTH, but these are uncommon in cats, and associated paraneoplastic hypoglycaemia has not been reported. Possible mechanisms include aberrant secretion of big insulin growth factor 2; however, this could not be confirmed. NICTH should be considered in the differential diagnosis of cats with persistent hypoglycaemia.