RESUMO
INTRODUCTION: Hypoglycaemia associated with non-islet cell tumours (NICTH) is a rare entity in patients with extra-pancreatic malignancies, mostly attributed to large mesenchymal or epithelial tumours. Anaplastic large cell lymphoma has not previously been associated with NICTH, making this the first publication of such a report. PATIENT AND METHODS: A 22-year-old, non-diabetic patient was admitted to our department with malaise, itching, night sweats and weight loss. Serum glucose levels at presentation were extremely low, reaching 3 mg/dl at the lowest. Further investigations revealed undetectable blood insulin and C-peptide levels, together with low IGF-1 (34 ng/ml) levels. Inguinal lymph node biopsy showed anaplastic large cell lymphoma, and bone marrow biopsy along with supporting blood tests revealed haemophagocytic lymphohistiocytosis. DISCUSSION: In conjunction with an adequate hyperglycaemic response to intravenous glucagon, all of the above findings indicate hypoglycaemia as a result of overproduction of high molecular weight IGF-2 precursor protein, generally referred to as 'Big IGF-2'. Large solid tumours can occasionally produce loosely bound or free Big IGF-2 molecules which circulate throughout the plasma and bind to insulin as well as IGF receptors, thus increasing glucose intake by body tissues, decreasing the release of glucose to the bloodstream by the liver and causing feedback suppression of insulin, IGF-1 and growth hormone production. Therefore, it is exceptional to find Big IGF-2-related hypoglycaemia in non-solid tumours. Our case shows that, although extremely uncommon, rare instances of NICTH can be attributed to the production of Big IGF-2 in non-solid malignancies including anaplastic large cell lymphoma. LEARNING POINTS: Although extremely rarely, haematological malignancies can produce non-islet cell tumours (NICTH) as a result of IGF-2 and Big IGF-2 secretion.Insulin, C-peptide and IGF-1 levels may be sufficient to diagnose NICTH.
