Endocrine Abstracts

Introduction: Non-islet cell tumor induced hypoglycemia (NICTH) is a paraneoplastic phenomenon involving many types of tumors. It is associated with the secretion of incompletely processed precursors of IGF-2 resulting in a persistent insulin-like activity and hypoglycemia. Most commonly, IGF-2–linked hypoglycemia has been observed in patients with solid mesenchymal or epithelial tumors. Typically, elevated IGF-2 levels are associated with suppressed plasma levels of insulin, IGF-1, and GH. Although the true incidence is unknown, the more recent epidemiologic data suggest that IGF-2-oma tumors are more frequent than previously thought.

Clinical case: A 60-year-old man was admitted in the emergency room with severe asthenia, weigh loss and abdominal pain. Over the last three years he had lost 20 kg in weight. His past medical history was irrelevant. On admission, the physical examination revealed an emaciated patient with a palpable and bulky abdominal mass. Abdominal CT scan showed a very large retroperitoneal tumor, measuring 29.9 cm of greater diameter, with necrotic areas and calcifications of the matrix, occupying virtually the entire abdominal cavity, which histologically proved to be a leiomyosarcoma. Fasting recurrent hypoglycemias associated with neuroglycopenic symptoms were recorded during hospitalization, despite intravenous dextrose. Biochemical investigations revealed: plasma glucose 48 mg/dl with suppressed serum insulin (0.5 μU/ml, normal 2.6–24.9 μU/ml) and C-peptide (0.86 ng/ml, normal 1.1–4.4 ng/ml). Spontaneous hypokalemia was documented (3.2 mmol/l, normal 3.5–5.00 mmol/L). The patient had normal renal and hepatic tests. Thyroid function and serum morning cortisol levels were normal. IGF-1 and IGFBP3 were below normal (8 ng/ml [normal 97–292] and 0.602 mg/dl [normal 3.40–6.90], respectively). β-hydroxybutyrate and IGF-2 levels were not evaluated. The hypothesis of IGF-2-oma was placed and prednisolone 40 mg/day was started with an improvement on glycemic levels. Unfortunately, few days later, the patient suffered from coronary heart failure and died.

Discussion: IGF-2-oma should be considered in unwell patients with very large mesenchymal or epithelial tumors suffering from hypoglycaemic episodes, when insulin and C-peptide levels are suppressed. In our patient, despite the unavailability of high IGF-2 confirmatory levels, GH-dependent proteins IGF-1 and IGFBP-3 reduced levels represent useful additional markers as well as the occurrence of hypokalemia, that is often present and associated with the insulin-like activity of IGF-2.