Hyperglucagonemia

Hyperglucagonemia is the condition characterized by abnormally elevated levels of glucagon in the bloodstream. Glucagon, a hormone secreted by pancreatic alpha cells, promotes hepatic glucose production and raises blood glucose during fasting. In hyperglucagonemia, glucagon concentrations exceed the upper limit of normal, with higher levels seen in certain diseases such as pancreatic neuroendocrine tumors or metabolic stress.

Major etiologies include glucagon-secreting pancreatic neuroendocrine tumors (glucagonoma), which produce excessive glucagon and can drive a distinctive syndrome. Other causes include severe liver disease, renal failure, prolonged fasting or malnutrition, and states of insulin deficiency or resistance that disrupt normal glucagon regulation. Some cases reflect a laboratory artifact or interference with immunoassays, or elevated glucagon-like peptides.

In glucagonoma syndrome, necrolytic migratory erythema, weight loss, diabetes mellitus or hyperglycemia, stomatitis, glossitis and cheilitis, anemia, and venous thromboembolism are characteristic. Non-tumor hyperglucagonemia may contribute to hyperglycemia and catabolic states but lacks the full tumor-associated syndrome.

Diagnosis rests on demonstrating fasting hyperglucagonemia and locating the cause. Fasting plasma glucagon measured by immunoassay is compared to the reference range. If elevated, imaging such as contrast-enhanced CT or MRI, and somatostatin receptor imaging may identify a glucagon-secreting tumor. Evaluation includes metabolic and infectious workup and assessment for liver or kidney disease.

Management targets the underlying cause. Surgical resection or medical therapy with somatostatin analogs is used for glucagonoma; diabetes is managed accordingly; skin lesions are treated supportively. In advanced disease, palliative therapies and multidisciplinary care are used. Prognosis depends on etiology and stage, with glucagonoma often presenting with metastasis and requiring ongoing systemic therapy.