Refractory Hyperglycemia in Metastatic Adenocarcinoma: A Case of Suspected Paraneoplastic Hyperglucagonemia

Paraneoplastic syndromes are uncommon manifestations of malignancy that can produce significant metabolic derangements. Paraneoplastic hyperglucagonemia due to non-pancreatic malignancy is particularly rare and may present with refractory hyperglycemia. An 84-year-old female admitted following a fall from standing height was found to have a pathological fracture of cervical spine. Imaging demonstrated a destructive mass involving C5 vertebral body with widespread metastatic disease involving the lungs and liver. Biopsy of the cervical lesion revealed metastatic adenocarcinoma of suspected pancreaticobiliary, upper gastrointestinal, or pulmonary origin. Throughout her hospital course, the patient developed persistent hyperglycemia despite escalating insulin therapy and required intensive insulin management. Further evaluation demonstrated markedly elevated serum glucagon levels of 1,116 pg./mL, while adrenocorticotropic hormone (ACTH) levels remained within normal range. Following surgical debulking of the cervical lesion, the patient’s insulin requirements substantially decreased, with subsequent improvement in glycemic control. The combination of refractory hyperglycemia, markedly elevated glucagon levels, widespread metastatic disease, and decreased insulin requirements following tumor debulking raised suspicion for a paraneoplastic endocrine process involving glucagon excess. However, tumor immunohistochemical staining for glucagon was not performed; serial glucagon measurements were unavailable, and other uncommon causes of insulin resistance, including anti-insulin receptor antibodies, were not evaluated. Therefore, ectopic glucagon secretion could not be definitively established. This case highlights the importance of considering paraneoplastic endocrine syndromes in patients with malignancy and otherwise unexplained worsening hyperglycemia despite insulin therapy.