What cancers can cause hyperglycemia?

Cancers That Cause Hyperglycemia

Pancreatic adenocarcinoma and neuroendocrine tumors (particularly insulinomas, glucagonomas) are the primary cancers that can directly cause hyperglycemia through various mechanisms including pancreatic tissue destruction and hormone dysregulation. 1

Pancreatic Cancers

• Pancreatic adenocarcinoma can cause hyperglycemia by destroying insulin-producing beta cells in the pancreas, leading to impaired insulin secretion and subsequent hyperglycemia 1
• Sudden onset of type 2 diabetes in patients over 50 years of age may be an early warning sign of pancreatic cancer and should prompt consideration of this diagnosis, especially when accompanied by weight loss and abdominal symptoms 1
• Pancreatic cancer can cause diabetes even when only a small portion of the pancreas is involved, suggesting mechanisms beyond simple reduction in beta-cell mass 1

Neuroendocrine Tumors

Glucagonomas

• Glucagonomas are pancreatic neuroendocrine tumors that secrete excessive glucagon, directly causing hyperglycemia by antagonizing insulin action 2
• The classic presentation includes the "glucagonoma syndrome" with necrolytic migratory erythema, diabetes mellitus, weight loss, stomatitis, and diarrhea 2
• Diagnosis involves measuring plasma glucagon levels and performing multiphasic CT or MRI in patients with recent-onset diabetes, cachexia, and/or characteristic skin rash 1, 2

Other Neuroendocrine Considerations

• Insulinomas, while typically causing hypoglycemia, can paradoxically cause hyperglycemia in certain contexts, particularly during treatment with somatostatin analogs like octreotide 1
• Octreotide should be used with caution in patients with insulinoma as it can suppress counterregulatory hormones (growth hormone, glucagon, catecholamines), potentially worsening glycemic control 1

Endocrine-Related Cancers

• Several hormone-secreting tumors can cause hyperglycemia through insulin antagonism 1:
  • Acromegaly (growth hormone-secreting pituitary tumors)
  • Cushing's syndrome (cortisol-producing adrenal tumors or ACTH-producing tumors)
  • Glucagonomas (as discussed above)
  • Pheochromocytomas (catecholamine-secreting tumors)
• Somatostatinomas and aldosteronoma-induced hypokalemia can cause diabetes partly by inhibiting insulin secretion 1

Cancer Treatment-Related Hyperglycemia

• Corticosteroids used in cancer treatment commonly cause hyperglycemia through multiple mechanisms 3:
  • Deterioration of insulin secretion by pancreatic beta cells
  • Increased insulin resistance in peripheral tissues
  • Enhanced hepatic gluconeogenesis
  • Increased renal glucose reabsorption
• Immune checkpoint inhibitors can cause checkpoint inhibitor-associated diabetes mellitus (CIADM), which presents similarly to type 1 diabetes with autoimmune destruction of beta cells 1
• Cancer patients with insulin resistance may benefit from increasing the ratio of fat to carbohydrates in their diet to reduce glycemic load 1

Clinical Implications and Management

• Weight-losing cancer patients often develop insulin resistance, which impairs glucose uptake and oxidation in muscle cells 1
• Hyperglycemia in cancer patients can lead to increased risk of infections, poor wound healing, and worse clinical outcomes 4, 5
• Monitoring recommendations for patients on immune checkpoint inhibitors should be tailored to their risk of developing significant hyperglycemia 1
• Patients with pre-existing diabetes and cancer should have careful glucose monitoring, particularly when starting treatments like corticosteroids 1, 3

Pathophysiological Connections

• Chronic hyperglycemia may create a tumor-favorable microenvironment through inflammation and immune dysregulation 6
• Hyperglycemia provides energy to cancer cells and may contribute to tumor growth and progression 5, 7
• The association between diabetes and cancer risk appears to be bidirectional - diabetes increases cancer risk, and some cancers cause diabetes 8, 7

When evaluating a patient with new-onset hyperglycemia, clinicians should consider underlying malignancy, particularly pancreatic cancer or neuroendocrine tumors, especially in patients over 50 years with unexplained weight loss or other concerning symptoms.