Can glucagon cause tissue necrosis?

Can Glucagon Cause Tissue Necrosis?

Yes, glucagon can cause tissue necrosis in the form of necrolytic migratory erythema (NME), particularly when administered as a continuous infusion. This is clearly documented in the FDA drug label for glucagon 1.

Evidence for Glucagon-Induced Tissue Necrosis

FDA Drug Label Evidence

The FDA drug label for glucagon explicitly warns about necrolytic migratory erythema (NME) as a potential adverse effect:

• NME is described as "a skin rash commonly associated with glucagonomas and characterized by scaly, pruritic erythematous plaques, bullae, and erosions" 1
• This condition has been reported in post-marketing surveillance following continuous glucagon infusion 1
• The FDA label states that "NME lesions may affect the face, groin, perineum and legs or be more widespread" 1
• In reported cases, NME resolved with discontinuation of glucagon, and treatment with corticosteroids was not effective 1

Clinical Guidelines Evidence

The 2005 guidelines for management of gastroenteropancreatic neuroendocrine tumors specifically mention that glucagonomas can cause necrolytic migratory erythema:

• "The characteristic rash of necrolytic migratory erythema can be life threatening" in patients with glucagonoma 2
• This indicates that excessive glucagon levels (whether from endogenous production or exogenous administration) can lead to tissue necrosis

Mechanism and Clinical Presentation

Necrolytic migratory erythema appears to be related to metabolic disturbances caused by glucagon excess:

• Excessive stimulation of metabolic pathways by hyperglucagonemia leads to hypoaminoacidemia, which contributes to NME pathogenesis 3
• The condition presents as a characteristic skin rash with scaly, pruritic erythematous plaques, bullae, and erosions 1
• The rash can affect multiple body areas including the face, groin, perineum, and legs 1

Management of Glucagon-Induced Tissue Necrosis

If necrolytic migratory erythema occurs during glucagon therapy:

1. Discontinue the glucagon infusion - This is the primary intervention as NME typically resolves with discontinuation of glucagon 1
2. Consider the risk-benefit ratio - The FDA label advises to "consider whether the benefits of continuous glucagon infusion outweigh the risks" 1
3. Monitor for resolution - NME typically resolves after discontinuation of glucagon 1
4. Note that corticosteroid treatment is generally ineffective for glucagon-induced NME 1

Risk Factors and Considerations

Certain clinical scenarios may increase the risk of tissue necrosis with glucagon:

• Continuous infusion appears to pose a higher risk than bolus administration 1
• Patients with pre-existing metabolic disorders may be at increased risk
• Patients receiving glucagon for beta-blocker or calcium channel blocker overdose should be monitored for skin changes 4

Conclusion

When administering glucagon, especially as a continuous infusion, healthcare providers should:

• Monitor patients for skin changes suggestive of NME
• Be aware that this is a documented adverse effect in the FDA label
• Recognize that discontinuation of glucagon is the most effective treatment if NME occurs
• Consider alternative therapies if NME develops during treatment with glucagon