Melanoma often metastasizes to the adrenal glands. Damage to these glands can cause adrenal insufficiency (Addison’s disease), leading to electrolyte imbalances, including hyperkalemia.
Immunotherapy can cause adrenal insufficiency as a side effect, though it’s less common than some other immune-related issues. This usually happens when checkpoint inhibitors (like nivolumab, pembrolizumab, or ipilimumab) trigger an autoimmune attack on the pituitary gland (hypophysitis) or the adrenal glands themselves.
Adrenal insufficiency (AI) in patients with skin cancer, particularly melanoma, is most commonly associated with immune checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab (anti-PD-1), and ipilimumab (anti-CTLA-4). These treatments can lead to immune-related adverse events (irAEs), including primary or secondary adrenal insufficiency.
Incidence of Adrenal Insufficiency in Skin Cancer Patients
• Primary adrenal insufficiency (PAI) – Addisons Disease
Less common but can occur due to direct adrenal gland inflammation (adrenalitis) from ICIs. Incidence is estimated at 0.8–2% in patients receiving ICIs.
• Secondary adrenal insufficiency (SAI)
More common and results from hypophysitis (pituitary inflammation), leading to ACTH deficiency. Reported incidence:
• Ipilimumab (anti-CTLA-4)
Hypophysitis occurs in 5–17% of patients, often leading to adrenal insufficiency.
• Anti-PD-1/PD-L1 therapies
Hypophysitis is rarer, affecting <1–5% of patients.
• Combination therapy (anti-CTLA-4 + anti-PD-1)
Increased risk, with hypophysitis occurring in 8–25% of cases.
Risk Factors
• Combination immunotherapy (e.g., ipilimumab + nivolumab) increases risk.
• Male sex and older age may be associated with higher rates of hypophysitis.
• AI often presents late, sometimes after stopping treatment.
Clinical Presentation
• Fatigue, weight loss, nausea, hypotension, and electrolyte imbalances (hyponatremia, hyperkalemia in PAI).
• Secondary AI (due to hypophysitis) often presents without hyperkalemia due to intact aldosterone secretion.
Management
• Lifelong glucocorticoid replacement (hydrocortisone, prednisolone).
• Mineralocorticoid replacement (fludrocortisone) if primary AI.
• Stress-dose steroids during illness or surgery.
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