Low Sodium in Melanoma: What It Means and Next Steps

Low sodium (hyponatremia) can have several possible causes in people with melanoma, and the level of concern depends on how low it is, how fast it fell, and your symptoms. In many cases, it can be related to treatment side effects, dehydration, or hormone (endocrine) changes from immunotherapy. ^[1] Some hormone-related side effects from immunotherapy can present with low sodium along with fatigue, dizziness, confusion, or low blood pressure. ^{[2] [3]}

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What “Low Sodium” Means

• Hyponatremia refers to sodium below the normal range in blood and can cause symptoms like headache, nausea, confusion, and in severe cases seizures. ^[1]
• In melanoma, hyponatremia may be a clue to immune-related endocrine problems such as adrenal insufficiency or hypophysitis (inflammation of the pituitary) from checkpoint inhibitor therapy. ^[3] These conditions can lead to cortisol deficiency, which often lowers sodium. ^[1]

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Common Causes in Melanoma Care

• Immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) can trigger endocrine side effects particularly adrenal insufficiency and hypophysitis which may present with hyponatremia. ^[3] Typical accompanying symptoms include severe fatigue, dizziness, headache, nausea, confusion, and low blood pressure. ^[2]
• Secondary adrenal insufficiency has been reported as a frequent immune-related event in melanoma patients receiving combination immunotherapy, and recovery of adrenal function can be incomplete, necessitating ongoing hormone replacement. ^[4]
• Late-onset endocrine irAEs can occur even months after stopping nivolumab, including hypophysitis or isolated ACTH deficiency, so new hyponatremia warrants evaluation even if treatment ended. [PM9] [PM11]
• Other contributors include dehydration, infections, certain medicines, and less commonly a syndrome of inappropriate antidiuretic hormone (SIADH), which causes water retention and dilution of sodium. ^{[5] [6]}

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When to Be Concerned

• Seek urgent care if low sodium is accompanied by decreased consciousness, lethargy, seizures, or coma; these are medical emergencies that require immediate evaluation and treatment. ^[1]
• If you have significant fatigue, dizziness, nausea, low blood pressure, or confusion while on or after immunotherapy, clinicians generally advise withholding treatment temporarily and urgently checking endocrine labs. ^[3] Adrenal crisis should be ruled out promptly, and steroid treatment may be started if suspected. ^[1]

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What Your Team May Check

• Endocrine assessment typically includes morning cortisol and ACTH, thyroid function tests, electrolytes (including sodium), and sometimes pituitary imaging if hypophysitis is suspected. ^[3]
• If adrenal crisis is excluded but endocrine side effects are confirmed, management usually involves physiologic steroid replacement in consultation with an endocrinologist, with consideration of resuming immunotherapy after stabilization. ^[2] In suspected adrenal crisis, clinicians may give urgent IV steroids with mineralocorticoid activity (e.g., hydrocortisone) and refer to endocrinology. ^[1]

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How Hyponatremia Is Managed

• Treatment depends on cause and severity: correcting dehydration, adjusting medications that lower sodium, and carefully managing fluids in SIADH. ^[5]
• For immune-related adrenal insufficiency or hypophysitis, steroid hormone replacement is typically required, and some patients need long-term therapy. ^{[2] [4]}
• Your oncology team may pause immunotherapy during the work-up and restart once you are stable, guided by symptom resolution and endocrine input. ^[2]

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Practical Tips

• Track symptoms: Report new or worsening fatigue, dizziness, headaches, nausea, confusion, low blood pressure, or reduced alertness promptly. ^{[2] [1]}
• Know your timing: Endocrine side effects can appear early or months after stopping immunotherapy, so don’t dismiss late symptoms. [PM9] [PM11]
• Coordinate care: Endocrinology input is often helpful to confirm diagnosis and tailor replacement therapy. ^{[1] [3]}

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Bottom Line

Low sodium in someone with melanoma can be benign (like mild dehydration) but may also signal an immune-related endocrine issue especially if you’re on or have recently been on checkpoint inhibitors. It’s reasonable to be cautious: if sodium is low or you have concerning symptoms, timely evaluation with endocrine labs and clinical assessment is important, and treatment may include steroid replacement if adrenal insufficiency is found. ^{[3] [2] [1] [4]} [PM9] [PM11]

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