Can cancer cause hypernatremia?

Can Cancer Cause Hypernatremia?

Yes, cancer can cause hypernatremia, though it is far less common than hyponatremia—the mechanism is primarily through ectopic ACTH secretion leading to Cushing's syndrome, which occurs in 1.6-4.5% of small cell lung cancer (SCLC) cases. 1

Primary Mechanism: Ectopic ACTH Production

The most well-documented pathway for cancer-induced hypernatremia involves paraneoplastic endocrine syndromes, particularly in SCLC:

• Ectopic ACTH secretion from SCLC tumors leads to Cushing's syndrome with characteristic hypernatremia, hypokalemia, and metabolic alkalosis 1
• This occurs in 1.6-4.5% of clinically apparent SCLC cases, though biochemical abnormalities may be present in 30-50% of patients 2
• The hypernatremia results from mineralocorticoid excess causing sodium retention and potassium wasting 1

Clinical Presentation

When evaluating for cancer-related hypernatremia, look for these specific features:

• Weight gain, moon facies, hypertension, hyperglycemia, and generalized weakness accompanying the hypernatremia 1
• High serum cortisol and ACTH levels with hypernatremia, hypokalemia, and alkalosis on laboratory testing 1
• Skin hyperpigmentation that is typically more prominent compared to other causes of Cushing's syndrome 2
• Poor prognosis association, as ectopic Cushing syndrome indicates aggressive disease 2

Important Contrast: Hyponatremia is Far More Common

It is critical to recognize that hyponatremia, not hypernatremia, is the predominant electrolyte disorder in cancer patients:

• Hyponatremia occurs in 47% of cancer patient admissions, while hypernatremia is rare 3
• SIADH affects 5-10% of SCLC patients clinically, making it far more common than ectopic ACTH syndrome 1, 2
• SIADH causes hyponatremia through ectopic vasopressin (ADH) secretion 1, 2
• Multiple cancers cause SIADH including SCLC (15% incidence), head and neck cancer (3%), and various other malignancies 4

Diagnostic Approach for Suspected Ectopic ACTH

When hypernatremia is present with cancer, particularly SCLC:

• Check serum cortisol and ACTH levels to confirm ectopic ACTH syndrome 2
• Perform dexamethasone suppression test for definitive diagnosis 2
• Evaluate for metabolic alkalosis and assess for hypertension as supporting features 2
• Measure concurrent serum sodium and potassium to document the characteristic pattern 2

Management Considerations

• Treat the underlying SCLC with appropriate chemotherapy, which can lead to resolution of paraneoplastic syndromes 2
• Successful anti-tumor therapy typically reverses endocrine paraneoplastic syndromes 1
• Early recognition and treatment of these metabolic derangements is crucial, as they cause significant morbidity and mortality if untreated 2
• Patients with successfully treated SCLC often experience improvement in their paraneoplastic syndromes 2

Common Pitfall to Avoid

Do not assume all electrolyte abnormalities in cancer patients are hypernatremia—the overwhelming majority (47% of admissions) will be hyponatremia, not hypernatremia 3. When you encounter a cancer patient with sodium abnormalities, your default suspicion should be SIADH-related hyponatremia unless the clinical picture clearly suggests ectopic ACTH syndrome with its characteristic features of Cushing's syndrome 1, 2.