Small cell lung carcinoma (SCLC) is derived from neuroendocrine cells (Kulchitsky cells) of the bronchial mucosa. Which paraneoplastic syndrome is most characteristic of SCLC due to ectopic ACTH production?

• A SIADH causing euvolemic hyponatremia
• B Lambert-Eaton myasthenic syndrome from anti-VGCC antibodies
• C Ectopic Cushing syndrome with hypokalaemic alkalosis and hyperglycemia ✓
• D Hypercalcemia due to PTHrP secretion

Explanation

SCLC can secrete ectopic ACTH, producing Cushing syndrome; however, because of the very high ACTH levels produced, the dominant biochemical picture is hypokalaemic metabolic alkalosis (ACTH driving mineralocorticoid-like effects) with hyperglycemia, rather than the full classic Cushing features seen in pituitary disease. SIADH from ectopic ADH is also a well-known SCLC paraneoplasm. Lambert-Eaton syndrome (anti-VGCC) and hypercalcemia from PTHrP are also associated with SCLC and squamous cell carcinoma respectively.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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