A 58-year-old man with small-cell lung carcinoma develops hyponatremia with serum sodium of 118 mEq/L, urine osmolality 520 mOsm/kg and urine sodium of 65 mEq/L. The tumor cells express the same gene whose product is normally synthesized exclusively in the hypothalamus and posterior pituitary. Which of the following best describes the molecular mechanism responsible for this presentation?

• A Tumor-secreted PTHrP activates PTH receptors in the distal nephron causing water retention
• B Serotonin secretion from tumor cells causes inappropriate aldosterone release via adrenal cortical stimulation
• C IL-6-driven upregulation of hepatic acute-phase proteins reduces plasma oncotic pressure
• D Ectopic AVP gene expression in neuroendocrine tumor cells leads to constitutive V2 receptor activation in renal collecting ducts ✓

Explanation

Small-cell lung carcinoma frequently causes SIADH through ectopic production of arginine vasopressin (AVP). The neuroendocrine tumor cells express the AVP gene, whose product normally originates only in hypothalamic magnocellular neurons. Constitutive secretion of AVP activates V2 receptors on collecting duct principal cells, increasing aquaporin-2 insertion, leading to water retention, dilutional hyponatremia, high urine osmolality, and high urine sodium. PTHrP causes hypercalcemia, not SIADH.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.