A 58-year-old male smoker (40 pack-years) presents with a 3-month history of progressive dyspnea, cough, and chest pain. He reports recent onset of proximal muscle weakness and diplopia. Chest X-ray shows a central hilar mass with mediastinal widening. CT chest confirms a 4 cm central lung mass. Serum sodium is 118 mEq/L (normal 135–145). Which of the following paraneoplastic syndromes is most likely responsible for his hyponatremia?

Explanation

## Clinical Presentation & Pathophysiology This patient has small cell lung cancer (SCLC) with paraneoplastic syndrome. The combination of **central hilar mass**, **mediastinal involvement**, and **severe hyponatremia (Na 118)** in a heavy smoker is classic for SCLC with SIADH. **Key Point:** SIADH is the most common paraneoplastic endocrine syndrome in SCLC, occurring in 10–15% of cases. SCLC cells produce and secrete vasopressin (ADH) ectopically, leading to: - Inappropriate water retention - Dilutional hyponatremia - Low serum osmolality with inappropriately concentrated urine ## Differential Diagnosis of Hyponatremia in Lung Cancer | Syndrome | Mechanism | Serum Osmolality | Urine Osmolality | Urine Na | SCLC Frequency | |----------|-----------|------------------|------------------|----------|----------------| | **SIADH** | Ectopic ADH secretion | Low | High (>200) | Normal/High | **Most common** | | Ectopic ACTH | Cortisol → salt retention | Normal/High | Variable | Variable | 10–15% | | Nephrotic syndrome | Proteinuria + renal dysfunction | Variable | Variable | Low | Rare | | Cerebellar syndrome | Neurologic, not endocrine | Normal | Normal | Normal | Rare cause of hyponatremia | **High-Yield:** SIADH in SCLC is characterized by: - Hyponatremia with **low serum osmolality** (<280 mOsm/kg) - **High urine osmolality** (>200 mOsm/kg) — paradoxical concentration despite low serum osmolality - Normal renal and adrenal function - Absence of volume depletion or edema ## Clinical Correlation The patient's **proximal muscle weakness and diplopia** suggest concurrent Lambert–Eaton myasthenic syndrome (LEMS), another paraneoplastic syndrome in SCLC caused by anti-voltage-gated calcium channel (VGCC) antibodies. However, LEMS does not cause hyponatremia — the hyponatremia is attributable to SIADH. **Clinical Pearl:** SCLC is notorious for **multiple simultaneous paraneoplastic syndromes**. Always screen for SIADH, LEMS, paraneoplastic encephalomyelitis, and ectopic ACTH when SCLC is diagnosed. **Mnemonic: SIADH in SCLC** — **"Small Cell = SIADH Central"** — SCLC is the classic malignancy for SIADH; look for hyponatremia with low serum osmolality and high urine osmolality. [cite:Robbins 10e Ch 15]