A 68-year-old heavy smoker presents with weight loss and confusion. Serum calcium is 13.8 mg/dL with suppressed intact PTH. CT shows a cavitating hilar mass. Biopsy shows nests of large polygonal cells with intercellular bridges and keratin pearls. The humoral mediator responsible for the metabolic abnormality is:

• A Parathyroid hormone related peptide ✓
• B Antidiuretic hormone
• C Ectopic calcitriol production by granuloma macrophages
• D Antibodies against the voltage gated calcium channel

Explanation

The histology confirms squamous cell carcinoma, the lung tumor most classically linked to hypercalcemia of malignancy through secretion of PTHrP, which mimics PTH at bone and kidney but is not measured by the intact PTH assay. ADH excess causes hyponatremia, seen with small cell carcinoma. Granuloma derived calcitriol explains hypercalcemia in sarcoidosis. Antibodies to the presynaptic calcium channel cause Lambert Eaton myasthenic syndrome, a neuromuscular rather than metabolic paraneoplastic syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.