A 62-year-old male smoker with a squamous cell carcinoma of the lung presents with confusion, constipation and a corrected serum calcium of 13.8 mg/dL. Parathyroid hormone level is undetectable and phosphate is low-normal. The most likely mediator of his hypercalcaemia acts by:

• A Inhibiting the calcium-sensing receptor on parathyroid chief cells
• B Stimulating 1-alpha hydroxylase to raise circulating 1,25-dihydroxyvitamin D
• C Directly activating osteoclasts through the RANKL-independent secretion of IL-6 alone
• D Binding the PTH-1 receptor and increasing osteoclastic resorption and renal tubular calcium reabsorption ✓

Explanation

Squamous cell lung carcinoma produces PTHrP, the classic cause of humoral hypercalcaemia of malignancy. PTHrP binds the same PTH-1 receptor as native PTH, driving osteoclastic bone resorption and distal tubular calcium reabsorption. Unlike PTH, PTHrP does not meaningfully stimulate renal 1-alpha hydroxylase, so vitamin A levels are not elevated, which kills option B and distinguishes it from primary hyperparathyroidism.

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.