A 58-year-old male smoker presents with a hilar mass, weight loss, and corrected calcium of 12.8 mg/dL with a suppressed intact parathyroid hormone level. Biopsy shows squamous cell carcinoma. The humoral mediator responsible for this hypercalcaemia is:

• A 1,25-dihydroxyvitamin D produced by the tumour
• B Osteoclast activating factor from bone metastases
• C Parathyroid hormone-related peptide (PTHrP) ✓
• D Ectopic parathyroid hormone secretion

Explanation

Humoral hypercalcaemia of malignancy in squamous cell carcinomas is mediated by PTHrP, which binds the same PTH receptor in bone and kidney, increasing osteoclastic resorption and distal tubular calcium reabsorption. Ectopic true PTH secretion by non-parathyroid tumours is vanishingly rare, which kills option D. Calcitriol-mediated hypercalcaemia is characteristic of lymphomas through extrarenal 1-alpha hydroxylase, and local osteolytic factors apply to lytic bone metastases such as multiple myeloma.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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