A 50-year-old male smoker with central lung mass undergoes bronchoscopy; biopsy shows a squamous cell carcinoma. Laboratory reveals serum calcium of 12.8 mg/dL. Which molecule secreted by the squamous cell carcinoma is responsible for the hypercalcaemia?

• A 1,25-dihydroxyvitamin D3 (calcitriol)
• B Authentic parathyroid hormone (PTH)
• C Osteoclast activating factor (IL-1β)
• D Parathyroid hormone-related protein (PTHrP) ✓

Explanation

Squamous cell carcinoma of the lung is the classic cause of humoral hypercalcaemia of malignancy through ectopic secretion of PTHrP (parathyroid hormone-related protein). PTHrP shares the N-terminal amino acid sequence homology with PTH, binds the PTH/PTHrP receptor (PTHR1), and mimics all actions of PTH (bone resorption, renal calcium reabsorption, phosphaturia). Unlike PTH, PTHrP is not detected by PTH immunoassays; this explains a suppressed PTH with elevated calcium. Calcitriol-mediated hypercalcaemia occurs in lymphomas via activated macrophages in granulomata.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.