A 58-year-old man with squamous cell carcinoma of the lung develops hypercalcemia with a serum calcium of 13.2 mg/dL, a low PTH, and an elevated PTH-related protein (PTHrP). This paraneoplastic hypercalcemia is primarily mediated by PTHrP acting on which receptor?
- A PTH2R (type 2 PTH receptor)
- B RANK receptor on osteoclasts
- C PTH1R (type 1 PTH/PTHrP receptor) ✓
- D Calcium-sensing receptor (CaSR)
Correct answer: C. PTH1R (type 1 PTH/PTHrP receptor)
Explanation
PTHrP binds and activates the PTH1R receptor — the same receptor used by native PTH — triggering cAMP-mediated osteoclast activation and renal calcium retention. PTH2R responds to PTHrP poorly and is not the dominant mediator of hypercalcemia of malignancy. RANK is downstream of RANKL signalling and is not the primary PTHrP receptor. The CaSR senses calcium levels but is not activated by PTHrP.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.