A 65-year-old heavy smoker has a peripheral lung mass with hypercalcaemia. Histology shows large cells with intercellular bridges, keratinisation, and abundant pink cytoplasm. Which receptor mechanism does PTH-rP use to cause hypercalcaemia?
- A Binds vitamin D receptor, increasing intestinal calcium absorption
- B Binds calcitonin receptor, inhibiting osteoblast activity
- C Directly activates TRPV5 in renal distal tubule, bypassing PTH1R
- D Binds PTH/PTH-rP receptor (PTH1R), activating osteoclasts and increasing renal calcium reabsorption ✓
Explanation
Squamous cell carcinoma of the lung secretes parathyroid hormone-related protein (PTH-rP), which binds to the same PTH/PTH-rP receptor (PTH1R) as native PTH. Activation of PTH1R stimulates osteoclast-mediated bone resorption (via RANKL upregulation) and increases renal tubular calcium reabsorption, causing hypercalcaemia of malignancy without skeletal metastases (humoral hypercalcaemia). The vitamin D receptor mediates calcitriol effects; calcitonin receptor inhibits osteoclasts (not osteoblasts); TRPV5 is a renal calcium channel not directly activated by PTH-rP in this manner.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.