A patient presents with hypercalcemia, low PTH, high PTHrP (PTH-related protein), and elevated 1,25-dihydroxyvitamin D. The most likely etiology of hypercalcemia is:
- A Primary hyperparathyroidism
- B Granulomatous disease (sarcoidosis)
- C Milk-alkali syndrome
- D Humoral hypercalcemia of malignancy (squamous cell lung cancer) ✓
Explanation
Humoral hypercalcemia of malignancy (HHM) is characterized by elevated PTHrP secreted by tumor cells (most commonly squamous cell lung carcinoma, renal cell carcinoma, breast cancer) that activates PTH receptors. PTH itself is suppressed. PTHrP does NOT stimulate 1α-hydroxylase significantly, so 1,25-dihydroxyvitamin D is usually normal or low in HHM. However, elevated 1,25-dihydroxyvitamin D in the presence of suppressed PTH and elevated PTHrP still points toward HHM over granulomatous disease, where PTHrP would be absent. In sarcoidosis, activated macrophages express 1α-hydroxylase, but PTHrP is not elevated.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.