NBME Form 10 Step 2 Practice Test

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Which cancer is most commonly associated with PTHrP-mediated hypercalcemia?

Small cell carcinoma

Adenocarcinoma of colon

Hepatocellular carcinoma

Squamous cell carcinoma

PTHrP-mediated hypercalcemia happens when a tumor secretes a PTH-related peptide that mimics PTH, leading to increased bone resorption and more calcium reabsorption by the kidneys, with suppressed endogenous PTH. The classic tumor driver of this humoral hypercalcemia is squamous cell carcinoma, especially of the lung, which frequently produces PTHrP.

Small cell carcinoma tends to produce hormones like ACTH or ADH rather than PTHrP, while colon adenocarcinoma and hepatocellular carcinoma are not typically associated with PTHrP-driven calcium rise. Therefore, squamous cell carcinoma is the cancer most commonly linked to this mechanism.