A 50-year-old man self-medicating with high-dose vitamin D drops for joint pain develops constipation, polyuria, and confusion. Labs show serum calcium 12.8 mg/dL, intact PTH 6 pg/mL (low), and markedly elevated 25-hydroxyvitamin D with a normal 1,25-dihydroxyvitamin D level. The pattern indicates that his hypercalcemia results from:
- A Direct vitamin D receptor activation by accumulated 25-hydroxyvitamin D itself ✓
- B Extrarenal conversion of 25-hydroxyvitamin D to calcitriol
- C Parathyroid hormone-mediated osteoclast activation
- D Renal failure causing phosphate retention and secondary hyperparathyroidism
Correct answer: A. Direct vitamin D receptor activation by accumulated 25-hydroxyvitamin D itself
Explanation
In exogenous vitamin D intoxication, massive doses saturate hepatic production of 25-hydroxyvitamin D, which accumulates to supraphysiologic concentrations. At these levels, 25-hydroxyvitamin D itself binds and activates the vitamin D receptor despite normal circulating calcitriol, increasing intestinal calcium absorption. Suppressed PTH excludes parathyroid-driven osteoclast activation, and the normal calcitriol level rules out extrarenal 1-alpha hydroxylation, which is seen in granulomatous disease instead.
Reference: Williams Textbook of Endocrinology, 14th ed.
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