What is the etiology of hypercalcemia?

Updated: Dec 03, 2020
  • Author: Mahendra Agraharkar, MD, MBBS, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Approximately 90% of cases of hypercalcemia are caused by hyperparathyroidism or malignancy. About 20-30% of patients with cancer have hypercalcemia during the course of the disease, and its occurrence may signify an unfavorable prognosis. Of the cases that result from malignancy, approximately 80% are due to the effects of parathyroid hormone–related peptide (PTHrP), while the other 20% are due to bony metastases. Hypercalcemia secondary to malignancy may be classified into the following four types, based on the mechanism involved:

  • Humoral hypercalcemia of malignancy (HHCM) from an increased secretion of PTHrP - Most common form, accounting for up to 80% of cases
  • Osteolytic hypercalcemia from osteoclastic activity and bone resorption surrounding the tumor tissue - The second most common mechanism, accounting for about 20% of cases
  • Secretion of active vitamin D by some lymphomas
  • Ectopic parathyroid hormone (PTH) secretion - Very rare

The remaining 10% of cases of hypercalcemia are caused by many different conditions, including vitamin D–related problems, disorders associated with rapid bone turnover, thiazides or renal failure, and in rare cases, familial disorders. Treatment with recombinant human PTH for postmenopausal osteoporosis is also a cause. [6]

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