Hypercalcemia and cancer: Differential diagnosis and treatment

CA Cancer J Clin. 2018 Sep;68(5):377-386. doi: 10.3322/caac.21489. Epub 2018 Sep 21.


Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone-related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.

Keywords: evaluation; malignancy; management; paraneoplastic syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Diagnosis, Differential
  • Female
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / diagnosis*
  • Hypercalcemia / etiology
  • Hypercalcemia / therapy*
  • Hyperparathyroidism, Primary / complications
  • Male
  • Melanoma / blood
  • Melanoma / complications*
  • Middle Aged
  • Osteolysis / complications
  • Parathyroid Hormone-Related Protein / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / complications*
  • Young Adult


  • PTHLH protein, human
  • Parathyroid Hormone-Related Protein