Diagnosis, Pathophysiology and Management of Hypercalcemia in Malignancy: A Review of the Literature

Horm Metab Res. 2019 Dec;51(12):770-778. doi: 10.1055/a-1049-0647. Epub 2019 Dec 11.


Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical mediators of hypercalcemia. Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcitriol / blood
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / diagnosis*
  • Hypercalcemia / drug therapy*
  • Hypercalcemia / pathology
  • Parathyroid Hormone / blood
  • Parathyroid Hormone-Related Protein / blood


  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Calcitriol