Hypercalcaemia of malignancy

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Evidence last reviewed: 2 Apr 2026

Topic last updated: 18 Jul 2023

Hypercalcaemia of malignancy can result from: humoral hypercalcaemia of malignancy (characterised by tumour secretion of parathyroid hormone-related peptide [PTHrP]); local osteolytic hypercalcaemia (characterised by local release of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and function); calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcaemia (characterised by autonomous production of calcitriol [(1,25-dihydroxyvitamin D)] by lymphoma cells); and ectopic hyperparathyroidism (characterised by tumour production of parathyroid hormone [PTH]), which is very rare.

Pharmacological therapy can transiently improve hypercalcaemia. However, sustained maintenance of normocalcaemia requires eradication of underlying malignancy.

Treatment options include intravenous bisphosphonates, denosumab, calcitonin, glucocorticoids (for calcitriol [1,25-dihydroxyvitamin D]-mediated hypercalcaemia), and calcimimetics (for ectopic PTH production).

Definition

Hypercalcaemia occurs in 20% to 30% of patients with cancer.[1][2] Cancer represents the most common aetiology of hypercalcaemia in the inpatient setting.[3] It can result from: humoral hypercalcaemia of malignancy (characterised by tumour secretion of parathyroid hormone-related peptide [PTHrP]); local osteolytic hypercalcaemia (characterised by local release of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and function); calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcaemia (characterised by autonomous production of calcitriol [(1,25-dihydroxyvitamin D)] by lymphoma cells); and ectopic hyperparathyroidism (characterised by tumour production of parathyroid hormone), which is very rare.[4][5]

História e exame físico

Principais fatores diagnósticos

presence of risk factors
history of malignancy

Detalhes completos

Outros fatores diagnósticos

normal physical exam
poor skin turgor and/or dry mucous membranes
confusion
fatigue
constipation
loss of appetite
nausea
polyuria
polydipsia
bone pain
use of hypercalcaemia-inducing medication
stupor
coma

Detalhes completos

Fatores de risco

non-metastatic malignancy
metastatic skeletal involvement
lymphoma

Detalhes completos

Investigações diagnósticas

Primeiras investigações a serem solicitadas

total serum calcium
serum ionised calcium
serum albumin
comprehensive metabolic panel
resting ECG
serum intact parathyroid hormone
serum parathyroid hormone-related peptide
serum phosphorus
serum calcitriol (1,25-dihydroxyvitamin D)
serum 25-hydroxyvitamin D

Detalhes completos

Investigações a serem consideradas

skeletal survey
chest x-ray

Detalhes completos

Algoritmo de tratamento

AGUDA

mild hypercalcaemia or asymptomatic moderate hypercalcaemia

symptomatic moderate or severe hypercalcaemia: without advanced kidney disease

symptomatic moderate or severe hypercalcaemia: with advanced kidney disease

Colaboradores

Autores

Albert Shieh, MD

Assistant Professor of Medicine

Division of Geriatric Medicine

Department of Medicine

University of California, Los Angeles

Los Angeles

Declarações

AS declares that he has no competing interests.

Dorothy Martinez, MD

Clinical Professor of Medicine

Division of Endocrinology

Department of Medicine

University of California, Los Angeles

Los Angeles

Declarações

DM declares that she has no competing interests.

Revisores

Ken C. Chiu, MD, FACE

Professor

Endocrinology Fellowship Training Program

Department of Clinical Diabetes, Endocrinology, and Metabolism

City of Hope National Medical Center

Duarte

Declarações

KCC declares that he has no competing interests.

Richard Quinton, MD

Consultant and Senior Lecturer

Endocrine Unit

Newcastle University and Royal Victoria Infirmary

Newcastle-upon-Tyne

Declarações

RQ has been reimbursed by Amgen, the manufacturer of Cinacalcet, for attending a conference and for giving an educational seminar (total under £1,200 over past 3 years).

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Referências

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Principais artigos

Cancer Institute NSW. Hypercalcaemia of malignancy (HCM). Jul 2019 [internet publication].Texto completo

Guise TA, Wysolmerski JJ. Cancer-associated hypercalcemia. N Engl J Med. 2022 Apr 14;386(15):1443-51. Resumo

Horwitz MJ. Chapter 84: Non-parathyroid hypercalcemia. In: Bilezikian JP, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Washington, DC: American Society of Bone and Mineral Research; 2018:639-45.

El-Hajj Fuleihan G, Clines GA, Hu MI, et al. Treatment of hypercalcemia of malignancy in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2023 Feb 15;108(3):507-28.Texto completo Resumo

Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9. Resumo

Alberta Provincial Tumour Council. Oncologic emergencies: a guide for family physicians. Sep 2014 [internet publication].Texto completo

Horwitz MJ, Hodak SP, Steward AF. Non-parathyroid hypercalcemia. In: Rosen CJ, ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. 8th ed. Washington, DC: American Society of Bone and Mineral Research; 2013:562-71.

Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9. Resumo

Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001 Jan 15;19(2):558-67. Resumo

Alberta Provincial Tumour Council. Oncologic emergencies: a guide for family physicians. Sep 2014 [internet publication].Texto completo

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais
- Primary hyperparathyroidism
- Hyperthyroidism
- Adrenal insufficiency
Mais Diagnósticos diferenciais
Diretrizes
- Cancer guidelines: symptom management. Oncologic emergencies
- Treatment of hypercalcemia of malignancy in adults: an Endocrine Society clinical practice guideline
Mais Diretrizes
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Hypercalcaemia of malignancy

Summary

Definition

História e exame físico

Principais fatores diagnósticos

Outros fatores diagnósticos

Fatores de risco

Investigações diagnósticas

Primeiras investigações a serem solicitadas

Investigações a serem consideradas

Algoritmo de tratamento

mild hypercalcaemia or asymptomatic moderate hypercalcaemia

symptomatic moderate or severe hypercalcaemia: without advanced kidney disease

symptomatic moderate or severe hypercalcaemia: with advanced kidney disease

Colaboradores

Autores

Albert Shieh, MD

Declarações

Dorothy Martinez, MD

Declarações

Revisores

Ken C. Chiu, MD, FACE

Declarações

Richard Quinton, MD

Declarações

Créditos aos pareceristas

Declarações

Referências

Principais artigos

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais

Diretrizes

Conectar-se ou assinar para acessar todo o BMJ Best Practice

Conectar-se ou assinar para acessar todo o BMJ Best Practice

Conectar-se para acessar todo o BMJ Best Practice