Question 5

A patient is admitted to ICU because of severe symptomatic hypercalcaemia.    List the manifestations and common causes.   It is found to be due to metastatic carcinoma  of the breast.  How should the hypercalcaemia be treated?

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College Answer

(see J Am Soc Nephrol 2001; 12: S3-9) (a) Manifestations include

-kidney: polyuria, polydipsia, muscle weakness, oliguria, renal failure

-GIT   : anorexia, nausea, vomiting, constipation

-CNS   : weakness, lethargy and depression

-CVS   : hypertension, shortened QT

-Musculoskeletal: bone pain

Common causes:

-hyperparathyroidism (primary, secondary, tertiary)

-neoplasia (humeral)



-Vit D intoxication

-recovery stage of pancreatitis or rhabdomyolysis.

(b) Treatment, if due to metastatic carcinoma of breast:

-     rehydration with saline

-     frusemide if fluid overloaded

-     aggressive diuresis has a limited potential to remove calcium and may lead to renal dysfunction if inappropriate negative fluid balances ensues.

-     Bisphosphonates are first line therapy in malignancy. They prevent osteolysis

-     Calcitonin may be adjuvant

-     Haemodialysis may be necessary if acute oliguric renal failure occurs.


This question closely resembles Question 8 from the second paper of 2000 (How  would  you  determine the  aetiology of  severe hypercalcaemia? List  the  treatments appropriate for each aetiology) and Question 9 from the second paper of 2013 (List the clinical features of severe symptomatic hypercalcaemia and outline the treatment of this condition).

Question 18.1 from the the first paper of 2011 also deals with hypercalcaemia of malignancy, but in the context of a clinical scenario.

Causes and consequences of hypercalcemia are treated in slightly greater detail elsewhere.

Causes of Hypercalcemia

Primary endocrine causes

  • Primary hyperparathyroidism
  • Thyrotoxicosis
  • Adrenal insufficiency

Paraneoplastic causes

  • PTH-related protein
    • carcinoma of lung
    • oesophageal carcinoma
    • head and neck SCC
    • renal cell carcinoma
    • Breast cancer
    • Ovarian cancer
    • Bladder cancer
  • Ectopic 1,25-dihydroxyvitamin D
    • Lymphoma
  • Lytic bone lesions
    • Multiple myeloma
    • Breast cancer
    • Hematological malignancies
  • Phaeochromocytoma
  • VIP-secreting gastric adenoma

Granulomatous disease

  • Sarcoidosis
  • HIV
  • Tuberculosis
  • Histoplasmosis
  • Coccidioidomycosis
  • Leprosy

Drug-induced hypercalcemia

  • Vitamin D oversupplementation
  • Thiazide diuretics
  • Lithium carbonate
  • Oestrogens and HRT
  • Androgens 
  • Theophylline and aminophylline
  • Vitamin A
  • Aluminum toxicity
  • Total parenteral nutrition (TPN)

Random miscellaneous causes

  • Immobilization (eg. spinal injury)
  • Chronic renal failure
  • Milk alkali syndrome
  • Rhabdomyolysis
Clinical Manifestations of Hypercalcemia

Early manifestations (levels < 3.5mmol/L)

  • Constipation
  • Peptic ulcer exacerbation
  • Polyuria
  • Nephrogenic diabetes insipidus
  • Nephrolithiasis
  • Type 1 (distal) renal tubular acidosis
  • Shortened QT interval
  • Bone pain

Late manifestations (levels over 3.5mmol/L)

  • Pancreatitis
  • Renal failure (due to vasoconstriction)
  • Hypertension
  • Delirium, progressing to coma
  • Arrhythmia
  • Muscle weakness


  • Dilute serum calcium
    • Rehydration with IV fluids
  • Decrease calcium resportion from bone
    • Calcitonin
    • Bisphosphonates
    • Gallium nitrate
  • Decrease calcium resportion from renal tubule
    • Loop diuretics (this has fallen out of favour)
    • Calcitonin
  • Decrease calcium absorption from the gut
    • Corticosteroids (also they decrease the 1,25-dihydroxyvitamin D production by monocytes within granulomae)
  • Forcibly remove excess calcium from the circulation
    • Haemodialysis
    • EDTA administration (as chelating agent)