Introduction
Under physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management.
Severity of hypercalcaemia
<3.0 mmol/L: often asymptomatic and does not usually require urgent correction
3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated
>3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and coma
Clinical features of hypercalcaemia
Polyuria and thirst
Anorexia, nausea and constipation
Mood disturbance, cognitive dysfunction, confusion and coma
Renal impairment
Shortened QT interval and dysrhythmias
Nephrolithiasis, nephrocalcinosis
Pancreatitis
Peptic ulceration
Hypertension, cardiomyopathy
Muscle weakness
Band keratopathy
Causes
Ninety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancy
Less common causes include
Thiazide diuretics
Familial hypocalciuric hypercalcaemia
Non-malignant granulomatous disease
Thyrotoxicosis
Tertiary hyperparathyroidism
Hypervitaminosis D
Rhabdomyolysis
Lithium
Immobilisation
Adrenal insufficiency
Milk-alkali syndrome
Hypervitaminosis A
Theophylline toxicity
Phaeochromocytoma
Investigation
History
Examination
ECG
Bloods
High calcium and high PTH = primary or tertiary hyperparathyroidism*
High calcium and low PTH = malignancy or other less common causes
(*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency)
Management
Rehydration
Intravenous 0.9% saline 4–6 L in 24 h
If further treatment required after intravenous saline, consider intravenous bisphosphonates
Zoledronic acid 4 mg over 15 min
OR Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/h
OR Ibandronic acid 2–4 mg
Second-line treatments
Glucocorticoids (inhibit 1,25OHD production)
Calcimimetics, denosumab, calcitonin
Parathyroidectomy
Disclaimer
The document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. The doctors concerned must make the management plan for an individual patient.
Sources
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Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zuber MA, Chapman R, Henderson IC & Malette IE. Single-dose intravenous therapy for the treatment of hypercalcaemia of malignancy: comparison of 30-, 60-, and 90mg doses. American Journal of Medicine 1993 95 297–304. (doi:10.1016/0002-9343(93)90282-T)
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Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J & Quebe-Fehling E et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Journal of Clinical Oncology 2001 19 558–567.
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Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26–S30.
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Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR & Lu J et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 2766–2772. (doi:10.1210/jc.2008-2640)
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Rostoker G, Bellamy J & Janklewicz P. Cinacalcet to prevent parathyrotoxic crises in hypercalcaemic patients awaiting parathyroidectomy. BMJ Case Reports 2011 2011 bcr1220103663. (doi:10.1136/bcr.12.2010.3663)
