SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients

in Endocrine Connections
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  • 1 The Mellanby Centre for Bone Research, The Medical School, The University of Sheffield, Sheffield, UK
  • 2 Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham & University of Birmingham, Birmingham Health Partners, Birmingham, UK
  • 3 Department of Medicine, Manchester Royal Infirmary, Manchester, UK
  • 4 The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK

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

  • 1

    LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259263. (doi:10.7326/0003-4819-149-4-200808190-00007)

    • Search Google Scholar
    • Export Citation
  • 2

    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 297304. (doi:10.1016/0002-9343(93)90282-T)

    • Search Google Scholar
    • Export Citation
  • 3

    Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J & Quebe-Fehling E 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 558567.

    • Search Google Scholar
    • Export Citation
  • 4

    Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26S30.

  • 5

    Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR & Lu J Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 27662772. (doi:10.1210/jc.2008-2640)

    • Search Google Scholar
    • Export Citation
  • 6

    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)

    • Search Google Scholar
    • Export Citation

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  • 1

    LeGrand SB, Leskuski D & Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine 2008 149 259263. (doi:10.7326/0003-4819-149-4-200808190-00007)

    • Search Google Scholar
    • Export Citation
  • 2

    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 297304. (doi:10.1016/0002-9343(93)90282-T)

    • Search Google Scholar
    • Export Citation
  • 3

    Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, Yunus F, Bell R, Body J & Quebe-Fehling E 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 558567.

    • Search Google Scholar
    • Export Citation
  • 4

    Wineski LA. Salmon calcitonin in the management of hypercalcaemia. Calcified Tissue International 1990 46 (Supplement) S26S30.

  • 5

    Marcocci C, Chanson P, Shoback D, Bilezikian J, Fernandez-Cruz L, Orgiazzi J, Henzen C, Cheng S, Sterling LR & Lu J Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 2009 94 27662772. (doi:10.1210/jc.2008-2640)

    • Search Google Scholar
    • Export Citation
  • 6

    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)

    • Search Google Scholar
    • Export Citation