causes and management of hypercalcaemia

Clinical answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

Causes of Hypercalcaemia

Hypercalcaemia can be caused by various factors, including primary hyperparathyroidism . Other potential causes include malignancy, granulomatous disease, renal disease, thyroid disease, and lithium use . Certain medications such as thiazide diuretics, lithium, and supplements containing calcium and/or vitamin D can also exacerbate hypercalcaemia . In chronic kidney disease (CKD), abnormal bone metabolism and vitamin D levels can contribute to hypercalcaemia, particularly in those with a GFR less than 30 ml/min/1.73 m .

Management of Hypercalcaemia

The management of hypercalcaemia depends on the severity of the calcium level and the presence of symptoms .

Severe Hypercalcaemia (Calcium > 3.5 mmol/L) or Severe Symptoms

Offer emergency hospital admission for specialist assessment and management, which may include intravenous fluids and bisphosphonate therapy .
Liaise with the person's oncologist or palliative care specialist if there is uncertainty about ongoing management .
Consider referral to a palliative care specialist for additional support if appropriate .

Moderate Hypercalcaemia (Calcium 3–3.5 mmol/L) or Symptoms

Offer urgent assessment in a hospital or hospice setting, depending on clinical judgement and the person's wishes, as well as the involvement and local availability of palliative care services .
Liaise with the person's oncologist or palliative care specialist if possible when making arrangements for urgent assessment and treatment .
Consider immediate same-day referral to hospital and/or liaise with the appropriate specialist, depending on the clinical picture, as prompt treatment is usually required .
If the cause is unknown, prompt investigation, correction, and rehydration are usually required in a setting where this can be done swiftly. Refer to the on-call endocrinologist, ambulatory care unit, or medical team, depending on local pathways .

Mild Hypercalcaemia (Calcium < 3 mmol/L) or Asymptomatic

Liaise with the person's oncologist or palliative care specialist about ongoing management. Treatment in a hospice or hospital setting may be advised .
Review and consider stopping medications that may be exacerbating the hypercalcaemia, such as thiazide diuretics, lithium, or medications containing calcium and/or vitamin D .
Arrange monitoring and follow-up in primary care as appropriate .
If a reversible cause is identified and corrected, and calcium levels return to normal, referral may not be necessary .
If the cause is unknown, a full clinical assessment and initial investigations should be arranged to establish the probable cause and refer to the appropriate speciality .
If the person is on a thiazide diuretic, consider stopping it if possible and repeating the calcium level after 3 weeks. If it remains raised, refer to an appropriate specialist .
If the person is on lithium, liaise with their mental health specialist .
Correct any identified excess intake of calcium, vitamin D, or vitamin A. Repeat the calcium level at least 3 weeks later, and refer if it is not reducing or remains high .
If malignancy is suspected, refer via local suspected cancer pathways highlighting the presence of a raised calcium level .
If a previously undiagnosed condition is suspected (e.g., granulomatous disease, renal or thyroid disease), refer to the relevant specialist using usual local referral pathways, highlighting the raised calcium level .
Where calcium is mildly raised and parathyroid hormone level is raised, primary hyperparathyroidism is the most likely diagnosis. Refer to an endocrinologist for further diagnostic investigation and management .
Where a specific cause is not identifiable, refer to an endocrinologist for further investigation and management .
Advise the person to maintain adequate oral fluid intake .

Specific Considerations

For primary hyperparathyroidism, specialist advice should be sought if suspected . Management may include surgical or non-surgical treatments, with information provided on advantages, disadvantages, and potential complications . Advice on lifestyle factors such as exercise, diet, hydration, and pain relief should be given .
In CKD, monitor serum calcium and phosphate concentrations in people receiving alfacalcidol or calcitriol supplements .
For hypercalcaemia of malignancy, management depends on severity, symptoms, clinical situation, and patient wishes. It may include intravenous rehydration, bisphosphonates, denosumab, calcitonin, treatment of underlying malignancy, corticosteroids for calcitriol-mediated hypercalcaemia, correction of vitamin D deficiency, or surgical removal of abnormal parathyroid hormone secretion sources . Cinacalcet may be used in cases like parathyroid carcinoma when surgery is not possible .
In palliative care, treatment of hypercalcaemia may not be appropriate if the person is approaching the end of life .

Key References

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