causes and management of hypercalcaemia

Causes of Hypercalcaemia

Hypercalcaemia can be caused by various factors, including primary hyperparathyroidism ². Other potential causes include malignancy, granulomatous disease, renal disease, thyroid disease, and lithium use ¹. Certain medications such as thiazide diuretics, lithium, and supplements containing calcium and/or vitamin D can also exacerbate hypercalcaemia ¹. 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^{2 3}.

Management of Hypercalcaemia

The management of hypercalcaemia depends on the severity of the calcium level and the presence of symptoms ¹.

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 ¹.
• Liaise with the person's oncologist or palliative care specialist if there is uncertainty about ongoing management ¹.
• Consider referral to a palliative care specialist for additional support if appropriate ¹.

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 ¹.
• Liaise with the person's oncologist or palliative care specialist if possible when making arrangements for urgent assessment and treatment ¹.
• 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 ¹.
• 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 ¹.

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 ¹.
• Review and consider stopping medications that may be exacerbating the hypercalcaemia, such as thiazide diuretics, lithium, or medications containing calcium and/or vitamin D ¹.
• Arrange monitoring and follow-up in primary care as appropriate ¹.
• If a reversible cause is identified and corrected, and calcium levels return to normal, referral may not be necessary ¹.
• 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 ¹.
• 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 ¹.
• If the person is on lithium, liaise with their mental health specialist ¹.
• 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 ¹.
• If malignancy is suspected, refer via local suspected cancer pathways highlighting the presence of a raised calcium level ¹.
• 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 ¹.
• 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 ¹.
• Where a specific cause is not identifiable, refer to an endocrinologist for further investigation and management ¹.
• Advise the person to maintain adequate oral fluid intake ¹.

Specific Considerations

• For primary hyperparathyroidism, specialist advice should be sought if suspected ². Management may include surgical or non-surgical treatments, with information provided on advantages, disadvantages, and potential complications ². Advice on lifestyle factors such as exercise, diet, hydration, and pain relief should be given ².
• In CKD, monitor serum calcium and phosphate concentrations in people receiving alfacalcidol or calcitriol supplements ³.
• 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 ¹. Cinacalcet may be used in cases like parathyroid carcinoma when surgery is not possible ¹.
• In palliative care, treatment of hypercalcaemia may not be appropriate if the person is approaching the end of life ¹.