Hypercalcaemia

Hypercalcaemia is a condition characterised by an abnormally high calcium (Ca2+) level in the blood serum. The normal range for calcium in the blood is between 2.1 and 2.6 mmol/L. Hypercalcaemia is defined by levels greater than 2.6 mmol/L.

Signs and Symptoms

Patients with mild increases in calcium levels often remain asymptomatic, particularly if the rise is gradual. However, those with more significant elevations or rapid onset may exhibit various symptoms. The mnemonic "Stones, Bones, Groans, Moans, Thrones, and Psychiatric Overtones" can be useful:

• Stones: Kidney stones or biliary stones.
• Bones: Bone pain due to the effects on bone metabolism.
• Groans: Abdominal discomfort and gastrointestinal symptoms.
• Moans: Non-specific complaints such as fatigue and weakness.
• Thrones: Polyuria and constipation.
• Psychiatric Overtones: Depression, anxiety, and cognitive disturbances.

Other symptoms may include cardiac arrhythmias, fatigue, nausea, vomiting, and decreased muscle tone.

Hypercalcaemic Crisis

A hypercalcaemic crisis is a medical emergency typically involving calcium levels above 14 mg/dL (3.5 mmol/L). Symptoms include oliguria or anuria, somnolence, or even coma. Urgent measures to lower serum calcium are very important, often involving intravenous hydration, calcitonin, and bisphosphonates.

Causes

Primary hyperparathyroidism and malignancy account for the majority of hypercalcaemia cases. Other causes include:

• Parathyroid Function: Solitary parathyroid adenoma, primary hyperparathyroid hyperplasia, and certain genetic conditions.
• Cancer: Tumours that release parathyroid hormone-related protein (PTHrP), and local osteolytic hypercalcaemia from bone metastasis.
• Vitamin-D Disorders: Hypervitaminosis D, sarcoidosis, and other granulomatous diseases.
• High Bone-turnover: Hyperthyroidism, multiple myeloma, prolonged immobilisation, and Paget's disease.
• Kidney Failure: Tertiary hyperparathyroidism and milk-alkali syndrome.
• Others: Adrenal insufficiency, acromegaly, and excessive calcium consumption.

Diagnosis

Diagnosis involves measuring either corrected calcium or ionised calcium levels and confirming the diagnosis after a week. A detailed history and examination are essential to identify underlying causes. Laboratory tests include intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), calcitriol, and calcifediol levels.

Treatments

The primary goal is to treat the hypercalcaemia and subsequently address the underlying cause. Immediate treatment is required for calcium levels above 13 mg/dL or rapidly rising levels.

Fluids and Diuretics

Initial therapy involves intravenous (IV) fluids to correct dehydration and enhance renal calcium excretion. Following rehydration, loop diuretics such as furosemide can be used to maintain a high urine output while preventing fluid overload.

Bisphosphonates and Calcitonin

Bisphosphonates such as pamidronate and zoledronate inhibit bone resorption by osteoclasts and are often the first-line treatment for hypercalcaemia of malignancy. Calcitonin can also be used for immediate but short-term reduction of calcium levels.

Other Therapies

Other therapies include denosumab, glucocorticoids for vitamin D-related hypercalcaemia, and dialysis in severe cases. Phosphate therapy and rarely used drugs like plicamycin and gallium nitrate may also be considered.

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Self-assessment MCQs (single best answer)

What is the normal range for calcium in the blood?

What mnemonic is useful for remembering the symptoms of hypercalcaemia?

Which symptom is NOT typically associated with hypercalcaemia?

What is considered a medical emergency in hypercalcaemia?

Which of the following is NOT a common cause of hypercalcaemia?

What initial therapy is often used to treat hypercalcaemia?

Which class of drugs inhibits bone resorption by osteoclasts and is often used to treat hypercalcaemia of malignancy?

What laboratory test is NOT typically used to diagnose hypercalcaemia?

Which of the following treatments is used for immediate but short-term reduction of calcium levels?

In animals, what is a common cause of hypercalcaemia in grazing animals?