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Hypercalcemia – Causes, Symptoms and Treatment

Hypercalcemia refers to abnormally high calcium levels in the blood. It can affect the bones, kidneys, and nervous system and has a range of underlying causes.

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Things worth knowing about "Hypercalcemia"

Hypercalcemia refers to abnormally high calcium levels in the blood. It can affect the bones, kidneys, and nervous system and has a range of underlying causes.

What is Hypercalcemia?

Hypercalcemia is a condition in which the calcium level in the blood is higher than normal. In healthy adults, total serum calcium typically ranges from 2.2 to 2.6 mmol/l (8.8–10.4 mg/dl). Calcium is essential for muscle contraction, nerve function, blood clotting, and bone structure. However, persistently elevated calcium levels can damage various organs and require medical evaluation and treatment.

Causes

The most common causes of hypercalcemia include:

Primary hyperparathyroidism: Overproduction of parathyroid hormone (PTH) by the parathyroid glands, leading to excessive release of calcium from bones.
Malignant diseases (cancer): Cancers such as breast cancer, lung cancer, kidney cancer, or multiple myeloma can release calcium from bones or produce PTH-related protein.
Vitamin D toxicity: Excessive intake of vitamin D supplements increases calcium absorption from the gut.
Sarcoidosis and other granulomatous diseases: These conditions lead to increased conversion of vitamin D to its active form, raising calcium levels.
Prolonged immobilization: Extended bed rest can accelerate bone breakdown and increase calcium release into the blood.
Certain medications: For example, thiazide diuretics or lithium.

Symptoms

The severity of symptoms depends on how high the calcium level is and how quickly it has risen. Mild hypercalcemia is often asymptomatic. More pronounced elevations can cause:

General symptoms: Fatigue, weakness, lethargy
Gastrointestinal complaints: Nausea, vomiting, constipation, abdominal pain
Kidney-related symptoms: Increased urination, kidney stones, impaired kidney function
Neurological symptoms: Difficulty concentrating, confusion, depression, and in severe cases loss of consciousness (hypercalcemic crisis)
Cardiovascular effects: Irregular heartbeat, high blood pressure
Bone pain: Due to accelerated bone resorption

Diagnosis

Hypercalcemia is primarily diagnosed through a blood test measuring total serum calcium and ionized (free) calcium. To determine the underlying cause, additional tests are performed, including:

Parathyroid hormone (PTH) levels
Vitamin D levels (25-OH-vitamin D and 1,25-OH-vitamin D)
Kidney function markers (creatinine, urea)
Tumor markers if malignancy is suspected
24-hour urinary calcium excretion

Imaging studies such as ultrasound, scintigraphy, or CT scans may be used to identify enlarged parathyroid glands or tumors.

Treatment

Treatment depends on the underlying cause and the severity of the condition.

Mild Hypercalcemia

In mild, asymptomatic cases, a watchful waiting approach with regular monitoring is often recommended. Adequate hydration (at least 2–3 liters of fluid per day) is important to promote calcium excretion through the kidneys.

Moderate to Severe Hypercalcemia

Intravenous fluids: Saline infusion to dilute calcium levels and encourage renal excretion.
Bisphosphonates (e.g., zoledronate, pamidronate): Inhibit bone resorption and thereby lower calcium levels.
Calcitonin: Rapidly reduces calcium by inhibiting bone breakdown.
Corticosteroids: Particularly effective in granulomatous diseases or vitamin D toxicity.
Dialysis: Reserved for life-threatening cases unresponsive to other treatments.

Treating the Underlying Cause

The root cause must be addressed directly -- for example, surgical removal of a parathyroid adenoma or treatment of an underlying malignancy.

References

Bilezikian JP. - Hypercalcemia. In: Jameson JL et al. (eds.), Harrison's Principles of Internal Medicine, 21st edition, McGraw-Hill, 2022.
Lamy O, Jenzer-Closuit A, Burckhardt P. - Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. Journal of Internal Medicine, 2001; 250(1): 73–79. PubMed PMID: 11454141.
Carroll MF, Schade DS. - A practical approach to hypercalcemia. American Family Physician, 2003; 67(9): 1959–1966. PubMed PMID: 12751658.

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