Alternative names for hypercalcaemia

Excess blood calcium; high blood calcium level; raised blood calcium; hypercalcemia

What is hypercalcaemia?

Hypercalcaemia is the presence of abnormally high calcium levels in the blood.

What causes hypercalcaemia?

Calcium metabolism is affected by three hormones. They are parathyroid hormone, vitamin D and calcitonin (which only has a minor effect). Parathyroid hormone and vitamin D increase circulating calcium, whereas calcitonin acts to reduce it. Calcium is introduced to the body through the diet and is found particularly in dairy products. Most diets will contain a sufficient daily intake of calcium. The body’s main calcium stores are in the bones, although calcium can be found to some degree in most parts of the body.

Hypercalcaemia has several common causes, including:

1. Enlargement or adenoma on one or more of the four parathyroid glands, causing it (them) to secrete an increased amount of parathyroid hormone. As this hormone has the primary role in calcium metabolism and controls the amount of calcium in the blood, enlargement of the parathyroid gland(s) can result in an increase in calcium in the blood (this condition is called primary hyperparathyroidism).
    
2. An association with various cancers:
   • cancers of lung and kidney can cause high calcium levels by producing a hormone similar to parathyroid hormone, known as parathyroid hormone related peptide (PTHrp) 
   • direct spread of a cancer to bones especially from breast cancer, which results in increased breakdown of bone and release of calcium
   • blood-related cancers such as leukaemia, lymphoma and myeloma can also increase the breakdown and release of calcium from bones.

Rarer causes of hypercalcaemia include:

1. Excess intake of vitamin A and/or vitamin D.
2. Medications such as lithium and bendrofluomethiazide.
3. An overactive thyroid gland (hyperthyroidism) or kidney failure.
4. Rarely, it can run in families and is passed on through the genes to other family members.

What are the signs and symptoms of hypercalcaemia?

A mild rise in calcium levels will generally cause very few symptoms or none at all. 

Moderate hypercalcaemia can cause a number of symptoms including nausea, vomiting, constipation, lethargy, depression, weakness, vague joint pains, feeling excessively thirsty, increased frequency of urination, abdominal pain and kidney stones, which might cause lower back pain.

Severe hypercalcaemia can cause headaches, heart rhythm disturbances, confusion and, ultimately, coma.

How common is hypercalcaemia?

Hypercalcaemia is fairly common in adults, with primary hyperparathyroidism being the commonest cause. Three times as many women as men are affected by hypercalcaemia. It affects approximately 25 in every 100,000 general patients and 75 in every 100,000 hospitalised patients. The peak for the start of hypercalcaemia is between 50 and 60 years of age.

In patients with cancer, 20–40% will develop hypercalcaemia at some stage.

Is hypercalcaemia inherited?

Most cases of hypercalcaemia are not inherited. One very rare cause of hypercalcaemia, which runs in families, is familial hypocalciuric hypercalcaemia and is a condition associated with passing less calcium in the urine. Hypercalcaemia as a result of hyperparathyroidism can be inherited as part of multiple endocrine neoplasia type 1 syndrome as well as other rare inherited conditions.

How is hypercalcaemia diagnosed?

Hypercalcaemia is generally diagnosed through a series of tests including:

• blood tests for calcium, albumin, parathyroid hormone and kidney function tests (urea, creatinine and estimated glomerular filtration rate, eGFR)
• thyroid function tests and tests for phosphate and vitamin D
• blood and urine test for myeloma.

In addition, chest X-rays, electrocardiogram (ECG), computerised tomography scans of the chest, and nuclear medicine scans (‘MIBI’ or ‘SPECT-CT’) of the parathyroid glands, as well as ultrasound scans of the parathyroids, may also be employed. 

All these tests can be undertaken as an outpatient unless the patient is too unwell, in which case they will be carried out as a hospital inpatient.

How is hypercalcaemia treated?

Management of hypercalcaemia depends on the patient’s physical state, including levels of hydration, mental state, the severity of the hypercalcaemia and the results of a kidney function test. It also depends on the cause of the hypercalcaemia.

Mild to moderate hypercalcaemia can be managed as an outpatient.

Moderate to severe hypercalcaemia, where the patient shows signs of dehydration and confusion, needs treatment as an inpatient. The following measures can help in managing more serious cases of hypercalcaemia:

1. Vigorous rehydration by giving fluids via an intravenous drip is always important in initial management.
2. Medication called bisphosphonates can help in reducing the blood levels of the calcium.
3. Steroid therapy is found to be useful in some specific causes of hypercalcaemia.
4. Other medications such as denosumab and calcitonin, rarely.
5. Dialysis may be needed in cases of severely impaired kidney function caused by hypercalcaemia.

If hypercalcaemia is caused by primary hyperparathyroidism, it is important to treat this condition in order to improve symptoms and prevent long-term problems such as osteoporosis or kidney stones. Primary hyperparathyroidism requires an early specialist opinion to determine if symptoms are related to the hyperparathyroidism. Expertise is required to identify whether a parathyroid swelling (adenoma) is present before surgical removal. If an adenoma is identified, the aims of surgical removal are reversal of symptoms, prevention of long-term complications and normalisation of calcium levels. In patients where an operation is not possible, specialist medication may be needed to lower parathyroid hormone levels.

Are there any side-effects to the treatment?

The majority of patients do not suffer from any side-effects to the treatment. Medical management of hypercalcaemia can lead to a number of side-effects in rare cases:

• Excessive fluid replacement may lead to heart failure, especially if heart failure has previously been diagnosed.
• Bisphosphonates need to be used cautiously as they sometimes lead to impaired kidney function.

Side-effects following parathyroid surgery may include a reduction in calcium levels. Levels usually return to normal but occasionally remain low for the rest of the patient’s life.  

What are the longer-term implications of hypercalcaemia?

The longer-term implications of hypercalcaemia depend on the underlying cause of the condition. Many patients, particularly those with only a mild case of hypercalcaemia that is successfully treated, can make a full recovery. However, the ongoing presence of hypercalcaemia can lead to a number of conditions, specifically osteoporosis, kidney stones and kidney failure, and patients should be monitored for this.