Hypercalcemia

What is Hypercalcemia?

Calcium is the most plentiful mineral in the human body and it’s really important for several functions, including nerve signal transmission, certain chemical reactions in the body (enzyme activity), heart function, blood clotting, and other cell activities. Most calcium in our body is stored in our bones in the form of calcium phosphate, while a small part is located in cells and the fluid outside of cells. In our blood, roughly 45% of calcium is attached to proteins, 45% is in its active form (free or ionized), and the remaining 10% is linked to other negative molecules (anions).

The normal range for calcium in our blood is about 8.9 to 10.1 milligrams per deciliter (mg/dL), though this figure may vary depending on the lab conducting the test. The calcium levels in our blood can change based on the amount of albumin, a protein in our blood, because a lot of calcium is attached to it. So, it’s necessary to adjust the calcium level test according to the albumin level. Also, hydrogen ions can bind with albumin, therefore, both high and low levels of acidity or alkalis in the blood can affect blood calcium levels. For example, in a condition where there is too much acid in the body (acidosis), more hydrogen ions attach to albumin which can raise free calcium levels. Hence, it’s also important to adjust the calcium level according to the acidity or alkalinity in the blood.

What Causes Hypercalcemia?

Hypercalcemia, or having too much calcium in your blood, can be due to two main reasons: those related to a hormone called parathyroid hormone, and those not related to it.

Parathyroid Hormone-Related

1. Primary hyperparathyroidism: This condition happens when there’s too much parathyroid hormone and calcium in your body. It’s often caused by a non-cancerous growth on your parathyroid gland. You typically feel normal but may have slightly high calcium levels. In severe cases, it can lead to serious issues like weak bones, kidney stones, and kidney failure.

2. Tertiary hyperparathyroidism: This also causes high levels of calcium and parathyroid hormones, but it’s usually because of kidney failure or a history of kidney transplants.

3. Familial hypocalciuric hypercalcemia: This is a genetic condition that causes high levels of calcium and parathyroid hormone. But it can be recognized by the low amount of calcium in the urine.

Certain medicines can also cause hypercalcemia. For instance, lithium can change how calcium manages parathyroid hormone levels, leading to higher calcium levels for hormone control. Teriparatide and aboloparatide, used to treat osteoporosis, can temporarily cause hypercalcemia.

Non-Parathyroid Hormone-Related

1. Induced by medication: Some water pills make your kidneys hold onto more calcium, leading to high calcium levels. Overusing calcium carbonate to treat things like acid reflux or indigestion can lead to milk-alkali syndrome, resulting in hypercalcemia, poor kidney function, and an imbalance of body chemicals. Long-term use of certain skin medications can also increase calcium levels.

2. Hypercalcemia due to cancer: This occurs when tumors produce a protein similar to parathyroid hormone or when cancer spreads to the bone, increasing the activity of cells that break down bone. This results in high calcium levels. Some blood cancers and lung diseases can lead to hypercalcemia by overproducing a hormone that helps manage calcium levels.

3. Vitamin D toxicity: This is when high levels of vitamin D lead to too much calcium. Overusing vitamin D supplements or eating too many fortified dairy products can cause this.

4. Other hormone-related conditions: Hyperthyroidism, a condition where the body produces too much thyroid hormone, can lead to more bone breakdown and high levels of calcium. Certain adrenal conditions can lead to high calcium levels, often due to dehydration or unknown mechanisms.

Immobility also contributes to high calcium levels in some people, especially those with limited movement. Not moving can lead to an imbalance of cell activity in your bones, causing them to release more calcium.

There are other rare causes of hypercalcemia highlighted in specialized reports.

Risk Factors and Frequency for Hypercalcemia

Hypercalcemia, a condition where there is too much calcium in your blood, affects around 1% to 2% of all people. The majority of hypercalcemia cases (about 90%) result from two main causes: primary hyperparathyroidism and cancer-associated hypercalcemia.

• Primary hyperparathyroidism affects around 0.2% to 0.8% of all people and its occurrence increases with age.
• Hypercalcemia is associated with about 2% of all cancer cases.
• However, in children, the rate of cancer-related hypercalcemia is lower, ranging from 0.4% to 1.3%.

Signs and Symptoms of Hypercalcemia

Hypercalcemia is a condition where the body has too much calcium in the blood. Sometimes, this condition is detected incidentally during lab work for other health issues. When blood calcium levels rise above 12 mg/dL, people may start to experience various symptoms. Some of these may include excessive urination, excessive thirst, constipation, weakness, changes in mental status, nausea, vomiting, fatigue, loss of appetite, and confusion. These symptoms can be caused by different factors like suppressed nerve transmissions, kidney dysfunctions, and effects on the brain.

Because the heart relies on balanced calcium levels, hypercalcemia can also affect the heart, showing up as abnormal patterns on an electrocardiogram (ECG). This can lead to conditions like slow heart rate, heart block, and other dangerous arrhythmias. In severe cases, hypercalcemia can cause stupor or coma.

Continuously high levels of calcium in the blood can lead to kidney stones, inflammation of the pancreas, and peptic ulcers. If hypercalcemia is caused by an overactive parathyroid gland, patients may also experience bone fractures due to weakened bones. The full range of hypercalcemia symptoms is often remembered by the phrases: groans, bones, stones, moans, thrones, and psychiatric overtones, which refer to general discomfort, bone problems, kidney stones, mental changes, bladder/bowel troubles, and psychological issues respectively.

On a physical checkup, patients with hypercalcemia might appear completely normal. However, some may show altered heart rate or rhythm, decreased deep tendon reflexes, decreased muscle tone, and generalized pain. But any additional physical signs would depend largely on the underlying cause of the hypercalcemia.

Testing for Hypercalcemia

Hypercalcemia, or high levels of calcium in the blood, is typically discovered during routine health checkups. If you’re diagnosed with hypercalcemia, the level of severity can range from mild (10.5 to 11.9 mg/dL of calcium in your blood) to moderate (12.0 to 13.9 mg/dL) or even critical (14.0 to 16.0 mg/dL, also known as a hypercalcemic crisis).

To figure out the cause of your hypercalcemia, your doctor will look at your medical history, conduct thorough physical examinations, and check any medication you’re currently taking. An important part of the diagnosis is a test to measure your parathyroid hormone level. This can help determine whether the hypercalcemia is happening because of issues related to this hormone or not. More tests or examinations may be necessary in some cases.

If your parathyroid hormone levels are normal or higher than normal (which isn’t usually the case for people with hypercalcemia), this indicates that the excess calcium is possibly due to a hormone-related issue. In this case, potential causes include conditions like primary or tertiary hyperparathyroidism or familial hypocalciuric hypercalcemia. To differentiate between these conditions, you’ll likely undergo a 24-hour urine calcium test. This test checks the amount of calcium in your urine; high levels suggest hyperparathyroidism, while low levels point towards familial hypocalciuric hypercalcemia.

If your parathyroid hormone levels are unusually low, that means your hypercalcemia isn’t related to this hormone. Other possible reasons could be certain medications, lack of mobility, some types of cancer, disorders related to granuloma formation, or certain hormonal diseases. In this case, further tests may include measuring other substances in your blood like ionized calcium, specific minerals, certain enzymes, and other hormones. These will help zero in on the most likely cause.

Just measuring calcium levels in the blood can confirm hypercalcemia, but identifying the cause often requires additional tests, which will also guide treatment.

An ECG, which is a test that measures electrical activity of the heart, may show changes linked to hypercalcemia. Additionally, your kidney may be causing issues; a renal ultrasound can spot any kidney stones which hypercalcemia may cause. A bone density scan could reveal osteoporosis, which can be caused by primary hyperparathyroidism. Cancer screening may be necessary if there’s a chance your hypercalcemia is related to cancer. If a parathyroid issue is suspected, an ultrasound can check for an adenoma (a non-cancerous tumor) on your parathyroid gland. Other imaging tests may be necessary if the ultrasound doesn’t provide a clear answer.

Treatment Options for Hypercalcemia

The aim of treating high levels of calcium in the blood, also known as hypercalcemia, involves getting rid of extra calcium, reducing the amount of calcium absorbed by the stomach, and stopping calcium from being released from the bones. Different treatments may apply depending on the cause and seriousness of the hypercalcemia.

Dehydration is a common problem in patients with hypercalcemia. These patients need to be replenished with fluids, usually via an infusion of saline solution until their urine output is adequate and they are properly hydrated.

Hypercalcemia can sometimes accompany other imbalances of electrolytes in the blood, such as low levels of potassium, magnesium or phosphate. These should all be restored to maintain a healthy balance.

The hormone calcitonin can help to quickly lower blood calcium levels. It can be given as an injection into the muscle or under the skin once every 12 hours. However, its effects only last up to a week, so it’s not suitable for long-term treatment. Calcitonin is often used in combination with other treatments that lower calcium levels.

Bisphosphonate drugs like pamidronate and zoledronic acid are often used to treat hypercalcemia resulting from cancer. These drugs take about three days to bring calcium levels down to normal and are usually given at the same time as rehydration and calcitonin treatment.

Denosumab is a drug that inhibits cells in the bone that break down bone tissue and release calcium into the blood. It’s a good treatment choice for hypercalcemia in cancer patients who have kidney problems and is usually given along with bisphosphonates and fluids.

If high blood calcium is caused by over-production of parathyroid hormone, a condition called primary hyperparathyroidism, surgery to remove the parathyroid glands might be needed. Criteria that warrant surgery include excessively high calcium levels, presence of osteoporosis or fractures, excess calcium in the urine, kidney stones, or if the patient is younger than 50.

Cinacalcet is a drug that’s used to reduce the release of parathyroid hormone and is typically given to patients with hyperparathyroidism who can’t have surgery. It is also being used to treat hypercalcemia in some cancer patients.

Patients with severe hypercalcemia and kidney failure, or those who can’t tolerate intravenous rehydration, might require dialysis. This treatment usually involves a low- or zero-calcium solution.

In cases of hypercalcemia caused by lymphoma or granulomatous diseases, a steroid medication called prednisone is often used to inhibit production of an active form of vitamin D and lower calcium levels.

Some other drugs used to treat hypercalcemia include gallium nitrate, mithramycin, and ketoconazole are also used in some cases. However, these drugs have potential side effects that involve the liver and kidneys, so their use is often avoided.

Lastly, as there are many reasons why someone could have high calcium levels, it’s crucial to diagnose and treat the underlying condition causing hypercalcemia to achieve long-lasting results.

What else can Hypercalcemia be?

Hypercalcemia, or high calcium levels in the blood, can cause a variety of symptoms. The two most common symptoms people experience are dehydration and frequent urination (known as polyuria).

In the case of dehydration, people may experience high calcium levels due to the concentration of calcium in a smaller volume of blood. This can be brought on by not drinking enough liquids. However, more visible signs like a dry mouth and skin, loose skin that doesn’t snap back quickly when pinched (known as reduced skin turgor), fast heart rate (tachycardia), low blood pressure (hypotension), and decreased urination can also point to dehydration. To correct dehydration and help bring calcium levels back to normal, patients may need to increase their fluid intake either by mouth or through an IV.

If someone is experiencing polyuria, or passing abnormally large volumes of urine, there could be several underlying causes. For instance, people with uncontrolled diabetes might have polyuria because high levels of blood sugar can cause an increase in urine volume. Similarly, people suffering from diabetes insipidus (whether it happens because of a problem with their brain or kidneys) might also present with polyuria due to an imbalance of water in their body leading to excessive urine production and high sodium levels. Other possible causes for polyuria include urinary tract infections and a decrease in blood potassium (hypokalemia).

What to expect with Hypercalcemia

The chances of getting better from hypercalcemia, a condition where you have too much calcium in your blood, can greatly depend on its cause. In many cases, hypercalcemia is caused by factors that are not dangerous and can be easily treated, leading to a good chance of recovery. These factors include hypercalcemia induced by medication and primary hyperparathyroidism, a condition where one or more of your parathyroid glands produce too much parathyroid hormone.

However, if hypercalcemia is caused by severe illnesses like cancer or granulomatous disorders, a group of diseases caused by the immune system causing inflammation in tissues, then the chances of recovery may be very poor. Therefore, finding not only if you have hypercalcemia, but also its cause, is very important in managing the condition properly.

Possible Complications When Diagnosed with Hypercalcemia

Hypercalcemia, or having too much calcium in your blood, can lead to various complications. These include:

• Feeling down or depressed
• Kidney stones
• Pain in the bones
• Constipation
• Inflammation of the pancreas (pancreatitis)
• Failure of the kidneys (renal failure)
• Stomach ulcers
• Feeling of pins and needles (paresthesias)
• Fainting (syncope) and heart rhythm problems (arrhythmias)
• Changes in mental status

Preventing Hypercalcemia

Dealing with high levels of calcium in the blood, medically known as hypercalcemia, requires a clear plan that includes proven treatments and direct investigations. This is done to make sure the care given is not just cost-effective, but tailored to the individual patient. Often, patients will need to make changes in their lifestyle and diet to prevent hypercalcemia from getting worse. This means that you, as a patient, may need to learn about such changes, with the help of doctors or dietitians. Working well with your health care team, in terms of communication, is important so you can understand and participate in all your treatment options. This way, you can make decisions about your care based on the best information.