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Hypercalcemia

Definition


Disease: Hypercalcemia Hypercalcemia
Category: Endocrine and metabolic diseases
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Disease Definition:

The condition in which the calcium level in the blood is above normal is called hypercalcemia. Calcium is needed for bone formation, and it plays an important role in contracting muscles, ensuring that the nerves and brain function properly and releasing hormones. However, these processes could be affected by high calcium levels.

Overactivity in one or more of the parathyroid glands that regulate calcium is the main cause of hypercalcemia. Overactive parathyroid glands usually cause post-menopausal women to develop hypercalcemia. Excessive use of calcium and vitamin D supplements, certain medical disorders, cancer and some medications could also cause hypercalcemia.

The signs and symptoms of hypercalcemia could be nonexistent or severe. Treatment will be based on the underlying cause of this condition.

Work Group:


Prepared by: Scientific Section

Symptoms, Causes

Symptoms:

People may have few or no signs and symptoms of hypercalcemia, especially if their condition is mild. Some of the more severe symptoms of hypercalcemia may be:

 

  • Excessive thirst
  • Abdominal pain
  • Lethargy and fatigue
  • Frequent urination
  • Nausea and vomiting
  • Muscle weakness
  • Loss of appetite
  • Muscle and joint aches
  • Confusion
  • Constipation


The severity of signs and symptoms usually don't have anything to do with the amount of excess calcium in a person's blood. For instance, pain and muscle weakness are common in older adults.

In case someone develops signs and symptoms that might indicate hypercalcemia such as frequent urination, abdominal pain and excessive thirst, they should contact a doctor.

Causes:

Calcium is mainly stored in the bones but it also exists in certain cells, especially in the blood and muscles. Milk, cheese and leafy green vegetables contain calcium and the body usually keeps a normal level of calcium in the blood by ridding itself of any excess in the urine.

TWO KEY REGULATORS:
Parathyroid hormone and calcitonin are the two hormones that serve as primary regulators of calcium in the blood.
Someone's body will produce more parathyroid hormone when the calcium in their blood falls, and it will produce less of the hormone when the calcium in their blood rises. Parathyroid will:

 

  • Stimulate the bones to release calcium into the blood
  • Stimulate the digestive tract to absorb more calcium
  • Stimulate the kidneys to excrete less calcium and activate more vitamin D, which plays an essential role in the absorption of calcium.


In the normal cases, when the calcium level in the blood rises too high, the thyroid gland will produce calcitonin, which is a hormone that slows the release of calcium from the bones. In hypercalcemia, this balance is thrown off and the body won't be able to counter the effects of too much calcium.

Some of the conditions that could cause hypercalcemia include:

Cancer:
People's risk of hypercalcemia is increased in case they have certain types of cancer, such as breast cancer, lung cancer in addition to some cancers of the blood, such as multiple myeloma. A protein that acts like parathyroid hormone is produced by some malignant (cancerous) tumors. This protein stimulates the release of calcium from the bones into the blood. This is called paraneoplastic syndrome, which is the body's response to the presence of cancer or a substance that the cancer produces. People's risk of hypercalcemia is also increased by the spread of cancer (metastasis) to their bones.

Overactivity of parathyroid glands:
As mentioned before, overactivity in one or more of the four parathyroid glands (primary hyperparathyroidism) is the main cause of hypercalcemia.

Other diseases:
Someone's blood levels of vitamin D (calcitriol) may be raised due to some diseases that produce areas of inflammation because of tissue injury (granulomas). Sarcoidosis, which is an inflammatory disease that usually begins in the lungs, and tuberculosis, which is an infectious lung disease, are included in granulomatous diseases. The person's digestive tract will be stimulated by elevated levels of calcitriol to absorb more calcium, which will raise the levels of calcium in their blood. Familial hypocalciuric hypercalcemia, which is a rare genetic disorder, could cause an increase of calcium in the body due to faulty calcium receptors in the body.

Medications:
The release of parathyroid hormone may be increased by certain drugs such as lithium, which is used to treat bipolar disorder. This causes the development of hypercalcemia. By decreasing the amount of calcium lost in the urine, thiazide diuretics could cause elevated calcium levels in the blood.

Disease effects:
Over time, bones that don't bear weight release calcium into the blood. This causes people with cancer or other diseases that cause them to spend a great deal of time sitting or lying down to develop hypercalcemia.

Dehydration:
When there's less fluid in the blood, calcium concentrations rise. So, dehydration is a common cause of mild or transient hypercalcemia.

Supplements:
Over time, calcium levels in the blood could rise above normal due to excessive intake of calcium or vitamin D supplements.

More than 90% of cases of sustained hypercalcemia are caused by cancer and hyperparathyroidism.

Complications

Complications:

Complications could be caused in various bodily systems if severe hypercalcemia is left untreated. Some of those complications may include:

Kidney failure:
Someone's kidneys could be damaged, and their ability to cleanse the blood and eliminate fluid may be limited due to severe hypercalcemia. Someone may lose kidney function permanently in case their kidney damage is severe, which will result in end-stage renal disease. In order to survive, people with end-stage renal disease will need either a permanent dialysis, which is a mechanical filtration system for removing toxins and waste from the body, or a kidney transplant.

Kidney stones:
Crystals could form in someone's kidneys in case their urine contains too much calcium. The crystals could combine over time, and end up forming kidney stones (renal lithiasis). Passing a stone could be extremely painful, and kidney damaged could result due to a blockage from a stone.

Osteoporosis:
A person may develop osteoporosis, which is a bone-thinning disease, in case their bones continue to release calcium into the blood. Osteoporosis could cause loss of height, bone fractures and spinal column curvature.

Arrhythmia (abnormal heart rhythm):
A person's heart could beat irregularly due to hypercalcemia because this condition could affect the electrical impulses that regulate heartbeat.

Nervous system dysfunction:
Severe hypercalcemia could lead to confusion, dementia and coma, which could be fatal because calcium helps regulate the nervous system.

Treatments:

To reduce calcium to a safe level and protect the kidney and bones, the person may need to be hospitalized if they have severe hypercalcemia. In this case, treatment for hypercalcemia may include:
 

  • Intravenous bisphosphonates: These medications are used to inhibit bone breakdown. An example is a group of drugs that includes zolendronate and pamidronate.
  • Intravenous fluids: These will be administered in order to rehydrate the patient.
  • Loop diuretic medications: These medications are used to help flush excess calcium from the patient's system and keep the kidneys functioning. One example is furosemide.
  • Glucocorticoids (corticosteroids): Corticosteroids are used to help counter the effects of too much vitamin D in the blood caused by hypercalcemia.
  • Calcitonin: This hormone, which reduces bone reabsorption and slows bone loss, is produced by the thyroid gland.
  • Hemodialysis: In case someone's kidneys are impaired and don't respond to other treatments, hemodialysis will be used to remove excess waste and calcium from the blood.


Treatment for hypercalcemia will depend on the underlying cause after the blood calcium returns to a safe level.

PRIMARY HYPERPARATHYROIDISM:
People may choose to wait and observe their condition in case the hypercalcemia is mild. During this time, the patient's bones and kidneys should be monitored to make sure that they remain healthy. The patient may be recommended surgery in case they've already lost bone mass or developed kidney stones. Surgery will remove the affected parathyroid gland or glands (parathyroidectomy), which in most cases cures the condition. However, the patient may be recommended mediation in case they're not a good candidate for surgery.

Medication:
For some people with hyperparathyroidism, cinacalcet may be effective, which is a drug that has shown to reduce the production of parathyroid hormone and thus lower calcium levels in the blood. In case the patient has developed osteoporosis, to preserve bone mass in their spine and hip and reduce their risk of fractures, they could take medications called bisphosphonates like ibandronate, alendronate, risedronate.

Surgery:
In a traditional surgery, a noticeable incision is made and both sides of the neck are explored while using general anesthesia. However, minimally invasive radioguided parathyroidectmy, which is a newer technique, could offer an easier option for some people. A radioisotope scan (sestamibi scan) will be used in this procedure in order to help locate the abnormal parathyroid gland before surgery. For the scan, the patient will be given a small dose of a radioactive material that will be absorbed only by the overactive parathyroid gland and not by the healthy ones. The sestamibi scan results will be used as a map to locate the abnormal gland during the operation. Sometimes, to confirm the location, a probe that detects radioactive is also used.
Damage to the nerves that control the vocal cords could be experienced by some people who undergo parathyroid surgery. In some cases, chronically low calcium levels could develop in some people, and so they need treatment with calcium and vitamin D. in some cases, parathyroid surgery may not cure the problem in every case despite the fact that it's usually very effective.

CANCER:
The overall treatment goals the patient has established with the doctor will determine the decision of whether and how to treat hypercalcemia caused by cancer. To relieve the signs and symptoms of hypercalcemia, intravenous fluids may be administered in addition to mediations such as bisphosphonates or other drugs in order to stop the breakdown of bone.

The patient's pain could be reduced, their quality of life improved, and they may remain active and undergo cancer treatments in case the hypercalcemia is treated.

Prognosis:

Not Available

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