Hypercalcemia (Elevated Calcium Levels)

Picture of the parathyroid glands

• Calcium is important for bone strength, as well as muscle and nerve function
• Calcium levels in the bloodstream are regulated by PTH, vitamin D, and calcitonin
• Hypercalcemia can vary in severity and chronicity
• The main cause of hypercalcemia is hyperparathyroidism
• Malignancies may be associated with hypercalcemia, and the presence of hypercalcemia usually heralds a worse prognosis
• The signs and symptoms of hypercalcemia can be remembered by the phrase "moans, stones, groans, and bones."
• Treatment depends on the underlying cause of hypercalcemia as well as the degree of severity
• Both surgical and medical treatments are available as treatment options
• The prognosis depends on the underlying cause of hypercalcemia

Calcium is a mineral that is important in the regulation and processes of many body functions including bone formation, hormone release, muscle contraction, and nerve and brain function. Hypercalcemia is the term that refers to elevated levels of calcium in the bloodstream.

Regulation of Calcium

Calcium levels are tightly regulated in the body. Calcium regulation is primarily controlled by parathyroid hormone (PTH), vitamin D, and calcitonin.

• Parathyroid hormone is a hormone produced by the parathyroid glands, which are four small glands that surround the thyroid and are found in the anterior part of the lower neck.
• Vitamin D is obtained through a process that begins with sun exposure to the skin, the process then continues in the liver and kidneys. Vitamin D can also be found in foods such as eggs and dairy products.
• Calcitonin is produced in specialized cells in the thyroid gland.

Together, these three hormones act on the bones, the kidneys, and the GI tract to regulate calcium levels in the bloodstream.

One of the most common causes of high calcium levels (hypercalcemia), is an overproduction of the parathyroid hormone, or hyperparathyroidism.

• Hyperparathyroidism tends to be more common in women over 50.
• It can be the result of all four parathyroid glands producing too much PTH (parathyroid hyperplasia), or one gland specifically producing an excessive amount of hormone (usually the result of a parathyroid adenoma, or benign tumor).

Hypercalcemia can occur due to other medical conditions. These conditions can vary in severity and chronicity and may be life-threatening. Malignancy is a common cause of elevated blood calcium. Up to 20% of individuals with cancer will develop hypercalcemia at some point in their disease.

Other conditions associated with hypercalcemia include:

• Cancers, especially lung cancer and breast cancer
• Immobilization over a long period
• Kidney failure
• Overactive thyroid (hyperthyroidism) or excessive thyroid hormone intake
• Use of certain medications such as the thiazide diuretics
• Inherited kidney or metabolic conditions
• Excessive vitamin D levels from vitamins, excessive dietary calcium, or diseases that may result in excess vitamin D production

In the majority of patients with hypercalcemia, the signs and symptoms are minimal. In general, the symptoms increase with higher levels of calcium in the blood. In severe cases, elevated calcium levels can cause abnormal heart rhythms with specific findings on electrocardiogram (EKG).

Because of the clinical findings that are seen in hypercalcemia, the symptoms are often described as "moans, stones, groans, and bones".

Some of the symptoms include the following:

• Moans (gastrointestinal conditions)
  • Constipation
  • Nausea
  • Decreased appetite
  • Abdominal pain
  • Peptic ulcer disease
• Stones (kidney-related conditions)
  • Kidney stones
  • Flank pain
  • Frequent urination
• Groans (psychological conditions)
  • Confusion
  • Dementia
  • Memory loss
  • Depression
• Bones (bone pain and bone-related conditions)
  • Bone aches and pains
  • Fractures
  • Curving of the spine and loss of height

Hypercalcemia is easily diagnosed with a blood test. Diagnosing the causes of hypercalcemia, however, is a more involved process; in addition to a detailed history and physical examination, it may require further blood tests (such as a PTH level and vitamin D level), urine evaluation, X-rays, and other imaging procedures.

The treatment of elevated levels of calcium in the blood involves the evaluation of the following:

1. Is the level of calcium elevated enough to be dangerous, or is it causing symptoms?
2. What is the underlying cause of hypercalcemia, and does it need treatment?

If the hypercalcemia is causing severe symptoms, or if the values are critically high, lowering the blood levels may require hospitalization and the use of hydration, steroids, or even dialysis. There are intravenous medications that can be used to lower calcium as well.

If the hypercalcemia is modest, treatment with medications can be administered on an outpatient basis.

If the underlying cause is hyperparathyroidism (particularly from an adenoma), certain criteria are reviewed to discuss if surgery should be considered. These criteria include the absolute calcium level, a history of kidney stones or other calcium-related complications, and the amount of calcium seen in a 24-hour urine collection. Based on these findings, surgical removal of the adenoma may be considered.

The results of treatment for hypercalcemia depend on the underlying cause of the condition. If hypercalcemia is seen in the presence of cancer, the average 30-day survival rate is about 50%. The prognosis is excellent for many of the other causes of hypercalcemia provided the underlying cause is addressed and treated.

Hypercalcemia cannot be prevented, but early detection can both allow for the normalization of calcium levels and lead to an early work-up to define the cause. If there is a known family history of hypercalcemia or hyperparathyroidism, it is worth mentioning this to the healthcare practitioner; together the patient and healthcare practitioner can determine if screening is warranted.