People with high blood calcium, also called hypercalcemia, have above-normal levels of calcium in their blood. The most common cause of high blood calcium is a condition called primary hyperparathyroidism, or PHPT. In this condition, one or more of the parathyroid glands produces too much parathyroid hormone. This, in turn, causes the bones to release too much calcium into the blood. Women over the age of 50 are more likely than others to have PHPT.
Hormone problems are some of the many possible causes of high blood calcium. Certain types of cancer can also cause high blood calcium. This usually occurs late in the course of the cancer and is referred to as hypercalcemia of malignancy (HCM). HCM is estimated to affect between 2% to 30% of patients with cancer, rates that vary depending on cancer type and disease stage. In patients with HCM, you will see an increased blood calcium level, but it is a result of the cancer, which can produce a hormone that is similar to what is produced from the parathyroid gland called parathyroid-related peptide (PTHrp) or other hormones described below.
HCM causes can split into different categories, including:
Humoral hypercalcemia of malignancy (HHM) is caused by too much parathyroid hormone-related peptide (PTHrP) from malignant tumors.
Local osteolytic hypercalcemia (LOH) is caused by decreased mobility or cancer that attacks the bone, which will cause high blood calcium levels.
Hypercalcemia due to multiple myeloma happens through a combination of different factors, including LOH from tumors in the bone, along with injury to the kidneys that prevents them from urinating out the excess calcium.
Calcitriol-mediated hypercalcemia, also called Vitamin D 1,25-mediated hypercalcemia, is caused by the increased conversion of inactive vitamin D to the active form of vitamin D (calcitriol). This is seen in diseases such as lymphoma, sarcoidosis, and other granulomatous diseases. Too much calcitriol can lead to high blood calcium levels.
Endocrine Connection
Calcium is a mineral found mostly in your bones, where it builds and maintains bone strength. A small amount of calcium is also found in muscle and blood cells, where it plays several important roles:
Helps muscles contract,
Helps nerves and the brain work properly, and
Helps regulate (control) your heart rhythm and blood pressure.
Normally, your body controls blood calcium by adjusting the levels of several hormones. When blood calcium levels are low, your parathyroid glands (four pea-sized glands in your neck usually behind the thyroid) secrete a hormone called parathyroid hormone (PTH). PTH helps your bones release calcium into the blood. When blood calcium becomes high, PTH should fall to very low levels to try to lower it.
Vitamin D is also important in keeping calcium levels in the normal range. Vitamin D, which is actually a hormone, helps your body absorb calcium and move it from your intestines into your blood. Together, PTH and vitamin D, along with other hormones and minerals, help move calcium in or out of body tissues to keep your blood calcium at a normal level.
High blood calcium often does not cause any symptoms. But over time, some causes of high blood calcium can lead to osteoporosis (thinning of the bones), bone fractures, and kidney stones. Very high blood calcium can cause more serious problems, including kidney failure, abnormal heart rhythm, mental confusion, and even coma.
Diagnosing HCM begins with a blood test that measures calcium levels. To help pinpoint the cause, your healthcare provider may check PTH and vitamin D levels, as well as kidney function and levels of calcium in your urine. Your provider may do other tests to further assess your condition, such as checking your blood levels of phosphorus (a mineral). Imaging studies also may be helpful, such as bone mineral density, ultrasound, or other types of scans.
The signs and symptoms of HCM vary by the severity of the case, how quickly calcium levels rose, and if the cancer has spread to the bone. The severity of HCM can be split into mild (serum calcium [SCa] <12 mg/dL; 3 mmol/L), moderate (SCa 12-14 mg/dL; 3-3.5 mmol/L), or severe (SCa >14 mg/dL; 3.5 mmol/L). HCM can affect the cardiovascular, gastrointestinal, renal, neurological, and musculoskeletal systems with the following symptoms.
Mild HCM
Fatigue
Constipation
Decreased appetite
Increased urine output
Mild confusion/fatigue
Mild bone and muscle pain
Moderate HCM
Irregular heartbeat
Constipation
Stomach pain
Nausea
Vomiting
Decreased urine outpit and renal function
Increased fatigue
Mild altered mental status
Moderate muscle and bone paiin
Severe HCM
Irregular heartbeat
Constipation
Stomach pain
Nausea
Vomiting
Decreased Appetite
Rapid kidney failure
Pain with urination
Significant decreased urination
Lethargy (severe fatigue)
Altered mental status
Increased bone and muscle pain
Your treatment will depend on the cause of your high blood calcium. In general, the best treatment is to take care of the condition that is causing the high blood calcium. For instance, people with primary hyperparathyroidism who have symptoms usually have surgery to remove the problem-causing parathyroid gland(s). However, there are several medicines that can help lower blood calcium, independent of the cause, including:
Bisphosphonate: This is a class of medications that can be used in patients with high blood calcium levels. It works by preventing the destruction of bone caused by osteoclast. By preventing the destruction of old bone, calcium will not be released in the blood, thereby preventing the blood calcium level from increasing. Side effects of this medication are flu-like symptoms, including low grade fever, bone and body aches, and fatigue. You should let your healthcare provider know if you have or need any dental work done.
Denosumab: This injectable subcutaneous medication can be used if patients have failed the first line of treatment for hypercalcemia, which is bisphosphonate, or have decreased renal function. It works by preventing the breakdown of bones. When the bone breaks down, your body will release more calcium in the blood, which can cause higher calcium levels. Sides effects of this medication are tiredness, headache, back and joint pain, and nausea.
Hydration: Water intake is the single most important treatment of high calcium. Increasing hydration, either intravenously or orally, will help your body get rid of the excess calcium
Calcitonin: This is a hormone made by your thyroid gland. It works by affecting how your kidney and bone handle calcium so calcium levels can decrease. If calcium levels are high, this medication can be given in the form of subcutaneous (SubQ) injection under the skin every 12 hours for up to 4-6 doses. This medication can rapidly decrease calcium, although the effect often wears off after a few days. Common side effects are burning and pain at the injection site, nausea, vomiting, burning dry or itchy eyes, flushing and muscle pain.
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Our physician referral directory is comprised of over 6,500 members of the Society. The referral is updated daily with clinicians who are accepting new patients.
