Cancer-Related Hypercalcemia

This page explains high blood calcium in people with cancer: why it happens, how it is treated, and when it is an emergency.

Call the oncology team the same day if you notice increasing thirst or are passing much more urine than usual. Call the same day for new constipation, belly pain, nausea, weakness, or unusual tiredness as well. The American Cancer Society says to get emergency help for confusion or trouble thinking, a seizure, an irregular heartbeat, or passing out. Also go to an emergency department for vomiting that stops you keeping fluids down, or if someone is so drowsy they are hard to wake.

Hypercalcemia means too much calcium in the blood. In cancer it happens in three main ways. Knowing which one is at work changes the tests your team orders.

A hormone-like protein (PTHrP). This is the most common cause. StatPearls says it accounts for about 80 percent of cases. Some tumors make parathyroid hormone-related protein, or PTHrP. It acts like the body's own parathyroid hormone. It makes bone break down and release calcium. It also makes the kidneys hold on to more calcium. Doctors call this humoral hypercalcemia of malignancy.

Cancer in the bone. Cancer that has spread to bone can release calcium into the blood. StatPearls explains that some of these cancer cells make PTHrP right in the bone. They also boost a signal called RANKL. RANKL switches on osteoclasts, the cells that dissolve bone.

Extra active vitamin D. Some cancers, lymphomas most often, make the active form of vitamin D (calcitriol). The gut then takes in more calcium from food.

Blood tests can help tell these causes apart. The Endocrine Society lists tests for PTH, PTHrP and vitamin D. Ask which of these tests were sent.

Calcium in the blood comes in two forms. Some is bound to proteins, mainly albumin. The rest is free, also called ionized calcium. MedlinePlus says the body normally keeps about equal amounts of each. The free form is the one that is active in the body. A standard calcium test measures the total of both.

When albumin is low, the total can look lower than the active free calcium really is. Labs and doctors handle this in two ways. One is a formula that adjusts the total for a low albumin, called corrected calcium. FDA drug labels use this formula. It is an estimate, so it is not something to work out on your own result at home. The other way is an ionized calcium test, which measures the free calcium directly. MedlinePlus says this test is often used when someone is seriously ill.

So the useful question is not just "what was my calcium." It is "was that corrected for albumin, or did you measure ionized calcium."

The Endocrine Society sorts calcium levels into three bands.

• Mild: below 12 mg/dL (but above normal)
• Moderate: 12 to 14 mg/dL
• Severe: above 14 mg/dL

Mild hypercalcemia may cause few or no symptoms, or tiredness and constipation. Severe hypercalcemia can cause kidney failure and changes in thinking, such as confusion. The American Cancer Society lists seizures, an irregular heartbeat and loss of consciousness among the signs that need emergency care.

StatPearls says that "asymptomatic patients with mild to moderate hypercalcemia do not require immediate therapy." Treating the cancer itself still matters. Symptoms plus a severe number is a different matter. That is urgent.

The timing helps explain why you may get more than one treatment at once.

IV fluids (saline) come first. The FDA label for zoledronic acid says fluids should start promptly and that people should be well hydrated before the drug is given. Your team also watches how much urine you pass. Fluid has to be given with care in people with heart failure, because too much can overload them.

Calcitonin is the fastest-acting drug. On its FDA label, calcium started to fall within 1 to 2 hours. The Endocrine Society notes that the effect is short, lasting a few days. It is a bridge until slower drugs start to work.

Bisphosphonates take a few days to work. In the studies on the zoledronic acid label, calcium was back to normal by day 4 in about 45 in 100 people, and by day 7 in about 83 in 100. The median time before calcium rose again was about 30 days with zoledronic acid and 17 days with pamidronate. These two drugs are the ones used most. They are given by vein. The label says kidney function is checked before each dose. Ask which one is planned for you and why.

Denosumab (Xgeva) works in a different way, by blocking RANKL. It is given as a shot under the skin. The FDA approved it for hypercalcemia of malignancy that has not responded to bisphosphonates. The Endocrine Society notes it is also an option when kidney function is poor. Ask whether it fits your situation.

Loop diuretics such as furosemide have a narrow role. The zoledronic acid label says they should not be used until a person is fully rehydrated. Given too early, they can make dehydration worse.

Dialysis may be used when the kidneys are failing, the American Cancer Society says.

Do not cut back on fluids because you are urinating more. The American Cancer Society advises drinking plenty of fluids, unless your team has told you to limit them. Dehydration makes high calcium worse.

The American Cancer Society also advises avoiding calcium supplements and antacids that contain calcium. Do not start or stop calcium or vitamin D supplements without asking. Do not take a water pill (diuretic) that was not prescribed for this.

Staying active, as far as you can, may also help, the American Cancer Society says. Ask your team first if there is a reason not to move, such as a bone at risk of breaking.

High calcium that is not treated can damage the kidneys. Ask how your kidney function will be checked.

The treatment itself can also cause problems. The FDA label for zoledronic acid lists kidney problems and osteonecrosis of the jaw, which means bone death in the jaw. The label says a dental exam should be considered before treatment in people with risk factors such as cancer. It also advises good care of your mouth and routine dental check-ups during treatment. So ask about your teeth before you start. Tell your team before any dental surgery or tooth removal.

• New confusion, trouble thinking, or someone is hard to wake
• A seizure, or passing out
• An irregular heartbeat
• Vomiting that prevents keeping any fluid down
• Passing no urine, or far less than usual
• Severe muscle weakness that stops normal walking

If someone is hard to wake, has fainted, or cannot safely get to hospital, call 911 or your local emergency number rather than driving them.

Take the medicine list with you. Take the most recent calcium and albumin results too.

Tumor Lysis Syndrome Action Guide, Spinal Cord Compression: A Cancer Emergency, and Preparing for an Emergency Department Visit With Cancer.

• American Cancer Society — Hypercalcemia (High Calcium Levels)
• Endocrine Society — Hypercalcemia of Malignancy (patient guide)
• MedlinePlus — Calcium Blood Test
• DailyMed — Zoledronic acid injection (4 mg) prescribing information
• DailyMed — Xgeva (denosumab) prescribing information
• DailyMed — Miacalcin (calcitonin salmon) injection prescribing information
• NCBI Bookshelf (StatPearls) — Malignancy-Related Hypercalcemia