Hypercalcemia is quite a common condition that can occur in both hospital and non-hospital settings. It’s essentially when there’s too much calcium in your blood. The severity of this condition is determined by the amount of calcium in your blood. It’s considered mild if the calcium levels are between 10 to 12 mg/dL, moderate if they’re between 12 to 14 mg/dL, and severe if they’re more than 14 mg/dL.

Calcium in our blood is usually attached to a protein called albumin, making up about 40% to 45% of the total calcium. Because of this, the calcium levels in our blood can change based on the amount of albumin present. Therefore, if hypercalcemia is suspected, the free calcium level, or the calcium that isn’t attached to proteins, should be measured. You can also calculate the corrected calcium by using the equation: serum calcium + 0.8 multiplied by (4 – patient’s albumin level); where a normal albumin level is 4.0 g/dL.

Most cases of hypercalcemia, over 90%, are caused by primary hyperparathyroidism (an issue with the parathyroid glands causing them to produce too much parathyroid hormone) and cancer-induced hypercalcemia. In a hospital setting, cancer is the most common cause of high calcium levels in the blood.

Hypercalcemia, or high calcium levels in the blood, can be caused by a variety of things. It’s most commonly due to primary hyperparathyroidism (PHPT), cancer, certain medications, genetic factors, or a problem with the endocrine system, which controls hormones in the body.

When a person is diagnosed with hypercalcemia, the doctor first needs to figure out if it’s a result of a harmless condition or if it’s caused by cancer. The most common non-cancerous cause is PHPT, where people generally don’t show symptoms and often have a slightly high calcium level over time.

If a patient’s calcium level is over 13 mg/dL when tested for the first time, doctors may suspect that cancer is causing the hypercalcemia. Severe hypercalcemia symptoms caused by cancer usually signal a serious condition that needs immediate treatment.

Hypercalcemia of malignancy, a condition of high calcium levels in the blood, is seen in about 20% of all cancer patients at some point during their illness. The type of cancer most frequently associated with this condition is multiple myeloma. However, overall, only about 2 to 3% of people diagnosed with cancer experience hypercalcemia of malignancy. It’s worth noting that these numbers have slowly been decreasing over time, thanks to improved treatment options.

Hypercalcemia, or high calcium levels in the blood, can result in a variety of symptoms, but there aren’t any specific physical signs that doctors can pinpoint through a physical examination. Some people might not show any symptoms at all, while others might have problems connected to various organ systems such as the digestion, muscles and skeletal structure, heart and blood vessels, kidneys, and the brain or mental health.

Kidney issues can range from excessive urination and thirst, inability of kidneys to concentrate urine, gradual decline in kidney function, to imbalance of kidney acid levels triggered by kidney stones. If not treated, ongoing high calcium levels can eventually lead to damaged kidneys with calcium deposits, a condition known as nephrocalcinosis.
Digestive symptoms can vary from loss of appetite to nausea and constipation. Too much calcium can get deposited in the pancreatic duct causing inflammation of the pancreas. Increased levels of calcium can also boost the release of a hormone called gastrin, which may contribute to stomach ulcers.
Musculoskeletal symptoms can show up as muscle weakness and bone pain.
Heart-related signs are usually subtle and might include QTc intervals shortening in an EKG, and in rare cases, more dangerous irregular heartbeats. Excess calcium can get deposited in the heart valves and the heart’s blood vessels which can contribute to heart disease.
Brain-related symptoms depend on the levels of calcium. People with mild hypercalcemia typically have no symptoms, while those with more severe hypercalcemia can experience lethargy, confusion, or even coma, especially in older adults.
Common mental health disturbances include anxiety, depression, or cognitive disturbances.

If you have hypercalcemia, or high calcium levels in your blood, your doctor will likely start by taking a detailed medical history and performing a physical examination. This can give them clues about what might be causing your condition. They’ll look at past blood tests to see what your calcium levels have been over time, and they’ll ask you about any medicines you’re taking (including prescriptions, over-the-counter vitamins, and supplements) as well as your diet, family medical history, and any past diseases you’ve had.

One of the first tests they might order is a PTH (parathyroid hormone) level test. This can help your doctor determine if your hypercalcemia is due to having too much PTH (which can be caused by certain genetic disorders or problems with your parathyroid glands), or if it’s due to something else. Other causes could include cancer, certain immune system disorders, hormonal disorders, and taking too much vitamin D.

If you have slightly elevated PTH levels and a 24-hour urine test shows that you’re not excreting much calcium in your urine, you could have a condition called Familial Hypocalciuric Hypercalcemia (or FHH).

If your PTH levels are low or low-normal (less than 20 pg/mL), then your doctor might suspect that your hypercalcemia is not related to PTH. They may order additional tests, checking levels of other hormones and vitamin D metabolites (substances resulting from metabolism). For instance, high levels of PTHrP (another hormone) can indicate a specific type of hypercalcemia related to cancer. High levels of certain types of vitamin D can suggest lymphoma (a type of cancer) or an immune system disorder.

If vitamin D levels turn out to be normal, then your doctor may order blood and urine tests to rule out multiple myeloma, which is a type of cancer that affects plasma cells in your bone marrow.

For patients with cancer-related hypercalcemia, PTH levels should also be checked, as they could have both cancer and a condition that affects the parathyroid glands at the same time. In rare cases, your doctor might see something called band keratopathy if they examine your eyes with a special tool called a slit lamp. This means there are calcium phosphate deposits in your cornea.

The treatment for high calcium levels in the blood (hypercalcemia) should be personalized, focusing on alleviating the patient’s symptoms and addressing the underlying cause. It’s also vital to monitor and replenish phosphorus levels in the blood, as low levels (hypophosphatemia) often occur alongside hypercalcemia and can make treatment more challenging.

If hypercalcemia is mild or moderate and the patient is not experiencing symptoms, immediate therapy is typically not necessary. However, a proactive approach in managing the underlying cause is required. In such cases, patients need guidance about their diet, medication, and maintaining hydration and physical activity.

Those with severe hypercalcemia and symptoms will need urgent treatment. This often involves admission to a hospital for fluids given directly into a vein (IV). This helps restore the body’s water balance and encourages excess calcium to be removed from the body in urine.

Alongside hydration, medications such as calcitonin and bisphosphonates are commonly used. Calcitonin works within a few hours to slow down the release of calcium from the bones into the blood and increase its removal in urine. Bisphosphonates also slow the release of calcium from bones but take a few days to become effective. However, the effects of these medications can last for weeks. This cumulative approach aims to reduce calcium levels in the blood and keep them within a normal range as effectively as possible while the underlying cause of the hypercalcemia is being investigated and treated.

Loop diuretics, a type of medication, can also be used to increase calcium removal through urine, but it’s crucial this treatment is given after the patient has been sufficiently rehydrated with IV fluids. Special care should be taken for patients who have heart or kidney conditions.

If bisphosphonates don’t work, a drug called denosumab may be used. Denosumab is also often used to treat patients with kidney impairment or in cancer patients to prevent complications related to the bones. Another type of medication called glucocorticoids are beneficial for patients whose high calcium levels are driven by an increase in a specific type of vitamin D. They reduce the production of this vitamin D variant and decrease the absorption of calcium in the intestines.

Calcimimetic agents, such as cinacalcet, may be preferred in patients who are on dialysis or who have hypercalcemia due to parathyroid cancer. If all these strategies don’t improve the calcium levels in the blood, hemodialysis, a procedure that filters and cleans the blood, may be necessary. Hemodialysis might also be considered for patients with severe heart or kidney failure who cannot tolerate adequate IV hydration.

These conditions are medically significant and may need to be considered during diagnosis:

Adrenal insufficiency
Berylliosis (a lung condition)
Coccidioidomycosis (a type of fungal infection)
Crohn’s disease
Hyperkalemia (high potassium levels)
Hypermagnesemia (high magnesium levels)
Hypernatremia (high sodium levels)
Hyperparathyroidism (overactive parathyroid glands)
Hyperphosphatemia (high phosphate levels)
Hyperthyroidism (overactive thyroid)
Milk alkali syndrome
Vitamin D toxicity

The outlook for patients with high calcium levels due to cancer largely depends on what’s causing the problem and the type of cancer involved. If the disease is caught early on, the prognosis is often more positive. However, if the condition is diagnosed in its advanced stages or is discovered late, the prognosis tends to be worse.

If hypercalcemia, a condition of excessively high levels of calcium in the blood, is not diagnosed or treated effectively, it can have severe consequences. These could include significantly damaging the kidneys, leading potentially to kidney failure. Complications can also emerge in the bones, such as reduced bone density, osteoporosis (a disease that weakens the bones), and fractures.

Possible Complications:

Kidney damage leading to kidney failure
Decreased bone density
Osteoporosis
Fractures

Patients who have issues with their calcium levels that are linked to underlying cancer conditions are usually advised to also consult with a hormone specialist (endocrinologist), in addition to their cancer specialist (oncologist), for further assessment and treatment. If problems arise in other parts of the body from this condition, it’s also recommended that they see doctors who specialize in those affected areas. This might include seeing a heart specialist (cardiologist), an eye specialist (ophthalmologist), a brain and nervous system specialist (neurologist), or even a brain surgeon (neurosurgeon).