Hypercalcemia occurs when there are higher-than-normal levels of calcium in the blood. It affects approximately 1-2% of the general population. While calcium is an important mineral for human health, its excess in the bloodstream can spell trouble. From subtle symptoms like fatigue and digestive issues to more severe complications like heart rhythm disturbances and cognitive impairment, the impact of high calcium levels can be profound.
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What Does High Calcium Mean?
Calcium is the most abundant electrolyte in the human body. Most (99%) of this mineral is stored in bones and teeth, contributing to skeletal health and bone density. The remaining 1% that is present in the blood plays essential roles in:
Hypercalcemia is a condition characterized by elevated calcium levels in the blood. The body works hard to tightly regulate blood calcium levels, generally between 8.9 and 10.1 milligrams per deciliter (mg/dL). However, it's important to recognize that this number will vary based on age and the laboratory used.
Total calcium reference ranges based on age are as follows:
- Less than 10 days: 7.6-10.4 mg/dL
- 10 days to 2 years: 9-10.6 mg/dL
- Children: 8.8-10.8 mg/dL
- Adult: 9-10.5 mg/dL
Calcium levels exceeding the upper limit of the normal reference range are diagnostic for hypercalcemia. The severity of hypercalcemia can vary, with mild cases involving calcium levels just above the upper limit of normal and severe cases involving levels significantly higher:
- Mild Hypercalcemia: 10.5-11.9 mg/dL
- Moderate Hypercalcemia: 12.0-13.9 mg/dL
- Hypercalcemic Crisis: 14.0-16.0 mg/dL
Mild cases of hypercalcemia may not result in any symptoms. As hypercalcemia becomes more severe, patients will experience symptoms that reflect the affected body parts. Examples include:
- Fatigue
- Muscle weakness and cramping
- Bone pain
- Confusion
- Headaches
- Anxiety
- Depression
- Gastrointestinal upset, including nausea, vomiting, constipation, and abdominal pain
- Frequent thirst and urination
- High blood pressure (8, 29)
Complications of long-term, untreated hypercalcemia include:
- Dehydration
- Kidney stones
- Kidney failure
- Osteoporosis
- Arrhythmia (irregular heartbeat)
- Dementia
- Coma (8, 28)
Causes of High Calcium Levels
One of the most common causes of hypercalcemia is a condition called hyperparathyroidism. The four small parathyroid glands located in the neck secrete a hormone called parathyroid hormone (PTH), which stimulates calcium release from bones into the bloodstream, increasing blood calcium levels. Overactive parathyroid glands caused by gland enlargement or benign tumors can lead to excessive release of PTH and, consequently, high blood calcium. (6)
Other potential causes of hypercalcemia include:
- Dehydration
- Prolonged immobilization
- Lung diseases, such as sarcoidosis and tuberculosis
- Kidney failure
- Thyrotoxicosis (having too much thyroid hormone in the body)
- Paget's disease of the bone (a chronic bone disorder characterized by excessive bone turnover)
- Pheochromocytoma (a type of adrenal gland tumor)
- Excessive intake of vitamin D, which causes the body to absorb more calcium
- Excessive intake of calcium-containing supplements and medications
- Taking certain medications, including lithium, thiazide diuretics, and retinoic acid
Is High Calcium a Sign of Cancer?
Cancer is the most common cause of hypercalcemia in the inpatient setting. Hypercalcemia occurs in 20-30% of cancer cases. The most common types of cancer associated with hypercalcemia include:
- Lung cancer
- Breast cancer
- Renal cell carcinoma
- Multiple myeloma
- Squamous cell cancers (27)
Serum calcium levels greater than 13 mg/dL should raise suspicion of cancer as the underlying cause of hypercalcemia and warrant a referral to an oncologist for further evaluation (50).
Mechanisms involved in cancer-related hypercalcemia (also called hypercalcemia of malignancy) include:
- Excessive secretion of PTH-related protein (PTHrP)
- Bony metastases and the release of osteoclast activating factors
- Production of calcitriol
Secretion of PTHrP by malignant tumors is responsible for 80% of hypercalcemia of malignancy cases. PTHrP mimics the action of PTH, leading to increased calcium release from bones, reduced calcium excretion by the kidneys, and enhanced calcium absorption in the intestines. The most common cancers associated with PTHrP-mediated hypercalcemia (also called humoral hypercalcemia of malignancy) include squamous cell carcinomas of the head, neck, and lungs, breast cancer, ovarian cancer, renal carcinoma, and leukemia. (41, 50)
Osteoclast activating factors are substances that promote the activity of osteoclasts (bone-destroying cells). This type of cancer-related hypercalcemia is commonly seen in patients with multiple myeloma and solid organ tumors that have metastasized (spread) to bones. (50)
Some cancers increase 1,25-dihydroxyvitamin D (calcitriol), the most active form of vitamin D. Examples include the hematologic (blood) cancers Hodgkin and non-Hodgkin lymphoma.
Lab Tests for High Calcium
There are two types of calcium blood tests:
- Total Calcium measures the amount of calcium in the blood that is bound and unbound to proteins. It is routinely measured on a basic or comprehensive metabolic panel.
- Ionized Calcium only measures the pool of calcium unbound to proteins (called "free calcium") in the blood. Normal ionized calcium levels are 4-5.6 mg/dL.
Total serum calcium must be corrected for patients with abnormal albumin concentrations. To do so, use a calculator such as this one. Directly measuring ionized calcium provides a more accurate assessment of hypercalcemia without the need to adjust for albumin. (49)
When hypercalcemia is detected (total calcium > 10.5 mg/dL or ionized calcium > 5.6 mg/dL), the first step is to conduct a thorough patient history and physical exam to screen for causative supplements/medications, underlying health conditions, and clinical signs and symptoms of hypercalcemia. (13)
To determine the underlying cause of hypercalcemia, measure intact PTH and order kidney function tests. Low glomerular filtration rate (GFR) suggests impaired kidney function as the cause of hypercalcemia.
If PTH is normal or high, order a 24-hour urine collection for calcium and creatinine. High 24-hour urinary calcium indicates hyperparathyroidism. Additional testing is recommended for patients with hyperparathyroidism, including a sestamibi parathyroid scan, an imaging procedure that locates parathyroid tumors, and a DEXA scan, which measures bone mineral density. (13, 49)
If PTH is low, suspect malignancy (13, 49). Tests to order as part of a cancer work-up include:
- PTHrP
- 1,25-dihydroxyvitamin D
- 25-hydroxyvitamin D
- Alkaline phosphatase
- Serum protein electrophoresis
If the malignancy workup is negative, consider ordering thyroid function tests to rule out hyperthyroidism and vitamin A to screen for vitamin A toxicity.
Treatment for High Calcium Levels
Treatment of hypercalcemia will depend on its severity and what's causing it.
In mild cases of hypercalcemia caused by lifestyle factors, your doctor may recommend a treatment plan that includes:
- Drinking more water to stay well-hydrated
- Increasing physical activity levels
- Modifying supplements and medications. For example, your doctor may switch you to a different type of diuretic, advise you to stop taking calcium supplements, or prescribe a lower dose of vitamin D than you are currently taking.
Hypercalcemic crisis is a medical emergency and needs to be treated immediately. Doctors will treat a hypercalcemic crisis with the following combination of treatments:
- Intravenous saline rehydration for 1-3 days
- Furosemide: a type of diuretic medication that inhibits calcium reabsorption by the kidneys
- Bisphosphonates: a class of medication that act to inhibit osteoclast cells
- Calcitonin: a thyroid hormone that inhibits bone break-down, decreases calcium absorption from the digestive tract, and encourages calcium elimination by the kidneys
The treatment plan will also include interventions that address and treat the underlying cause of high calcium levels. For example, hyperparathyroidism is often treated with surgical removal of the affected parathyroid glands – a procedure called parathyroidectomy. However, asymptomatic patients may be candidates for medical observation and nonsurgical interventions that primarily involve moderating their intake of calcium and vitamin D. (48)
Patients diagnosed with cancer-related hypercalcemia should establish care with an oncologist. Integrative oncology is an approach to cancer care that combines conventional medical treatments (chemotherapy, immunotherapy, surgery, and radiation) with targeted evidence-based complementary therapies (e.g., diet, botanical medicine, intravenous therapy) to improve patient outcomes and quality of life.
Life Expectancy with High Calcium
Hypercalcemia can significantly impact life expectancy, especially when it is associated with cancer. Cancer-related hypercalcemia typically indicates an advanced stage of disease and is associated with a poorer prognosis, with up to 50% of patients dying within 30 days of their diagnosis.
Hypercalcemia has also been associated with cardiovascular risk factors, including hypertension, high cholesterol, and metabolic syndrome – translating to a higher risk of heart attack and cardiovascular-related mortality (30, 35).
A Note on Calcium Scores
It is important to distinguish between blood calcium levels and coronary calcium scores. Blood calcium levels measure the amount of calcium circulating in the bloodstream. A coronary calcium score, often referred to simply as a calcium score, is a measure obtained from a computed tomography (CT) scan of the heart. This score quantifies the amount of calcified plaque in the heart's arteries and is used to assess the risk of coronary artery disease (CAD). A higher coronary calcium score indicates a greater burden of coronary artery calcification, which correlates with more extensive heart disease and an increased risk of cardiovascular events, like heart attacks.
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Key Takeaways
- Hypercalcemia, or high calcium levels in the blood, poses significant negative health implications.
- Symptoms that may indicate hypercalcemia include fatigue, muscle weakness, and nausea. More severe complications associated with long-term hypercalcemia include kidney stones, cardiac arrhythmias, and cognitive disturbances.
- Cancer-related hypercalcemia often indicates advanced disease and is associated with poorer prognosis and decreased life expectancy.
- Regardless of the cause of high blood calcium levels, early detection and management are essential for ensuring positive health outcomes.
- Regular monitoring of serum calcium, such as annual testing during an annual wellness exam, can facilitate prompt diagnosis and intervention, reducing the risk of serious health issues.
- Individuals with persistently high calcium levels should seek medical advice to identify and treat underlying causes.
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