Calcium is a mineral that plays a widespread role in the body, helping nerves transmit signals, muscles contract, and blood clot effectively. The vast majority of this mineral is stored in the bones, but a small amount circulates in the bloodstream where it is tightly regulated. When the calcium level in the blood rises above the normal range, typically exceeding 10.4 milligrams per deciliter (mg/dL), the condition is called hypercalcemia. This elevation disrupts the delicate balance required for normal bodily function and can impact multiple organ systems. Hypercalcemia is a common metabolic finding, frequently discovered incidentally during routine blood tests performed for other health monitoring purposes.
Recognizing the Signs
High calcium levels often produce symptoms that are vague and can easily be mistaken for other common ailments. Mild hypercalcemia may cause no noticeable symptoms at all. When the levels are higher or the condition has persisted for a long time, the effects become more pronounced across different body systems.
One of the most common manifestations involves the renal system, where the kidneys struggle to process the excess mineral. This often results in excessive thirst and frequent urination (polydipsia and polyuria) as the kidneys attempt to excrete the extra calcium. Gastrointestinal symptoms are also common, including nausea, loss of appetite, and significant constipation.
The skeletal and neuromuscular systems can also be affected, leading to generalized weakness and profound fatigue. Over time, the leaching of calcium from the bones into the blood can cause bone aches and contribute to thinning bones, or osteoporosis. Higher calcium concentrations can also affect the brain, presenting as neuropsychiatric symptoms from difficulty concentrating and depression to confusion.
Understanding the Main Causes
The body normally maintains calcium levels through a feedback system involving the parathyroid glands, the kidneys, and the bones. Hypercalcemia results when this fine balance is disrupted, usually by a condition that either increases the absorption of calcium or accelerates its release from bone tissue. The two most frequent causes account for the vast majority of cases: primary hyperparathyroidism and malignancy.
Primary Hyperparathyroidism
Primary hyperparathyroidism (PHP) is the most common cause of hypercalcemia in people not hospitalized. This condition arises when one or more of the four small parathyroid glands becomes overactive and inappropriately secretes too much parathyroid hormone (PTH). In approximately 85% of cases, this overactivity is due to a benign tumor (adenoma) on a single parathyroid gland. The excess PTH acts on its target organs to raise blood calcium levels without proper regulation.
The hormone increases the activity of osteoclasts, cells that break down bone tissue, releasing stored calcium into the bloodstream. PTH also signals the kidneys to reabsorb more calcium back into the blood instead of excreting it. Additionally, PTH indirectly increases the production of active Vitamin D, which enhances calcium absorption from the gut.
Hypercalcemia of Malignancy
The second most common cause, especially in hospitalized patients, is hypercalcemia of malignancy (HCM), caused by certain types of cancer. This occurs through two primary mechanisms that accelerate the breakdown of bone.
The first is humoral hypercalcemia of malignancy (HHM), where tumor cells secrete parathyroid hormone-related peptide (PTHrP). This protein structurally mimics PTH, binding to receptors on bone and kidney cells, causing widespread bone resorption and calcium retention.
The second mechanism is local osteolytic hypercalcemia (LOH), seen most often in cancers that have spread to the bone. In these cases, cancer cells within the bone tissue release localized factors that stimulate osteoclasts in the immediate area. This localized destruction of bone tissue releases calcium into the circulation.
Other Causes
Less commonly, high calcium can be caused by certain medications or excessive intake of supplements. Thiazide diuretics can reduce calcium excretion by the kidneys, causing a mild elevation. Excessive Vitamin D supplementation also leads to hypercalcemia by increasing calcium absorption from the digestive tract. Other conditions, such as hyperthyroidism or granulomatous diseases like sarcoidosis, can also disrupt calcium homeostasis.
Confirmatory Testing and Treatment
The discovery of high blood calcium requires further investigation to confirm the finding and determine the underlying cause. Physicians typically order a repeat blood test, including a measurement of the patient’s intact Parathyroid Hormone (PTH) level. The PTH level is the most important diagnostic tool because it helps differentiate between the primary causes.
If the PTH level is high or upper-normal when calcium is elevated, it strongly suggests primary hyperparathyroidism. Conversely, if the PTH level is suppressed or very low, it indicates a cause not driven by the parathyroid glands, most commonly malignancy. Other tests, such as Vitamin D levels and sometimes a 24-hour urine collection, may be performed to complete the diagnostic picture.
For patients with mild, asymptomatic hypercalcemia, the initial approach involves observation and ensuring adequate hydration to help the kidneys excrete the excess mineral. For those with significantly elevated calcium levels or severe symptoms, treatment often begins with intravenous hydration using saline solution to restore fluid balance and promote urinary calcium excretion.
Medications are used to rapidly lower calcium levels by targeting the bone. Bisphosphonates, such as pamidronate or zoledronic acid, inhibit the bone-resorbing activity of osteoclasts. For severe cases, calcitonin may also be used for its rapid, short-lived effect. Long-term management involves treating the root cause, which may mean surgery for PHP or specific systemic treatment for malignancy-related hypercalcemia.