Calcium is a mineral known for building strong bones, and it is also necessary for functions like muscle contraction, nerve signaling, and blood clotting. The body maintains the concentration of this mineral in the bloodstream within a very narrow range through a finely tuned system of hormones. When a routine blood test shows an elevated level of calcium, it indicates a disruption in this precise balance. Understanding the cause of this imbalance is the first step toward appropriate care and maintaining long-term health.
Understanding Hypercalcemia and Normal Ranges
The medical term for having an elevated blood calcium level is hypercalcemia, typically identified when the total serum calcium concentration exceeds 10.5 milligrams per deciliter (mg/dL) in adults. The standard adult reference range for total serum calcium is generally between 8.9 and 10.1 mg/dL. Since nearly half of the calcium in the blood is bound to proteins like albumin, a corrected calcium calculation or a direct measurement of ionized (free) calcium is often necessary for an accurate diagnosis.
Hypercalcemia is categorized into severity levels based on the measured concentration. Mild hypercalcemia is defined as a total calcium level between 10.5 and 11.9 mg/dL, where symptoms may be minimal or absent. Levels ranging from 12.0 to 13.9 mg/dL are considered moderate, often leading to more noticeable physical effects. A total calcium concentration of 14.0 mg/dL or higher constitutes a hypercalcemic crisis, requiring immediate medical intervention.
Primary Causes of Elevated Calcium
The vast majority of hypercalcemia cases stem from two main disease categories: primary hyperparathyroidism (PHPT) and malignancy. PHPT is the most frequent cause in outpatient settings, resulting from the inappropriate overproduction of parathyroid hormone (PTH) by one or more of the four parathyroid glands. Normally, PTH raises calcium levels when they are low, but in PHPT, the glands become insensitive to rising calcium and continue to secrete the hormone autonomously. This excess PTH stimulates the release of calcium from bones, increases its reabsorption in the kidneys, and enhances its absorption from the gut.
The second major cause is malignancy-associated hypercalcemia (MAH), which is the most common cause in hospitalized patients. This condition often occurs in advanced cancer and is most commonly caused by the secretion of parathyroid hormone-related peptide (PTHrP) by tumor cells. PTHrP mimics the action of actual PTH, driving calcium out of bone and increasing its reabsorption in the kidney. Unlike PHPT, the body’s own PTH is suppressed in response to the high calcium.
Other malignancy-related causes include the local destruction of bone by metastatic cancer cells, releasing large amounts of calcium directly into the bloodstream, often seen in multiple myeloma and breast cancer. Less common causes of elevated calcium include excessive intake of Vitamin D supplements, certain medications like thiazide diuretics or lithium, and endocrine disorders.
Recognizing the Physical Symptoms
The physical manifestations of hypercalcemia vary widely, depending on the concentration and speed of the calcium rise. Mild elevations may be completely asymptomatic, often discovered only through routine laboratory work. When symptoms appear, they affect multiple organ systems, a presentation classically summarized by the mnemonic “stones, bones, abdominal groans, and psychiatric moans.”
“Stones” refers to the renal system, where excessive calcium can lead to kidney stones or impair the kidney’s ability to concentrate urine, resulting in excessive thirst and urination. “Bones” describes the effect on the skeleton, ranging from bone pain and joint aches to osteoporosis and an increased risk of fractures. “Abdominal groans” encompasses gastrointestinal effects like nausea, vomiting, indigestion, and chronic constipation. The neurological effects (“psychiatric moans”) include fatigue, lethargy, memory loss, depression, and confusion.
Diagnostic Tests and Management Approaches
Once an elevated calcium level is confirmed, the next crucial step involves specific blood and urine tests to determine the precise cause. The most informative initial test is the measurement of intact parathyroid hormone (PTH) levels. This helps differentiate between PTH-driven causes, like primary hyperparathyroidism (PHPT), and non-PTH-driven causes, such as malignancy or Vitamin D toxicity. High or inappropriately normal PTH levels strongly suggest PHPT, while suppressed PTH levels point toward a non-parathyroid cause.
Additional tests often include measuring Vitamin D metabolites, phosphorus, and parathyroid hormone-related peptide (PTHrP). Management depends entirely on the underlying cause and the severity of the calcium elevation. For mild, asymptomatic hypercalcemia, a doctor may recommend observation, adequate hydration, and dietary changes.
Moderate to severe cases require more aggressive treatment, beginning with intravenous fluids to correct dehydration and promote calcium excretion. Medications such as bisphosphonates or denosumab may be used to rapidly lower calcium by inhibiting the breakdown of bone, especially in cancer-related cases. For PHPT, surgical removal of the overactive gland is the definitive cure.