Hypercalcemia: Causes, Risks, and Effective Management Strategies

Hypercalcemia occurs when the total serum calcium level exceeds 2.75 mmol/L, surpassing the normal physiological range of 2.25–2.6 mmol/L. This metabolic imbalance can lead to a cascade of health complications if left untreated. While mild cases may present with subtle or no symptoms, severe hypercalcemia poses significant risks to vital organ systems, particularly the nervous system, cardiovascular system, and kidneys.

Primary Causes of Elevated Calcium Levels

The most prevalent cause of hypercalcemia is primary hyperparathyroidism, a condition in which one or more of the parathyroid glands become overactive and secrete excessive parathyroid hormone (PTH). This hormone directly regulates calcium levels in the blood, and its overproduction leads to increased calcium release from bones, enhanced intestinal calcium absorption, and reduced renal calcium excretion.

Tumor-Related Hypercalcemia

Malignant tumors are another major contributor to high calcium levels. Certain cancers—especially those involving the bone marrow or metastatic to bone, such as multiple myeloma, breast cancer, and lung cancer—can trigger humoral hypercalcemia of malignancy. These tumors produce a substance similar to PTH (PTHrP), disrupting normal calcium regulation. Additionally, direct bone destruction by tumor infiltration releases large amounts of calcium into the bloodstream, a process known as osteolytic hypercalcemia.

Endocrine Disorders Linked to Hypercalcemia

Besides parathyroid dysfunction, other endocrine diseases can also elevate calcium levels. Conditions like pheochromocytoma, a rare tumor of the adrenal medulla, and adrenal insufficiency (Addison's disease) have been clinically associated with hypercalcemia. Though less common, these disorders affect hormonal balance and fluid regulation, indirectly contributing to increased serum calcium concentrations.

Impact of Hypercalcemia on Organ Systems

Elevated calcium levels exert toxic effects across multiple body systems. In the cardiovascular system, calcium enhances myocardial contractility but simultaneously depresses electrical conduction. This dual effect increases the risk of arrhythmias and can result in a dangerous pause during cardiac diastole, potentially leading to cardiac arrest in extreme cases.

Nervous system function is also significantly impaired. High calcium reduces neuronal excitability, causing symptoms ranging from fatigue and confusion to lethargy and coma in severe instances. Patients often report muscle weakness, diminished reflexes, and cognitive fog, all of which compromise daily functioning and quality of life.

The kidneys bear a heavy burden as they attempt to filter excess calcium. Chronic hypercalcemia can lead to nephrocalcinosis, kidney stones, and even progressive renal failure due to calcium deposition in renal tissue.

Diagnosis and Treatment Approaches

Effective management begins with identifying the underlying cause. A comprehensive diagnostic workup—including serum PTH, vitamin D levels, imaging studies (such as neck ultrasound or sestamibi scans for parathyroid adenomas), and oncological evaluation—is essential. For patients with primary hyperparathyroidism due to an adenoma or hyperplasia, surgical removal of the affected gland(s) remains the definitive treatment.

In cases linked to malignancy, treatment focuses on addressing the cancer itself through chemotherapy, radiation, or targeted therapies. Adjunctive measures such as intravenous hydration, bisphosphonates, or calcitonin may be used to rapidly lower calcium levels in acute settings.

For endocrine-related causes like pheochromocytoma or adrenal insufficiency, correcting the primary disorder typically resolves the hypercalcemia. Hormonal replacement therapy, surgical resection of tumors, and close monitoring are key components of long-term care.

Early detection and intervention are crucial in preventing irreversible organ damage. Individuals experiencing unexplained fatigue, bone pain, frequent urination, or mental status changes should seek medical evaluation to rule out hypercalcemia and its underlying causes.