What is the primary cause of hypercalcemia?

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From the Guidelines

The number one cause of hypercalcemia is primary hyperparathyroidism. This condition occurs when one or more of the parathyroid glands become overactive and secrete excessive amounts of parathyroid hormone (PTH) 1. The parathyroid glands are four small glands located in the neck near the thyroid gland. When functioning normally, they help maintain appropriate calcium levels in the blood by releasing PTH when calcium levels drop. In primary hyperparathyroidism, the glands produce too much PTH regardless of calcium levels, leading to increased calcium absorption from the intestines, increased calcium release from bones, and decreased calcium excretion by the kidneys. This results in elevated blood calcium levels, or hypercalcemia. Primary hyperparathyroidism is most commonly caused by a benign tumor (adenoma) on one of the parathyroid glands, though it can occasionally be caused by enlargement of all four glands or, rarely, parathyroid cancer. The condition is more common in women, particularly after menopause, and the risk increases with age.

Some key points to consider:

  • Primary hyperparathyroidism is diagnosed by biochemical testing, specifically serum calcium and serum PTH 1.
  • Treatment typically involves surgical removal of the affected parathyroid gland(s) 1.
  • The role of imaging in primary hyperparathyroidism is to localize the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery 1.
  • Other causes of hypercalcemia, such as secondary hyperparathyroidism, are less common and typically occur in the context of chronic kidney disease 1.

Overall, primary hyperparathyroidism is the most common cause of hypercalcemia, and its diagnosis and treatment are critical to preventing long-term complications and improving patient outcomes.

From the Research

Causes of Hypercalcemia

  • The most common cause of hypercalcemia in the outpatient setting is primary hyperparathyroidism 2, 3, 4, 5.
  • Primary hyperparathyroidism is characterized by hypercalcemia and elevated or inappropriately normal serum levels of parathyroid hormone 4.
  • In hospitalized patients, the most common cause of hypercalcemia is malignancy 6.

Primary Hyperparathyroidism

  • Primary hyperparathyroidism can manifest with osteoporosis, hypercalciuria, vertebral fractures, and nephrolithiasis 4.
  • Parathyroidectomy is the only curative treatment for primary hyperparathyroidism and is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae 4, 5.
  • Medical management may be considered in patients with mild asymptomatic disease, contraindications to surgery, or failed previous surgical intervention 2.

Diagnosis and Treatment

  • Diagnosis of primary hyperparathyroidism occurs in most cases in asymptomatic patients by a routine calcium measurement with corrected high total calcium associated with high or inappropriately abnormal PTH 5.
  • Surgical indications for primary hyperparathyroidism include osteoporosis, hypercalciuria, spine fractures, age <50 years, calcemic values above 1.0 mg/dL threshold value, creatinine clearance ≤60 mL/min, and nephrolithiasis or nephrocalcinosis 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Hypercalcemia].

Duodecim; laaketieteellinen aikakauskirja, 2014

Research

Primary hyperparathyroidism.

Nature reviews. Endocrinology, 2018

Research

Primary hyperparathyroidism.

Best practice & research. Clinical rheumatology, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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