From the Guidelines
Hypercalcemia is most commonly caused by primary hyperparathyroidism, where overactive parathyroid glands secrete excessive parathyroid hormone, increasing bone resorption and calcium absorption, as noted in the study published in the Journal of the American College of Radiology in 2021 1.
Causes of Hypercalcemia
The causes of hypercalcemia can be categorized into several groups, including:
- Primary hyperparathyroidism, which is the most common cause, accounting for approximately 80% of cases, as stated in the study published in the Journal of the American College of Radiology in 2021 1
- Malignancy, which is the second leading cause, either through direct bone destruction by metastatic tumors or through production of parathyroid hormone-related protein by certain cancers
- Granulomatous diseases like sarcoidosis and tuberculosis, which increase vitamin D activation
- Excessive vitamin D intake
- Medications such as thiazide diuretics and lithium
- Endocrine disorders like hyperthyroidism and adrenal insufficiency
- Familial hypocalciuric hypercalcemia
- Prolonged immobilization
- Milk-alkali syndrome from excessive calcium and antacid consumption
- Certain rare genetic disorders
Underlying Mechanism
The underlying mechanism of hypercalcemia typically involves increased bone resorption, enhanced intestinal calcium absorption, or decreased renal calcium excretion, disrupting the body's calcium homeostasis, as discussed in the study published in the Annals of Internal Medicine in 2018 1.
Treatment
Treatment of hypercalcemia depends on the underlying cause and severity of the condition, and may involve hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, as recommended in the study published in the Journal of the National Comprehensive Cancer Network in 2020 1.
Prevention
Prevention of hypercalcemia is crucial, especially in patients with chronic kidney disease, and may involve avoiding excessive calcium intake, maintaining adequate hydration, and monitoring serum calcium levels regularly, as suggested in the study published in the Annals of Internal Medicine in 2018 1.
Management
Management of hypercalcemia requires a comprehensive approach, including diagnosis, treatment, and prevention of complications, and may involve a multidisciplinary team of healthcare professionals, as noted in the study published in the Journal of the American College of Radiology in 2021 1.
From the Research
Causes of Hypercalcemia
- Primary hyperparathyroidism (PHPT) and malignancy are the most common causes of hypercalcemia, accounting for approximately 90% of cases 2, 3, 4
- Other causes of hypercalcemia include:
- Granulomatous disease such as sarcoidosis 2, 4, 5
- Endocrinopathies such as thyroid disease 2, 4, 6
- Immobilization 2, 4
- Genetic disorders such as familial hypocalciuric hypercalcemia 4, 6
- Medications such as thiazide diuretics, calcium, vitamin D, or vitamin A 2, 4
- Sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, although these account for less than 1% of causes 2
- Vitamin D-mediated hypercalcemia can occur due to excessive ingestion of vitamin D, ectopic production of 1,25-dihydroxyvitamin D, or impaired degradation of 1,25-dihydroxyvitamin D 5
Classification of Hypercalcemia
- Hypercalcemia can be classified into mild, moderate, and severe, depending on calcium values 3
- Mild hypercalcemia is usually asymptomatic, while severe hypercalcemia can cause nausea, vomiting, dehydration, confusion, somnolence, and coma 2, 3
Diagnosis and Treatment
- Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, distinguishing PTH-dependent from PTH-independent causes 2
- Treatment of hypercalcemia depends on the underlying cause and severity, and may include hydration, intravenous bisphosphonates, glucocorticoids, and parathyroidectomy 2, 3