From the Guidelines
Hypercalcemia is caused by several conditions that disrupt calcium regulation in the body, including primary hyperparathyroidism, malignancy, granulomatous diseases, medications, endocrine disorders, and genetic disorders, as noted in the study by 1.
Causes of Hypercalcemia
The causes of hypercalcemia can be categorized into several groups, including:
- Primary hyperparathyroidism, where overactive parathyroid glands secrete excessive parathyroid hormone, increasing bone resorption and calcium absorption
- Malignancy, either through direct bone destruction by metastases or production of parathyroid hormone-related protein by tumors
- Granulomatous diseases like sarcoidosis and tuberculosis, which increase vitamin D activation
- Medications such as thiazide diuretics, lithium, and excessive vitamin D or calcium supplements
- Endocrine disorders including hyperthyroidism and adrenal insufficiency
- Familial hypocalciuric hypercalcemia, a genetic disorder
- Prolonged immobilization leading to bone breakdown
- Milk-alkali syndrome from excessive calcium and absorbable alkali intake
- Rarer causes include recovery from acute kidney injury and certain rare genetic disorders
Treatment of Hypercalcemia
Treatment of hypercalcemia depends on identifying and addressing the underlying cause, with severe cases requiring immediate intervention with:
- Intravenous fluids
- Bisphosphonates
- Calcitonin
- Dialysis As noted in the study by 2, excess bone resorption from bone disease can lead to excessive release of calcium into the blood, contributing to hypercalcemia, and treatment should focus on addressing the underlying cause and preventing further bone resorption.
Prevention of Hypercalcemia
Prevention of hypercalcemia is also crucial, especially in patients with chronic kidney disease, where avoiding hypercalcemia is recommended, as noted in the study by 3. This can be achieved by:
- Monitoring serum calcium levels regularly
- Adjusting dialysate calcium concentration as needed
- Avoiding excessive calcium intake
- Managing underlying conditions that may contribute to hypercalcemia
By understanding the causes and treatment of hypercalcemia, healthcare providers can provide effective management and prevention strategies to improve patient outcomes, as supported by the studies by 1 and 3.
From the Research
Causes of Hypercalcemia
- Primary hyperparathyroidism (PHPT) and malignancy are the most common causes of hypercalcemia, accounting for approximately 90% of cases 4, 5
- Other causes of hypercalcemia include: + Granulomatous disease such as sarcoidosis 4, 5, 6 + Endocrinopathies such as thyroid disease 4, 5 + Immobilization 4, 5 + Genetic disorders 4 + Medications such as thiazide diuretics, lithium, and supplements like calcium, vitamin D, or vitamin A 4, 5, 7 + Vitamin D-related causes, including vitamin D intoxication and lymphoma 5, 6 + Familial hypocalciuric hypercalcemia 5
- Less common causes of hypercalcemia include: + Sodium-glucose cotransporter 2 protein inhibitors 4 + Immune checkpoint inhibitors 4 + Denosumab discontinuation 4 + SARS-CoV-2 4 + Ketogenic diets 4 + Extreme exercise 4
Medication-Related Hypercalcemia
- Vitamin D supplements and 1α-hydroxylated vitamin D analogues can increase intestinal calcium absorption, renal calcium reabsorption, and bone resorption, leading to hypercalcemia 7
- Thiazide-induced hypercalcemia is mainly explained by enhanced renal proximal calcium reabsorption 7
- Lithium can cause hypercalcemia mainly by drug-induced hyperparathyroidism 7
- Recombinant human PTH can cause transient hypercalcemia in patients with hypoparathyroidism, usually during acute illness 7
Vitamin D-Mediated Hypercalcemia
- Ingestion of excessive amounts of vitamin D3 or vitamin D2 can result in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] [6]
- Ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D] in granulomatous disease or tumors can lead to hypercalcemia 6
- Impaired degradation of 1,25(OH)2D due to mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1) can cause non-PTH-mediated hypercalcemia 6