From the Guidelines
Hypercalcemia is most commonly caused by primary hyperparathyroidism, where overactive parathyroid glands produce too much parathyroid hormone, leading to increased calcium release from bones, as supported by the most recent study 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 1
- Cancer, particularly cancers that have metastasized to bone or produce parathyroid hormone-related protein (PTHrP)
- Certain medications like thiazide diuretics, lithium, or excessive vitamin D supplements
- Granulomatous diseases like sarcoidosis or tuberculosis
- Prolonged immobilization
- Certain endocrine disorders like hyperthyroidism or adrenal insufficiency
- Familial hypocalciuric hypercalcemia, a genetic condition
Symptoms and Treatment
Symptoms of hypercalcemia may include:
- Fatigue
- Weakness
- Constipation
- Bone pain
- Kidney stones
- Cognitive changes
- In severe cases, cardiac arrhythmias Treatment depends on the underlying cause and may include:
- Addressing the primary condition
- Increasing fluid intake
- Medications like bisphosphonates or calcitonin to lower calcium levels
- In some cases, surgery to remove overactive parathyroid glands, as recommended in the study 1 It is essential to note that excessive calcium intake alone rarely causes hypercalcemia unless kidney function is impaired, as mentioned in the study 1.
Importance of Recent Studies
The most recent study 1 provides the most up-to-date information on the causes and treatment of hypercalcemia, and its findings should be prioritized in clinical practice.
Clinical Practice Guidelines
Clinical practice guidelines, such as those provided in the study 1, recommend avoiding hypercalcemia in patients with chronic kidney disease and suggest using a dialysate calcium concentration between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) in patients with CKD stage G5D.
Morbidity, Mortality, and Quality of Life
Hypercalcemia can have significant effects on morbidity, mortality, and quality of life, particularly if left untreated or undertreated, as highlighted in the study 1. Therefore, it is crucial to prioritize the treatment of hypercalcemia and address the underlying cause to improve patient outcomes.
From the FDA Drug Label
Osteoclastic hyperactivity resulting in excessive bone resorption is the underlying pathophysiologic derangement in hypercalcemia of malignancy (HCM, tumor-induced hypercalcemia) and metastatic bone disease. Patients who have hypercalcemia of malignancy can generally be divided into two groups according to the pathophysiologic mechanism involved: humoral hypercalcemia and hypercalcemia due to tumor invasion of bone In humoral hypercalcemia, osteoclasts are activated and bone resorption is stimulated by factors such as parathyroid hormone-related protein, which are elaborated by the tumor and circulate systemically. Extensive invasion of bone by tumor cells can also result in hypercalcemia due to local tumor products that stimulate bone resorption by osteoclasts.
A person may have hypercalcemia due to various reasons, including:
- Humoral hypercalcemia: caused by factors such as parathyroid hormone-related protein, which are elaborated by the tumor and circulate systemically.
- Hypercalcemia due to tumor invasion of bone: caused by local tumor products that stimulate bone resorption by osteoclasts.
- Osteoclastic hyperactivity: resulting in excessive bone resorption, which is the underlying pathophysiologic derangement in hypercalcemia of malignancy (HCM, tumor-induced hypercalcemia) and metastatic bone disease. 2
From the Research
Causes of Hypercalcemia
- Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, accounting for approximately 90% of cases, along with malignancy 3, 4
- Other causes of hypercalcemia include:
- Granulomatous disease such as sarcoidosis 3
- Endocrinopathies such as thyroid disease 3
- Immobilization 3
- Genetic disorders 3
- Medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A 3
- Vitamin-D toxicity 4, 5
- Milk alkali syndrome 4
- Multiple myeloma 4
- Tuberculosis 4
- Chronic kidney disease 4
- Lymphoma 4
- Sarcoidosis 4
- Familial benign hypercalcemia or familial hypocalciuric hypercalcemia (FHH) 5
Less Common Causes of Hypercalcemia
- Sodium-glucose cotransporter 2 protein inhibitors 3
- Immune checkpoint inhibitors 3
- Denosumab discontinuation 3
- SARS-CoV-2 3
- Ketogenic diets 3
- Extreme exercise 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 3
- Treatment of hypercalcemia depends on the underlying cause and severity of the condition, and may include hydration, intravenous bisphosphonates, glucocorticoids, and parathyroidectomy 3