What is hypercalcemia
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Understanding Hypercalcemia: Causes, Symptoms, and Management
Definition and Normal Physiology of Hypercalcemia
Hypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean. This condition can vary with age and sex, reflecting changes in normal physiology at each developmental stage1. The metabolic pathways that maintain serum calcium concentration within a narrow physiological range include bone remodeling, intestinal absorption, and renal tubule resorption. Dysregulation in these processes can lead to hypercalcemia4.
Causes of Hypercalcemia
Parathyroid Hormone (PTH)-Dependent and Independent Causes
Hypercalcemia can be classified into PTH-dependent and PTH-independent categories. PTH-dependent hypercalcemia is usually caused by parathyroid tumors, leading to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, often associated with chronic renal failure1. PTH-independent hypercalcemia, which is more common in children, can be due to hypervitaminosis, granulomatous disorders, and endocrinopathies1.
Malignancy and Other Causes
Malignancy is a significant cause of hypercalcemia, particularly in adults. It is often associated with advanced cancers, such as breast cancer, where hormone therapy can induce hypercalcemia2 3. Other causes include renal failure, kidney transplantation, and long-term treatment with certain medications like vitamin D and lithium4. Genetic factors also play a role, with conditions like familial hypocalciuric hypercalcemia and multiple endocrine neoplasia (MEN) contributing to the disorder4.
Symptoms and Clinical Manifestations
The symptoms of hypercalcemia can vary widely depending on the severity and underlying cause. Common symptoms include hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures in children1. In severe cases, it can lead to renal failure, pancreatitis, and reduced consciousness. Older children and adolescents may present with psychiatric symptoms1. In adults, hypercalcemia can affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems9.
Diagnosis and Management
Diagnostic Approach
The initial diagnostic work-up for hypercalcemia should include the measurement of intact parathyroid hormone (PTH) levels. Elevated PTH levels suggest primary hyperparathyroidism, while suppressed PTH levels indicate malignancy-associated hypercalcemia9. It is crucial to exclude other causes before considering parathyroid surgery9.
Management Strategies
The management of hypercalcemia depends on the severity of the condition. Mild hypercalcemia often does not require specific treatment, while moderate to severe cases necessitate a more targeted approach. Aggressive intravenous rehydration is the mainstay of management in severe hypercalcemia, along with the use of antiresorptive agents like calcitonin and bisphosphonates9. In cases related to malignancy, addressing the underlying cancer is essential2 3.
Conclusion
Hypercalcemia is a complex condition with various causes and manifestations. Understanding the underlying mechanisms and appropriate diagnostic and management strategies is crucial for effective treatment. Whether due to parathyroid disorders, malignancy, or other factors, timely intervention can significantly improve patient outcomes.
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Most relevant research papers on this topic
Hypercalcemic Disorders in Children
Pediatric hypercalcemia can be caused by congenital or acquired causes, and can be managed with fluids, antiresorptive medications, and parathyroid surgery.
Very Rigorous Journal
Highly CitedHypercalcemia, a complication of hormone therapy of advanced breast cancer.
Hypercalcemia is a potential serious complication during hormone therapy for advanced breast cancer patients, and detection and management of this condition are essential for effective treatment.
Case ReportHypercalcemia, a complication of hormone therapy of advanced breast cancer.
Hypercalcemia is a potential complication during hormone therapy for advanced breast cancer patients, and detection and management are essential for effective treatment.
Case ReportHighly CitedHypercalcemia. Pathophysiological aspects.
Hypercalcemia is a potentially life-threatening condition caused by imbalances in bone remodeling, intestinal absorption, and renal tubule resorption, with genetic and environmental factors playing a role.
Systematic ReviewClinical review 51: Management of hypercalcemia.
Hypercalcemia is a very common electrolyte abnormality that is most often seen as a mild elevation in the setting of asymptomatic primary hyperparathyroidism. The hypercalcemia is usually less than 11.2 mg/dL and does not call for specific or vigorous approaches to management. However, more marked elevations in the serum calcium are also seen and call for a more specific approach to management. When the serum calcium is only moderately elevated, the therapeutic approach should be tempered by clinical assessments about the presence of symptoms and the underlying etiology. When the serum calcium is markedly elevated, a more targeted therapeutic approach is called for which now is independent of the presence of symptoms and usually of the underlying etiology. Considerations of hypercalcemia in these three different ranges will tailor the therapeutic approach to the clinical setting.
Highly CitedSodium sulfate treatment of hypercalcemia.
Sodium sulfate effectively lowers serum calcium levels in hypercalcemia patients, potentially preventing death in cases of acute hypercalcemic crisis.
Highly CitedHypercalcemia and renal failure. Etiology, pathophysiology, diagnosis, and treatment.
Hypercalcemia in dogs and cats leads to alterations in renal function and morphology, and early recognition and treatment are crucial for successful management.
Hypercalcemia in malignant and inflammatory diseases.
Hypercalcemia in malignant and inflammatory diseases is often caused by neoplasia, and understanding its pathophysiology can lead to accurate diagnosis and effective therapy for most patients.
A practical approach to hypercalcemia.
Hypercalcemia is a common disorder with various causes, and diagnosis and treatment require careful consideration of potential causes and individualized approaches.
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