Etiology of hypercalcemia
- Elizabeth Shane, MD
Elizabeth Shane, MD
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
Hypercalcemia is a relatively common clinical problem. It results when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in bone. This occurs when there is accelerated bone resorption, excessive gastrointestinal absorption, or decreased renal excretion of calcium. In some disorders, however, more than one mechanism may be involved. As examples, hypervitaminosis D increases both intestinal calcium absorption and bone resorption, and primary hyperparathyroidism increases bone resorption, tubular calcium reabsorption, and renal synthesis of calcitriol (1,25-dihydroxyvitamin D, the most active metabolite of vitamin D), and intestinal calcium absorption.
Among all causes of hypercalcemia, primary hyperparathyroidism and malignancy are the most common, accounting for greater than 90 percent of cases (table 1).
This topic card will review the etiology of hypercalcemia. The clinical manifestations, diagnostic approach, and treatment are reviewed separately. (See "Clinical manifestations of hypercalcemia" and "Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia".)
Primary hyperparathyroidism — Hypercalcemia in primary hyperparathyroidism is due to parathyroid hormone (PTH)-mediated activation of osteoclasts leading to increased bone resorption. In addition, intestinal calcium absorption is elevated. Primary hyperparathyroidism is most often due to a parathyroid adenoma. Patients typically have only small elevations in serum calcium concentrations (less than 11 mg/dL or 2.75 mmol/L), and many have mostly high-normal values with intermittent hypercalcemia. Thus, when one suspects primary hyperparathyroidism, as with high-normal serum calcium values in a patient with calcium nephrolithiasis, it may be necessary to obtain a series of serum calcium measurements to detect hypercalcemia. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation".)
Secondary and tertiary hyperparathyroidism — Patients with severe chronic kidney disease and secondary hyperparathyroidism usually have low or normal serum calcium concentrations, but with prolonged disease, may develop hypercalcemia. The rise in plasma calcium most often occurs in patients with adynamic bone disease and markedly reduced bone turnover. In such patients, hypercalcemia is due to a marked reduction in the bone uptake of calcium after a calcium load, as with calcium carbonate to treat hyperphosphatemia . (See "Overview of chronic kidney disease-mineral bone disease (CKD-MBD)", section on 'Abnormalities in bone turnover, mineralization, volume linear growth, or strength'.)
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- BONE RESORPTION
- Primary hyperparathyroidism
- Secondary and tertiary hyperparathyroidism
- CALCIUM ABSORPTION
- Increased calcium intake
- - Chronic kidney disease
- - Milk alkali syndrome
- Hypervitaminosis D
- MISCELLANEOUS CAUSES
- Thiazide diuretics
- Adrenal insufficiency
- Rhabdomyolysis and acute renal failure
- Theophylline toxicity
- Familial hypocalciuric hypercalcemia
- Metaphyseal chondrodysplasia
- Congenital lactase deficiency
- SUMMARY AND RECOMMENDATIONS