Hypercalcemia
Hypercalcemia is an elevated serum calcium concentration, most often caused by primary hyperparathyroidism in ambulatory patients or malignancy in hospitalized patients. Mild disease requires only treatment of the underlying cause, while severe or symptomatic hypercalcemia is treated with aggressive IV isotonic fluids, followed by an IV bisphosphonate or denosumab for sustained control and subcutaneous calcitonin as a rapid but short-lived bridge.
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What this article covers
- Overview
Definition: hypercalcemia is a serum calcium concentration above the normal range, categorized as mild (below 12 mg/dL [3 mmol/L]), moderate (12 to 14 mg/dL [3 to 3.5 mmol/L]), or severe (above 14 mg/dL [3.5 mmol/L]).
- Epidemiology
Primary hyperparathyroidism is the most common cause of hypercalcemia in ambulatory patients, typically caused by a solitary parathyroid adenoma, with a peak incidence in the seventh decade of life and a higher prevalence in women.
- Risk factors
Underlying primary hyperparathyroidism, almost always from a solitary parathyroid adenoma.
- Pathophysiology
PTH-mediated hypercalcemia: an elevated or inappropriately normal PTH level in a hypercalcemic patient drives renal calcium reabsorption, bone resorption, and 1,25-dihydroxyvitamin D-mediated…
- Clinical features
Often asymptomatic, discovered incidentally on routine blood testing, particularly in mild primary hyperparathyroidism.
- Differential diagnosis
Primary hyperparathyroidism: an elevated or inappropriately normal PTH with usually mild hypercalcemia, unlike the suppressed PTH of non-PTH-mediated causes.
- Diagnosis
The diagnosis is confirmed by a repeat serum calcium measurement, and hypercalcemia is graded by severity (mild <12 mg/dL, moderate 12-14 mg/dL, severe 14 mg/dL [3 mmol/L, 3-3.5 mmol/L, and 3.5…
- Management
First, for mild hypercalcemia (below 12 mg/dL), treat only the underlying disorder; no specific calcium-lowering therapy is needed.
- Complications
Acute kidney injury, nephrolithiasis, or nephrocalcinosis from severe hypercalcemia and hypercalciuria.
- Prognosis
Excellent for mild, incidentally discovered primary hyperparathyroidism, safely observed with periodic monitoring if surgical criteria are not met.
- Prevention
Recheck serum calcium and creatinine annually in patients with asymptomatic primary hyperparathyroidism who defer surgery, since about one in three develop a surgical indication within 10 to 15 years.
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Related articles
- Primary hyperparathyroidism
Primary hyperparathyroidism is autonomous PTH oversecretion, most often from a solitary parathyroid adenoma, producing hypercalcemia with an elevated or inappropriately normal PTH and low or low-normal phosphorus. Most patients are asymptomatic and identified on routine labs; parathyroidectomy is curative and is first-line for symptomatic disease or when specific biochemical, skeletal, or renal criteria are met, while observation with annual monitoring suffices for mild, asymptomatic disease.
- Familial hypocalciuric hypercalcemia
Familial hypocalciuric hypercalcemia is an autosomal dominant, lifelong, asymptomatic hypercalcemia caused by an inactivating mutation of the calcium-sensing receptor, which raises the parathyroid hormone and renal calcium reabsorption set point. The clinching test is a 24-hour urine calcium-creatinine clearance ratio below 0.01, and management is reassurance and family screening, since parathyroidectomy does not correct the calcium and is not indicated.
- Hypocalcemia
Hypocalcemia is a low serum calcium concentration, most often from insufficient parathyroid hormone action (postsurgical or autoimmune hypoparathyroidism, hypomagnesemia, or PTH resistance) or from vitamin D deficiency and chronic kidney disease. Severe or symptomatic disease requires urgent intravenous calcium, while chronic disease is managed with oral calcium, vitamin D repletion, and calcitriol when PTH is absent or the kidney cannot activate vitamin D.