Hypercalcemia Causes — Differential Diagnosis & Calcium Levels
Explore the main causes of high calcium levels including primary hyperparathyroidism, malignancy, and medications. Understand severity thresholds and symptoms. Free calculator.
Common Causes of Hypercalcemia
The two most common causes of hypercalcemia account for approximately 90% of all cases: primary hyperparathyroidism (most common in outpatients) and malignancy (most common in inpatients). Differentiating between them drives the workup and treatment.
| Cause | Frequency | PTH Level | Key Distinguishing Feature |
|---|---|---|---|
| Primary hyperparathyroidism | ~55% of cases | High/normal | Often asymptomatic, outpatient |
| Malignancy (PTHrP) | ~35% of cases | Low/suppressed | Acute, severe, inpatient |
| Vitamin D toxicity | ~5% of cases | Low | History of supplements |
| Sarcoidosis/granulomas | ~2% of cases | Low | Elevated 1,25-OH vitamin D |
| Thiazide diuretics | ~2% of cases | Normal | Medication history, mild |
| Milk-alkali syndrome | ~1% of cases | Low | Excess calcium carbonate intake |
Severity Classification
Mild hypercalcemia (10.5–12.0 mg/dL) is usually managed with hydration and treatment of the underlying cause. Moderate hypercalcemia (12.0–14.0 mg/dL) typically requires IV saline hydration and bisphosphonate therapy. Severe hypercalcemia (>14.0 mg/dL) is a medical emergency requiring aggressive IV fluid resuscitation, loop diuretics, bisphosphonates (zoledronate), and potentially calcitonin or dialysis for refractory cases.
Frequently Asked Questions
What calcium level is considered hypercalcemia?
Hypercalcemia is defined as a total serum calcium above 10.5 mg/dL (2.62 mmol/L) in adults, confirmed on at least two separate measurements. Ionized calcium above 1.32 mmol/L is also diagnostic. Mild hypercalcemia (10.5–12 mg/dL) may be asymptomatic; levels above 14 mg/dL constitute a hypercalcemic crisis.
Can calcium supplements cause hypercalcemia?
Yes, though it requires substantial intake. The tolerable upper intake level for calcium from all sources is 2,500 mg/day for adults. Milk-alkali syndrome, caused by high calcium carbonate intake (often from antacids) combined with metabolic alkalosis, is now the third most common cause of severe hypercalcemia among hospitalized patients.