Hypercalcemia in Emergency Medicine Workup

Updated: Dec 22, 2017
  • Author: Thomas E Green, DO, MPH, MMM, CPE, FACEP, FACOEP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Workup

Laboratory Studies

When calcium levels are reported as abnormal, the first step is to measure the albumin level. The following is a common formula used in calculating a corrected calcium level [12] :

Corrected total calcium (mg/dL) = (measured total calcium mg/dL) + 0.8 (for every decrement in the serum albumin of 1 g/dL below the reference value [in many cases 4.1 g/dL]; subsequently, subtract 0.8 for every increment in the serum albumin of 1 g/dL above the reference value)

If the corrected serum calcium level still is not accurate, it is possible to measure the free calcium ion activity (ie, ionized calcium level).

Other nonspecific laboratory abnormalities commonly found in patients with hypercalcemia result from disordered renal function. Patients commonly have significant azotemia at presentation.

Hypercalcemia may produce ECG abnormalities related to altered trans-membrane potentials that affect conduction time. QT interval shortening is common, and, in some cases, the PR interval is prolonged. At very high levels, the QRS interval may lengthen, T waves may flatten or invert, and a variable degree of heart block may develop. Digoxin effects are amplified.

After a diagnosis of hypercalcemia is established, the next step is to determine the cause. Initial testing is directed at malignancy, hyperparathyroidism, and hyperthyroidism, the most common causes of hypercalcemia.

  • The measurement of circulating PTH in the serum is the most direct and sensitive measure of parathyroid gland function. A reference range is 2-6 mol/L. A nonsuppressed PTH level in the presence of hypercalcemia suggests a diagnosis of primary hyperparathyroidism. If the PTH level is suppressed in the face of an elevated calcium level, hyperparathyroidism is unlikely.
  • Parathyroid hormone-related peptide (PTHrP) is thought to mediate the hypercalcemia that develops with many malignancies. Assays to measure this peptide are available. [16]
  • Measurement of calcitriol is difficult but can be accomplished. This laboratory value is useful in diagnosing hypercalcemia secondary to a granulomatous disease such as sarcoidosis. It is often elevated in primary hyperparathyroidism.
  • Other electrolytes also may be disturbed in hypercalcemia. Serum phosphate levels tend to be low or normal in primary hyperparathyroidism and hypercalcemia of malignancy. Phospate levels are elevated in hypercalcemia secondary to vitamin D–related disorders or thyrotoxicosis. Serum chloride levels usually are higher than 102 mEq/L in hyperparathyroidism and less than this value in other forms of hypercalcemia.

A study by Balentine et al suggested that a large percentage of patients with hypercalcemia are not appropriately evaluated for hyperparathyroidism, while many of those who are diagnosed with hyperparathyroidism do not get a surgical referral. Looking at figures from a tertiary referral center, the investigators found that only 3200 (31%) of 10,432 patients with hypercalcemia underwent parathyroid hormone measurement, with a hypercalcemia diagnosis documented in just 2914 patients (28%) and a hyperparathyroidism diagnosis found in the medical records of 880 patients (8%). Of 2666 patients with classic hyperparathyroidism (ie, abnormal calcium and parathyroid hormone levels), only 592 (22%) received a surgical referral. [17]  

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Imaging Studies

No imaging studies definitively diagnose hypercalcemia. However, the chest radiograph may reveal malignancy or granulomatous disease. [5]

Consider hypercalcemia in patients with multiple nonspecific complaints and an associated lung mass.

If laboratory evidence of primary hyperparathyroidism is present, CT scan of the head, MRI, ultrasound, or nuclear parathyroid scans may be helpful. Preoperative diagnostic imaging is essential in patients with previous neck surgery.

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