Calcium

The total calcium level is a measurement of free (also called ionized) calcium, protein-bound calcium, and a chelated fraction. Approximately 50% of total calcium is ionized, 40% to 50% is bound to albumin, and 5% to 20% is bound to other ions. Only the free or ionized portion of calcium is physiologically active. Because of the binding of calcium with albumin, simultaneous measurements of calcium and albumin need to be performed to interpret calcium abnormalities. For every 1 g/dL that serum albumin is decreased below 4 g/dL, the estimated serum calcium is corrected by adding 0.8 mg/dL to the measured calcium level. An alternative is to measure ionized calcium levels in patients with abnormalities of serum albumin. The reference range for serum calcium is 8.5 to 10.5 mg/dL and for ionized calcium, 4.65 to 5.28 mg/dL. Serum calcium measurements are not precise enough to differentiate normal levels from mildly elevated calcium levels reliably; therefore a number of measurements are needed to confirm true mild hypercalcemia.

The etiology of hypercalcemia is either hyperparathyroidism or malignancy in more than 90% of hypercalcemic patients. In the ambulatory setting, most patients with hypercalcemia have hyperparathyroidism. Typically the hypercalcemia of hyperparathyroidism is modest, with calcium levels less than 11 mg/dL and minimal symptoms. Hospitalized patients are more likely to have malignancy as a cause of hypercalcemia. Calcium levels greater than 13 mg/dL are usually associated with malignancy. Intact parathyroid hormone (PTH, parathormone) levels can differentiate hyperparathyroidism from other causes of hypercalcemia. Nonhyperparathyroid causes of hypercalcemia will give low or "normal" intact PTH levels in a setting of hypercalcemia, whereas the PTH level will be increased in hyperparathyroidism. Occasionally, patients with a family history of hypercalcemia show a reduction in calcium excretion and have familial hypocalciuric hypercal-cemia. Other causes of hypercalcemia are related to increased gastrointestinal (GI) absorption, increased bone resorption, and decreased renal excretion (Table 15-9).

Perhaps the most common cause of a low total calcium level is a low albumin level. When hypocalcemia is found, one should establish that the serum albumin is normal. If serum albumin is also reduced, one should perform the above correction to confirm true hypocalcemia. Another important cause of hypocalcemia is hypomagnesemia, which can lead to PTH resistance or reduced PTH secretion. Correction of the magnesium deficiency usually results in correction of the hypocalcemia. Other causes of hypocalcemia include chronic kidney disease, vitamin D deficiency, malabsorption, acute pancreatitis, transfusion with citrated blood, rhabdomyoly-sis, hypoparathyroidism, and pseudohypoparathyroidism, and occasionally bisphosphonate therapy.

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