A comparative study of serum ultrafiltrable, ionized, and total calcium in the diagnosis of primary hyperparathyroidism in patients with intermittent or no elevation in total calcium

Measurement of serum ionized calcium has been shown to be more sensitive a method of diagnosing primary hyperparathyroidism than total calcium in patients with subtle or intermittent elevations of total calcium. The measurement of ionized calcium, however, is technically difficult. The measurement of serum ultrafiltrable calcium would circumvent technical difficulties because atomic absorption spectroscopy would be used to measure the calcium of a filtrate produced by passing serum through a filter which excludes protein-complexed calcium (Worthington ultrafree filter). The normal range for ultrafiltrable calcium (4.7 to 6.8 mg/dl) was determined in 138 patients by nonlinear least-squares analysis and chart review. The serum concentration of ultrafiltrable calcium correlated well with ionized calcium (r = 0.91). Previous studies have demonstrated no benefit in measuring ionized calcium, as opposed to total calcium, in the diagnosis of primary hyperparathyroidism unless there was subtle, intermittent, or no elevation of the total calcium. This comparative study of ultrafiltrable, ionized, and total calcium was, therefore, done in six patients with primary hyperparathyroidism who exhibited intermittent, minimal, or no elevations in serum total calcium. All six patients had symptoms referrable to hyperparathyroidism. All six underwent parathyroid surgery, and a parathyroid adenoma was found in each case. These six patients had a total of 24 concurrent preoperative determinations of ionized, ultrafiltrable, and total calcium levels. The total calcium value was elevated in only 9 of these 24 determinations (38%), ultrafiltrable calcium was elevated in 15 (63%), and ionized calcium was elevated in 23 (96%). The values of ionized calcium were elevated more frequently than both total calcium (p less than 0.0005) and ultrafiltrable calcium (p less than 0.025). The values for ultrafiltrable calcium were more frequently elevated than those for total calcium; this difference, however, was not significant. This study confirms our previous reports showing that ionized calcium is a more sensitive indicator of primary hyperparathyroidism in patients with intermittent or borderline elevation of the total calcium and extends those observations to show that ionized calcium is also a more sensitive indicator of primary hyperparathyroidism than ultrafiltrable calcium in this group of patients.