The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism.

This report details our continued study of the role of ionized calcium (CAI) in the diagnosis of symptomatic primary hyperparathyroidism (HPT) in patients with persistently normal total serum calcium (CAT) or fluctuating normal total serum calcium levels with elevated CAT. A patient was considered to have fluctuating CAT values if at least 40% of the CAT values were within the normal range. Our previous study demonstrated that CAI provided no additional diagnostic benefit in patients with HPT who had persistently elevated CAT levels. This retrospective study adds 15 additional patients to the four previously reported patients whose workup for HPT included normal or fluctuating normal total serum calcium with elevated CAT values. Eighteen of these 19 patients had complications or symptoms referable to HPT. Nine of these patients had renal calculi. CAT was measured by atomic absorption spectroscopy and CAI was measured by a calcium-selective ion flow-through electrode. One hundred fifty-one concurrent preoperative measurements of CAT and CAI from these 19 patients were used for analysis. Overall, 46 (30.5%) of the CAT values were elevated, whereas 134 (88.7%) of the concurrent CAI values were elevated (P less than 0.001). In three of these 19 patients all preoperative CAT values were within normal limits, however, 20 of the 21 (95%) concurrent CAI values were elevated. In the remaining 16 patients the CAT values fluctuated between normal and elevated. In all of these patients, at least 40% of the preoperative CAT values were normal, and in 15 of these 16 patients at least 50% of the preoperative CAT values were within the normal range. In this fluctuating category there were 130 concurrent values of CAT and CAI. Only 46 of these 130 (35.4%) CAT values were elevated, whereas 114 of the 130 (87.7%) CAI values were elevated (P less than 0.001). All patients underwent parathyroid operation; 15 patients had a parathyroid adenoma and four had hyperplasia. The CAI and CAT values returned to normal in all patients subsequent to operation. These data indicate that the measurement of serum ionized calcium appears to play an important role in the identification of symptomatic HPT in patients who have normal or fluctuating normal total serum calcium with elevated CAT values.