Ionized vs serum calcium in the diagnosis and management of primary hyperparathyroidism: which is superior?

BACKGROUND: The diagnosis of primary hyperparathyroidism (PHPT) is based on the presence of an elevated serum calcium level. The study objective was to compare ionized calcium levels to serum calcium levels with respect to parathyroid hormone level (PTH) and several patient outcomes.

METHODS: The study population comprised a retrospective cohort of 268 patients with PHPT who underwent primary parathyroidectomy. Serum calcium levels were compared with ionized calcium levels regarding their association with PTH level, presence of multiglandular disease, adenoma size, and extent of neck exploration.

RESULTS: Serum calcium level was correlated with ionized calcium level (R(2) = .68, 95% confidence interval [CI], .56 to .79; P < .0001) and PTH was associated with both serum (R(2) = .19; 95% CI, .04 to .33; P = .012) and ionized (R(2) = .23; 95% CI, .07 to .38; P = .004) calcium levels. Ionized calcium level was a more sensitive indicator of PHPT because there was a greater incidence of ionized calcium being elevated without concordant serum calcium elevation than vice versa (P < .0001). Ionized calcium was also more linearly associated with adenoma size than was serum calcium (P = .0001). There were no differences between serum and ionized calcium levels in predicting the presence of multiglandular disease or the extent of neck dissection.

CONCLUSIONS: Serum calcium level is an appropriate first-line biochemical test for the diagnosis of PHPT. However, ionized calcium measurements may provide additional benefit in certain cases of PHPT because it is correlated with PTH level and adenoma size, and it may be a more sensitive marker of disease severity than serum calcium.