The reliable diagnosis of
primary hyperparathyroidism depends on the measurement of PTH. The PTH assays in widespread use measure not only the
hormone but also
hormone fragments, thus limiting the clinical utility of the assays. A new immunoradiometric assay (IRMA) using an
antigenic determinant at the extreme amino-terminal of the PTH molecule detects only full-length
PTH (1-84). We compared three PTH assays and determined the presence of
PTH (1-84) and PTH fragments in serum and
parathyroid adenomas of patients with
primary hyperparathyroidism. We studied 56 patients with
primary hyperparathyroidism. PTH levels were increased in 63% using the midmolecule RIA; in 73% in the "intact" IRMA; and in 96% in the PTH (1-84)-IRMA. The PTH (1-84)-IRMA correlated with the other assays (midmolecule RIA R = +0.736; P < 0.0001; "intact"-IRMA R = +0.951; P < 0.0001) and indices of disease activity (serum
calcium R = +0.511, P < 0.0001;
alkaline phosphatase R = +0.489, P = 0.001; and radius bone density R = -0.366, P < 0.01). In 21 consecutive patients undergoing
parathyroidectomy, 18 had
parathyroid adenomas. Intact PTH was higher than PTH (1-84)-IRMA in both serum and glandular homogenates from these patients. Similar proportions of
PTH (1-84) and
hormone fragments were found in both
adenomas [66 +/- 3% of "intact" PTH-reflected
PTH (1-84) and sera (73 +/- 2% of "intact" PTH reflected
PTH (1-84)]. We conclude that the
PTH (1-84)-IRMA offers improved diagnostic sensitivity in patients with
primary hyperparathyroidism than other currently available assays. This study also provides evidence that both
PTH (1-84) and PTH fragments are produced in
parathyroid adenomas and that peripheral metabolism of
hormone and fragment does not alter the proportion of bioactive
hormone.