Immunoheterogeneity of parathyroid hormone in parathyroid cysts: diagnostic implications

Abstract

Parathyroid cysts are uncommon lesions of the neck leading to hypercalcemia in a significant percentage of cases. The distinction between parathyroid and thyroid cysts is difficult to make on a clinical basis alone and relies on the demonstration of elevated PTH levels in cyst fluid. We describe a case of a parathyroid cyst in which intact PTH (1–84) levels were misleadingly low while midmolecule 44–68 PTH was markedly elevated. To explain this discrepancy, we studied cyst fluid from this and two other patients using Sephadex G-75 gel chromatography. Fractions were analyzed using an immunoradiometric assay for intact hPTH (1–84) and a RIA specific for the midmolecular 44–68 region of hPTH. Immunoreactivity corresponding to hPTH (1–84) was absent in the first case but present in the remaining two. Immunoreactive peaks corresponding to PTH fragments were demonstrable in all three cyst samples. Patients with elevated hPTH (1–84) in cyst fluid were hypercalcemic; in contrast, the patient with a low cyst level of hPTH (1–84) was normocalcemic despite having markedly elevated levels of mid-molecule PTH (44–68) in both serum and cyst fluid. Parathyroid cysts may thus produce fragments rather than intact PTH; reliance on an intact hPTH assay could lead to misdiagnosis. The measurement of PTH by a midmolecular assay may be preferable to the measurement of intact PTH in the evaluation of fluid from cystic neck masses.