Immunoheterogeneity of parathyroid hormone in parathyroid cysts: diagnostic implications

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 midmolecule 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.