Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism

Background: To separate non-(1-84)parathyroid hormone. [non-(1-84)PTH] :from PTH(1-84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1-84) could be separated into two entities recognized-by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure. Methods: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the.(15-20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84) structure requirement were used to measure basal and fractionated PTH values. Results: T-PTH was higher than CA-PTH in all healthy controls [mean (SD),, 3.13 (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients,[47 (35.1) vs 33.4 (26.1) pmol/L; P < 0.01]. By contrast, CA-PTH concentrations were similar to or higher than T-PTH in three of five patients with primary hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA-PTH assay reacted with the hPTH(1-84) peak and with a minor peak different from the non-(1-84) peak recognized by the. T-PTH assay. This minor peak was not recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25 (23) % in patients with primary hyperparathyroidism, and 22 (7)% in renal failure patients;: assuming equimolar reactivity to hPTH(1-84) in the CA-PTH assay. It was not oxidized hPTH(1-84), which migrated differently on HPLC and reacted similarly, in the CA, and T-PTH assays. Conclusions: This, new molecular form of PTH has structural integrity of the (1-4) region but presumably is modified in the:region (15-20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined. (C) 2003 American Association for Clinical Chemistry.