Role of cyclase activating parathyroid hormone (1-84 PTH) measurements during parathyroid surgery: potential improvement of intraoperative PTH assay

Abstract

Summary background data: Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay.

Methods: This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value.

Results: The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands.

Conclusions: The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.

Figure 1. Regression parameters of preoperative plasma intact parathyroid hormone (iPTH) values measured by the Nichols and cyclase activating parathyroid hormone (CAP) in primary (A) and secondary (B) hyperparathyroidism.

Figure 2. Decline of cyclase activating parathyroid hormone (CAP), intact parathyroid hormone (iPTH), and 7-84 parathyroid hormone (PTH) after excision of one enlarged parathyroid gland in the 29 patients with primary hyperparathyroidism. Results are shown as the percentage of the higher value of either basal or preexcision and means (standard error). There were significant differences in the percentage decrease among them (P = .0001) by a generalized linear regression analysis. CAP was significantly lower than iPTH at all times (P = .0001) by analysis of variance. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value.

Figure 3. Decline of cyclase activating parathyroid hormone (CAP), intact parathyroid hormone (iPTH), and 7-84 parathyroid hormone (PTH) after excision of the last parathyroid gland in the seven patients with secondary hyperparathyroidism. Results are shown as the percentage of the preexcision and means (standard error). There were significant differences in the percentage decrease among them (P = .0001) by a generalized linear regression analysis. CAP was significantly lower than iPTH at all times (P = .001) by analysis of variance. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value.