Parathyroid hormone (PTH) is an 84-amino acid protein secreted by the parathyroid gland that plays an important role in calcium regulation and indirectly influences intestinal calcium absorption by regulating 1,25-dihydroxyvitamin D synthesis. Overactive parathyroid glands, primary hyperparathyroidism, is one of the most common endocrine disorders in North American and European countries. These patients present with elevated plasma calcium and PTH concentrations and can be effectively managed with parathyroidectomy.
Because of the relatively short in vivo PTH half-life (2-5 minutes), PTH concentration decreases rapidly after parathyroid gland excision and can indicate successful removal of hypersecreting glands. Therefore, intraoperative monitoring of PTH (IOPTH) concentrations allows surgeons to perform minimally invasive parathyroidectomy with smaller incisions and dissection and shorter operating times under anesthesia. Multiple studies have reported successful utilization of various instruments for IOPTH monitoring to guide parathyroidectomy for patients with primary disease with high sensitivities, specificities, and overall accuracies of 95% and 98.5% (1, 2). In addition, IOPTH monitoring can also help surgeons differentiate patients with single-gland from those with multi-gland disease because IOPTH concentrations will not decrease below the expected threshold until all hypersecreting glands are removed (1).
In a recent article publish by Leung et al. (3), the analytical performance of two different PTH immunoassays were compared for monitoring IOPTH monitoring. An interesting observation was made where the choice of the PTH immunoassay may affect the decision making of surgeons relying on the decrease of IOPTH as a guide to operative success. The authors observed the relative percent decrease of IOPTH values in the same patient sample series were significantly different between the two different PTH immunoassays. At the end of their study, the data presented showed the observed rate of PTH decline was significantly slower using one PTH immunoassay platform versus the other platform in approximately 20% of the patients. The authors hypothesize that one PTH immunoassay may cross react with circulating truncated PTH fragments whereas the other PTH immunoassay preferentially recognizes the full-length intact PTH.
What is the potential impact of this observation? Even though it is well known that different immunoassays may have varying degrees of cross reactivity, Leung et al. brings up how this cross reactivity may impact IOPTH monitoring. If a PTH immunoassay that is susceptible to this slower decrease is used for IOPTH, a number of patients with single-gland disease may be erroneously implicated to have multi-gland disease and the surgeon may prolong surgery to search for additional hypersecreting PTH tissue. Therefore, this article highlights the importance of using IOPTH specimens from multiple patient series as part of the validation process of PTH assays used for IOPTH. This will help determine the prevalence of the false non-drop in the patient population and with this information, the laboratory and clinic team can determine the best method to provide the best outcome.
- Irvin GL, Deriso GT. A new, practical intraoperative parathyroid hormone assay. The American Journal of Surgery 1994;168:466-8.
- Barassi A, Porreca W, De Pasquale L, Bastagli A, d'Eril GVM. Use of intraoperative samples to optimize efficacy of central laboratory parathyroid hormone analyses. Clin Chem 2007;53:535-6.
- Leung EKY, Lee CL, Angelos P, Kaplan EL, Grogan RH, Sarracino DA, Krastins B, Lopez MF, Karrison T, Yeo KTJ. Analytical Differences in Intraoperative Parathyroid Hormone Assays. JALM 2019;3:788-798.