Editors: Jieli Shirley Li, MD, PhD, DABCC, NRCC, Assistant Professor, Department of Pathology, The Ohio State University, Columbus, OH; Yu Jada Zhang, MD, PhD, DABCC, NRCC, Associate Director of Clinical Chemistry and POCT, UMass Memorial Health Care, Worcester, MA.
Author: Rongrong Huang, PhD, DABCC, Assistant Professor, Department of Pathology and Immunology Baylor College of Medicine, Houston, TX;
Parathyroid hormone (PTH), which is secreted from parathyroid glands and controls blood calcium and phosphorus, have been usually used to monitor hyperparathyroidism and the response to calcimimetic drugs in routine clinical practice. One unique application is intraoperative parathyroid hormone (IOPTH), which can indicate whether the overactive parathyroid glands have been successfully removed or not. A special case of ectopic supernumerary parathyroid adenoma has been recently published in Clinical Chemistry[1]. This report not only emphasizes the importance of IOPTH to evaluate parathyroidectomy response but also highlights the advantage of new technique, attracting broadly attention[2, 3]. Below are some take-home-points:
1. How is primary hyperparathyroidism diagnosed?
Primary hyperparathyroidism (pHPT) is characterized by the elevation of calcium and parathyroid hormone (PTH), with multiple complications mainly associated with renal and bone. The diagnostic tests include serum and urine calcium, bone mineral density assessment, ultrasound, parathyroid radionuclide scanning and/or computed tomography (CT) examinations of parathyroid glands. Decreased bone density and kidney stones are the two most common complications. A single parathyroid adenoma accounts for about 80% of pHPT cases, with double adenoma and multiglandular hyperplasia accounting for the remaining incidence of cases.
2. What are the criteria used to screen patients for parathyroidectomy?
Parathyroidectomy is the only cure for pHPT. For asymptomatic pHPT, as seen in this case, the International Workshop on the Management of Asymptomatic pHPT provides guidelines for surgical management based on four main categories of criteria, including serum calcium, skeletal, renal, and age.
A minimally invasive focused parathyroidectomy is preferred than bilateral neck exploration when a parathyroid adenoma is localized on preoperative imaging. It is worth noting that the majority of preoperative imaging studies have a limited sensitivity of 70-80%.
3. How is the parathyroid hormone (PTH) test used for intra-operative monitoring?
Given its short half-life of 3-5 minutes, the drop of PTH could be monitored intra-operatively by using a rapid PTH test (8-20 minutes testing time). The most widely used Miami protocol employs a criteria of > 50% drop in a 10-minutes post-excision PTH level compared to the highest baseline of either the pre-skin incision or pre-gland excision level with an accuracy of 96% in predicting surgical cure. Persistent PTH elevation is both sensitive and specific for predicting the presence of a contralateral parathyroid adenoma.
4. Why was intra-operative PTH monitoring critical for the success of this case?
Ectopic and/or supernumerary parathyroid glands, while uncommon, is the major cause of operative failure of parathyroidectomy, leading to persistent and recurrent pHPT. Both preoperative imaging studies and initial surgical operation could potentially miss an ectopic supernumerary parathyroid adenoma as seen in this case. Intra-operative PTH monitoring, therefore, is critical in guiding the surgeon for making decisions of concluding operation or continue exploration.
With portable rapid PTH platforms becoming available, an increased number of hospital laboratories have switched intra-operative PTH testing from core lab to inside or close to operation room (OR) for optimal turn-around-time (TAT). Our case demonstrated the improved TAT will not only cut down the OR time and cost in typical cases, but also provide a more timely accurate assessment to prevent potential reoperation.
甲状旁腺激素术中监测的应用: 一例罕见多发性甲状旁腺腺瘤
甲状旁腺激素PTH，作为一种由甲状旁腺分泌的调控人体钙磷水平的激素，在常规临床实践通常用于监测甲状旁腺功能亢进症 和拟钙剂药物的治疗效果。术中甲状旁腺激素IOPTH通过检测PTH 水平反映甲状旁腺切除效果。来自贝勒医学院的黄蓉荣助理教授最近在Clinical Chemistry发表了一份病例报道。 通过该异位旁腺腺瘤病例，他们不仅证实了IOPTH的重要性，而且指明了新技术应用的价值。 该报道引起了广泛关注。以下是本文要点。
1. 如何诊断原发性甲状旁腺功能亢进？
原发性甲状旁腺功能亢进症 (pHPT) 的特点是钙和甲状旁腺激素 (PTH) 升高，并伴有主要与肾脏和骨骼相关的多种并发症。诊断测试包括血清和尿钙、骨矿物质密度评估以及超声波、甲状旁腺放射性核素扫描和/或甲状旁腺的计算机断层扫描 (CT) 检查。骨密度降低和肾结石是两种最常见的并发症。单个甲状旁腺腺瘤约占pHPT病例的80%，其余病例还包括双腺瘤和多腺体增生。
2. 用于筛查甲状旁腺切除术患者的标准是什么？
甲状旁腺切除术是 治疗pHPT 的唯一方法。如本例所示，对于无症状 pHPT，无症状 pHPT 管理国际研讨会根据血清钙、骨骼、肾脏和年龄等四大类标准提供了手术管理指南。
根据术前影像学检查定位甲状旁腺腺瘤，微创聚焦甲状旁腺切除术优于双侧颈部探查术。需要注意的是，多数情况下术前影像学定位的敏感性有限，只有 70-80%。
3. 甲状旁腺激素 (PTH) 检测如何用于术中监测？
由于PTH的半衰期比较短，只有 3-5 分钟，临床上可通过使用快速 PTH 测试（8-20 分钟测试时间）在术中监测 PTH 的下降，来监测术中甲状旁腺瘤的切除效果。使用最广泛的是迈阿密操作方法。该方法以皮肤切口或者腺体切除前的最高PTH结果为基准线，采用了切除后 10 分钟 PTH 水平下降 > 50% 的标准，达到了96%的手术治愈率。持续性 PTH 升高对于发现对侧甲状旁腺腺瘤有着很高的特异性和敏感性。
4. 为什么术中 PTH 监测对本病例的成功至关重要？
异位和/或多余的甲状旁腺虽然不常见，但却是甲状旁腺切除术手术失败的主要原因，导致 pHPT 持续和复发。术前影像学检查和初始外科手术都可能漏掉本例中所见的异位甲状旁腺腺瘤。因此，术中 PTH 监测对于指导外科医生做出结束手术或继续探查的决定至关重要。
随着便携式快速 PTH 检测平台的出现，越来越多的医院实验室将术中 PTH 测试从中心实验室换到手术室内 (OR) 内或附近，以达到最佳报告周转时间 (TAT)。我们的案例表明，优化后的报告周转时间不仅可以降低典型病例的手术时间和成本，而且还可以提供更及时的腺瘤切除准确评估，减少再次手术可能性。
Reference:
1. Kundert, P., et al., Unexpected Persistently Increased Intraoperative Parathyroid Hormone Concentrations in a Patient with Primary Hyperparathyroidism. Clin Chem, 2021. 67(9): p. 1182-1186.
2. Bachmann, L.M., Commentary on Unexpected Persistently Increased Intraoperative Parathyroid Hormone Concentrations in a Patient with Primary Hyperparathyroidism. Clin Chem, 2021. 67(9): p. 1186-1187.
3. Malabanan, A.O., Commentary on Unexpected Persistently Increased Intraoperative Parathyroid Hormone Concentrations in a Patient with Primary Hyperparathyroidism. Clin Chem, 2021. 67(9): p. 1187.