Intraoperative Parathyroid Hormone Testing Research Articles

The Necessity and Reliability of Intraoperative Parathyroid Hormone (PTH) Testing in Patients with Mild Hyperparathyroidism and PTH Levels in the Normal Range

Intraoperative parathyroid hormone (IoPTH) testing is useful in the management of hyperparathyroidism. The successful removal of hypersecreting parathyroids is indicated by a decrease in PTH levels >50% within 15 min. A subset of patients with mild hyperparathyroidism will actually have starting PTH levels in the normal range. We sought to determine if IoPTH testing is necessary in these patients and if the 50% rule delineating surgical cure is reliable. A retrospective review was performed on all patients who underwent parathyroidectomy for hyperparathyroidism at a single institution from 3/2001 to 8/2008. Of the 1,001 patients, 142 (14%) had mild hyperparathyroidism and normal baseline PTH levels (<65 pg/ml). Their mean PTH was 59 ± 1 pg/ml. During surgery, 105 (74%) had a >50% decline in PTH levels after resection of hyperfunctioning parathyroid glands, and their operations were terminated. In contrast, 37 (26%) patients did not have a >50% decline in PTH levels leading to further surgical exploration. In these 37 patients, the PTH levels fell by >50% after the removal of the additional glands in 25 patients (17.6%) and dropped after 20 min in 7 patients (4.9%). In 5 patients (3.5%) the IoPTH did not drop. Of the 142 total patients, 91 had single adenomas and 51 patients had multi-gland disease. All patients (100%) were cured (normal serum calcium after 6 months). Intraoperative PTH testing plays an important role in the operative management in 14% of patients with mild hyperparathyroidism. Importantly, a 50% decline in IoPTH level within 15 min of parathyroidectomy is 96.5% reliable in predicting cure in these patients with PTH starting in the normal range.

Radioguided Reoperative Parathyroidectomy for Persistent Primary Hyperparathyroidism

We report a case of reoperative radioguided parathyroidectomy in a patient with primary hyperparathyroidism. A 58-year-old man presented to our center with persistent hypercalcemia and hyperparathyroidism after 2 previous parathyroid explorations at an outside facility. Despite the use of preoperative and intraoperative localization, identification of the hyperfunctioning gland was unsuccessful during the initial operations. Because of the continued presence of symptoms, the patient was referred to our center for reoperation. Repeat Tc-99m sestamibi parathyroid scan showed an inferior right parathyroid adenoma. With the intraoperative guidance of a hand-held gamma probe, an enlarged parathyroid gland was localized on the spine behind the esophagus on the right, and successfully removed. Intraoperative parathyroid hormone testing confirmed a surgical cure. The use of radioguidance and intraoperative parathyroid hormone testing were essential to the successful resection. The patient remained disease-free at follow-up.

Emerging Trends in the Performance of Parathyroid Surgery

The management of hyperparathyroidism has evolved rapidly in the past decade with the introduction of intraoperative parathyroid hormone testing, radioguided surgery, and endoscopic surgery. Not surprisingly, there is a corresponding movement toward specialization of surgeons providing increasingly sophisticated treatments for head and neck endocrine disorders. We sought to identify trends in the disciplines performing parathyroid surgery. Nonrandomized, controlled comparison of surgical caseloads and publication volumes. Two metrics designed to reflect the proportion of parathyroidectomies being performed by otolaryngologist-head and neck surgeons (OHNS) and general surgeons (GS) were chosen: the operative case logs of graduates from American training programs in OHNS and GS from 1996 through 2005 and the number of scientific papers published relating to parathyroid surgery during two timeframes (1991-1995 and 2001-2005). There was a gradual increase in the mean number of parathyroid surgeries performed by GS residents from 6.0 in 1996 to a peak of 9.2 in 2004; this volume has begun to decline (to 8.5 in 2005). During the same timeframe, the mean number of parathyroidectomies performed by OHNS residents rose sharply and steadily from 1.8 in 1996 to 10.9 in 2005. The number of American GS parathyroid publications from 1991 to 1995 was 41, compared with 108 in the period 2001 to 2005. During the same timeframe, the number of American OHNS parathyroid papers increased from 1 to 27. The relative proportion of parathyroid publications authored by American otolaryngologists rose from 2.4% to 20.0% (P = .006). Increasingly, otolaryngologists are the primary surgeons in parathyroid operations as indicated by two surrogate metrics. Graduating chief residents in otolaryngology now perform more parathyroid procedures than chief residents in general surgery, and a growing proportion of parathyroid publications are being authored by otolaryngologists.

Update on Point-of-Surgery Testing

In the approximately 10-year period since the introduction of intra-operative parathyroid hormone testing, a variety of hormones have proven to be valuable tools in the surgical management of patients with various types of resectable tumors. To what extent the current list of hormones/markers performed intraoperatively will expand will be related, in part, to the speed with which new hormones/tumor markers are identified that meet the criteria indicated below for useful markers in point-of-surgery testing (POST). With the exception of intra-operative parathyroid hormone (ioPTH) testing, testing for the other hormones indicated below is performed at specialized centers using either modified commercial (“home-brew”) or research use only (RUO) assays.

The role of intraoperative parathyroid hormone testing in patients with tertiary hyperparathyroidism after renal transplantation

Intraoperative parathyroid hormone (PTH) testing has been shown to accurately define adequacy of parathyroid resection in patients with primary hyperparathyroidism (HPT) and alters the operative management in 10% to 15% of cases. However, the benefit of this technique in patients with tertiary HPT after renal transplantation undergoing parathyroidectomy is unclear. Intraoperative PTH was measured in 32 consecutive patients undergoing parathyroidectomy for tertiary HPT after renal transplantation between March 2001 and November 2004 by using the Elecsys assay at baseline and, subsequently, 5, 10, and 15 minutes after curative resection. The outcomes of these patients were evaluated. All patients were cured after surgery. Of the 32 patients, 29 were found to have parathyroid hyperplasia, while 1 had a single adenoma and 2 had double adenomas. The average drop in intraoperative PTH levels after curative resection was 69 +/- 3.5% at 5 min., 77 +/- 2.3% at 10 minutes, and 83 +/- 3.4% at 15 minutes. PTH testing changed the intraoperative management in 5 (16%) patients. One patient with a single adenoma and 2 patients with double adenomas had a >50% drop at 10 minutes. after excision; therefore, the operation was terminated without further resection. Two patients did not have a >50% drop at 10 minutes after 3.5 gland resection. These patients were explored further, and additional supernumerary parathyroid glands were identified and resected. After resection of these additional glands, the PTH fell by >50%, indicating cure. In patients undergoing parathyroidectomy for tertiary HPT after renal transplantation, a decrease in intraoperative PTH levels >50% at 10 minutes after completion of the operation indicated adequate resection. Furthermore, intraoperative PTH testing altered the operative management in 16% of patients. Therefore, similar to its role in patients with primary HPT, intraoperative PTH testing appears to play an equally important role in the management of patients with tertiary HPT undergoing parathyroidectomy.

Intraoperative parathyroid hormone testing improves cure rates in patients undergoing minimally invasive parathyroidectomy

Intraoperative parathyroid hormone (iPTH) testing often is used during minimally invasive parathyroidectomy for primary hyperparathyroidism (1 degrees HPT). However, several investigators report that these assays are not cost effective and do not improve outcomes significantly. To determine the impact of iPTH testing on the outcomes of patients with 1 degrees HPT, we reviewed our experience. From January 1990 to June 2004, there were 345 consecutive patients with 1 degrees HPT and positive localization studies for a single parathyroid adenoma who were candidates for minimally invasive parathyroidectomy. Group 1 patients (n = 157) underwent parathyroid exploration without iPTH testing and group 2 patients (n = 188) had an operation with iPTH testing. Of the group 1 patients, 15 (10%) still were hypercalcemic postoperatively owing to additional unidentified hyperfunctioning parathyroid glands. In contrast, among 188 group 2 patients, 170 (90%) had resection of a single parathyroid adenoma, a greater than 50% decrease in iPTH levels, and were cured. The remaining 18 (10%) patients did not have an adequate reduction in iPTH levels and underwent bilateral neck exploration with resection of additional parathyroids. Of these 18 patients, 9 had double adenomas and 9 had 3- or 4-gland hyperplasia. Importantly, all patients in group 2 were cured. iPTH testing improves cure rates in patients undergoing minimally invasive parathyroidectomy. iPTH testing allowed intraoperative recognition and resection of additional hyperfunctioning parathyroids missed by preoperative imaging studies. Consequently, we strongly advocate the routine use of iPTH testing in patients who undergo minimally invasive parathyroidectomy for 1 degrees HPT.

The surgeon's armamentarium to the surgical treatment of primary hyperparathyroidism

Parathyroidectomy cures the vast majority of patients with primary hyperparathyroidism (HPT). While bilateral neck exploration has been the mainstay of therapy, recent advances in technology have revolutionized the field making a focused approach to parathyroidectomy a reality. The development of accurate pre-operative localization with sestamibi scanning, effective unilateral, endoscopic and video-assisted techniques, and rapid intra-operative parathyroid hormone (PTH) testing have made it possible to cure patients with the least amount of surgical dissection possible. In this paper, we will explore the role of focused parathyroidectomy in the surgical treatment of primary HPT.

Rapid Intraoperative Parathyroid Hormone Testing With Surgical Pathology Correlations

The classic surgical approach to patients undergoing parathyroidectomy for primary or secondary hyperparathyroidism has experienced a dramatic shift owing to preoperative localization of the affected glands and/or the use of rapid intraoperative parathyroid hormone (RI-PTH) assays, allowing for minimally invasive surgical excisions. Institutional experience with 141 patients who underwent parathyroidectomy aided by the use of RI-PTH is reviewed. The orientation provided by the intraoperative assay is essential in guiding the surgeon in these minimally invasive procedures, it helps reveal the cases of primary hyperparathyroidism with involvement of more than 1 gland, and it replaces the need for performing frozen sections, except for cases of secondary hyperparathyroidism.

Rapid Intraoperative Parathyroid Hormone Testing With Surgical Pathology Correlations: The "Chemical Frozen Section"

The classic surgical approach to patients undergoing parathyroidectomy for primary or secondary hyperparathyroidism has experienced a dramatic shift owing to preoperative localization of the affected glands and/or the use of rapid intraoperative parathyroid hormone (RI-PTH) assays, allowing for minimally invasive surgical excisions. Institutional experience with 141 patients who underwent parathyroidectomy aided by the use of RI-PTH is reviewed. The orientation provided by the intraoperative assay is essential in guiding the surgeon in these minimally invasive procedures, it helps reveal the cases of primary hyperparathyroidism with involvement of more than 1 gland, and it replaces the need for performing frozen sections, except for cases of secondary hyperparathyroidism.

Challenges in the application of intraoperative intact PTH testing: A clinical algorithm

Problem: To describe the results of iPTH testing and preoperative imaging in a cohort of patients undergoing parathyroid surgery and to develop a comprehensive algorithm for the clinical use of iPTH. Methods: The medical and operative records of 38 patients undergoing surgery for primary hyperparathyroidism between 2001 and 2003 were reviewed for patient demographics, complications, iPTH values, and correlation of preoperative imaging with operative findings. Patients with single adenomas and >50% drop in iPTH after excision were considered cured. In cases of multi-glandular disease or failure of iPTH drop, bilateral exploration was undertaken and the iPTH was repeated until an appropriate drop was achieved. Immediate and delayed postoperative serum calcium levels were reviewed. Results: All 38 patients (mean age, 58 years; 71% female) had primary hyperparathyroidism (82% adenoma and 18% hyperplasia). Thirty-six patients experienced >50% PTH drop at the end of surgery and were considered cured of disease. At follow-up, one patient experienced a 47.7% drop and was deemed cured of disease and one patient experienced a 10.9% drop with persistent disease. The sensitivity and PPV of >50% drop in iPTH values with cure of hyperparathyroidism were 97.4% and 100%, respectively. Preoperative imaging was most accurate for identifying a single parathyroid adenoma (76.0%) and fell significantly for unilateral (25%) or bilateral (20%) multi-glandular disease. Mean follow-up was 62 days (range 7–377 days). Conclusion: Intraoperative iPTH testing and preoperative imaging are valuable adjuncts to parathyroid surgery. Used properly, iPTH has a high predictive value for disease cure. Nonetheless, it is not a replacement for surgical judgment especially in situations of borderline parathyroid gland enlargement or marginal decline in iPTH values. Significance: Demonstration of the utility and limitations of intraoperative intact parathyroid hormone testing and preoperative imaging for parathyroid surgery. Development of a clinical algorithm for the practical use of intraoperative iPTH testing. Support: None reported.

Intraoperative parathyroid hormone assay and parathyroid reoperations

Background The purpose of this study was to determine whether intraoperative parathyroid hormone (IOPTH) assay improved results of reoperations. Methods One hundred two patients with persistent/recurrent sporadic primary hyperparathyroidism underwent 108 reoperations (1996-2002). IOPTH was not used (n = 58) from 1996-1998 (group 1). IOPTH was used (n = 50) from 1999-2002 (group 2). Sensitivity and positive predictive value of IOPTH and its influence on surgical strategy were analyzed. A 50% decrease occurring 10 minutes after removal of parathyroid tumor was used to determine if all abnormal tissue had been removed. Results Groups 1 (58 patients) and 2 (50 patients) were comparable except for duration of follow-up. The cure rate was 84% (group 1, 87%; group 2, 82%, P = 0.7). Hypocalcemia developed in 20 patients (permanent in 2 patients). There was 1 permanent vocal cord paralysis and 1 patient died of toxic shock syndrome. IOPTH successfully predicted cure in 44 of 49 patients (sensitivity, 90%); the positive predictive value was 90%. Values for parathyroid hormone level and the ratio parathyroid hormone/calcium at day 1 were at least as accurate as IOPTH in predicting cure. IOPTH was helpful in 1 patient but misleading in 4 patients. It failed to modify intraoperative strategy in most other patients. Conclusions IOPTH testing was relatively reliable in patients with persistent or recurrent sporadic primary hyperparathyroidism, but the test unfortunately failed to improve the overall success rate at reoperation.

Differing histologic findings after bilateral and focused parathyroidectomy.

Minimally invasive parathyroid surgery with intraoperative parathyroid hormone testing has been reported to be as successful as a bilateral operation. This study aimed to determine whether the histologic findings and outcomes differ in patients with primary sporadic hyperparathyroidism treated by a focal or a bilateral parathyroid exploration with intraoperative parathyroid hormone testing. To make the two groups comparable all patients had a solitary parathyroid adenoma identified preoperatively. Eighty unselected patients with primary hyperparathyroidism and a single abnormal parathyroid gland identified preoperatively by sestamibi scanning or ultrasonography were included in this study. All patients had intraoperative parathyroid hormone testing. Forty-five patients had standard bilateral neck explorations and 35 patients had focal neck explorations. In the bilateral neck exploration group a single adenoma was found in 38 patients (84%), a double adenoma in 3 patients (7%), hyperplasia in 3 patients (7%), and carcinoma in 1 patient (2%). In contrast, a single adenoma was identified in all patients in the focal neck exploration group. Sestamibi scanning and intraoperative parathyroid hormone assay were accurate in 87% and 84%, respectively, in the bilateral neck exploration group and in 96.9% and 94.3%, respectively, in the focal neck exploration group. All patients were normocalcemic (mean followup 17 months). Patients with primary hyperparathyroidism having a bilateral exploration had about a 15% higher rate of multiple parathyroid tumors than did patient having a focal approach. Despite this observation all patients were normocalcemic postoperatively. This suggests that either some histologically abnormal parathyroid glands do not function or there will be recurrences in patients treated by a focused approach. Longterm followup will be necessary to determine whether patients treated by focal neck exploration will develop recurrent primary hyperparathyroidism.

Intraoperative parathyroid hormone testing: what have we learned?

The development of rapid, sensitive assays for measuring the intact parathyroid hormone (iPTH) molecule has the potential to allow the surgeon to determine the success of parathyroid surgery intraoperatively. The purpose of the study was to review our results in the context of currently held beliefs regarding the ability of the intraoperative iPTH to predict resolution of hyperparathyroidism. Retrospective review. The study series is a retrospective review of 107 consecutive parathyroidectomies performed by a single surgeon. Patients with primary, secondary, and tertiary hyperparathyroidism were included. The intraoperative assay allowed an overall success rate of 93.4% across all patient categories. The success rate in patients with primary hyperparathyroidism was 95.7%. Measuring the iPTH level at 10 versus 15 minutes after the removal of tissue did not significantly affect the predictive value of the test. A decrease of 50% in the iPTH level after the resection of hyperfunctioning tissue was prognostic of successful treatment of the hyperparathyroid state. By contrast, a postexcision iPTH level that was within the normal range was not always predictive of cure. The intraoperative iPTH assay is particularly useful in the treatment of primary hyperparathyroidism. The assay eliminates the need for intraoperative frozen-section analysis in most cases and allows the surgeon to perform limited resections with confidence. This is especially true in complicated parathyroid surgeries, such as revision surgeries or those requiring concomitant thyroid surgery. The assay is also useful in secondary hyperparathyroidism, although it appears that the inability to identify small nonfunctional or hypofunctional supernumerary parathyroid glands means that long-term normocalcemia may not be assured.

Intraoperative parathyroid hormone testing: survey of testing program characteristics.

To examine the number and testing characteristics of laboratories that offer intraoperative testing of intact parathyroid hormone (PTH). Laboratories (n = 355) that participated in 2001 in PTH proficiency testing with the College of American Pathologists Special Ligand Survey were surveyed about intraoperative PTH testing. Of the 320 laboratories that responded to the survey, 92 performed intraoperative PTH testing. Testing practices were divided nearly equally among laboratories that performed intraoperative PTH testing for all parathyroidectomies (40%), most but not all cases (31%), and less than half of cases (30%). Testing frequency usually was low, with about two thirds of laboratories reporting 5 or fewer cases per month. A surprising finding was that, although intraoperative PTH testing originally became widely practiced as a point-of-care test, 71% of laboratories performed testing in a central laboratory, 6% in satellite laboratories, and only 23% in operating suites. A survey of methods showed that 33% used the manual QuiCk-Intraoperative test, 47% used the automated Immulite Turbo intact PTH assay, and 20% used other methods. Intraoperative testing of intact PTH, although relatively new, has come into widespread practice during parathyroid surgery. Service delivery has evolved from a point-of-care model toward a central laboratory model, with this test serving as an illustrative example of factors that affect the balance between point-of-care and laboratory testing.

Intraoperative vs Central Laboratory PTH Testing During Parathyroidectomy Surgery

Intact parathyroid hormone (PTH) testing can be performed rapidly, directly in the operating room, using the QuiCK-Pak System (Nichols Institute Diagnostics, San Juan Capistrano, CA) or in a central laboratory using the IMMULITE Immunoassay System and Turbo PTH assay (Diagnostic Products, Los Angeles, CA). Correlation between parathyroid hormone values obtained on EDTA plasma samples using these systems was good (r = 0.84); at 20-minutes after excision of a suspected hyperfunctioning parathyroid gland, diagnostic agreement between the two systems was 100%. Based on 50 parathyroid gland surgeries for each of a 3-year contract period, the cost of intraoperative vs central laboratory PTH testing per surgery was $760 and $360, respectively. Intraoperative parathyroid hormone testing using the QuiCK-Pak System provides faster, more reliable turnaround time for intraoperative PTH results and has other advantages over central laboratory PTH testing during parathyroid gland surgery.

Intraoperative Parathyroid Hormone Analysis: A Study of 200 Consecutive Cases

Immunoassays for parathyroid hormone (PTH), with short incubation times and results available in <15 min, have allowed intraoperative monitoring of the success of parathyroid surgery. The purpose of this study was to evaluate the analytical performance of a rapid PTH assay and its clinical performance in a series of 200 patients. PTH was measured with a modified immunochemiluminometric assay with a 7-min incubation time (QuiCk-IntraOperative(TM) Intact PTH assay). The rapid assay was compared with results in a central laboratory (immunoradiometric assay) in 44 EDTA-plasma specimens. The rapid assay was used intraoperatively in 200 consecutive cases with specimens analyzed before and 5-10 min after resection of the hypersecreting parathyroid gland(s). Intraassay imprecision was 12% at 28 ng/L and 11% at 278 ng/L. Regression analysis of results of the rapid PTH assay and the IRMA PTH assay in 44 parathyroidectomy patients yielded y = 1.26x - 12 ng/L, S:(y|x) = 26.3 ng/L, r = 0.984, and in 40 of 44 patients with values <200 ng/L, y = 1.02x + 1.9, S:(y|x) = 13.9, r = 0.947. In the 195 cases using intraoperative PTH testing with complete results and defined clinical outcomes, the overall accuracy of the assay in predicting surgical success was 88% using the criterion of a 50% decrease at 5-10 min and 97% including the subset of patients with delayed decreases of PTH. The rapid PTH assay had excellent analytical performance and excellent agreement with the PTH immunoradiometric assay and predicted the success of parathyroid surgery in this large series of consecutive patients.