Recurrent disease after limited parathyroidectomy for sporadic primary hyperparathyroidism

BACKGROUND: Limited parathyroidectomy guided by intraoperative parathyroid hormone (PTH) assay (QPTH) is highly successful (97% to 99%) in predicting postoperative eucalcemia, usually with less extensive dissection when compared with bilateral neck exploration. Because fewer glands are excised when resection is guided by QPTH as opposed to resection guided by gland size, a higher recurrence rate may occur. Recurrence rate after bilateral neck exploration is 0.4% to 5%, but frequency of recurrence after limited parathyroidectomy is unknown. This study reports outcomes of this operative approach in sporadic primary hyperparathyroidism. STUDY DESIGN: Four-hundred twenty-three patients with sporadic primary hyperparathyroidism undergoing limited parathyroidectomy, followed 6 months or more or considered operative failures, were studied. In most patients, calcium and PTH levels were measured immediately after operation, and then at 2 and 6 months and yearly intervals. Operative failure is defined as hypercalcemia and high PTH within 6 months after operation, and recurrent hyperparathyroidism is hypercalcemia and elevated PTH occurring after a successful parathyroidectomy. Recurrence distributions were estimated using Kaplan-Meier analysis. RESULTS: The success rate of limited parathyroidectomy is 97% (412/423). Four-hundred six patients were eucalcemic over an average of 34 months (median 27, range 6 to 118 months) of followup and recurrent hyperparathyroidism developed in 6 of 412 (1.5%). Estimated 5 years recurrence-free rate was 97% (95% confidence interval, 91% to 99%). Earliest and latest recurrences were diagnosed at 24 and 83 months, respectively. QPTH results did not predict any recurrence. Overall success rate was achieved, with multiple gland resections performed in only 3% of patients. CONCLUSIONS: Recurrence rate after limited parathyroidectomy is similar to rates reported after bilateral neck exploration. Parathyroidectomy guided by QPTH is successful not only in resolving hypercalcemia in the short term, but also in providing longterm eucalcemia.     

Consequences of targeted parathyroidectomy guided by localization studies without intraoperative parathyroid hormone monitoring

BACKGROUND: After excision of an abnormal gland, the dynamics of intraoperative parathyroid hormone (PTH) levels signal whether or not more hypersecreting tissue is present. This quantitative assurance of operative success has led to targeted exploration of the hyperfunctioning gland(s). Some have questioned the need for intraoperative PTH monitoring (IPM) in the presence of positive nuclear scanning. The purpose of this study was to examine the accuracy of nuclear scans in correctly localizing and guiding the complete excision of all abnormal gland(s) in patients with sporadic primary hyperparathyroidism (SPHPT) and to demonstrate how IPM changed the operative management in these patients. STUDY DESIGN: Five hundred nineteen consecutive patients with sporadic primary hyperparathyroidism had technetium 99-m-sestamibi scans (MIBI) as localization studies obtained before undergoing parathyroidectomy guided exclusively by IPM. All patients were either followed for more than 6 months, or their procedures were identified as operative failures. MIBI reports were correlated with operative findings, hormone dynamics, and postoperative outcomes. RESULTS: Operative success was achieved in 506 of 519 patients (97%). MIBI correctly localized all involved glands in 411 patients (80%). Among the 105 patients (20%) with incorrect or negative scans, IPM changed the operative management in 86 of 105 (82%) by pointing out incomplete resection in patients with a single MIBI incorrect focus (21 of 28) or unrecognized multiglandular disease by scan (13 of 15); avoiding unnecessary exploration in patients with additional incorrect foci (20 of 21); and guiding the surgeon to successful excision or unilateral neck exploration in patients with negative MIBI (32 of 41). CONCLUSIONS: MIBI as a single adjunct missed 87% of patients with multiglandular disease. Including patients with negative (8%) and incorrect (12%) MIBI, IPM changed the operative management in 17% of patients and led to operative success in 97%. We suggest that IPM should be used to guide parathyroid excision in every patient with sporadic primary hyperparathyroidism.     

Operative Failure in Minimally Invasive Parathyroidectomy Utilizing an Intraoperative Parathyroid Hormone Assay

Background

Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP.

Methods

Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation.

Results

Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons’ inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50–59 %) had a treatment failure rate of 20 %.

Conclusions

The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons’ failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome.     

Changing Intraoperative Parathyroid Hormone Collection Sites from Peripheral to Central Does Not Affect Predictive Accuracy during Minimally Invasive Parathyroidectomy

Background

Intraoperative parathyroid hormone (ioPTH) monitoring (IPM) is vital to minimally invasive parathyroidectomy. Techniques vary in assay sampling, potentially affecting predictive accuracy of operative success. Initial guidelines were established using peripheral sites, but central sites may be preferred or necessary when peripheral access is not feasible. We hypothesize that changing collection sites from preexcision peripheral sites to postexcision central sites would not affect IPM accuracy.

Methods

Analysis of 64 consecutive patients who underwent parathyroidectomy for primary hyperparathyroidism was undertaken. PTH assays were collected simultaneously from a peripheral vein (PV) and central vein (CV) preexcision and at a 10-min interval after initial parathyroid excision. IPM success was defined as PTH decrease ≥50% 10 min after initial excision. Predictive accuracy was determined by the need to resect another abnormal gland and biochemical normalization in the postoperative clinic. Receiver operating characteristic (ROC) method with area under the curve (AUC) compared diagnostic accuracy of different assay approaches.

Results

Centrally, a statistically higher mean pre- and postexcision ioPTH of 391 pg/ml and 58 pg/ml was found compared with peripheral means of 156 pg/ml and 49 pg/ml, respectively (p < 0.001). The AUC when changing from a PV preexcision to a CV postexcision ioPTH was 0.89, comparable to AUC for peripheral or central assay collections alone (AUC = 0.83 and 0.85, respectively).

Conclusions

This study suggests that altering collection sites does not alter assay validity. In cases where peripheral sampling is compromised, changing from a peripheral to central sites will not likely alter the predictive accuracy of IPM significantly.     

The role of parathyroid hormone measurements after surgery for primary hyperparathyroidism

BACKGROUND: During parathyroidectomy for primary hyperparathyroidism (pHPT), intraoperative parathyroid hormone (IOPTH) levels are used to confirm removal of all hyperfunctioning parathyroid tissue. The phenomenon of elevated parathyroid hormone (PTH) levels with normocalcemia after curative parathyroidectomy, seen in up to 40% of patients, continues to be an unexpected and unexplained finding. We therefore investigated whether postoperative PTH levels are as reliable as IOPTH levels in predicting cure after surgery for pHPT. METHODS: We reviewed our prospective database of consecutive patients undergoing surgery for pHPT between December 1999 and November 2004. Curative parathyroidectomy was defined as normocalcemia 6 months or longer postoperatively. RESULTS: A total of 328 patients who underwent 330 operations for pHPT had IOPTH measurements and serum follow-up calcium levels at 6 months or longer. Surgery was curative in 315 (95.5%) operations. IOPTH levels correctly predicted operative success in 98.2% (positive predictive value [PPV]. Postoperatively, the PPV of a normal PTH level at 1 week, 3 months, and 6 months was 97.1%, 97.3%, and 96.5%, respectively. Of all patients with an elevated postoperative PTH level at 1 week, 3 months, or 6 months, only 13.7%, 14.3%, and 14%, respectively, were not cured. CONCLUSIONS: Normal postoperative PTH levels reliably predict operative success. However, they do not improve upon results predicted by IOPTH levels. Elevated postoperative PTH levels do not predict operative failure in most patients. We propose that PTH measurements after surgery for pHPT may be misleading, costly, and not indicated in normocalcemic patients.     

Intraoperative Parathyroid Hormone Monitoring

The principles of minimally invasive parathyroidectomy include the successful preoperative localization of a solitary adenoma, a targeted operative approach that does not disturb the normal parathyroid glands, and intraoperative confirmation of excision of all hypersecreting parathyroid tissue. By providing real-time feedback to the surgical team, the rapid PTH assay allows surgeons to assess the completeness of parathyroid resection without visualizing all the parathyroid glands. Intraoperative PTH monitoring facilitates the use of local anesthesia, decreases the duration of surgery, and allows ambulatory surgery in most patients. This article reviews current recommendations and controversies surrounding the use of intraoperative PTH monitoring during parathyroidectomy.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Quick Intraoperative Parathyroid Hormone Assay: Surgical Adjunct to Allow Limited Parathyroidectomy,Improve Success Rate,and Predict Outcome

Intraoperative parathyroid hormone (PTH) assay (QPTH) has made possible less invasive operative approaches in the treatment of primary hyperparathyroidism with stated advantages. When compared to the traditional bilateral neck exploration (BNE), only the targeted, hypersecreting gland is excised, leaving in situ non-visualized but normally functioning parathyroids. The QPTH-guided limited parathyroidectomy (LPX) must be able to identify multiglandular disease (MGD), predict a successful outcome, and have a low recurrence rate. In our series, 421 patients who underwent LPX were compared to 340 undergoing BNE; all operative failures and patients followed for 6 months or longer were included. Operative failure occurred if serum calcium and PTH levels were elevated within 6 months of parathyroidectomy. Multiglandular disease was defined in the LPX group as more than one gland excision guided by QPTH or operative failure after removal of a single abnormal gland; in the BNE group it was defined as excision of more than one enlarged gland. Recurrence was defined as elevated calcium and PTH after 6 months of eucalcemia. Operative failure and MGD rates were compared using chi-squared analysis. The method of Kaplan-Meier and the log-rank test were used to compare recurrence rates. Operative success was seen in 97% of LPX patients and in 94% of the BNE group (p = 0.02). Multiglandular disease was identified in 3% of LPX patients and 10% of BNE patients (p < 0.001). There was no statistical difference in the overall recurrence rates (p = 0.23). The QPTH-guided parathyroidectomy identifies MGD and allows an improved success rate with the same low recurrence rate when compared to the results of BNE.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14-17, 2004.     

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

Background

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.

Methods

A retrospective review was performed on all patients who underwent parathyroidectomy for hyperparathyroidism at a single institution from 3/2001 to 8/2008.

Results

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).

Conclusions

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.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Impact of Intraoperative Parathyroid Hormone Levels on Surgical Results in Patients with Renal Hyperparathyroidism

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.     

New Point-of-care Intraoperative Parathyroid Hormone Assay for Intraoperative Guidance in Parathyroidectomy

The use of the intraoperative parathyroid hormone assay (QPTH) to guide a limited parathyroidectomy in patients with sporadic primary hyperparathyroidism (SPHPT) is well established. The advantage of having this assay performed in the operating room is immediate feedback for (1) confirming the complete excision of all hyperfunctioning parathyroid(s); (2) differential jugular venous sampling for localization; and (3) diagnosing suspected tissue without histopathology. For these reasons, the reliability of the hormone measurement and a short assay turnaround time are essential for surgical guidance. We report our experience using a new "point-of-care" assay for intact parathyroid hormone (iPTH). A new two-site chemiluminescent immunometric assay was used. The antibodies are inside a microtiter well, where the iPTH is measured by a strip luminometer after incubation for 5 minutes. Sixteen frozen samples were measured simultaneously using the traditional iPTH assay and this new assay for comparison. Fifty-one patients with SPHPT underwent parathyroidectomy guided by this new assay. The criteria used to predict postoperative normocalcemia was a drop in the hormone level of ≤ 50% from the highest preincision or preexcision levels at 10 minutes after excision of all hypersecreting gland(s). The correlation between the traditional and new assays was 0.98. The assay predicted the postoperative calcium levels in all patients except one (false negative-delayed drop). The assay turnaround time was 8 minutes. This new point-of-care assay is reliable for predicting postoperative calcium levels when used with the described criteria. It has advantages over the traditional assay in that it is faster and easier to perform.     

Intraoperative parathyroid hormone measurement during parathyroidectomy for treatment of primary hyperparathyroidism: When should you end the operation?

IntroductionThe study objective was to evaluate the intraoperative 50% decrease in PTH level ± PTH normalization for its accuracy and efficiency in predicting cure during parathyroidectomy (PTx) for the treatment of primary hyperparathyroidism (PHP).MethodsA retrospective review of patients undergoing PTx was conducted. The timepoints at which the 50% PTH decrease was reached were recorded. The accuracy of intraoperative PTH for predicting cure, defined as normocalcemia at 6 months postoperatively, was evaluated.ResultsThe study population was made up of 248 PHP patients, with 247 patients achieving normocalcemia at 6 months postoperatively. If a 50% PTH decrease was used to indicate operation conclusion, 1 patient would not be cured. Persistent PTH elevation above normal range at T10 had a PPV of 77%, NPV of 99.5%, sensitivity of 95.2% and specificity of 97.3% for predicting the presence of a contralateral pathological parathyroid gland. For the study cohort, 24.5 h of cumulative operating time would be saved if the 50% PTH decrease triggered operation conclusion.DiscussionA decrease in the pre-excision PTH level to 50% of the baseline level, or a decrease in the higher of the baseline or pre-excision PTH levels by 50% at 5 or 10 min post pathological parathyroid gland removal, regardless of whether the PTH level normalizes, reliably predicts cure from PHP and should be used to guide the surgeon during parathyroidectomy.     

Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufficiency

BACKGROUND: 25-OH Vitamin D (VitD) plays a role in serum calcium (Ca) and parathyroid hormone (PTH) homeostasis. VitD insufficiency in patients with primary hyperparathyroidism (HPT) may be associated with greater disease severity and a higher incidence of multi-gland disease and postoperative normocalcemic PTH elevation. MATERIALS AND METHODS: One hundred ten patients with HPT undergoing parathyroidectomy had preoperative VitD levels as follows: levels were insufficient (< or =20 ng/mL) in 55 patients (group 1) and sufficient (>20 ng/mL) in 55 patients (group 2). All patients had preoperative localizing sestamibi scans and/or ultrasounds and postoperative serum Ca and PTH levels. A focused approach was performed when possible, and intraoperative PTH monitoring (IPM) was used in all patients. RESULTS: Patients with VitD insufficiency had significantly higher preoperative Ca (11.3 +/- 1.2 versus 10.8 +/- 0.9 mg/dL, P = 0.012) and PTH levels (204 +/- 138 versus 156 +/- 179 pg/mL; P = 0.006) as well as higher bone specific alkaline phosphatase (P = 0.006). Localization studies were similar. IPM levels were significantly higher in group 1 at all time intervals. Both groups were similar in operative time, conversions to bilateral explorations, number of glands removed, and number of frozen sections. The glands in group 1 were larger (1757 versus 524 g; P = 0.005). Postoperative Ca levels, PTH levels, rates of eucalcemia, and rates of eucalcemic PTH elevation were all similar. CONCLUSION: Patients with HPT and VitD insufficiency may have significantly more severe disease based on preoperative serum Ca and PTH levels, bone markers, and gland size. IPM levels in these patients are higher but can be used to predict postoperative eucalcemia, an outcome which appears be independent of VitD status.     

Surgical Treatment of Patients with Mildly Elevated Parathormone and Calcium Levels

Background

Patients with mildly elevated parathormone (PTH) and calcium levels consistent for primary hyperparathyroidism (pHPT) may present with more underlying multiglandular disease (MGD) and higher operative failure and recurrence rates than those with conventional, or “classic” pHPT. This study compared the clinical characteristics and surgical outcomes of patients with biochemically mild versus conventional pHPT.

Methods

A series of 707 consecutive patients underwent initial targeted parathyroidectomy with intraoperative parathormone monitoring (IPM) at a single institution. Biochemically mild (BM) pHPT was defined as PTH > 65 and <100 pg/ml with serum calcium >10.4 and <11 mg/dl. Conventional pHPT was defined as calcium ≥11 mg/dl and PTH ≥ 100 pg/ml. Prospectively collected data for all patients, including operative indication, preoperative laboratory values, imaging, IPM dynamics, and postoperative laboratory values were retrospectively reviewed. Additional assessments included presence of MGD, bilateral neck exploration (BNE), single-gland volume, and operative failure or success, and recurrence.

Results

Of 60 patients with BM-pHPT, 46 reported preoperative bone pain, kidney stones, fatigue, and/or mental disturbances. The remaining 14 BM-pHPT patients underwent parathyroidectomy based on published asymptomatic guidelines. Patients with BM-pHPT had significantly more kidney stones, MGD, and BNE. Average single-gland volume and postoperative PTH levels were significantly lower in BM-pHPT patients. There were no significant differences between groups regarding preoperative localization accuracy, IPM dynamics, or operative success/failure, recurrence rates.

Conclusions

BM-pHPT patients had more MGD requiring BNE but achieved operative success rates similar to those of patients with conventional disease. IPM successfully identifies MGD in BM-pHPT patients, who should be counseled regarding more extensive operations than limited parathyroidectomy.     

Minimally invasive endoscopic-assisted parathyroidectomy for primary hyperparathyroidism

Background: Minimally invasive surgery for primary hyperparathyroidism (pHPT) depends on both an accurate preoperative localization and the availability of intraoperative parathyroid hormone monitoring. Methods: Patients with sporadic pHPT and one unequivocally enlarged parathyroid gland on preoperative imaging underwent endoscopic-assisted parathyroidectomy. Intraoperative rapid parathyroid hormone (quick PTH) monitoring was performed, and surgical success was confirmed when there was a >50% decrease in quick PTH level 10 min after excision as compared with the baseline level at induction. The surgical outcome and the use of preoperative localization, together with the role played by quick PTH assay in enhancing the operative success, were evaluated. Results: From 1999 to 2002, 66 of 107 patients (62%) were selected for this approach. The accuracy of ^99mTc-Sestamibi scintigraphy and ultrasonography was 97% and 70%, respectively. Conversion was required in four cases due to technical problems, and four additional patients failed to show a significant decline in quick PTH levels postexcision. Two patients underwent cervical exploration without the finding of any additional pathology, and another two patients had a delayed drop in quick PTH that was confirmed 30 min postexcision. All patients had a solitary adenoma and were cured of hypercalcemia during a median follow-up of 9 months. Conclusions: Minimally invasive endoscopic-assisted parathyroidectomy can be performed expeditiously in a select group of patients based on ^99mTc-Sestamibi scintigraphy. The use of quick PTH assay can ensure surgical success, but careful interpretation of the results is mandatory.     

When Initial Postexcision PTH Level Does Not Fall Appropriately During Parathyroidectomy: What to Do Next?

Background  Inadequate fall in the intraoperative parathyroid hormone (PTH) level after removing enlarged parathyroid gland(s) typically signifies additional hyperfunctioning gland(s), prompting further neck dissection, but it may also be a false negative result. We analyzed intraoperative management of patients with an inadequate fall on PTH after excision of enlarged parathyroid gland(s). Methods  Analysis involved a prospective database of 189 patients undergoing 193 procedures for primary hyperparathyroidism. The PTH level was determined before neck incision and 10–15 min after excision of enlarged parathyroid gland(s). A PTH decrease > 50% and into normal range was used as the criterion of successful parathyroidectomy. Results  In 48 of 193 operations, initial postexcision PTH level did not fall appropriately. That inadequate fall in PTH level was a false negative result in 16 patients (33%) and cure was achieved without additional neck exploration in all but one patient, who had additional (negative) neck exploration after excision of a parathyroid adenoma. In all patients with false negative postexcision PTH assay, operative findings concurred with preoperative imaging tests. Conclusions  Inadequate fall in intraoperative PTH may be false negative, particularly after removal of an adenoma found in the location determined by preoperative imaging. Repeat PTH may confirm the initial assay as false negative, obviating the need for additional neck dissection. Importantly, if repeat PTH does not fall appropriately, additional neck exploration needs to be performed. Some of the results reported here were part of an oral presentation at the 88th Annual Meeting of the New England Surgical Society, Burlington, VT, September 29, 2007.     

Parathyroid autotransplantation in forty-four patients with primary hyperparathyroidism: the role of thallium scanning

Forty-four patients with primary hyperparathyroidism were followed for 18 to 126 months after subtotal or total parathyroidectomy and parathyroid autotransplantation. Indications for autotransplantation included the devascularization of parathyroid glands during concomitant thyroid lobectomy or total thyroidectomy and the excision of the only remaining parathyroid tissue in patients with persistent hyperparathyroidism after previous unsuccessful parathyroidectomies. Before implantation, all parathyroid tissue was histologically evaluated by frozen-section light microscopy with hematoxylin and eosin stain. Fifteen patients had histologically normal implants; to date none of these patients have developed recurrent hyperparathyroidism. Twenty-nine patients had either adenomatous or hyperplastic parathyroid tissue used for implants; two of these patients developed graft-dependent recurrent hyperparathyroidism 4 and 7 years later. In both patients the grafts were preoperatively localized by thallium scanning and their resection restored eucalcemia. One hundred thirty-one patients from 11 series in the current literature had a cumulative incidence of 17.5% for presumed graft-dependent recurrence and a 9.2% incidence of graft excision followed by eucalcemia. In comparison, in the present series the incidence of graft-dependent recurrent hyperparathyroidism in patients with either adenomatous or hyperplastic implants stands at 6.9%. In contrast, in 15 patients with normal parathyroid tissue implants, the incidence was zero.     

Sequential Changes in Plasma Intact and Whole Parathyroid Hormone Levels during Parathyroidectomy for Secondary Hyperparathyroidism

Most commercial assays for intact parathyroid hormone (iPTH) cross-react with non-PTH1-84 fragments (likely to be PTH7-84). We aimed to evaluate a whole PTH assay that measured only PTH1-84 by comparing it with an assay measuring iPTH levels during parathyroidectomy in secondary hyperparathyroidism (HPT). Twenty-eight patients with secondary HPT who underwent total parathyroidectomy with autotransplantation served as subjects. Blood samples for postoperative assay were drawn after anesthesia; immediately prior to excision of the last parathyroid gland; and at 5, 10, and 15 minutes after excision. The PTH7-84 level was calculated by subtracting the whole PTH value from the iPTH value. Plasma whole PTH decreased more rapidly than iPTH after parathyroidectomy (p < 0.0001). PTH levels that decreased by 50% or more from levels prior to excision to 10 minutes after excision were used to predict successful parathyroidectomy; decreases in whole PTH substantiated curative surgery for all patients without introducing false-positive and false-negative results. iPTH levels decreased by at least 50% in only 16 patients at 10 minutes after excision without false-positive results. Out of 11 cases in which iPTH decreased less than 50%, two were true-negatives and nine were false-negatives. Decreases in whole PTH levels more accurately reflect surgical outcome than do decreases in iPTH levels during parathyroidectomy in secondary HPT patients. Even though the quick iPTH assay is used infrequently during surgery for secondary HPT, our results suggest that a quick whole PTH assay may be more useful than the iPTH assay currently used in parathyroidectomy procedures for secondary HPT.     

Novel parathyroid hormone (1-84) assay as basis for parathyroid hormone monitoring in renal hyperparathyroidism

HYPOTHESIS: Cross-reactivity of parathyroid hormone (PTH) fragments with immunometric "intact" PTH assays limited the use of intraoperative PTH monitoring in renal hyperparathyroidism. A new assay generation measuring whole PTH (1-84) should be able to predict complete or incomplete resection of hyperfunctioning parathyroid tissue. DESIGN: Consecutive series for evaluation of intraoperative PTH monitoring using a second-generation assay. SETTING: University hospital section of endocrine surgery. PATIENTS: Twenty-two patients received hemodialysis; 9 patients showed good and 4 patients reduced graft function after kidney transplantation. INTERVENTIONS: Total parathyroidectomy, central neck dissection, bilateral thymectomy, and immediate autotransplantation was the standardized approach in 35 consecutive patients. Blood samples were drawn before incision and at 5-minute intervals after excision of the last gland. Stored samples were analyzed using a "second-generation" assay (Bio-Intact PTH [1-84]; Nichols Institute Diagnostics, San Clemente, Calif). Parathyroidectomy was classified as total, subtotal, or insufficient according to first-generation intact PTH values in the first postoperative week. MAIN OUTCOME MEASURES: Intraoperative ability to predict total, subtotal, or incomplete parathyroidectomy. RESULTS: Independent of renal function, Bio-Intact PTH dropped into the normal range in all patients with total and subtotal resections after a maximum of 20 minutes. It indicated insufficient parathyroidectomy in 4 (80%) of 5 patients. One failure was caused by devascularization of remaining parathyroid tissue. An intraoperative differentiation between total and subtotal resection was not possible. CONCLUSIONS: Intraoperative monitoring with quick, second-generation assays for PTH (1-84) seems to be a valuable new tool in surgery for renal hyperparathyroidism because a more accurate differentiation between sufficient and insufficient parathyroidectomy may be achieved. An intraoperative decision about the need for immediate or delayed autotransplantation seems impossible because a differentiation between total or subtotal parathyroidectomy cannot be made. Because of possible devascularization of parathyroid tissue, Bio-Intact PTH monitoring can only be interpreted in the context of the operative findings.     

Intraoperative parathyroid hormone measurement in patients with secondary hyperparathyroidism

HYPOTHESIS: Secondary hyperparathyroidism decreases renal clearance of parathyroid hormone (PTH). OBJECTIVE: To determine whether rapid PTH assays can be used to predict the success of a total parathyroidectomy to treat symptomatic secondary hyperparathyroidism. DESIGN: Case series from August 1 to December 31, 2000. SETTING: Tertiary referral center. PARTICIPANTS: Patients with symptomatic secondary hyperparathyroidism (n = 24) who underwent total parathyroidectomy and autotransplantation were included in the study. INTERVENTIONS: Blood samples for rapid PTH analyses were drawn from an indwelling catheter at the induction of anesthesia (baseline) and before (0 minutes), 10 minutes, and 30 minutes after the removal of the last parathyroid gland. Regular intact PTH (iPTH) assays were conducted later. MAIN OUTCOME MEASURE: If a patient's regular iPTH levels were below 65 pg/mL at 1 week or 3 months postoperatively, the operation was considered successful. RESULTS: All 24 patients had successful operations. Rapid PTH and regular iPTH correlated significantly at 0, 10, and 30 minutes. Rapid PTH levels decreased significantly at each time period and were 176 +/- 40.9 pg/mL (mean +/- SE) at 10 minutes. The percentage decrease in rapid PTH levels was 39.5% +/- 12.7% at 0 minutes, 75.1% +/- 6.2% at 10 minutes, and 91.0% +/- 0.1% at 30 minutes (mean +/- SE). A decrease of 60% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 30 minutes predicted the successful removal of all parathyroid glands. CONCLUSIONS: A drop in PTH levels is delayed until 30 minutes after total parathyroidectomy; however, a rapid PTH assay 10 minutes after the removal of the last parathyroid gland is as accurate as an assay performed at 30 minutes postoperatively. Intraoperative PTH monitoring demonstrates relevant decreases in rapid PTH levels after parathyroidectomy that are similar to those previously documented in patients with primary hyperparathyroidism.