Sporadic primary hyperparathyroidism in young individuals: different disease and treatment?

BACKGROUND: Younger individuals with hyperparathyroidism may experience severe disease with a higher incidence of multigland disease (MGD) and operative failure, thereby requiring subtotal parathyroidectomy. This study examines the characteristics and surgical outcome of younger compared with older patients with sporadic primary hyperparathyroidism (SPHPT). METHODS: Prospectively collected data of 1101 patients with SPHPT who underwent parathyroidectomy at a single institution were retrospectively reviewed. Patients with multiple endocrine neoplasia (MEN), familial, secondary, or tertiary hyperparathyroidism, parathyroid carcinoma, rickets, or lithium induced disease were excluded. Patients were subdivided into two groups: (1) younger individuals < or = 40 y of age (n = 110) and (2) older individuals > 40 y of age (n = 991). Both age groups were compared for gender, clinical manifestations, pre- and postoperative laboratory values, MGD, operative success, and recurrent disease. RESULTS: There was greater male predominance in younger compared with older patients treated for SPHPT (41% versus 25%, P = 0.0004). Of the clinical manifestations of SPHPT, kidney stones were more common in younger compared with older individuals (45% versus 29%, P = 0.0006). Conversely, bone pain was more common in older compared with younger patients (32% versus 14%, P = 0.0002). There was no statistical difference in biochemical values, MGD, and outcome between both groups. CONCLUSIONS: Despite male predominance and few differences in symptoms, SPHPT is a similar disease entity in both younger and older individuals. Patients from both age groups can be similarly treated for SPHPT with a high rate of operative success. Routine BNE and subtotal parathyroidectomy is not necessary in younger individuals.

Long-term results of parathyroidectomy for hypercalcemic crisis.

HYPOTHESIS: Hypercalcemic crisis is a rare complication of severe calcium intoxication usually caused by sporadic primary hyperparathyroidism that requires prompt diagnosis and definitive surgical treatment. Parathyroidectomy is essential for long-term successful treatment of hypercalcemic crisis. DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Forty-three patients treated for hypercalcemic crisis during a 35-year period who had signs and symptoms of acute calcium intoxication and serum calcium levels of 15 mg/dL (3.75 mmol/L) or greater. MAIN OUTCOME MEASURES: Operative success, operative failure, and disease recurrence after surgery. Kaplan-Meier analysis was used to estimate long-term survival after parathyroidectomy. RESULTS: Forty-two (98%) of 43 patients were eucalcemic after initial parathyroidectomy. There was 1 postoperative death. Of 27 patients with postoperative calcium data available for 6 months or longer, operative success was achieved in 26 (96%). There was 1 operative failure in a patient with multiglandular disease requiring reoperation. There were 3 recurrences (7%) at 7, 58, and 265 months. Overall median survival after parathyroidectomy was 11.7 years (95% confidence interval, 9.2-NE [not estimable]). The mean +/- SD serum calcium level of this group at a median follow-up of 4 years after surgery was 9.1 +/- 0.9 mg/dL (2.28 +/- 0.23 mmol/L). CONCLUSION: Hypercalcemic crisis can be successfully treated by parathyroidectomy with continued normal parathyroid function and excellent long-term survival.

Surgeon-performed ultrasonography as the initial and only localizing study in sporadic primary hyperparathyroidism.

BACKGROUND: With a secure diagnosis of hyperparathyroidism, preoperative localization of abnormal glands is the initial step toward limited parathyroidectomy. Nuclear scanning and ultrasonography done by third parties are costly. We investigated whether ultrasonography performed by the operating surgeon (SUS) could be the initial and only preoperative localization study in patients with sporadic primary hyperparathyroidism. STUDY DESIGN: Two hundred twenty-six patients underwent preoperative SUS and Sestamibi scans before limited parathyroidectomy guided by quick intraoperative parathyroid hormone assay. SUS findings were noted before the surgeon had access to the scan results. Charge for localization by nuclear scan was 1,315 dollars and 204 dollars for SUS. Successful localization was determined by operative findings, intraoperative hormone dynamics, and postoperative calcium levels. RESULTS: SUS correctly localized all the offending glands in 173 of 226 (77%) successfully treated patients. In 53 patients, SUS showed no parathyroid gland (n = 32), did not recognize multiglandular disease (n = 5), and showed an incorrect location of the abnormal gland (n = 16). In these patients, the technetium-99m-sestamibi scans successfully identified all abnormal tissue in 30 of 53 (57%). Localization using both methods was correct in 203 of 226 (90%) patients. Accuracy of SUS and scans used separately was equal. With use of quick intraoperative parathyroid hormone assay, successful parathyroidectomy was accomplished in 223 of 226 (99%), unilateral exploration in 88%, and overnight stay avoided in 78% of patients. CONCLUSIONS: With equal accuracy, SUS is more convenient, less expensive, and noninvasive when compared with scans. Sestamibi should be used when the SUS is negative or equivocal. SUS should be the initial localizing test in the treatment of sporadic primary hyperparathyroidism.

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.

Surgeon-performed ultrasound improves localization of abnormal parathyroid glands.

With a secure diagnosis of hyperparathyroidism, preoperative localization of abnormal glands is the initial step toward limited parathyroidectomy (LPX). We investigated whether ultrasonography in the hands of the surgeon (SUS) could improve the localization of abnormal parathyroids when sestamibi scans (MIBI) were negative or equivocal. One hundred eighty patients with sporadic primary hyperparathyroidism (SPHPT) underwent preoperative SUS and MIBI scans before LPX guided by intraoperative parathormone assay. When the sestamibi scans were negative, SUS was used to localize the parathyroid, distinguish parathyroid from thyroid tissue, and to guide the intraoperative jugular venous sampling for differential elevation of parathyroid hormone (PTH). Operative findings, intraoperative hormone dynamics, and postoperative calcium levels determined successful localization. MIBI was negative or equivocal in 36/180 (20%) patients: (1) showed no parathyroid gland in 22 patients, (2) suggested an incorrect location for the abnormal gland in 9, and (3) was insufficient in recognizing multiglandular disease in 5. In these 36 patients, the addition of SUS led to the successful identification of the abnormal tissue in 19/36 (53%). In the remaining 17 patients with negative/equivocal scans, the parathyroid could not be clearly visualized by SUS. In these patients, SUS facilitated LPX by aiding preoperative transcutaneous jugular venous sampling for differentially elevated PTH (n=3) and identifying questionable thyroid nodule versus parathyroid tissue (n=1). Overall, SUS was useful in 23/36 (67%) patients with nonlocalizing MIBI scans, thus improving the rate of localization from 80 per cent to 93 per cent (P < 0.01). Surgeon-performed cervical ultrasonography improved the localization of abnormal parathyroids by MIBI scan, adding to the success of limited parathyroidectomy.

Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas.

BACKGROUND: Solitary insulinomas are usually the cause of organic hypoglycemia, whereas 13% to 24% of patients with hyperinsulinemia have multiple tumors or nesidioblastosis. Intraoperative glucose levels confirming complete excision have variable accuracy. Intraoperative insulin levels have been shown to predict operative outcome. The purpose of this study was to establish criteria for predicting operative success by using a new, rapid insulin assay as an intraoperative adjunct. METHODS: Eight consecutive patients with organic hypoglycemia underwent pancreatic exploration. With an 8-minute immunochemiluminescent insulin assay, peripheral blood levels were obtained preoperatively, during resection, and at 5-minute intervals after surgical excisions. Operative findings and outcome were compared with intraoperative insulin/glucose ratios (I/G), glucose, and insulin levels. RESULTS: By using the return of insulin levels to normal range and I/G ratios < or = 0.4 15 minutes after tumor(s) resection as criteria to predict operative success, 6 patients had their outcomes correctly predicted (5 true-positive and 1 true-negative). One patient with nesidioblastosis had a false-negative result. One could not be evaluated because of diazoxide medication. These criteria predicted postoperative absence of hypoglycemia with specificity of 100% and accuracy of 89%. CONCLUSIONS: These 8-minute insulin assay and criteria can be a useful adjunct for intraoperative assurance of complete insulinoma resection and prediction of postoperative outcome.

Limited versus radical parathyroidectomy in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated primary hyperparathyroidism (FIHPT) is characterized by earlier onset, higher incidence of multiglandular disease, and higher recurrence rate when compared with sporadic primary hyperparathyroidism. Excision of 3.5 or 4 glands with autotransplantation has been recommended; however, these approaches lead to permanent hypoparathyroidism in 13% to 41% of patients. It is reported that many patients with FIHPT return to normocalcemia after single-gland excision. The use of preoperative localization and intraoperative parathyroid hormone assay permits limited resection of only hypersecreting glands. We report the outcome of this operative approach. METHODS: Fifteen consecutive patients with FIHPT underwent limited parathyroidectomy with resection guided by intact parathyroid hormone secretion in 2 university centers. Patients were followed up postoperatively for serum calcium and intact parathyroid hormone levels. RESULTS: With an operative success of 93%, 14 patients had only single-gland excision and 80% had unilateral neck exploration. All initial patients had their hypercalcemia corrected. In 4 reoperations, permanent hypoparathyroidism occurred in 2 patients. One recurrence was observed in 40 (8-122) months of follow-up. CONCLUSION: Limited parathyroidectomy allows successful single-gland excision in many patients with FIHPT, thus decreasing the risk of hypoparathyroidism. In these patients, a low incidence of hypoparathyroidism may be preferable to the possibility of late recurrence.

Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy: which criterion is the most accurate?

BACKGROUND: The quick parathyroid hormone assay (QPTH) reliably measures intact parathyroid hormone (iPTH) levels intraoperatively. The accuracy in predicting postoperative calcemia is related to blood sample timing and the criteria applied. To improve specificity or to decrease the cost of QPTH, several criteria have been used to predict complete excision. This study compares the Miami criterion with other published QPTH criteria in predicting operative outcome. METHODS: QPTH and the Miami criterion (iPTH drop > or =50% from the highest of either preincision or pre-excision level at 10 minutes after gland excision), were used to predict postoperative calcium levels of 341 consecutive patients with sporadic primary hyperparathyroidism who were followed > or =6 months after the operation or recognized as operative failures. Intraoperative iPTH values of these patients were reanalyzed with the use of 5 published criteria to predict complete resection. Postoperative calcium levels were correlated with criteria predictions. RESULTS: Miami criterion correctly predicted postoperative calcium levels in 329 of 341 patients and was incorrect in 12 (3 false positives, 9 false negatives). With the use of other criteria, 2 of the 3 false-positive results would be prevented, but the 3% rate of false-negative predictions would increase to between 6% and 24%, causing unnecessary neck explorations to search for multiglandular disease. CONCLUSIONS: Surgeons trying to increase QPTH specificity significantly decrease the accuracy and intraoperative usefulness of the assay. The Miami criterion has the highest accuracy when compared with other criteria.

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.

Surgeon-performed ultrasound in the management of thyroid malignancy.

Surgeon-controlled real-time ultrasound (US) is a new adjunct in the management of patients with thyroid malignancy. The introduction of US as a routine evaluation tool has increased the recognition of nonpalpable thyroid cancers and cervical lymph node metastases. We report our experience and the change in management of patients with thyroid cancer due to the use of US. We reviewed the records of all patients undergoing neck operations for thyroid cancer since 2002. US was performed by a surgeon preoperatively in all patients and intraoperatively when non-palpable cervical lymph nodes were present. Suspicious nonpalpable thyroid nodules underwent US-guided fine-needle aspiration (FNA) for cytology. Seventy-two patients underwent operations for thyroid cancer. US influenced the management in 57 per cent (41/72) of patients. US was useful in 1) identification and guidance for the FNA of nonpalpable cancers in 28 per cent (20/72), 2) identification of nonpalpable nodules in the contralateral lobe in 38 per cent (27/72), 3) preoperative diagnosis of nonpalpable metastatic lymph nodes in 24 per cent (17/72), and intraoperative guidance for their excision. Surgeon-performed US changed and enhanced the pre- and intraoperative management in more than half the patients with thyroid cancer.

Normocalcemic parathormone elevation after successful parathyroidectomy: long-term analysis of parathormone variations over 10 years.

BACKGROUND: The long-term significance of normocalcemic parathormone elevation (NPE) after successful parathyroidectomy for sporadic primary hyperparathyroidism remains unclear. METHOD: Of 239 consecutive patients who underwent targeted parathyroidectomy with intraoperative parathormone monitoring, 96 were followed for ≥ 10 years. NPE was defined as a normal serum calcium level and parathormone (PTH) above the normal reference range ≥ 6 months after successful parathyroidectomy. Recurrence was defined as elevated serum calcium and PTH levels ≥ 6 months after parathyroidectomy. Risk factors for NPE, patterns of postoperative PTH variation, and 10-year outcomes were analyzed. RESULTS: Of 96 patients followed ≥ 10 years, 42 had postoperative NPE. Only male gender (P = .008) was a risk factor for NPE, and NPE did not predict recurrence. Three patterns of postoperative NPE were identified in patients with ≥ 3 PTH measurements over this 10-year period. Group 1 (n = 11): 1 to 2 consecutive PTH elevations; none recurred, and most were explained by physiologic variation. Group 2 (n = 23): multiple PTH fluctuations; 3 recurred, and almost all had physiologic variations. Group 3 (n = 4): PTH always elevated; 2 recurred. CONCLUSION: Postoperative NPE may be a dynamic, reversible, and transient clinical entity that does not predict recurrence. Nevertheless, patients with postoperative NPE should be monitored and an attempt made to correct any obvious potential causes of PTH elevation.

Operative failure in the era of focused parathyroidectomy: a contemporary series of 845 patients.

HYPOTHESIS: Focused parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) may lead to higher failure rates because of missed multiglandular disease. DESIGN: Retrospective review of prospectively collected data. SETTING: Tertiary referral center. PATIENTS: From September 8, 1993, through January 30, 2009, a total of 845 consecutive patients with sporadic primary hyperparathyroidism underwent focused parathyroidectomy guided by IPM at a single institution. MAIN OUTCOME MEASURES: Parathyroid hormone dynamics and perioperative data were analyzed for factors affecting outcome. Operative failure was defined as hypercalcemia with elevated parathyroid hormone levels within 6 months after parathyroidectomy. Detailed intraoperative data from the failed operations were also reviewed. RESULTS: Of 723 patients followed up for at least 6 months, 702 (97.1%) had successful parathyroidectomy, and 21 (2.9%) had failed parathyroidectomy. The major cause of operative failure was the surgeon's inability to find the abnormal parathyroid gland (16 of 21 patients [76.2%]). In the remaining patients, IPM results were false-positive in 5 of 21 patients (23.8%) or 0.7% overall. Among the cohort, IPM correctly identified missed multiglandular disease in 33 of 38 patients (86.8%). Patients having operative failure were more likely to have a history of thyroidectomy or parathyroidectomy and were less likely to have correct findings on technetium Tc 99m sestamibi or ultrasonographic localizing studies compared with patients having operative success. CONCLUSION: Inability of the surgeon to find the abnormal parathyroid gland-not missed multiglandular disease-is the main cause of operative failure in focused parathyroidectomy guided by IPM.

Focused parathyroidectomy guided by intra-operative parathormone monitoring does not miss multiglandular disease in patients with sporadic primary hyperparathyroidism: a 10-year outcome.

BACKGROUND: There remains concern that focused parathyroidectomy guided by intra-operative parathormone monitoring (IPM) will miss multiglandular disease (MGD) leading to a higher recurrence rate. This study reports the 10-year outcome of patients with sporadic primary hyperparathyroidism treated by focused parathyroidectomy guided by IPM. METHODS: From 1993 to 1998, 173 consecutive patients with sporadic primary hyperparathyroidism underwent focused parathyroidectomy guided by IPM. When IPM showed >50% decrease 10 minutes after abnormal gland excision, the operation was completed. Recurrent hyperparathyroidism was defined as elevated serum calcium and parathormone (PTH) levels >6 months after successful parathyroidectomy. RESULTS: There were 164 patients with a mean follow-up of 83 months. In this group, 96% patients had single gland disease (SGD) and 4% had MGD. Five (3%) patients developed recurrent hyperparathyroidism at 2, 4, 9, 10, and 12 years. In 43 eucalcemic patients followed for >10 years, PTH levels remained normal in 54%, were constantly above normal range in 2%, or varied between normal and above normal range in 44%. CONCLUSION: In patients 10 years after treatment, IPM-guided parathyroidectomy does not fail to identify MGD, allows for limited dissection in SGD, and shows that various sized parathyroid glands left in situ do not cause higher recurrence rates.

Role of intraoperative parathormone monitoring during parathyroidectomy in patients with discordant localization studies.

BACKGROUND: Many patients with sporadic primary hyperparathyroidism (SPHPT) have discordant preoperative Tc-99m-sestamibi (MIBI) and ultrasonography studies prior to focused parathyroidectomy (PTX). This study examines the usefulness of intraoperative parathormone monitoring (IPM) during PTX in patients with discordant preoperative localization studies. METHODS: A retrospective series of 225 consecutive SPHPT patients with MIBI scans and surgeon performed ultrasonography (SUS) prior to focused parathyroidectomy were studied. All patient operations were reviewed, and how IPM changed operative management was determined. Correct gland localization, presence of multigland disease (MGD), and operative outcome were also examined. RESULTS: In 225 patients, overall operative success was 97%, and IPM changed operative management in 29% of patients. In 85 patients (38%) with discordant studies, operative success was 93%; IPM changed operative management in 74% of these patients. IPM allowed for 66% (56/85) of these operations to be performed as unilateral neck exploration and confirmed removal of abnormal glands in 7 patients with MGD. In 140 patients (62%) with concordant localization, in which operative success was 99%, IPM changed operative management in only 2% (3/140) of these patients with MGD. CONCLUSION: Although of marginal benefit in patients with concordant imaging studies, IPM remains essential for performing successful PTX with discordant or incorrect concordant localization.

Long-term outcome of patients with intraoperative parathyroid level remaining above the normal range during parathyroidectomy.

BACKGROUND: Criterion requiring intraoperative parathyroid hormone (IOPTH) drops >50% from the highest, preincision or preexcision level, 10 minutes after the abnormal gland's excision predicts operative success with 98% accuracy. The purpose of this study is to correlate IOPTH dynamics with recurrent hyperparathyroidism (RecHPT) and eucalcemia with high PTH (HPTH). METHODS: We followed 383 consecutive patients with parathyroidectomy guided by IOPTH monitoring using the above criterion for >6 months. Calcium and PTH levels were measured for 50 months (range, 6-173). Patients were divided in 2 groups: group 1 comprised 302 participants with IOPTH levels that decrease to the normal range (NR), and group 2, with 81 participants who had >50% IOPTH decrease but remained above the normal range. The incidence of RecHPT and eucalcemia with HPTH was evaluated. RESULTS: RecHPT was found in 2% (8/383) of patients and eucalcemia with HPTH was present in 19% (74/383). In group 1, 17% (52/302) had eucalcemia with HPTH, whereas in group 2, this incidence was 27% (22/81; P = .04). However, only 2% of those (6/302) in group 1 and 2.5% (2/81) in group 2 developed RecHPT (P = .76). Conversely, 70.5% of those (57/81) in group 2 were eucalcemic with normal PTH. CONCLUSION: Although postoperative eucalcemia with HPTH was significantly higher among patients with IOPTH above the normal range than in patients in group 1, the incidence of RecHPT was not increased. The majority of patients in whom IOPTH did not drop to the normal range continue to be biochemically normal after the operation.

Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism.

HYPOTHESIS: Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear. DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Five hundred seventy-six consecutive patients with HPT. INTERVENTION: Parathyroidectomy guided by intraoperative monitoring of PTH levels. MAIN OUTCOME MEASURES: Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy). RESULTS: Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency. CONCLUSION: Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.

Consequences of parathyroidectomy in patients with "mild" sporadic primary hyperparathyroidism.

BACKGROUND: The use of a targeted, less-invasive approach is changing the operative indications in sporadic primary hyperparathyroidism (SPHPT). Now, patients with "mild" HPT are offered parathyroidectomy. However, the operative findings and outcome of these patients are unknown. This study reports the differences between "mild" and "classic" biochemical SPHPT in incidence of multiglandular disease (MGD) and operative outcome. METHODS: All 343 patients underwent parathyroidectomy guided by intraoperative parathyroid hormone (PTH) monitoring (IPM). Among them, 301 patients (88%) had "classic" biochemical SPHPT (hypercalcemia and increased PTH) and 42 patients (12%) had "mild" HPT, which consisted of 28 patients with inappropriate secretion of PTH (ISP-hypercalcemia and normal PTH), and 14 patients with normocalcemic HPT (NCHPT-eucalcemia and increased PTH). Single or MGD was determined by IPM. Operative success is eucalcemia for greater than or equal to 6 months after operation and along with normal PTH levels in NCHPT. RESULTS: Thirty nine of 301 patients (13%) with "classic" biochemical SPHPT had MGD with an operative failure rate of 1% (3/301). In the "mild" HPT group, 14 of 42 patients (33%) had MGD with a failure rate of 5% (2/42). The incidence of MGD was statistically significant (P < .001). CONCLUSION: The incidence of MGD and operative failure are higher in patients with "mild" HPT when compared with classic SPHPT. Patients and surgeons should be aware of these consequences when parathyroidectomy is offered to patients with "mild" HPT.

Does histopathology predict parathyroid hypersecretion and influence correctly the extent of parathyroidectomy in patients with sporadic primary hyperparathyroidism?

BACKGROUND: Parathyroid histopathology has been used to predict single or multiglandular disease (MGD). "Hyperplasia" implies MGD, whereas "adenoma" suggests single gland involvement. Intraoperative parathyroid hormone (PTH) monitoring (IPM) guides parathyroidectomy based on function. We sought to evaluate the accuracy of histopathology in the diagnosis of single or MGD and in predicting operative success. METHODS: We reexamined the parathyroid glands from 402 patients with sporadic primary hyperparathyroidism (SPHPT) who underwent initial IPM-guided parathyroidectomies. Operative findings and outcome were correlated with histopathology of excised glands. Operative success was eucalcemia for >or=6 months and recurrence of hypercalcemia/high PTH after successful parathyroidectomy. RESULTS: Of 402 patients, 384 had 1 gland excised resulting in operative success; hyperplasia was diagnosed in 244 of the 384 (64%), with only 2 developing recurrence. Of the 384 patients, 140 (37%) had adenomas with 1 late recurrence. There were 18 patients with MGD (14 hyperplasias, 4 adenomas). There were 5 failures with hyperplasia predicting MGD. Histopathology was incorrect in predicting the number of glands involved in 249 of 402 (62%) patients, and IPM was incorrect in only 13 (3%). CONCLUSION: Histopathology of excised abnormal parathyroid glands does not predict the secretory function of the remaining parathyroid glands left in situ. IPM guided parathyroidectomy accurately based on function alone; however, histopathology was inaccurate in predicting MGD and should not be used to guide parathyroidectomy in patients with SPHPT.

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 < or = 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.

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.