A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003

A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003 JAMES M. RUDA, BS, CHRISTOPHER S. HOLLENBEAK, PHD, and BRENDAN C. STACK, JR, MD, FACS, Hershey and Allentown, Pennsylvania

OBJECTIVE: To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. STUDY DESIGN: A systematic literature review. RESULTS: Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc99m-sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. CONCLUSION: The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not “fool-proof” adjunct in parathyroid exploration surgery. SIGNIFICANCE: These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3. (Otolaryngol Head Neck Surg 2005;132:359-72.)

From the Pennsylvania State College of Medicine (Mr Ruda), the Departments of Surgery and Health Evaluation Sciences (Dr Hollenbeak) and Division of Otolaryngology-Head and Neck Surgery (Dr Stack), Penn State College of Medicine, Hershey, and the Department of Health Studies (Dr Hollenbeak), Lehigh Valley Hospital, Allentown, PA. Presented at the Annual Meeting of the American Academy of Otolarynogology–Head and Neck Surgery, Orlando, FL, September 21-24, 2003. Reprint requests: Brendan C. Stack, Jr, MD, FACS, Penn State College of Medicine, PO Box 850, 500 University Drive, 4833, Hershey, PA 17033; e-mail, [email protected]. 0194-5998/$30.00 Copyright © 2005 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. doi:10.1016/j.otohns.2004.10.005

P

rimary hyperparathyroidism is a common endocrine disease affecting nearly 1 of 500 women and 1 of 2000 men per year, most often in their fifth, sixth, and seventh decades of life.1-3 Of late, incidentally discovered hyperparathyroidism has become a common diagnosis in healthy asymptomatic adults with the advent of more routine screening. This condition traditionally has been diagnosed biochemically and radiographically in symptomatic individuals presenting with hypercalcemic sequelae or incidental discovery of hypercalcemia.4,5 When managed surgically, there is marked improvement in symptoms with resolution of hypercalcemia.6 Most reports in the literature suggest that a benign single adenoma (SA) is responsible in approximately 80% to 90% of all cases of primary hyperparathyroidism.7-9 Therefore, a decision to pursue normocalcemia via a minimally invasive approach is often successful when guided by this a priori assumption or when presented with a preoperative scan suspicious for a single solitary lesion. However, in cases where minimally invasive procedures fail to produce normocalcemia and in the remaining 10% to 20% of cases involving primary hyperparathyroidism, multiple gland disease (MGD) is often cited to be responsible.3,9 Faced with the possibility of bilateral multiple gland pathology, an exploration of the bilateral neck is routinely performed. Likewise, conversion to a bilateral neck exploration is commonly undertaken when the putative gland(s) remains elusive following unilateral exploration or when challenged with an unsatisfactory change in biochemical assay results intraoperatively. Not all reports include data on rapid PTH assays and those protocols reported vary widely. Exploration of the bilateral neck is reported to be 95% to 98% effective.10,11 Ultrasonography and Tc99m-sestamibi are standard modalities for imaging parathyroid lesions. A bilateral neck exploration (BNE), unilateral neck exploration (UNE), or minimally invasive radio-guided parathyroidectomy (MIRP) may be pursued conditional based on the results from these localization scans. BNE is defined as dissection of the bilateral tracheoesophageal grooves with identification of both normal and pathologic parathyroid glands. UNE is defined as exploration of 1 tracheoesophageal groove that is determined based on preoperative imaging. This can be done through a conventional incision or by limited access incisions. An ipsalateral normal parathyroid may or may not be iden359

360 RUDA et al

tified in the procedure. MIRP is a minimal access approach to resect a parathyroid adenoma utilizing a preoperative dose of sestamibi and intraoperative gamma probe guidance. Although historically treated by a BNE, the choice of surgical approach is increasingly guided by the adenoma location suggested by preoperative scans. Tc99m-sestamibi and high-resolution ultrasound are frequently used to guide MIRPs and UNEs and accurately detect solitary adenoma in 80% to 100% and 75% to 85% of patients, respectively.12,13 Reported cure rates commonly range from 75% to 95% and both MIRP and UNE have been demonstrated to be cost-effective alternatives to the traditional bilateral approach in the treatment of solitary adenomas.14 Tc99m-sestamibi and ultrasound are less useful in the diagnosis of multiple gland disease. Tc99m-sestamibi and ultrasound are commonly reported to be inconsistent and unreliable.15,16 Often the sensitivity of sestamibi ranges from 0-70% for hyperplastic glands and 0-45% for double adenomas.17 Multiple gland disease is imaged using ultrasonography with similar success from 10% to 50% for multiple hyperplastic glands and 10% to 35% for double adenomas.13,17-20 For the detection of multiple gland disease, not only does the choice of the preoperative scan influence prevalence, but so does the choice of the surgical approach. In studies by Lee and Norton21 and Genc et al,16 it was found that minimally invasive parathyroidectomies (MIP) underestimate the true prevalence of MGD by as much as 15% of cases that would have been discovered by exploration of the bilateral neck. Assuming that the prevalence of MGD might be grossly under-reported among surgeons who favor MIPs, 2 questions remain: First, does this represent a potential surgical failure in the 15% of patients offered MIP surgery instead of a more extensive exploration of the neck? Second, do all of these undiscovered abnormal glands ever produce a recurrent biochemical abnormality and hypercalcemia? In light of these questions and the limitations of Tc99msestamibi and ultrasound for the accurate detection of MGD, the merit of relying on any form of preoperative imaging, when BNE cures 90% to 98% of all patients with primary hyperparathyroidism, has been questioned.22,23 Given the subtle variations in the histopathologies and preoperative scan sensitivities reported among individual institutions, the utility of preoperative imaging and choice of the surgical strategy for the treatment of primary hyperparathyroidism is controversial. A discussion of the recent evolution of parathyroid surgery would be incomplete without acknowledging the impact of the rapid parathormone assay (IOPTH). These assays (now over 11)24 came into the clinical

Otolaryngology– Head and Neck Surgery March 2005

arena during the period of this review yet have been attributed as a major reason for improving surgical success rates overall and allowing for focused parathyroid operations. They use different reagents and have been used in differing protocols, which makes direct comparisons of surgical series using assays quite problematic. Since assays were not used in a majority of the reviewed literature, a subset of this literature where clearly reported assay data exist will be examined. The purpose of this article is to explore the utility of preoperative diagnostic imaging with Tc99m-sestamibi or high-resolution ultrasound as well as the optimal surgical strategy in patients with primary hyperparathyroidism. We performed a systematic review of the literature published from 1995 to 2003 that reported individual histopathologies, surgical success rates, and diagnostic modality sensitivities associated with primary hyperparathyroidism to estimate the overall prevalence of disease, the overall diagnostic accuracy of sestamibi and ultrasound, and the overall cure rate for surgical treatment of primary hyperparathyroidism. METHODS Literature A review of the current literature was performed by searching Medline for relevant articles published between 1995 and 2003 (Appendix 1). Articles were initially identified using all possible combinations of the following search terms: primary hyperparathyroidism, solitary adenomas, multiple gland hyperplasia, multiple gland disease, parathyroid carcinoma, radionuclide imaging, Tc99m-sestamibi, parathyroidectomy, ultrasonography, minimally-invasive radio-guided parathyroidectomy, unilateral neck exploration, minimally invasive surgery, and bilateral neck exploration. Additionally, the bibliographies of relevant articles were further searched to identify potentially relevant articles not captured in the original Medline search. As primary research articles were solely of interest, all review articles, letters, editorials, and case reports were excluded from the final analysis. Articles were selected for inclusion if data were stratified by number of pathologic parathyroid glands detected at surgery. For our study of diagnostic methods, articles involving any form of dual-phase Tc99msestamibi imaging or high-resolution ultrasonography were ineligible if their reported sensitivity rates failed to distinguish between solitary adenomas, double adenomas (DA), multiple gland hyperplasia (MGHD), or parathyroid carcinoma. For the imaging of multiple gland hyperplasia, sensitivity was estimated from studies that reported the overall number of hyperplastic glands visualized as a proportion to the expected number of glands for that population, assuming a normal

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

RUDA et al 361

4-gland anatomy. The total number of imaged hyperplastic glands were then collectively summed from each study and divided by the overall number of glands pooled from each study. For double adenomas, sensitivity was computed from studies that reported 2 pathological glands identified at surgery. Should only 1 gland positively image or the location of 1 or both glands be erroneously predicted by imaging, this was considered a diagnostic failure. Alternatively, diagnostic success was assumed if surgery confirmed the presence and location of both abnormal glands. Triple-gland or supernumerary pathology suspected by preoperative imaging was considered to represent hyperplasia. The subset of published studies addressing the correction of primary hyperparathyroidism by a bilateral neck exploration, minimally invasive radio-guided parathyroidectomy, or unilateral neck exploration was used to estimate the likelihood of a surgical cure. Studies of parathyroidectomy performed in the re-operant neck or aided by an endoscopic or video-assisted approach were excluded. Unilateral neck explorations and non-radio-guided minimally invasive approaches were categorized together as a unilateral neck exploration. Additionally, minimally invasive radio-guided parathyroidectomy procedures were considered successful in cases where (1) solitary adenomas were localized to the true neck quadrant at surgery without a need for intraoperative extension of the incision, and (2) permanent normocalcemia was achieved thereafter. Conversion to either a bilateral neck exploration or unilateral neck exploration from either a UNE or MIRP, respectively, was considered a surgical failure for the planned procedure. Likewise, failure to maintain eucalcemia at 1 year was considered a surgical failure for all procedures.

Parathyroid histopathologies

Prevalence (%)

95% CI

Solitary adenomas Multiple gland disease Multiple gland hyperplasia disease Double adenomas Carcinomas

88.90 9.84 5.74 4.14 0.74

88.89–88.92 9.84 5.33–6.15 3.74–4.53 0.53–0.95

Confidence intervals (CI) were computed for each individual study as follows: 95%CII ⫽ p1 ⫾ (t ⫻ sep1). Overall summaries were obtained by computing a weighted average of proportions across studies, where the weights were the inverse of the standard errors of the individual studies. CIs were constructed for both the overall summary proportion using the normal approximation: 95%CII ⫽ p ⫾ (t ⫻ sep), where p is the summary proportion, t is the 95% critical value from a standard normal distribution, and sep is the standard error of the overall summary proportion, computed N as sep ⫽ 共 i⫽1 共sepi兲2兲 1 Ⲑ 2 .25-27

兺

RESULTS Approximately 500 studies were initially evaluated. Of the 215 studies included in our data set, primary hyperparathyroidism was reported in 20,225 patients. Appendix 1 presents a list of all articles included in our study that reported their experience with the histopathologic prevalence, diagnostic sensitivity of Tc99m-sestamibi or high-resolution ultrasonography, or surgical success rates for the treatment of primary hyperparathyroidism. Prevalence

Meta-Analysis Once selected for inclusion in our study, results and measures of interest were extracted from each publication. Overall summary measures were estimated using a general variance-based method as follows. Proportion data for histopathologic prevalence, diagnostic modality sensitivity, and rates of surgical cure were assumed to be binomially distributed with a mean of pi ⫽ xi ni , where i ⫽ 1,. . ., N indexes individual studies, xi is the number of cases in study i, and ni is the total sample size of study i. The standard error for each binomial proportion was computed as:

Ⲑ

sepi ⫽

Table 1. Prevalence of histopathologies associated with primary hyperparathyroidism

冑

pi(1 ⫺ pi) ni

The prevalence of individual parathyroid histopathology associated with primary hyperparathyroidism is presented in Table 1. A total of 177 publications reported the prevalence of SAs associated with primary hyperparathyroidism. An SA was the most frequently encountered surgical pathology and occurred in an estimated 88.90% of cases (95%CI, 87.48% to 89.40%) (Fig 1). The summary of 177 articles suggests an overall histopathologic prevalence of MGD in 9.84% of cases (95%CI, 9.84%). Table 1 also presents the prevalence of MGD. Of studies reporting their experience with MGD in their practice 5.74% (95%CI, 5.33% to 6.15%) were MGHD and 4.14% were DA (95%CI, 3.74% to 4.53%). Parathyroid carcinoma occurred in 0.74% of cases (95%CI, 0.53% to 0.95%).

362 RUDA et al

Otolaryngology– Head and Neck Surgery March 2005

Fig 1. Graph of the prevalence of solitary adenomas associated with primary hyperparathyroidism as reported in 177 studies. Across all studies, the overall prevalence for solitary adenomas was estimated in 88.90% of cases.

Diagnostic Modalities The sensitivity of preoperative Tc99m-sestamibi and highresolution ultrasound for glandular disease associated with primary hyperparathyroidism is presented in Table 2. There were 96 and 54 articles reporting the sensitivity of preoper-

ative Tc99m-sestamibi and high-resolution ultrasound, respectively, for the detection of a SA. For SAs, Tc99m-sestamibi was 88.44% sensitive (95%CI, 87.48% to 89.40%). This was higher than the sensitivity of ultrasound, which was 78.55% (95%CI, 77.15% to 79.96%) for SA.

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

RUDA et al 363

Table 2. Sensitivity of Tc99m-sestamibi and highresolution ultrasonography for the histopathologies associated with primary hyperparathyroidism Diagnostic modalities Tc99m-Sestamibi Solitary adenomas Multiple gland hyperplasia disease (glands) Double adenomas Carcinomas High resolution ultrasound Solitary adenomas Multiple gland hyperplasia disease (glands) Double adenomas Carcinomas

Sensitivity (%)

95% CI

88.44

87.48–89.40

44.46 29.95 33

41.13–47.80 ⫺2.19–62.09 33

78.55

77.15–79.96

34.86 16.20 100

29.86–39.86 4.16–28.25 100

Preoperative scanning with Tc99m-sestamibi and ultrasound was less reliable in detecting MGD. Among all reported cases of hyperplastic gland disease and DA, the sensitivity of sestamibi ranged from 0% to 100% with an overall mean sensitivity of 44.46% (95%CI, 41.13% to 47.80%) for MGHD and 29.95% (95%CI, 2.19% to 62.09%) for DA. Similarly, high-resolution ultrasonography had an overall sensitivity of 34.86% (95%CI, 29.86% to 39.86%) for MGHD glands and 16.20% (95%CI, 4.16% to 28.25%) for DA. Surgical Success The probability of achieving curative normocalcemia via a MIRP, UNE, BNE, or BNE conversion surgery is presented in Table 3. As seen in this table, use of a minimally invasive parathyroidectomy resulted in postoperative normocalcemia in 96.66% (95%CI, 95.37% to 97.94%) of patients when radio guided, and in 95.25% (95%CI, 94.47% to 96.04%) of patients explored by UNE. In 20 and 45 studies reporting the surgical success with either MIRP or UNE, the success of MIRP ranged from 56.2% of cases to 100% of cases.28-31 Likewise, surgical success with UNE ranged from 53% to 100% of cases.32-36 For treatment of primary hyperparathyroidism by BNE, postoperative normocalcemia was achieved in 97.69%(95%CI, 97.36% to 98.02%) and in 99.08% (95%CI, 99.0% to 99.16%) of patients requiring conversion to a BNE. Among 98 and 18 studies that reported operative success with BNE and BNE conversion surgery, this ranged from 65.0% to 100% of cases cured by a BNE and from 85.6% to 100% of cases cured by conversion to a BNE. Notably, in 16 of the 17 reported BNE conversion surgery studies, 100% operative success was attained for all patients, which was slightly higher than the 97% to 98% success rate for conventional BNE surgery.

Table 3. Probability of cure among surgical procedures for treatment of primary hyperparathyroidism Surgical treatment Minimally invasive radio-guided parathyroidectomy Unilateral neck exploration Bilateral neck exploration Bilateral neck exploration conversion

Probability of cure (%)

95% CI

96.66 95.25 97.69

95.37–97.94 94.47–96.04 97.36–98.02

99.08

97.42–100

Rapid PTH Hormone Assays Forty-five of the 225 references for this article had data that was deemed reliable and/or interpretable for analysis. Fifteen of these papers were excluded because some or all of their data reported 100% (sensitivity, specificity, etc.), which would have resulted in a weighted mean skewing of our data and an artificially large standard deviation (Appendix 1). This analysis is presented below. Table 4 contains a selected group of these studies that had complete data to report. UNE was completed as intended 94.54% of the time when used in conjunction with IOPTH (Table 5); 5.46% of cases were converted to BNEC due to IOPTH results not meeting the reported criteria for the given study; and 3.23% of the original data set or approximately 60% of the BNEC achieved reduction in IOPTH as set forth by the respective study criteria. This compares to a 3.38% conversion rate of MIRP/UNE to BNE for technical reasons such as inaccurate preoperative localizing data and anatomic constraints. Persistent hypercalcemia after surgery in which IOPTH was used (includes UNE and BNEC) was 1.34%, (as compared to 5% to 8% of patients without intraoperative IOPTH monitoring). IOPTH gave true-positive test results in 98.4% of cases in which it was used. IOPTH gave false-positive results in 3.37% of cases when declines of greater than 50% were judged as indicative of cure and the patient was not rendered normocalcemic. Results of IOPTH were considered to be false negative in 1.94% of cases when a less than 50% decrease was observed, indicating fallaciously the presence of unresected diseased parathyroid glands in the neck. DISCUSSION Over the past decade, treatment of primary hyperparathyroidism has been increasingly managed with less-invasive means. Instead of the conventional 4-gland inspection afforded by a BNE, a minimally invasive parathyroidectomy that uses either radio-guidance or biochemical confirmation intraoperatively has been used. Rapid PTH assays were widely available

Otolaryngology– Head and Neck Surgery March 2005

364 RUDA et al

Table 4. Surgical series reviewed which had sufficient reported and interpretable data on the use of the rapid PTH assay (modified from Carter 2003) Average percent decline in parathyroid hormone (PTH); data collected from 7 intraoperative PTH studies Reference no.

Type of disease

No. of patients

Postexcision, min

Average decline, %

Standard deviation (range), %

29 77 115 158 182 197 207

SGD ALL ALL SGD ALL ALL SGD

41 120 99 31 21 32 173

10 5 5 15 10 5 5

80.00 69.20 64.00 78.63 78.00 70.00 72.80

(55–99) 1.10 No data 16.79 (19.61–97.67) (56–89.8) 2.00 12.30 (51–98)

SGD, indicates single gland disease; MGD, multigland disease; ALL, results of combined SGD and MGD patients.

Table 5. Impact of IOPTH on parathyroid surgery for pHPT IOPTH assay UNE completion rate (as intended) ALL BNE conversion surgery success rate IOPTH-mediated BNE conversion surgery rate Persistent hypercalcemia IOPTH TP FP FN

Value

95% CI

94.54%

93.87%–95.20%

89.24%

81.75%–96.74%

59.10% 1.34%

47.5%–70.7% 0.853%–1.83%

98.40% 3.37% 1.94%

97.9%–98.9% 2.07%–4.67% 1.27%–2.62%

during the latter half of this literature review. The protocols for assay utilization are not standardized either in required percentage of drop or in timing postexcision. Directed by preoperative imaging, minimal access procedures have achieved remarkable success. However, among patients who fail to achieve normocalcemia with these less invasive parathyroidectomies, failure has been attributed to the presence of multiple pathologic glands that occur in an estimated 10% to 20% of cases. Preoperative imaging has historically met with limited success in the detection of multiple pathologic glands. In such cases, a planned minimally invasive approach results in surgical failure or the need for conversion to a more extensive exploration. Surgical failures that manifest symptoms of rebound hypercalcemia months to years postoperatively suggest that the prevalence of MGD might be underestimated. Additionally, when the choice of parathyroidectomy limits visual inspection to only one quadrant or side of the neck while leaving the contralateral side unexplored, then there may exist other undetected, pathologic glands that might otherwise remain undiscovered. Given these concerns, it has been questioned whether the prevalence of MGD and SGD in patients

with primary hyperparathyroidism is accurately estimated and which parathyroidectomy is ultimately the most effective for correction of all glandular disease associated with primary hyperparathyroidism. The prevalence of SA and MGD is generally reported to range from 80% to 90% of cases and 10% to 20% of cases associated with primary hyperparathyroidism. In our review of 177 studies from the literature, the prevalence of SA and MGD was estimated to occur in 88.90% (95%CI, 87.48% to 89.40%) and 9.84% (95%CI, 9.84%) of cases, respectively. In a study by Lee and Norton,21 among 166 patients the prevalence of MGD ranged from 5.2% of cases when treated by a minimally invasive approach to 19.3% of cases treated by exploration of the bilateral neck. Similarly, Genc et al16 observed that among patients treated by a BNE rather than by a focused parathyroidectomy, the prevalence of MGD was more than 15%. Considering then that the prevalence of MGD has been reported as a function of the type of parathyroidectomy performed, it is conceivable that estimates may not truly reflect the actual prevalence of MGD in the general population.37 Possibly the choice of operation might reflect a selection bias toward patients with MGD. However, should our estimated prevalence of MGD be accurate, then this might support the utility of performing minimally invasive parathyroidectomies in patients who might otherwise undergo unnecessary BNEs. For detection of SAs, the sensitivity of preoperative imaging with Tc99m-sestambi and ultrasound is generally reported to range from 80% to 95% and 70% to 85%, respectively. In our review of 160 articles, sensitivity of sestamibi and ultrasonography for SAs was estimated as 88.44% (95%CI, 87.48%) and 78.55% (95%CI, 77.15% to 79.96%), respectively. As illustrated by the narrow confidence intervals for our overall estimates, the sensitivities of these preoperative diagnostic modalities were very precisely estimated among

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

all studies. Therefore, we assume our estimated sensitivity was a close approximation of the true sensitivity of sestamibi and ultrasonography for detecting SAs. For the detection of MGD, sestamibi was sensitive to 44.46% (95%CI, 41.13% to 47.80%) of all hyperplastic glands and 29.95% (95%CI, 2.19% to 62.09%) of DA. Likewise, ultrasound was sensitive to 34.86% (95%CI, 29.96% to 39.86%) and 16.20% (95%CI, 4.16% to 28.25%) of hyperplastic glands and Das, respectively. As was evidenced by the wide confidence intervals of sestamibi and ultrasound for MGHD and DAs, these were the least precise measures reported. With respect to the reported sensitivity of preoperative imaging for DAs and multiple hyperplastic glands, we could not find any published sensitivity that was reliably or consistently reported. Among all patients offered a BNE, 97.69% were reported to be normocalcemic postoperatively. Likewise, of all patients who required conversion to a BNE, 99.09% became normocalcemic postoperatively. The literature typically suggests that BNE is effective in 95% to 100% of patients, and our overall estimates for BNE and BNE conversion surgery closely approximated the rate reported throughout the literature. BNEC may be more successful due to preoperative imaging used for a planned operation of limited exploration or the use of IOPTH. However, when approached less invasively, we found that 96.66% (95%CI, 95.37% to 97.94%) of patients were cured when treated with MIRP, and 95.25% (95%CI, 94.47% to 96.04%) of patients were cured when offered a UNE. As evidenced by the narrow confidence intervals, the probability of cure using MIRP and UNE was also very precisely reported among all studies. As compared to the literature, our reported cure rates for MIRP and UNE were slightly higher than those generally reported. Since our estimates were robust and accurate, the utility of a less invasive parathyroidectomy may be justified over BNE in all patients with primary hyperparathyroidism. However, this is again contingent on the ability of preoperative imaging to accurately identify those patients most suited for less invasive parathyroidectomy. Our study was a systematic review of the literature for all series of primary hyperparathyroidism with diagnostic modalities and surgical procedures, and we acknowledge that certain limitations existed. First, our study was limited to a search of Medline. Therefore, not all databases were explored that could have resulted in the exclusion of pertinent articles from our data set. Second, due to resource and human capital constraints, only articles published in the English language were included. Third, among articles reporting their observed sensitivity of sestamibi, this included both dualphase sestamibi and on occasion sestamibi-SPECT in

RUDA et al 365

patients with equivocal conventional sestamibi scans. As most articles did not report the frequency with which sestamibi-SPECT was used, this could have artificially increased the sensitivity of dual-phase Tc99msestamibi. Among all articles reporting their surgical success with BNE, UNE, or MIRP, patients with persistent disease from a previously failed operation were included. As the surgical success rates did not distinguish between the nonoperant vs the reoperant neck in some cases, it was impossible to report only surgical successes achieved in the nonoperant neck. The feasibility of using a less invasive parathyroidectomy instead of a BNE for treatment of primary hyperparathyroidism is a reflection of the expertise of the institution’s radiologists.38 Because their interpretation determines the preoperative diagnosis as well as the sensitivity rates for both sestamibi scanning and high-resolution ultrasonography, the experience and skill of the radiologist ultimately influences the surgeon’s confidence and their selection of a surgical approach. There is considerable controversy regarding the timing of IOPTH assay draws postexcision.24 Some authors strictly observe the 10-minute mark and explored the contralateral neck whereas others disregarded a ⬍50% PTH reduction and redrew at 15 or 20 minutes. In the latter cases, they obviously reported fewer assay false-positive (FP) results as well as fewer mandated BNE conversion surgeries. Large adenomas (3 g and larger) may cause a slower clearance of PTH from the circulation.32,39,40 In addition, some patients were naturally slow metabolizers of PTH (renal insufficiency) and the half-life rule of 5-7 minutes therefore was not applicable.2,41 In these circumstances, they typically had a ⬎50% reduction in PTH after 20 to 60 minutes. Lastly, a few authors reported artificially high PTH levels following excision, manipulation, or intraoperative rupture of parathyroid cysts; this falsely elevated PTH levels for nearly 20 to 30 minutes following resection.37,42-45 In these circumstances, a 10-minute assay was most often inaccurate as a ⬎50% reduction in PTH was not observed, prompting unnecessary BNEC.46 In terms of BNE conversion surgery, most cases of conversion resulted chiefly from inaccurate preoperative scanning, as well as technical difficulty, inadequate exposure, or unanticipated concurrent thyroid pathology. IOPTH did not significantly alter the conversion rate of intended UNE to BNE. Some authors argued that depending on when the final PTH assay was drawn and the resulting FPs, more patients were usually unnecessarily explored than patients who really benefited from the contralateral exploration.47-51 This depended on the rate of FPs and when one drew the final IOPTH

Otolaryngology– Head and Neck Surgery March 2005

366 RUDA et al

assay. Additionally, among clinicians who frequently use the IOPTH assay for confirmation of intraoperative success, it has been reported that the detection rate of IOPTH for MGD typically ranges from 45% to 70%.52-54 As it is, the failure of this assay to reliably identify those patients who stand to maximally benefit from the use of IOPTH has called into question the true benefit/indication of routinely using the IOPTH assay. Some authors followed patients for 1 to 2 years and noted that calcium and PTH were often elevated immediately after surgery with PTH remaining elevated for weeks to months afterward, depending on the preoperative clinical levels.55-59 When patients had very high levels of PTH/Ca before surgery and had significant objective sequelae of pHPT such as ostepenia/ osteoporosis and BUN/Cr changes, they took a significant longer time to normalize their PTH postoperatively than patients with mild or even asymptomatic pHPT.60 In most cases, the degree and course of calcium was measured instead of the PTH, which was more volatile before stabilizing. The nomenclature for FP, false negative (FN), and true positive (TP) is inconsistent among the reports of IOPTH reviewed. We defined FP as the patient who had less than a 50% PTH reduction and needed another assay/BNE conversion surgery. FN was that the assay failed to detect additional glandular pathology when it

existed. FN and persistent hypercalcemia should be intimately related, as a patient with a missed pathologic gland can be persistently or recurrently hypercalcemic. We believe the literature often reverses FP/FN such that a FN is an assay that has failed to reach the 50% reduction and a FP has reached greater than a 50% reduction. Despite the many limitations described in this article, our research suggests that minimally invasive radio-guided parathyroidectomy and unilateral neck explorations are more successful than is often quoted. And among patients with primary hyperparathyroidism, multiple gland disease is less prevalent than is traditionally thought, which further supports a focused surgical approach. Detection of hyperplastic glands and DA, using preoperative Tc99m-sestamibi and high-resolution ultrasonography is less successful than suspected. Thus, despite the limited success of preoperative imaging for MGD, there still appears to be a significant role for treating primary hyperparathyroidism less invasively should the prevalence of MGD, as estimated in our study, accurately reflect the general population. The IOPTH has been a great intraoperative adjunct to parathyroid surgery but requires adoption of assay methodology and protocol standards to make its impact universal for all of its users.

APPENDIX 1 Measure Histopathologic Prevalence Solitary Adenoma Multiple Gland Disease Multiple Gland Hyperplasia

Double Adenomas

Carcinoma Diagnostic Modalities Tc99m-Sestamibi

High-Resolution Ultrasound IOPTH Surgical Treatment Success Minimally-Invasive Radioguided Parathyroidectomy Unilateral Neck Exploration Bilateral Neck Exploration

Bilateral Neck Exploration Conversion Surgery

Study

1–3; 5–21; 25; 27–34; 37–179, 211, 213 (1–3; 5–21; 27–34; 37–179, 211) (1–3; 5; 6; 8–11; 13–18; 20; 21; 25; 27–33; 37–40; 42; 43; 45; 46; 51; 53–67; 69–73; 75; 79; 81; 82; 85–87; 89–91; 93; 95–110; 112–124; 127; 128; 130–135; 137; 139–141; 146–148; 154; 157; 158; 160–163; 166–168; 171–174; 177; 179; 213) (1–3; 6; 8; 10; 11; 14; 18; 20; 21; 27; 28; 30–33; 37; 38; 40; 42–4; 46; 53; 57; 59; 61; 62; 64–67; 70; 71; 75; 76; 82; 83; 85; 87; 89; 93; 96; 100; 101; 108–113; 115– 120; 123–126; 128–130; 133; 134; 139–142; 148; 152; 154; 156; 158; 160–62; 164; 166; 171–173) (1; 5; 11; 13; 14; 21; 32; 37; 44; 46; 54; 57; 58; 66; 71; 72; 81; 84; 93; 97; 98; 111–113; 115; 117; 119; 122; 123; 142; 143; 147; 149; 162; 166; 172) (2; 3; 6; 8–11; 13–16; 20; 25; 27–29; 34; 35; 39; 41; 45–48; 50; 52; 53; 55; 61; 63; 66; 67; 69–71; 73; 75; 76; 81; 82; 85; 89; 91; 95; 96; 99; 100; 102; 106–108; 110; 114–120; 122–125; 132–135; 138–140; 144; 145; 148; 154; 157; 158; 160; 161; 163–166; 168; 170; 179–189–190; 209–210; 212–213) (2; 3; 11; 14; 16–18; 20; 31; 32; 35; 38; 40; 42; 45; 50; 52; 53; 56; 58; 76; 84; 86; 88; 100; 103; 104; 108; 111–113; 117; 122; 123; 127; 140–42; 147; 150; 160; 163; 166; 168; 170; 171; 175–178; 186; 191; 212–213) 10,56,77,78,93,96,115,123,135,139,152,162,169,181,182,187,188,194,197,200,202,207,215,216,219–221,223,224 (25–28; 32; 48; 57; 58; 75; 79; 81; 118; 132; 138; 149; 153; 156; 182; 192; 193) (2; 12; 29–33; 38; 40; 52; 56; 65; 66; 68; 82; 90; 93; 94; 105; 116; 122; 134; 141; 142; 147; 151; 152; 155; 158; 160; 161; 172; 173; 175–177; 183; 184; 194–198) (1; 3–5; 7; 8; 11; 14; 17; 20; 21; 25; 27–33; 38; 40; 42; 45; 48; 49; 52; 55; 59; 62; 64–68; 70; 72; 77; 78; 80–83; 85; 86; 94; 100; 105; 106; 108–110; 116; 120–122; 124–126; 132; 134–136; 139143; 146; 148; 149; 154; 156; 158; 159; 161; 162; 167; 169; 172; 176; 181; 182; 190; 196–208; 211) (2; 38; 52; 58; 66; 68; 75; 82; 132; 141; 149; 158; 161; 172; 175; 176; 183; 197)

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

REFERENCES 1. Delbridge LW, Younes NA, Guinea AI, et al. Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes. Med J Aust 1998;168(4):153-6. Grade B 2. Moore FD Jr, Mannting F, Tanasijevic M. Intrinsic limitations to unilateral parathyroid exploration. Ann Surg 1999;230(3): 382-8. Grade B 3. Summers GW. Parathyroid update: a review of 220 cases. Ear Nose Throat J 1996;75(7):434-9. Grade C 4. Chan AK, Duh QY, Katz MH, et al. Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy: a case-control study. Ann Surg 1995;222(3):402-12. Grade C 5. Flint RS, Harman CR, Carter J, et al. Primary hyperparathyroidism: referral patterns and outcomes of surgery. ANZ J Surg 2002;72(3):200-3. Grade C 6. Parikshak M, Castillo ED, Conrad MF, et al. Impact of hypercalcemia and parathyroid hormone level on the sensitivity of preoperative sestamibi scanning for primary hyperparathyroidism. Am Surg 2003;69(5):393-8. Grade C 7. Wei JP, Burke GJ. Analysis of savings in operative time for primary hyperparathyroidism using localization with technetium 99m sestamibi scan. Am J Surg 1995;170(5):488-91. Grade B 8. Sofferman RA, Nathan MH, Fairbank JT, et al. Preoperative technetium Tc 99m sestamibi imaging: paving the way to minimal-access parathyroid surgery. Arch Otolaryngol Head Neck Surg 1996;122(4):369-74. Grade C 9. Saaristo RA, Salmi JJ, Koobi T, et al. Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: a prospective study. J Am Coll Surg 2002;195(1):19-22. Grade B 10. Miller P, Kindred A, Kosoy D, et al. Preoperative sestamibi localization combined with intraoperative parathyroid hormone assay predicts successful focused unilateral neck exploration during surgery for primary hyperparathyroidism. Am Surg 2003;69(1):82-5. Grade C 11. Kountakis SE, Maillard AJ. Parathyroid adenomas: is bilateral neck exploration necessary? Am J Otolaryngol 1999;20(6): 396-9. Grade C 12. Norman J, Chheda H, Farrell C. Minimally invasive parathyroidectomy for primary hyperparathyroidism: decreasing operative time and potential complications while improving cosmetic results. Am Surg 1998;64(5):391-5. Grade B 13. Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy. Clin Endocrinol (Oxf) 2002;57(2):241-9. Grade C 14. Ruda J, Hollenbeak C, Stack B. The cost-effectiveness of sestamibi scanning compared to bilateral neck exploration for the treatment of primary hyperparathyroidism. Otolaryngol Clin North Am 2004;37(4):855-70. Grade C 15. Chang CW, Tsue TT, Hermreck AS, et al. Efficacy of preoperative dual-phase sestamibi scanning in hyperparathyroidism. Am J Otolaryngol 2000;21(6):355-9. Grade C 16. Genc H, Morita E, Perrier ND, et al. Differing histologic findings after bilateral and focused parathyroidectomy. J Am Coll Surg 2003;196(4):535-40. Grade B 17. Arici C, Cheah WK, Ituarte PH, et al. Can localization studies be used to direct focused parathyroid operations? Surgery 2001; 129(6):720-9. Grade C 18. Caixas A, Berna L, Hernandez A, et al. Efficacy of preoperative diagnostic imaging localization of technetium 99m-sestamibi scintigraphy in hyperparathyroidism. Surgery 1997;121(5):53541. Grade B 19. Chen CC, Holder LE, Scovill WA, et al. Comparison of parathyroid imaging with technetium-99m-pertechnetate/sestamibi subtraction, double-phase technetium-99m-sestamibi and technetium-99m-sestamibi SPECT. J Nucl Med 1997;38(6):834-9. Grade C

RUDA et al 367

20. Gofrit ON, Lebensart PD, Pikarsky A, et al. High-resolution ultrasonography: highly sensitive, specific technique for preoperative localization of parathyroid adenoma in the absence of multinodular thyroid disease. World J Surg 1997;21(3):287-90. Grade B 21. Lee NC, Norton JA. Multiple-gland disease in primary hyperparathyroidism: a function of operative approach? Arch Surg 2002;137(8):896-9. Grade C 22. Oertli D, Richter M, Kraenzlin M, et al. Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary. Surgery 1995;117(4):392-6. Grade C 23. Ebisuno S, Inagaki T, Yoshida T, et al. Preoperative localization of parathyroid adenomas using 99mTc-MIBI scintigraphy in patients with hyperparathyroidism. Int J Urol 1997;4(2): 126-9. Grade B 24. Carter AB, Howanitz PJ. Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Pathol Lab Med 2003;127:1424-42. Grade B 25. Stangl DK, Berry DA. Meta-analysis in medicine and health policy. New York: Marcel Decker; 2000. 26. Pettiti. Meta-analysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine, 2nd ed. New York: Oxford University Press; 2000. 27. Normand SL. Meta-analysis: formulating, evaluating, combining, and reporting. Stat Medicine 1999;15(18):321-59. 28. Goldstein RE, Blevins L, Delbeke D, et al. Effect of minimally invasive radioguided parathyroidectomy on efficacy, length of stay, and costs in the management of primary hyperparathyroidism. Ann Surg 2000;231(5):732-42. Grade C 29. Inabnet WB, III, Kim CK, Haber RS, et al. Radioguidance is not necessary during parathyroidectomy. Arch Surg 2002;137(8): 967-70. Grade C 30. Parel RJ, Bolton JS, Fuhrman GM. An analysis of sestamibipositive versus negative patients with primary hyperparathyroidism. Am Surg 2001;67(11):1101-4. Grade C 31. Angelos P. An initial experience with radioguided parathyroid surgery. Am J Surg 2000;180(6):475-7. Grade C 32. Irvin GL III, Sfakianakis G, Yeung L, et al. Ambulatory parathyroidectomy for primary hyperparathyroidism. Arch Surg 1996;131(10):1074-8. Grade B 33. Kacker A, Komisar A. Unilateral versus bilateral neck exploration in parathyroid surgery: an assessment of 55 cases. Ear Nose Throat J 2001;80(8):530-2,534. Grade C 34. Ryan JA Jr, Eisenberg B, Pado KM, et al. Efficacy of selective unilateral exploration in hyperparathyroidism based on localization tests. Arch Surg 1997;132(8):886-90. Grade B 35. Casara D, Rubello D, Pelizzo MR, et al. Clinical role of 99mTcO4/MIBI scan, ultrasound and intraoperative gamma probe in the performance of unilateral and minimally invasive surgery in primary hyperparathyroidism. Eur J Nucl Med 2001; 28(9):1351-9. Grade B 36. Hindie E, Melliere D, Jeanguillaume C, et al. Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning. Arch Surg 2000;135(12):1461-8. Grade B 37. Molinari AS, Irvin GL 3rd, Deriso GT, et al. Incidence of multiglandular disease in primary hyperparathyroidism determined by parathyroid hormone secretion. Surgery 1996; 120(6)934-7. Grade C 38. Schell SR, Dudley NE. Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques. Surgery 2003; 133(1): 32-9. Grade B 39. Kacker A, Scharf S, Komisar A. Reduced-time-window sestamibi scanning for nonlocalized primary hyperparathyroidism. Otolaryngol Head Neck Surg 2000;123(4):456-8. Grade C 40. Stratmann SL, Kuhn JA, Bell MS, et al. Comparison of quick parathyroid assay for uniglandular and multiglandular parathy-

Otolaryngology– Head and Neck Surgery March 2005

368 RUDA et al

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56. 57.

58. 59. 60.

roid disease. Am J Surg 2002;184(6):578-81; discussion 581. Grade C Pellitteri PK. Directed parathyroid exploration: evolution and evaluation of this approach in a single-institution review of 346 patients. Laryngoscope 2003;113(11):1857-69. Grade C Yang GP, Levine S, Weigel RJ. A spike in parathyroid hormone during neck exploration may cause a false-negative intraoperative assay result. Arch Surg 2001;136(8):945-9. Grade C Hallfeldt KK, Trupka A, Gallwas J, et al. Minimally invasive video-assisted parathyroidectomy and intraoperative parathyroid hormone monitoring: the first 36 cases and some pitfalls. Surg Endosc 2002;16(12):1759-63. Grade C Boggs JE, Irvin GL III, Molinari AS, et al. Intraoperative parathyroid hormone monitoring as an adjunct to parathyroidectomy. Surgery 1996;120(6):954-8. Grade C Boggs JE, Irvin GL III, Carneiro DM, et al. The evolution of parathyroidectomy failures. Surgery 1999;126(6):998-1002. Grade C Proctor MD, Sofferman RA. Intraoperative parathyroid hormone testing: what have we learned? Laryngoscope 2003;113(4):706-14. Grade C Gordon LL, Snyder WH III, Wians F Jr, et al. The validity of quick intraoperative parathyroid hormone assay: an evaluation in seventy-two patients based on gross morphologic criteria. Surgery 1999;126(6):1030-5. Grade C Miura D, Wada N, Arici C, et al. Does intraoperative quick parathyroid hormone assay improve the results of parathyroidectomy? World J Surg 2002;26(8):926-30. Grade C Sprouse LR, Roe SM, Kaufman HJ, et al. Minimally invasive parathyroidectomy without intraoperative localization. Am Surg 2001;67(11):1022-9. Grade B Dackiw AP, Sussman JJ, Fritsche HA Jr, et al. Relative contributions of technetium Tc 99m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay to the surgical management of hyperparathyroidism. Arch Surg 2000;135(5):550-5. Grade C Sebag F, Hubbard JG, Maweja S, et al. Negative preoperative localization studies are highly predictive of multiglandular disease in sporadic primary hyperparathyroidism. Surgery 2003; 134(6):1038-41; discussion 1041-2. Grade C Gauger PG, Agarwal G, England BG, et al. Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience. Surgery 2001;130(6):100510. Grade C Mandell DL, Genden EM, Mechanick JI, et al. The influence of intraoperative parathyroid hormone monitoring on the surgical management of hyperparathyroidism. Arch Otolaryngol Head Neck Surg 2001;127(7):821-7. Grade C Haciyanli M, Lal G, Morita E, et al. Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma. J Am Coll Surg 2003;197(5):739-46. Grade C Carty SE, Worsey J, Virji MA, et al. Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay. Surgery 1997;122(6):1107-14. Grade B Tisell LE, Jansson S, Nilsson B, et al. Transient rise in intact parathyroid hormone concentration after surgery for primary hyperparathyroidism. Br J Surg 1996;83(5):665-9. Grade B Ferrer-Ramirez MJ, Arroyo Domingo M, Lopez-Molla C, et al. Transient rise in intact parathyroid hormone concentration after surgery for parathyroid adenoma. Otolaryngol Head Neck Surg. 2003;128(6):771-6. Grade C Westerdahl J, Lindblom P, Bergenfelz A. Measurement of intraoperative parathyroid hormone predicts long-term operative success. Arch Surg 2002;137(2):186-90. Grade C Sprouse LR 2nd, Roe SM, Kaufman HJ, et al. Minimally invasive parathyroidectomy without intraoperative localization. Am Surg 2001;67(11):1022-9. Grade C Bergenfelz A, Valdemarsson S, Tibblin S. Persistent elevated serum levels of intact parathyroid hormone after operation for

61.

62.

63.

64.

65.

66.

67.

68. 69.

70. 71.

72. 73. 74.

75.

76.

77.

78.

sporadic parathyroid adenoma: evidence of detrimental effects of severe parathyroid disease. Surgery 1996;119(6):624-33. Grade B Ishibashi M, Nishida H, Hiromatsu Y, et al. Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands. J Nucl Med 1998;39(2):320-4. Grade B Ammori BJ, Madan M, Gopichandran TD, et al. Ultrasoundguided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile? Ann R Coll Surg Engl 1998; 80(6):433-7. Grade B Arbab AS, Koizumi K, Hemmi A, et al. Tc-99m-MIBI scintigraphy for detecting parathyroid adenoma and hyperplasia. Ann Nucl Med 1997;11(1):45-9. Grade B Arkles LB, Jones T, Hicks RJ, et al. Impact of complementary parathyroid scintigraphy and ultrasonography on the surgical management of hyperparathyroidism. Surgery 1996;120(5):845-51. Grade C Arveschoug AK, Bertelsen H, Vammen B. Presurgical localization of abnormal parathyroid glands using a single injection of Tc-99m sestamibi: comparison of high-resolution parallelhole and pinhole collimators, and interobserver and intraobserver variation. Clin Nucl Med 2002;27(4):249-54. Grade C Berczi C, Mezosi E, Galuska L, et al. Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism. Eur Radiol 2002;12(3):605-9. Grade B Bergenfelz A, Tennvall J, Valdermarsson S, et al. Sestamibi versus thallium subtraction scintigraphy in parathyroid localization: a prospective comparative study in patients with predominantly mild primary hyperparathyroidism. Surgery 1997; 121(6):601-5. Grade B Biertho L, Chu C, Inabnet WB. Image-directed parathyroidectomy under local anaesthesia in the elderly. Br J Surg 2003; 90(6):738-42. Grade C Billy HT, Rimkus DR, Hartzman S, et al. Technetium-99msestamibi single agent localization versus high resolution ultrasonography for the preoperative localization of parathyroid glands in patients with primary hyperparathyroidism. Am Surg 1995;61(10):882-8. Grade B Blanco I, Carril JM, Banzo I, et al. Double-phase Tc-99m sestamibi scintigraphy in the preoperative location of lesions causing hyperparathyroidism. Clin Nucl Med 1998;23(5):291-7. Grade B Blocklet D, Martin P, Schoutens A, et al. Presurgical localization of abnormal parathyroid glands using a single injection of technetium-99m methoxyisobutylisonitrile: comparison of different techniques including factor analysis of dynamic structures. Eur J Nucl Med 1997;24(1):46-51. Grade C Bonjer HJ, Bruining HA, Pols HA, et al. 2-Methoxyisobutylisonitrile probe during parathyroid surgery: tool or gadget? World J Surg 1998;22(6):507-11. Grade B Bonjer HJ, Bruining HA, Pols HA, et al. Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer. Eur J Nucl Med 1997;24(3):246-51. Grade C Bonjer HJ, Bruining HA, Valkema R, et al. Single radionuclide scintigraphy with 99mtechnetium-sestamibi and ultrasonography in hyperparathyroidism. Eur J Surg 1997;163(1):27-32. Grade C Borley NR, Collins RE, O’Doherty M, et al. Technetium-99m sestamibi parathyroid localization is accurate enough for scandirected unilateral neck exploration. Br J Surg 1996;83(7):98991. Grade C Burkey SH, Snyder WH III, Nwariaku F, et al. Directed parathyroidectomy: feasibility and performance in 100 consecutive patients with primary hyperparathyroidism. Arch Surg 2003; 138(6):604-8. Grade B Caixas A, Berna L, Piera J, et al. Utility of 99mTc-sestamibi scintigraphy as a first-line imaging procedure in the preoperative evaluation of hyperparathyroidism. Clin Endocrinol (Oxf) 1995;43(5):525-30. Grade B Carpentier A, Jeannotte S, Verreault J, et al. Preoperative lo-

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

79.

80.

81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

91.

92.

93.

94.

95.

96.

97.

98.

calization of parathyroid lesions in hyperparathyroidism: relationship between technetium-99m-MIBI uptake and oxyphil cell content. J Nucl Med 1998;39(8):1441-4. Grade C Carter WB, Sarfati MR, Fox KA, et al. Preoperative detection of sporadic parathyroid adenomas using technetium-99m-sestamibi: what role in clinical practice? Am Surg 1997;63(4):31721. Grade B Casara D, Rubello D, Cauzzo C, et al. 99mTc-MIBI radioguided minimally invasive parathyroidectomy: experience with patients with normal thyroids and nodular goiters. Thyroid 2002;12(1):53-61. Grade B Casara D, Rubello D, Piotto A, et al. 99mTc-MIBI radio-guided minimally invasive parathyroid surgery planned on the basis of a preoperative combined 99mTc-pertechnetate/99mTc-MIBI and ultrasound imaging protocol. Eur J Nucl Med 2000;27(9): 1300-4. Grade B Casas AT, Burke GJ, Mansberger AR Jr, et al. Impact of technetium-99m-sestamibi localization on operative time and success of operations for primary hyperparathyroidism. Am Surg 1994;60(1):12-6. Grade C Castellani M, Reschini E, Longari V, et al. Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decisionmaking process in primary hyperparathyroid disease. Clin Nucl Med 2001;26(2):139-44. Grade C Ceyssens S, Mortelmans L. Parathyroid imaging: basic principles and KU Leuven experience: MIBI-dual phase versus MIBI/ I-123. Acta Otorhinolaryngol Belg 2001;55(2):103-17. Grade C Chen H, Parkerson S, Udelsman R. Parathyroidectomy in the elderly: do the benefits outweigh the risks? World J Surg 1998;22(6):531-5. Grade B Cheung AH, Wheeler MS, Madanay LD, et al. Multi-center sestamibi parathyroid imaging study in Hawaii. Hawaii Med J 1997;56(5):114-7,120. Grade C Chigot JP, Menegaux F, Achrafi H. Should primary hyperparathyroidism be treated surgically in elderly patients older than 75 years? Surgery 1995;117(4):397-401. Grade C Civelek AC, Ozalp E, Donovan P, et al. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery 2002;131(2):149-57. Grade B Clark PB, Case D, Watson NE, et al. Experienced scintigraphers contribute to success of minimally invasive parathyroidectomy by skilled endocrine surgeons. Am Surg 2003;69(6): 478-83. Grade C Coston SD, Pelton JJ. Success of cervical exploration for patients with asymptomatic primary hyperparathyroidism. Am J Surg 1999;177(1):69-74. Grade C Delbridge LW, Dolan SJ, Hop TT, et al. Minimally invasive parathyroidectomy: 50 consecutive cases. Med J Aust 2000; 172(9):418-22. Grade B Demirkurek CH, Adalet I, Terzioglu T, et al. Efficiency of gamma probe and dual-phase Tc-99m sestamibi scintigraphy in surgery for patients with primary hyperparathyroidism. Clin Nucl Med 2003;28(3):186-91. Grade B Dillavou ED, Jenoff JS, Intenzo CM, et al. The utility of sestamibi scanning in the operative management of patients with primary hyperparathyroidism. J Am Coll Surg 2000;190(5):540-5. Grade B Dillavou ED, Cohn HE. Minimally invasive parathyroidectomy: 101 consecutive cases from a single surgeon. J Am Coll Surg 2003;197(1):1-7. Grade B Ditkoff BA, Chabot J, Feind C, et al. Parathyroid surgery using monitored anesthesia care as an alternative to general anesthesia. Am J Surg 1996;172(6):698-700. Grade C Falvo L, D’Andrea V, D’Ercole C, et al. Scintigraphy with 99mTcMIBI and echography in the study of primitive hyperparathyroidism. Panminerva Med 2002;44(1):3-6. Grade C Fjeld JG, Erichsen K, Pfeffer PF, et al. Technetium-99m-tetrofosmin for parathyroid scintigraphy: a comparison with sestamibi. J Nucl Med 1997;38(6):831-4. Grade B Flynn MB, Bumpous JM, Schill K, et al. Minimally invasive

RUDA et al 369

99.

100.

101.

102.

103.

104.

105.

106.

107.

108.

109. 110.

111. 112. 113. 114. 115. 116.

117.

118.

radioguided parathyroidectomy. J Am Coll Surg 2000;191(1): 24-31. Grade B Gallowitsch HJ, Fellinger J, Kresnik E, et al. Preoperative scintigraphic and intraoperative scintimetric localization of parathyroid adenoma with cationic Tc-99m complexes and a hand-held gamma-probe. Nuklearmedizin 1997;36(1):13-8. Grade B Garner SC, Leight GS Jr. Initial experience with intraoperative PTH determinations in the surgical management of 130 consecutive cases of primary hyperparathyroidism. Surgery 1999; 126(6):1132-7. Grade C Goldstein RE, Billheimer D, Martin WH, et al. Sestamibi scanning and minimally invasive radioguided parathyroidectomy without intraoperative parathyroid hormone measurement. Ann Surg 2003;237(5):722-30. Grade C Goss JC, Landerholm R. A changing experience with primary hyperparathyroidism at Group Health Cooperative, Seattle. Am J Surg 2001;181(5):445-8. Grade C Gupta VK, Yeh KA, Burke GJ, et al. 99m-Technetium sestamibi localized solitary parathyroid adenoma as an indication for limited unilateral surgical exploration. Am J Surg 1998;176(5): 409-12. Grade B Harman CR, van Heerden JA, Farley DR, et al. Sporadic primary hyperparathyroidism in young patients: a separate disease entity? Arch Surg 1999;134(6):651-5. Grade C Hewin DF, Brammar TJ, Kabala J, et al. Role of preoperative localization in the management of primary hyperparathyroidism. Br J Surg 1997;84(10):1377-80. Grade B Hindie E, Melliere D, Jeanguillaume C, et al. Parathyroid imaging using simultaneous double-window recording of technetium-99m-sestamibi and iodine-123. J Nucl Med 1998;39(6): 1100-5. Grade B Hindie E, Melliere D, Simon D, et al. Primary hyperparathyroidism: is technetium 99m-Sestamibi/iodine-123 subtraction scanning the best procedure to locate enlarged glands before surgery? J Clin Endocrinol Metab 1995;80(1):302-7. Grade B Hindie E, Melliere D, Perlemuter L, et al. Primary hyperparathyroidism: higher success rate of first surgery after preoperative Tc-99m sestamibi-I-123 subtraction scanning. Radiology 1997;204(1):221-8. Grade B Hiromatsu Y, Ishibashi M, Nishida H, et al. Technetium-99m tetrofosmin parathyroid imaging in patients with primary hyperparathyroidism. Intern Med 2000;39(2):101-6. Grade B Ho SI, Roach PJ, Bernard EJ, et al. Optimal pinhole techniques for preoperative localization with Tc-99m MIBI for primary hyperparathyroidism. Clin Nucl Med 2001;26(12):1002-9. Grade C Huang SH, Lai IR, Liaw KY, et al. Preoperative localization procedures for initial surgery in primary hyperparathyroidism. J Formos Med Assoc 1998;97(10):679-83. Grade B Hung GU, Wang SJ, Lin WY. Tc-99m MIBI parathyroid scintigraphy and intact parathyroid hormone levels in hyperparathyroidism. Clin Nucl Med 2003;28(3):180-5. Grade C Ikeda Y, Takami H, Tajima G, et al. Direct mini-incision parathyroidectomy. Biomed Pharmacother 2002; 56 (Suppl1)14s-17s. Grade B Inabnet WB III, Dakin GF, Haber RS, et al. Targeted parathyroidectomy in the era of intraoperative parathormone monitoring. World J Surg 2002;26(8):921-5. Grade B Irvin GL III, Carneiro DM. “Limited” parathyroidectomy in geriatric patients. Ann Surg 2001;233(5):612-6. Grade B Ishibashi M, Nishida H, Hiromatsu Y, et al. Localization of ectopic parathyroid glands using technetium-99m sestamibi imaging: comparison with magnetic resonance and computed tomographic imaging. Eur J Nucl Med 1997;24(2):197-201. Grade B Jaskowiak NT, Sugg SL, Helke J, et al. Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism. Arch Surg 2002;137(6):659-68. Grade B Johnston LB, Carroll MJ, Britton KE, et al. The accuracy of

370 RUDA et al

119.

120.

121.

122.

123.

124.

125.

126.

127.

128.

129. 130. 131.

132.

133. 134. 135. 136.

parathyroid gland localization in primary hyperparathyroidism using sestamibi radionuclide imaging. J Clin Endocrinol Metab 1996;81(1):346-52. Grade C Jones JM, Russell CF, Ferguson WR, et al. Preoperative sestamibi-technetium subtraction scintigraphy in primary hyperparathyroidism: experience with 156 consecutive patients. Clin Radiol 2001;(7):556-9. Grade B Katz SC, Wang GJ, Kramer EL, et al. Limitations of technetium 99m sestamibi scintigraphic localization for primary hyperparathyroidism associated with multiglandular disease. Am Surg 2003;69(2):170-5. Grade C Kim CK, Kim S, Krynyckyi BR, et al. The efficacy of sestamibi parathyroid scintigraphy for directing surgical approaches based on modified interpretation criteria. Clin Nucl Med 2002; 27(4):246-8. Grade C Klieger P, O’Mara R. The diagnostic utility of dual phase Tc-99m sestamibi parathyroid imaging. Clin Nucl Med 1998; 23(4):208-11. Grade B Koslin DB, Adams J, Andersen P, et al. Preoperative evaluation of patients with primary hyperparathyroidism: role of highresolution ultrasound. Laryngoscope 1997;107(9):1249-53. Grade B Krausz Y, Lebensart PD, Klein M, et al. Preoperative localization of parathyroid adenoma in patients with concomitant thyroid nodular disease. World J Surg 2000;24(12):1573-8. Grade B Kumar A, Cozens NJ, Nash JR. Sestamibi scan-directed unilateral neck exploration for primary hyperparathyroidism due to a solitary adenoma. Eur J Surg Oncol 2000;26(8):785-8. Grade B Lee VS, Spritzer CE, Coleman RE, et al. The complementary roles of fast spin-echo MR imaging and double-phase 99m Tc-sestamibi scintigraphy for localization of hyperfunctioning parathyroid glands. AJR Am J Roentgenol 1996;167(6):155562. Grade B Lee VS, Wilkinson RH, Jr, Leight GS Jr, et al. Hyperparathyroidism in high-risk surgical patients: evaluation with doublephase technetium-99m sestamibi imaging. Radiology 1995; 197(3):627-33. Grade B Light VL, McHenry CR, Jarjoura D, et al. Prospective comparison of dual-phase technetium-99m-sestamibi scintigraphy and high resolution ultrasonography in the evaluation of abnormal parathyroid glands. Am Surg 1996;62(7):562-7. Grade B Low RA, Katz AD. Parathyroidectomy via bilateral cervical exploration: a retrospective review of 866 cases. Head Neck 1998;20(7):583-7. Grade C Lowney JK, Weber B, Johnson S, et al. Minimal incision parathyroidectomy: cure, cosmesis, and cost. World J Surg 2000;24(11):1442-5. Grade C Lumachi F, Ermani M, Basso S, et al. Localization of parathyroid tumours in the minimally invasive era: which technique should be chosen? Population-based analysis of 253 patients undergoing parathyroidectomy and factors affecting parathyroid gland detection. Endocr Relat Cancer 2001;8(1):63-9. Grade C Lumachi F, Zucchetta P, Marzola MC, et al. Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism. Eur J Endocrinol 2000;143(6):755-60. Grade B Lumachi F, Zucchetta P, Varotto S, et al. Noninvasive localization procedures in ectopic hyperfunctioning parathyroid tumors. Endocr Relat Cancer 1999;6(1):123-5. Grade C Malhotra A, Silver CE, Deshpande V, et al. Preoperative parathyroid localization with sestamibi. Am J Surg 1996;172(6): 637-40. Grade C Martin RC, Greenwell D, Flynn MB. Initial neck exploration for untreated hyperparathyroidism. Am Surg 2000;66(3):26972. Grade C Mazzeo S, Caramella D, Lencioni R, et al. Comparison among sonography, double-tracer subtraction scintigraphy, and doublephase scintigraphy in the detection of parathyroid lesions. AJR Am J Roentgenol 1996;166(6):1465-70. Grade B

Otolaryngology– Head and Neck Surgery March 2005

137. McGreal G, Winter DC, Sookhai S, et al. Minimally invasive, radioguided surgery for primary hyperparathyroidism. Ann Surg Oncol 2001;8(10):856-60. Grade B 138. McHenry CR, Lee K, Saadey J, et al. Parathyroid localization with technetium-99m-sestamibi: a prospective evaluation. J Am Coll Surg 1996;183(1):25-30. Grade B 139. Merlino JI, Ko K, Minotti A, et al. The false negative technetium-99m-sestamibi scan in patients with primary hyperparathyroidism: correlation with clinical factors and operative findings. Am Surg 2003;69(3):225-9. Grade B 140. Meurisse M, Hamoir E, Defechereux T, et al. Bilateral neck exploration under hypnosedation: a new standard of care in primary hyperparathyroidism? Ann Surg 1999;229(3):401-8. Grade C 141. Mimura Y, Kanauchi H, Ogawa T, et al. Review of 41 patients operated on for primary hyperparathyroidism. Biomed Pharmacother 2000; 54(Suppl1)72s-76s. Grade C 142. Moka D, Eschner W, Voth E, et al. Iterative reconstruction: an improvement of technetium-99m MIBI SPET for the detection of parathyroid adenomas? Eur J Nucl Med 2000;27(5):485-9. Grade B 143. Moka D, Voth E, Dietlein M, et al. Preoperative localization of parathyroid adenomas using 99mTc-MIBI scintigraphy. Am J Med 2000;108(9):733-6. Grade B 144. Moka D, Voth E, Dietlein M, et al. Technetium 99m-MIBISPECT: a highly sensitive diagnostic tool for localization of parathyroid adenomas. Surgery 2000;128(1):29-35. Grade B 145. Monchik JM, Barellini L, Langer P, et al. Minimally invasive parathyroid surgery in 103 patients with local/regional anesthesia, without exclusion criteria. Surgery 2002;131(5):502-8. Grade B 146. Neumann DR, Esselstyn CB, Maclntyre WJ, et al. Comparison of FDG-PET and sestamibi-SPECT in primary hyperparathyroidism. J Nucl Med 1996;37(11):1809-15. Grade B 147. Neumann DR, Esselstyn CB Jr, Go RT, et al. Comparison of double-phase 99mTc-sestamibi with 123I-99mTc-sestamibi subtraction SPECT in hyperparathyroidism. AJR Am J Roentgenol 1997;169(6):1671-4. Grade B 148. Neumann DR, Esselstyn CB Jr, Kim EY, et al. Preliminary experience with double-phase SPECT using Tc-99m sestamibi in patients with hyperparathyroidism. Clin Nucl Med 1997; 22(4):217-21. Grade B 149. Nordin AJ, Larcos G, Ung O. Dual phase 99m-technetium Sestamibi imaging with single photon emission computed tomography in primary hyperparathyroidism: influence on surgery. Australas Radiol 2001;45(1):31-4. Grade C 150. Norman J, Chheda H. Minimally invasive parathyroidectomy facilitated by intraoperative nuclear mapping. Surgery 1997; 122(6):998-1003. Grade B 151. Norton KS, Johnson LW, Griffen FD, et al. The sestamibi scan as a preoperative screening tool. Am Surg 2002;68(9):812-5. Grade C 152. Orloff LA. Methylene blue and sestamibi: complementary tools for localizing parathyroids. Laryngoscope 2001;111(11 Pt 1): 1901-4. Grade B 153. Patel PC, Pellitteri PK, Patel NM, et al. Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease. Arch Otolaryngol Head Neck Surg 1998;124(5):559-62. Grade B 154. Pattou F, Torres G, Mondragon-Sanchez A, et al. Correlation of parathyroid scanning and anatomy in 261 unselected patients with sporadic primary hyperparathyroidism. Surgery 1999; 126(6):1123-31. Grade C 155. Perez-Monte JE, Brown ML, Shah AN, et al. Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT. Radiology 1996;201(1):85-91. Grade B 156. Perrier ND, Ituarte PH, Morita E, et al. Parathyroid surgery: separating promise from reality. J Clin Endocrinol Metab 2002; 87(3):1024-9. Grade B 157. Pinero A, Rodriguez JM, Ortiz S, et al. Relation of biochemical, cytologic, and morphologic parameters to the result of gammagraphy

Otolaryngology– Head and Neck Surgery Volume 132 Number 3

158.

159.

160.

161.

162.

163.

164. 165.

166.

167.

168.

169.

170. 171. 172. 173.

174. 175. 176. 177. 178.

with technetium 99m sestamibi in primary hyperparathyroidism. Otolaryngol Head Neck Surg 2000;122(6):851-5. Grade B Prager G, Czerny C, Ofluoglu S, et al. Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region. J Am Coll Surg 2003;196(4): 541-8. Grade B Prager G, Czerny C, Kurtaran A, et al. Minimally invasive open parathyroidectomy in an endemic goiter area: a prospective study. Arch Surg 2001;136(7):810-6. Grade B Preventza OA, Yang S, Karo JJ, et al. Preoperative ultrasonography guiding minimal, selective surgical approach in primary hyperparathyroidism. Int Surg 2000;85(2):99-104. Grade C Proye C, Carnaille B, Quievreux JL, et al. Late outcome of 304 consecutive patients with multiple gland enlargement in primary hyperparathyroidism treated by conservative surgery. World J Surg 1998;22(6):526-9. Grade B Purcell GP, Dirbas FM, Jeffrey RB, et al. Parathyroid localization with high-resolution ultrasound and technetium Tc 99m sestamibi. Arch Surg 1999;134(8):824-8. Grade C Rauth JD, Sessions RB, Shupe SC, et al. Comparison of Tc-99m MIBI and TI-201/Tc-99m pertechnetate for diagnosis of primary hyperparathyroidism. Clin Nucl Med 1996;21(8):602-8. Grade B Ready AR, Sabharawal T, Barnes AD. Parathyroidectomy in the west Midlands. Br J Surg 1996;83(6):823-7. Grade C Robertson GS, Johnson PR, Bolia A, et al. Long-term results of unilateral neck exploration for preoperatively localized nonfamilial parathyroid adenomas. Am J Surg 1996;172(4):311-4. Grade B Roe SM, Brown PW, Pate LM, et al. Initial cervical exploration for parathyroidectomy is not benefited by preoperative localization studies. Am Surg 1998;64(6):503-7. Grade B Rubello D, Piotto A, Casara D, et al. Role of gamma probes in performing minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: optimization of preoperative and intraoperative procedures. Eur J Endocrinol 2003; 149(1):7-15. Grade B Rubello D, Saladini G, Casara D, et al. Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction scintigraphy: a fast and effective technique. Clin Nucl Med 2000;25(7): 527-31. Grade B Scheiner JD, Dupuy DE, Monchik JM, et al. Preoperative localization of parathyroid adenomas: a comparison of power and colour Doppler ultrasonography with nuclear medicine scintigraphy. Clin Radiol 2001;56(12):984-8. Grade B Sfakianakis GN, Irvin GL, III, Foss J, et al. Efficient parathyroidectomy guided by SPECT-MIBI and hormonal measurements. J Nucl Med 1996;37(5):798-804. Grade B Shaha AR, Patel SG, Singh B. Minimally invasive parathyroidectomy: the role of radio-guided surgery. Laryngoscope 2002; 112(12):2166-9. Grade C Shen W, Sabanci U, Morita ET, et al. Sestamibi scanning is inadequate for directing unilateral neck exploration for first-time parathyroidectomy. Arch Surg 1997;132(9):969-74. Grade C Sidhu S, Neill AK, Russell CF. Long-term outcome of unilateral parathyroid exploration for primary hyperparathyroidism due to presumed solitary adenoma. World J Surg 2003;27(3): 339-42. Grade C Sidiropoulos N, Vento J, Malchoff C, et al. Radioguided tumorectomy in the management of parathyroid adenomas. Arch Surg 2003;138(7):716-20. Grade B Sinha CK, Hamaker R, Hamaker RC, et al. Utility of preoperative radionuclide scanning for primary hyperparathyroidism. Laryngoscope 1997;107(6):753-8. Grade C Sofferman RA, Standage J, Tang ME. Minimal-access parathyroid surgery using intraoperative parathyroid hormone assay. Laryngoscope 1998;108(10):1497-503. Grade B Sokoll LJ, Drew H, Udelsman R. Intraoperative parathyroid hormone analysis: a study of 200 consecutive cases. Clin Chem 2000;46(10):1662-8. Grade B Song AU, Phillips TE, Edmond CV, et al. Success of preoperative imaging and unilateral neck exploration for primary hy-

RUDA et al 371

179.

180.

181.

182.

183.

184.

185.

186.

187.

188.

189.

190.

191.

192.

193. 194.

195.

196.

197.

198.

perparathyroidism. Otolaryngol Head Neck Surg 1999; 121(4):393-7. Grade B Starr FL, DeCresce R, Prinz RA. Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism. Arch Surg 2001;136(5):536-42. Grade B Staudenherz A, Abela C, Niederle B, et al. Comparison and histopathological correlation of three parathyroid imaging methods in a population with a high prevalence of concomitant thyroid diseases. Eur J Nucl Med 1997;24(2):143-9. Grade B Sullivan DP, Scharf SC, Komisar A. Intraoperative gamma probe localization of parathyroid adenomas. Laryngoscope 2001;111(5):912-7. Grade C Takami H, Takayama J, Ikeda Y, et al. Minimally invasive radioguided parathyroidectomy. Biomed Pharmacother 2002; 56(Suppl1)37s-40s. Grade B Takami H, Oshima M, Sugawara I, et al. Pre-operative localization and tissue uptake study in parathyroid imaging with technetium-99m-sestamibi. Aust N Z J Surg 1999;69(9):62931. Grade B Takebayashi S, Hidai H, Chiba T, et al. Hyperfunctional parathyroid glands with 99mTc-MIBI scan: semiquantitative analysis correlated with histologic findings. J Nucl Med 1999; 40(11):1792-7. Grade B Takei H, Iino Y, Endo K, et al. The efficacy of technetium99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands. Surg Today 1999;29(4):307-12. Grade B Torregrosa JV, Palomar MR, Pons F, et al. Has double-phase MIBI scintigraphy usefulness in the diagnosis of hyperparathyroidism? Nephrol Dial Transplant 1998;13(Suppl3):37-40. Grade B Tziakouri C, Eracleous E, Skannavis S, et al. Value of ultrasonography, CT and MR imaging in the diagnosis of primary hyperparathyroidism. Acta Radiol 1996;37(5):720-6. Grade B Udelsman R. Six hundred fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 2002;235(5):665-70. Grade B Udelsman R, Donovan PI, Sokoll LJ. One hundred consecutive minimally invasive parathyroid explorations. Ann Surg 2000; 232(3):331-9. Grade B Ulanovski D, Feinmesser R, Cohen M, et al. Preoperative evaluation of patients with parathyroid adenoma: role of high-resolution ultrasonography. Head Neck 2002;24(1):1-5. Grade B van Dalen A, Smit CP, van Vroonhoven TJ, et al. Minimally invasive surgery for solitary parathyroid adenomas in patients with primary hyperparathyroidism: role of US with supplemental CT. Radiology 2001;220(3):631-9. Grade B van Vroonhoven TJ, van Dalen A. Successful minimally invasive surgery in primary hyperparathyroidism after combined preoperative ultrasound and computed tomography imaging. J Intern Med 1998;243(6):581-7. Grade B Vogel LM, Lucas R, Czako P. Unilateral parathyroid exploration. Am Surg 1998;64(7):693-6. Grade B Wakamatsu H, Noguchi S, Yamashita H, et al. Technetium99m tetrofosmin for parathyroid scintigraphy: a direct comparison with (99m)Tc-MIBI, (201)Tl, MRI and US. Eur J Nucl Med 2001;28(12):1817-27. Grade B Wei JP, Burke GJ. Cost utility of routine imaging with Tc-99msestamibi in primary hyperparathyroidism before initial surgery. Am Surg 1997;63(12):1097-100. Grade B Billotey C, Sarfati E, Aurengo A, et al. Advantages of SPECT in technetium-99m-sestamibi parathyroid scintigraphy. J Nucl Med 1996;37(11):1773-8. Grade B Chapuis Y, Fulla Y, Bonnichon P, et al. Values of ultrasonography, sestamibi scintigraphy, and intraoperative measurement of 1-84 PTH for unilateral neck exploration of primary hyperparathyroidism. World J Surg 1996;20(7):835-9. Grade B Inabnet WB, Fulla Y, Richard B, et al. Unilateral neck exploration under local anesthesia: the approach of choice for asymptomatic

Otolaryngology– Head and Neck Surgery March 2005

372 RUDA et al

199. 200. 201. 202. 203. 204. 205.

206.

207. 208.

209.

210.

211.

212.

primary hyperparathyroidism. Surgery 1999;126(6):1004-9. Grade B Ishiguro K, Ohgi S. Minimally invasive parathyroidectomy under local anesthesia. Biomed Pharmacother 2002; 56(Suppl1)31s-33s. Grade C Krausz Y, Shiloni E, Bocher M, et al. Diagnostic dilemmas in parathyroid scintigraphy. Clin Nucl Med 2001;26(12):9971001. Grade B Martin D, Rosen IB, Ichise M. Evaluation of single isotope technetium 99M-sestamibi in localization efficiency for hyperparathyroidism. Am J Surg 1996;172(6):633-6. Grade C TakamiHSasakiYIkedaY, et al. Intraoperative quick parathyroid hormone assay in the surgical management of hyperparathyroidismBiomed Pharmacother56Suppl1200226s-30sGrade C Thompson GB, Mullan BP, Grant CS, et al. Parathyroid imaging with technetium-99m-sestamibi: an initial institutional experience. Surgery 1994;116(6):966-72. Grade C Allendorf J, Kim L, Chabot J, et al. The impact of sestamibi scanning on the outcome of parathyroid surgery. J Clin Endocrinol Metab 2003;88(7):3015-18. Grade B Zmora O, Schachter PP, Heyman Z, et al. Correct preoperative localization: does it permit a change in operative strategy for primary hyperparathyroidism? Surgery 1995;118(6):932-5. Grade C Ben Haim M, Zwas ST, Munz Y, et al. Focused, minimally invasive radio-guided parathyroidectomy: a feasible and safe option for elderly patients with primary hyperparathyroidism. Isr Med Assoc J 2003;5(5):326-8. Grade B Rubello D, Casara D, Saladini G, et al. 99mTc-MIBI radioguided surgery in primary hyperparathyroidism: a prospective study of 128 patients. Tumori 2002;88(3):S63-S65. Grade B Agarwal G, Barakate MS, Robinson B, et al. Intraoperative quick parathyroid hormone versus same-day parathyroid hormone testing for minimally invasive parathyroidectomy: a costeffectiveness study. Surgery 2001;130(6):963-70. Grade B Agarwal G, Barraclough BH, Robinson BG, et al. Minimally invasive parathyroidectomy using the ’focused’ lateral approach. I. Results of the first 100 consecutive cases. ANZ J Surg 2002;72(2):100-104. Grade B Bergenfelz A, Lindblom P, Tibblin S, et al. Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial. Ann Surg 2002;236(5): 543-51. Grade A Chen H, Sokoll LJ, Udelsman R. Outpatient minimally invasive parathyroidectomy: a combination of sestamibi-SPECT localization, cervical block anesthesia, and intraoperative parathyroid hormone assay. Surgery 1999;126(6):1016-21. Grade B Smit PC, Rinkes IH, van Dalen A, et al. Direct, minimally invasive adenomectomy for primary hyperparathyroidism: an

213.

214. 215.

216.

217. 218.

219. 220.

221.

222. 223. 224.

225.

alternative to conventional neck exploration? Ann Surg 2000;231(4):559-65. Grade B Carneiro DM, Irvin GL III. Late parathyroid function after successful parathyroidectomy guided by intraoperative hormone assay (QPTH) compared with the standard bilateral neck exploration. Surgery 2000;128(6):925-9. Grade C Chou FF, Wang PW, Sheen-Chen SM. Preoperative localisation of parathyroid glands in primary hyperparathyroidism. Eur J Surg 1997;163(12):889-95. Grade C Lo GP. Bilateral neck exploration for parathyroidectomy under local anesthesia: a viable technique for patients with coexisting thyroid disease with or without sestamibi scanning. Surgery 1999;126(6):1011-4. Grade C Miccoli P, Bendinelli C, Berti P, et al. Video-assisted versus conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery 1999;126(6): 1117-21. Grade A Silverberg SJ, Shane E, Jacobs TP, et al. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 1999;341(17):1249-55. Grade B Vignali E, Picone A, Materazzi G, et al. A quick intraoperative parathyroid hormone assay in the surgical management of patients with primary hyperparathyroidism: a study of 206 consecutive cases. Eur J Endocrinol 2002;146(6):783-8. Grade B Walgenbach S, Hommel G, Junginger T. Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study. World J Surg 2000;24(5):564-9. Grade B Pattou F, Oudar C, Huglo D, et al. Localization of abnormal parathyroid glands with jugular sampling for parathyroid hormone, and subtraction scanning with sestamibi or tetrofosmine. Aust NZ J Surg 1998;68(2):108-11. Grade B Lorberboym M, Minski I, Macadziob S, et al. Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma. J Nucl Med 2003;44(6): 904-8. Grade B Sinha, SN, Subramaniam P. Initial parathyroid exploration: Current trends in Australia. Aust NZ J Surg 1996;66(5):279-81. Grade B Sekiyama K, Akakura K, Mikami K. Usefulness of diagnostic imaging in primary hyperparathyroidism. Int J Urol 2003;10(1): 7-11. Grade C De Feo M, Colagrande S, Carlo B. Parathyroid glands: combination of 99mTc MIBI Scintigraphy and US for demonstration of parathyroid glands and nodules. Radiology 2000;214:393-402. Grade C Sebag F, Hubbard JG, Maweja S, et al. Negative preoperative localization studies are highly predictive of multiglandular disease in sporadic primary hyperparathyroidism. Surgery 2003; 134(6):1038-41; discussion 1041-2. Grade C