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Published online before print May 15, 2008, 10.1148/radiol.2481071066
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(Radiology 2008;248:221-232.)
© RSNA, 2008

Nuclear Medicine

Preoperative Parathyroid Scintigraphic Lesion Localization: Accuracy of Various Types of Readings1

Kenneth J. Nichols, PhD, Maria B. Tomas, MD, Gene G. Tronco, MD, Josephine N. Rini, MD, Biju D. Kunjummen, MD, Keith S. Heller, MD, Laura A. Sznyter, MD, and Christopher J. Palestro, MD

1 From the Division of Nuclear Medicine and Molecular Imaging (K.J.N., M.B.T., G.G.T., J.N.R., B.D.K., C.J.P.) and Department of Surgery (L.A.S.), North Shore Long Island Jewish Health System, 270-05 76th Ave, New Hyde Park, NY 11040; and Division of Endocrine Surgery, New York University School of Medicine, New York, NY (K.S.H.). From the 2006 RSNA Annual Meeting. Received June 18, 2007; revision requested August 23; revision received October 12; accepted January 4, 2008; final version accepted January 31. Address correspondence to K.J.N. (e-mail: knichols@lij.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To retrospectively compare the accuracy of various parathyroid scintigraphy readings for single-gland disease (SGD) and multigland disease (MGD) in patients with primary hyperparathyroidism, with histologic analysis as the reference standard.

Materials and Methods: Institutional review board approval was obtained for this HIPAA-compliant study. Records of 462 patients with primary hyperparathyroidism who underwent preoperative imaging with a technetium 99m (99mTc) sestamibi and 99mTcO4– protocol that consisted of early and late pinhole 99mTc sestamibi, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography (SPECT) were retrospectively reviewed. An experienced nuclear medicine physician without knowledge of other test results or of the final diagnoses graded images on a scale from 0 (definitely normal) to 4 (definitely abnormal). Early pinhole 99mTc sestamibi images, late pinhole 99mTc sestamibi images, subtraction images, SPECT images, early and late pinhole 99mTc sestamibi images, all planar images, and all images—including SPECT images—were read in seven sessions. Receiver operating characteristic curves were generated for each session and were used to calculate sensitivity, specificity, and accuracy.

Results: A total of 534 parathyroid lesions were excised. Of the 462 patients, 409 had one lesion, whereas 53 had multiple lesions. Reading all images together was more accurate (89%, P = .001) than was reading early (79%), late (85%), subtraction (86%), and SPECT (83%) images seperately; however, it was not significantly more accurate than reading planar images (88%) or early and late images together (87%). Reading all images was significantly less sensitive in the detection of lesions with a median weight of 600 mg or less than in the detection of lesions with a median weight of more than 600 mg (86% vs 94%, P = .004). Per-lesion sensitivity for reading all images was significantly higher for SGD than for MGD (90% vs 66%, P < .001). Sensitivity of reading all images together in the identification of patients with MGD was 62%.

Conclusion: Reviewing early, late, and subtraction pinhole images together with SPECT images maximizes parathyroid lesion detection accuracy. Test sensitivity is adversely affected by decreasing lesion weight and MGD.

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
In America, primary hyperparathyroidism affects two per 1000 women older than 40 years (1). Some literature suggests that the prevalence of primary hyperparathyroidism could be as high as 1%–2% in the general population, with most cases being asymptomatic (2). Failure to diagnose and treat this disease can result in recurring renal calculi, debilitating bone demineralization, excessive calcium deposits, pronounced weakness, and reduced life expectancy (3,4). Surgery is the treatment of choice, and bilateral neck exploration has a success rate that approaches 95% (5,6). However, 80%–85% of primary hyperparathyroidism cases are caused by a solitary lesion (7), and unilateral neck exploration or minimally invasive surgery is often sufficient to detect this disease.

Preoperative imaging with technetium 99m (99mTc) sestamibi facilitates minimally invasive surgery as an alternative to bilateral neck exploration (8,9). Although the complication rate of minimally invasive surgery is 2%, which is similar to that of bilateral neck exploration, it substantially reduces cost and hospitalization time (10). In up to 15% of patients, however, more than one parathyroid gland is involved, sometimes in ectopic locations, and the sensitivity of 99mTc sestamibi is significantly lower in the detection of multigland disease (MGD) than in the detection of single-gland disease (SGD) (11). This is important because as minimally invasive surgery gains popularity, preoperative identification of patients with MGD will assume greater importance. To aid in confirming removal of all lesions, intraoperative parathyroid hormone level measurement often is used: A 50% reduction in the intraoperative parathyroid hormone level is considered to be predictive of surgical success (9,11,12). Adequacy of imaging studies with intraoperative parathyroid hormone monitoring to distinguish MGD from SGD remains controversial (8,13).

Scintigraphy with 99mTc sestamibi, which provides high image contrast and therefore is sensitive in the detection of parathyroid lesions, is based on rapid clearance of the radioactive agent from thyroid tissue, with slower clearance of activity from parathyroid lesions (15). Numerous imaging protocols are used, with some controversy regarding the optimal technique (14). At some centers, only planar imaging is performed; at others, only single photon emission computed tomography (SPECT) is performed; at still others, thyroid subtraction is performed with 99mTcO4– or iodine 123 (9). Improving the success of minimally invasive surgery for treatment of hyperparathyroidism may be accomplished more effectively by optimizing the imaging protocol rather than by incorporating radiation probe–guided information (14).

In our retrospective investigation, we sought to determine which technique would result in the most accurate detection of parathyroid lesions. We assessed the feasibility of using integrated readings to detect parathyroid lesions with early pinhole 99mTc sestamibi imaging, late pinhole 99mTc sestamibi imaging, pinhole thyroid imaging, digital image subtraction, and SPECT alone and in various combinations. We also sought to determine the effect of lesion weight on test efficacy for patients with SGD versus those with MGD, as well as to use the test to discriminate SGD from MGD on a per-patient basis. Differentiating SGD from MGD is important because minimally invasive surgery may be appropriate for the former but not the latter. Thus, results of radionuclide imaging procedures may profoundly affect surgical planning.

The purpose of our study was to retrospectively compare the accuracy of various parathyroid scintigraphy readings for SGD and MGD in patients with primary hyperparathyroidism, with histologic analysis as the reference standard.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Patient Group
Our retrospective study had institutional review board approval. The informed consent requirement was waived for our Health Insurance Portability and Accountability Act–compliant study. Data were included if the patient met the following criteria: (a) there was biochemical evidence of primary hyperparathyroidism; (b) he or she underwent early and late planar pinhole 99mTc sestamibi scintigraphy, SPECT, and pertechnetate thyroid imaging; (c) there was surgical confirmation of the final diagnosis, including disease limited to the neck; and (d) the weight of resected parathyroid lesions was available. There were 462 consecutive patients who met these criteria (Fig 1): 336 were female (mean age, 59 years ± 13 [standard deviation]; age range, 17–89 years), and 126 were male (age range, 15–85 years; mean age, 57 years ± 14).


Figure 1
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  		Figure 1: Flow diagram for patient enrollment and data analysis.

 
Imaging Protocol
We performed a 99mTc sestamibi and 99mTcO4– dual-tracer protocol by using a previously established image subtraction technique (4). Approximately 10 minutes after injection of 740–925 MBq (20–25 mCi) 99mTc sestamibi, patients underwent imaging (referred to as early imaging) performed by using a single-detector gamma camera (Argus; Philips Medical Imaging, Milpitas, Calif) with a 5-mm aperture pinhole collimator. We used a pinhole collimator because it provided the highest spatial resolution among commonly available collimators (15). Data were acquired dynamically as 128 x 128 matrices at a rate of 2 minutes per frame for five frames (10 minutes).

Immediately after early imaging was complete, SPECT was performed with a dual-detector gamma camera (Genesys; Philips Medical Imaging) or the aforementioned single-detector gamma camera equipped with identical high-spatial-resolution parallel-hole collimators. Data were acquired as 128 x 128 matrices for 64 projections at a rate of 40 seconds per projection.

After SPECT was complete and about 90 minutes after injection, pinhole imaging was repeated by using the single-detector gamma camera. Data were acquired as 128 x 128 matrices at a rate of 2 minutes per frame for 25 frames (50 minutes). For the first 10 frames, data were acquired by using only residual 99mTc sestamibi activity (referred to as late imaging). For the 11th and 12th frames, 185 MBq 99mTcO4– was injected intravenously, and imaging continued for the remainder of the examination (referred to as thyroid imaging) (4).

Image Processing
Cinematic playbacks of unprocessed early and late data were reviewed by the same observer, who interpreted all studies (M.B.T., a nuclear medicine physician with 10 years of experience) to identify and exclude frames that depicted patient motion or other artifacts likely to affect subsequent image interpretation. After frames were deleted, the remaining frames were summed to create composite early and late 99mTc sestamibi images and thyroid images. Early, late, and thyroid images were normalized to have the same total count per image. The thyroid image was digitally subtracted from the late image, and the subtraction image was thereby created (16). Tomograms were reconstructed by using filtered backprojection (transaxial Butterworth filter cutoff, 0.3; order, 8). This observer processed all data on the same day data were collected for each patient.

Surgery and Histologic Analysis
The mean interval between scintigraphy and surgery was 14 days ± 18 (range, 1–90 days). The identity of the surgeon who performed the procedures was neither an inclusion nor an exclusion criterion. Nonetheless, 323 (70%) of the 462 surgeries were performed by the same group of surgeons under the direction of endocrine surgeons (K.S.H., L.A.S.) who had more than 30 and more than 20 years of experience, respectively.

In our investigation, surgeons who performed surgery were aware of all initial scintigraphic results prior to surgery, and surgery was planned on the basis of scintigraphic results. If radionuclide findings indicated SGD and there was no reason to suspect four-gland hyperplasia—such as a history of multiple endocrine neoplasia syndrome, familial hyperparathyroidism, or lithium ingestion (17)—minimally invasive surgery was planned. Bilateral exploration was performed if scintigraphic findings indicated MGD.

Intraoperative parathyroid hormone levels were always monitored. Surgery was considered adequate if intraoperative parathyroid hormone levels decreased more than 50% from preoperative baseline levels and into the normal range. If intraoperative parathyroid hormone levels did not decrease sufficiently after removal of scintigraphically identified lesion(s), more extensive exploration was performed. The surgical report included statements made by the surgeon regarding the anatomic location of the resected glands.

All excised tissue was submitted for histologic analysis, which included determinations of whether an extracted tissue sample was parathyroid tissue or another type of tissue, of whether parathyroid tissue was diseased or normal, and of the weight of each excised tissue sample. Histologic analysis was performed by any one of four pathologists with 10–35 years of experience.

Image Interpretation
One experienced nuclear physician (M.B.T.) read all images without knowledge of surgical or histologic results. Images were graded on a five-point scale: A score of 0 indicated an image was definitely normal; a score of 1, an image was probably normal; a score of 2, an image was equivocal; a score of 3, an image was probably abnormal; and a score of 4, an image was definitely abnormal. A score of 0 meant no 99mTc sestamibi uptake outside the normal physiologic distribution of this tracer was identified, a score of 2 meant activity outside the normal physiologic distribution was questioned, and a score of 4 meant 99mTc sestamibi uptake outside the normal distribution was definitely identified.

To minimize bias, the nuclear physician performed each type of reading at least 1 month after data processing was performed. All reading sessions involved only one type of reading at a time. All reading sessions were separated from each other by at least 1 week.

Seven types of reading were performed. Initially, early, late, subtraction, and SPECT images were read separately. In each reading session, images obtained in 10–15 patients chosen at random were scored. Only one type of reading was performed in a given session. SPECT images were read with all three orthogonal views shown simultaneously, together with a cinematic playback of maximum intensity projection images (18). In a fifth reading, early and late images were reviewed together. In a sixth reading, all planar, early, late, and subtraction images were reviewed together. In a seventh reading, the observer reviewed early, late, subtraction, and SPECT images together (Fig 2). Image interpretation criteria were as follows: (a) For interpretation of early and late images separately, the observer looked for focally increased uptake outside normal 99mTc sestamibi biodistribution. (b) For interpretation of early and late images together, the observer looked for focally increased uptake outside normal 99mTc sestamibi biodistribution that persisted or increased in intensity from early to late images. (c) For interpretation of subtraction images, the observer looked for focally increased uptake. (d) For interpretation of planar images, the researcher looked for focally increased uptake outside normal 99mTc sestamibi biodistribution that persisted or increased in intensity from early to late images and was also seen on subtraction images. (e) For interpretation of SPECT images, the researcher looked for focally increased uptake outside normal 99mTc sestamibi biodistribution either posterior to the thyroid gland or in the same coronal plane as the thyroid gland but not within it. (f) For interpretation of all images, the researcher looked for focally increased uptake outside normal 99mTc sestamibi biodistribution on all images.


Figure 2A
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  		Figure 2a: Images show a 570-mg parathyroid adenoma. (a) Static anterior planar pinhole early (left), late (middle left), thyroid (middle right), and subtraction (right) images. (b) SPECT images were read with all three orthogonal views shown simultaneously for all sections and simultaneously with a cinematic playback of maximum intensity projection images (VOLUME) and shown here in the anterior projection. The three upper left images are transverse projections, the three middle left images are coronal projections, and the three lower left images are sagittal projections. The two upper right images are the transverse and coronal reference images. The numbers in the lower right corner of images indicate the section location.

 

Figure 2B
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  		Figure 2b: Images show a 570-mg parathyroid adenoma. (a) Static anterior planar pinhole early (left), late (middle left), thyroid (middle right), and subtraction (right) images. (b) SPECT images were read with all three orthogonal views shown simultaneously for all sections and simultaneously with a cinematic playback of maximum intensity projection images (VOLUME) and shown here in the anterior projection. The three upper left images are transverse projections, the three middle left images are coronal projections, and the three lower left images are sagittal projections. The two upper right images are the transverse and coronal reference images. The numbers in the lower right corner of images indicate the section location.

 
Statistical Analysis and Reference Standard
Statistical analysis was performed by using commercially available software (Medcalc, version 7.5.0.0.; Medcalc Software, Mariakerke, Belgium). Data are reported as means ± standard deviations. Normality of data distribution was determined with the Kolmogorov-Smirnov test. Frequencies and percentages were used to characterize categorical variables.

Receiver operating characteristic (ROC) curves were generated from scores assigned at visual analysis. The threshold for abnormality generated with each ROC curve for each imaging method was applied to dichotomize readings, from which sensitivity, specificity, accuracy, and positive and negative predictive values for dichotomous readings were computed. Analysis of proportions was used to compare results between all discrimination methods and to compare our results with results of previous investigations (19). ROC analyses were applied to all patients and separately to the subgroup of patients with SGD and the subgroup of patients with MGD. We used t tests to determine whether scores for any reading type were significantly higher than scores for another reading type for histologically proved positive sites and whether scores for any reading type were significantly lower than scores for another reading type for histologically proved negative sites.

Statistical analyses of readings were performed with histologic analysis as the reference standard. Scintigraphically identified lesions confirmed to be abnormal parathyroid tissue at histologic analysis were classified as true-positive findings. Scintigraphically identified lesions other than abnormal parathyroid tissue were classified as false-positive findings. Histopathologically confirmed parathyroid lesions that were not detected scintigraphically were classified as false-negative findings. For each patient, at least two scores were assigned (one for each side of the neck). If intraoperative parathyroid hormone levels decreased after resection of a lesion that was identified scintigraphically on one side of the neck, a score below the discrimination threshold for the opposite side of the neck was considered to be a true-negative finding for that method. If nonzero scores were assigned to more than one lesion location for any reading method, a score of 0 was assigned to those supposed lesion locations for the other reading methods. Otherwise, it would not have been possible to perform direct comparisons of ROC curves among methods without having the same total number of readings among all patients. Thresholds for maximum areas under the ROC curves were determined independently, specific to each image type.

To evaluate our ability to distinguish patients with MGD from those with SGD with each of the various methods, maximum scores were used for a method when more than one score was assigned to more than one lesion. To investigate the effects of weight on sensitivity, lesions were divided into two groups: Group 1 comprised lesions below the median weight, whereas group 2 comprised lesions above the median weight. Uni- and multivariate logistic regression analyses were used to determine which factor or combination of factors was most strongly associated with false-negative findings. To search for the possibility of clustering for subjects with MGD, linear regression analysis and analysis of proportions were performed to determine whether patterns of disease and patterns of readings conformed to patterns expected for random distributions or instead demonstrated correlations. For all tests, P < .05 indicated a significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Lesions and Reading Types
All acquisitions were performed between June 1, 1999, and December 31, 2002. All surgical procedures were performed sooner than 1 week after imaging. A total of 534 parathyroid lesions were removed from the 462 patients: 409 (89%) patients had one parathyroid lesion, whereas 53 (11%) patients had multiple lesions. Of these 53 patients, 38 had two lesions, 11 had three lesions, and four had four lesions. In relation to the thyroid gland, scintigraphically depicted lesions were distributed as follows: 80 (15%) were classified as left upper lesions; 32 (6%), as left middle lesions; 160 (30%), as left lower lesions; 43 (8%), as right upper lesions; 48 (9%), as right middle lesions; and 171 (32%), as right lower lesions.

Readings were not normally distributed for any method. The distribution of early readings was somewhat homogeneous (P < .001), while all other readings were clustered at the low and high ends of the scale (P < .001) (Fig 3). Scores for interpretation of all images were significantly higher than scores for interpretation of early images for histologically proved positive sites (3.5 ± 1.1 vs 2.7 ± 1.2, P < .001) and significantly lower than scores for interpretation of early images for histologically proved negative sites (0.5 ± 1.1 vs 0.7 ± 1.1, P < .001).


Figure 3A
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  		Figure 3a: Distribution of frequency of (a) early readings and (b) all readings, plotted from scores of 0 (definitely normal) to 4 (definitely abnormal). The estimated normal distribution is indicated by open squares.

 

Figure 3B
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  		Figure 3b: Distribution of frequency of (a) early readings and (b) all readings, plotted from scores of 0 (definitely normal) to 4 (definitely abnormal). The estimated normal distribution is indicated by open squares.

 
For all 534 lesions, interpretation of all images resulted in a sensitivity of 90%, a specificity of 89%, and an accuracy of 89%. This method was significantly more sensitive than any other reading method, with the exception of planar image reading. Interpretation of SPECT images was significantly less specific than all other reading types (Table 1, Fig 4).


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  		Table 1. Per-Lesion Localization for All Patients

 

Figure 4
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  		Figure 4: Per-lesion ROC curves are shown for interpretation of all images, early planar images, late planar images, digitally subtracted images (SUBT), and SPECT images. The curve for interpretation of all images had the highest area, thereby indicating the highest accuracy.

 
SGD Findings
In the 409 patients with SGD, planar image reading was significantly more sensitive and interpretation of all images together was significantly more specific than any other reading method. Interpretation of all images together was significantly more accurate (94%) than any other reading method, with the exception of interpretation of planar images (92%) (Table 2, Fig 5).


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  		Table 2. Per-Lesion Localization for Patients with SGD

 

Figure 5
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  		Figure 5: ROC curves for patients with SGD. The curve for interpretation of all images had the highest area, thereby indicating the highest accuracy. SUBT = subtraction images.

 
MGD Findings
There were no significant differences between any two reading types for patients with MGD with respect to sensitivity, specificity, accuracy, and positive and negative predictive values (Table 3). Every reading was significantly less sensitive in the detection of MGD than in the detection of SGD. Specificity was significantly lower for MGD than for SGD for interpretation of all images (73% vs 98%, P < .001) (Table 4).


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  		Table 3. Per-Lesion Localization for Patients with MGD

 

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  		Table 4. SGD versus MGD

 
Sensitivity, specificity, and accuracy for interpretation of all images in the discrimination of MGD from SGD on a per-patient basis, regardless of the number of glands involved, were 62% (33 of 53 patients), 83% (340 of 409 patients), and 81% (373 of 462 patients), respectively (Fig 6). These values were not significantly different from those for individual lesion detection in patients with MGD.


Figure 6
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  		Figure 6: ROC curves for the ability to distinguish between patients with SGD and those with MGD. The curve for interpretation of all images had the highest area, thereby indicating the highest accuracy. SUBT = subtraction images.

 
Effect of Lesion Weight on Sensitivity
Lesion weights were not normally distributed (skewness, 6.40; kurtosis, 59.5; P < .001 for both). Mean weight for all lesions was 1.14 g ± 2.29. Mean lesion weights for SGD were not significantly different from those for MGD (1.22 g ± 2.34 vs 0.84 g ± 2.99, respectively; P = .11). However, median lesion weights were 600 mg for all lesions, 620 mg for SGD, and 280 mg for MGD.

For all lesions, regardless of whether they were associated with SGD or MGD, sensitivity was significantly higher for group 2 (>600 mg) than for group 1 (≤600 mg) for all readings (Tables 5, 6). Similarly, for SGD, sensitivity was significantly higher for group 2 (>620 mg) than for group 1 (≤620 mg) for all seven readings. For MGD, there were no significant differences in sensitivity between group 2 (>280 mg) and group 1 (≤280 mg) among the seven reading types. Sensitivity of interpretation of all images for lesions that weighed more than 620 mg was significantly higher in patients with SGD than in patients with MGD (99% [205 of 211 lesions] vs 69% [41 of 59 lesions], P < .001) (Fig 7; Tables 5, 6).


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  		Table 5. Lesion Localization Accuracy for Smaller versus Larger Lesions

 

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  		Table 6. Lesion Localization Sensitivity for Smaller versus Larger Lesions

 

Figure 7A
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  		Figure 7a: Images obtained in a patient with MGD in whom a 120-mg right lower lesion was scored as 3 or greater with all viewing methods, a 120-mg right upper lesion was missed with each viewing method, and a 150-mg left upper lesion was seen on only the early image. (a) Static planar anterior pinhole early (left), late (middle left), thyroid (middle right), and subtraction (right) images. (b) SPECT images on which only the right lower lesion was detected, even though right upper and left upper lesions of similar weight were missed. The maximum intensity projection image (VOLUME) is shown in the anterior projection. The three upper left images are transverse projections, the three middle left images are coronal projections, and the three lower left images are sagittal projections. The two upper right images are the transverse and coronal reference images. The numbers in the lower right corner of images indicate the section location.

 

Figure 7B
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  		Figure 7b: Images obtained in a patient with MGD in whom a 120-mg right lower lesion was scored as 3 or greater with all viewing methods, a 120-mg right upper lesion was missed with each viewing method, and a 150-mg left upper lesion was seen on only the early image. (a) Static planar anterior pinhole early (left), late (middle left), thyroid (middle right), and subtraction (right) images. (b) SPECT images on which only the right lower lesion was detected, even though right upper and left upper lesions of similar weight were missed. The maximum intensity projection image (VOLUME) is shown in the anterior projection. The three upper left images are transverse projections, the three middle left images are coronal projections, and the three lower left images are sagittal projections. The two upper right images are the transverse and coronal reference images. The numbers in the lower right corner of images indicate the section location.

 
Analysis of False-Negative Readings
With single-variable logistic regression analysis, the factors that were the strongest predictors of false-negative findings for all readings (except early readings) were MGD and lesion weight. There was no parameter that could be used to significantly predict false-negative early readings. The method with which false-negative readings were most strongly associated with MGD was reading all images together ({chi}2 = 34.6, P < .001, 980 [97%] of 1009 cases predicted correctly), while the method with which false-negative readings were most strongly associated with lesion weight was reading late images ({chi}2 = 44.7, P < .001, 835 [83%] of 1009 cases predicted correctly). Only MGD remained a significant predictor of false-negative readings in multivariable logistic regression analysis (P < .001). Lesion location did not enable us to predict false-negative findings (P > .05).

Possibility of Clustering Effects
Our data followed a monotonically decreasing incidence of subjects with increasing numbers of lesions: Of 462 patients, 409 (89%), 38 (8%), 11 (2%), and four (1%) had one, two, three, or four affected glands, respectively. There was significant (P = .02) linear regression (r = 0.96) of natural logarithms (ln) of numbers of subjects (N) versus numbers of glands (G): ln(N) = [(–1.51 ± 0.23) · G] + (7.14 ± 0.62), so that incidence was related to gland number exponentially, indicating independence of the occurrence of affected glands. Thus, patients who had any number of affected glands were not predisposed to have an additional affected gland.

Another possibility for clustering effects was that the locations of glands could have influenced the locations of other affected glands. In examining the subgroup of patients with MGD who had two affected glands, the distribution of cases was as follows: Eight (21%) of 38 patients had both affected glands on the left side, seven (18%) had both affected glands on the right side, and 23 (61%) had affected glands on the right and left sides, similar to the ideal distribution of one (17%), one (17%), and four (66%) patients for the lateral distributions of a total of four (two right, two left) randomly affected glands.

A further clustering possibility was that readings were influenced by grouped locations of lesions. Sensitivity of reading all images together was not influenced by whether both glands were on the left side (50%, eight of 16 patients), both glands were on the right side (57%, eight of 14 patients) or glands were mixed on both sides (76%, 35 of 46 patients) (P = .13). For the 23 subjects with right- and left-sided lesions, reading of all images was incorrect for both sides in one case, correct for both sides in 12 cases, correct for only the left side in five cases, and correct for only the right side in five cases. There was no sensitivity bias as to laterality.

Thus, as there was nothing in our data to suggest that disease in one gland generated disease in another gland, that the location of one lesion influenced the likelihood of a lesion in a neighboring location, or that readings were influenced by lateral locations of lesions, no further tests were performed for clustering effects.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Numerous types of scintigraphic methods are used for preoperative parathyroid lesion localization. Combined SPECT/CT evaluations may prove advantageous in parathyroid lesion localization, but preliminary data have not enabled us to confirm this (20,21); therefore, it remains relevant to ascertain which commonly used scintigraphic method provides the highest accuracy.

In a 1998 meta-analysis of 894 parathyroid adenomas, researchers found an average sensitivity of 87% (778 of 894 findings); sensitivity ranged from 55% (26 of 47 findings) to 100% (64 of 64 findings), depending on the particular scintigraphic protocol used (11). Katz et al (22) reported on 123 patients, an unspecified number of whom underwent SPECT, for whom early and late planar images were read. These images presumably were acquired with parallel hole collimators and without thyroid imaging. Katz et al (22) found sensitivity, specificity, and accuracy values of 60% (94 of 156 findings), 89% (335 of 378 findings), and 80% (429 of 534 findings), respectively. These results are significantly less accurate than the 89% (903 of 1009 cases) accuracy of interpretation of all images (P < .001) in our series.

Lorberboym et al (19) reviewed 52 parathyroid adenomas and achieved a marginally significant improvement in sensitivity by including SPECT (96% [50 of 52 cases] with SPECT vs 79% [41 of 52 cases] without SPECT, P = .045). This is in agreement with our finding that SPECT did not significantly improve test results. Sensitivity of interpretation of all images in our study, including SPECT images, was not significantly different from the findings of Lorberboym et al (19) (90% vs 96%, P = .25).

In another investigation, researchers found evaluation of early and late planar images together with SPECT images had a sensitivity of 91% (55 of 64 cases) and a sensitivity of 87% (33 of 39 cases) for patients who underwent a second surgical procedure (23). In another investigation, in which early and late planar images were evaluated with SPECT images, neither sensitivity (94% [67 of 71 cases]) nor specificity (92% [144 of 156 cases]) of the test for 71 lesions was significantly different from our results for interpretation of all images (90% [480 of 534 cases]) (24). Sensitivity of interpretation of all images in our investigation also agrees with a report that reading SPECT images with planar images resulted in a test sensitivity of 89% (31 of 35 cases) (25).

In a recent study, researchers found that early planar imaging alone for 138 patients was less sensitive than SPECT imaging alone for 165 different patients (62% [86 of 138 patients] vs 73% [120 of 165 patients], P < .05); these results are consistent with our findings (26). However, the sensitivity of SPECT reported by Sharma et al (26) was significantly lower than that in our study, possibly because our reader viewed SPECT data in a multiplanar format with simultaneous maximum intensity projection cine images, whereas maximum intensity projection cine images were not used in the other investigation. In other studies in which 99mTc sestamibi was used without thyroid imaging, researchers found sensitivity similar to that in our study (84% [213 of 254 cases] vs 83% [443 of 534 cases], P = .80) (27). In one study in which early and late planar 99mTc sestamibi scintigraphy examinations were incorporated with combined SPECT/CT, researchers reported sensitivity similar to that for interpretation of all images in our series (92% [33 of 36 cases] vs 90% [480 of 534 cases], P = .92) (28). In another investigation involving 75 patients, researchers reported a specificity similar to that for interpretation of all images in our study (88% [132 of 150 cases] vs 89% [423 of 475 cases], P = .95) but a significantly lower sensitivity (65% [98 of 150 cases] vs 90% [480 of 534 cases], P < .001); subtraction imaging was not used (29).

In our investigation, although the results of SPECT were not significantly better than the results of planar imaging, the addition of SPECT to planar imaging yielded the highest accuracy among reading types. Although it was not part of our investigation, SPECT provides information about lesion location that is not as reliably obtained with planar imaging; thus, this modality may be useful (19,24).

The incidence of MGD in our population was 11% (53 of 462 patients), which is consistent with the reported incidence of 10%–20% (30). Sensitivity for detecting all glands in patients with MGD has varied from 28%–88%, with a mean sensitivity of 55% (472 of 858 cases) in an aggregate of 303 patients (11). This is similar to the 66% sensitivity (90 of 136 cases) that we are reporting. In our study, the paired t test revealed that mean lesion weight for SGD was not different from mean lesion weight for MGD; therefore, differences in sensitivity could not be explained by differences in gland weight. Moreover, we found that sensitivity for detecting lesions in patients with MGD was significantly lower than sensitivity for detecting lesions in patients with SGD, even when analyses were limited to glands that weighed more than 620 mg. Thus, for unknown reasons, parathyroid scintigraphy is less sensitive in the detection of MGD than in the detection of SGD (Fig 7).

Even if all lesions were not detected, it would be useful to identify those patients with MGD to facilitate appropriate surgical planning. Unfortunately, in our investigation, 99mTc sestamibi imaging was no more sensitive in the identification of patients with MGD than in the identification of the lesions themselves (62% [33 of 53 patients] vs 66% [90 of 136 lesions]).

Another factor that could adversely affect sensitivity is decreasing lesion weight. Lorberboym et al (19) reported that sensitivity was not affected by lesion weight. The mean weight of lesions in their investigation (1.14 g) was identical to that in our study; however, in our series, sensitivity was significantly higher for larger lesions than for smaller lesions. While the reason for this discordance is uncertain, a major difference is that we examined data obtained in 534 lesions, whereas Lorberboym et al investigated data obtained in only 60 lesions.

There were limitations to our investigation. The surgeons were aware of all initial scintigraphic imaging results—including SPECT findings—at the time of surgery, and this may have introduced verification bias. The improved three-dimensional localization provided by SPECT may have aided them in identifying and removing lesions that otherwise may have been more difficult to find. This potential advantage of SPECT could decrease the duration of surgery and possibly improve the success rate, although our study was not designed to assess these effects.

It is possible that some of the patients were taking thyroid or antithyroid medications at the time of imaging, which could have resulted in suboptimal thyroid images. This could account for the fact that there was little activity seen on four of the thyroid images in our study. In spite of this, lesions were identified successfully on subtraction images in all four of these patients. As these four patients represented less than 1% of our study population, data are insufficient to address this issue further.

The same experienced observer performed all seven types of readings. Thus, it is possible that some recall bias may have been involved despite our attempts to preclude this by separating each reading session by more than a week. Nonetheless, there is a considerable methodologic advantage in having all readings performed by one expert, as this promotes continuity of observations.

Because of the large number of patients with MGD, there was the potential for clustering effects. It is reasonable to hypothesize that the presence of one affected gland in a subject could somehow generate disease in another gland, analogous to the situation in which clustering effects need to be corrected in imaging experiments involving lymph glands, which are connected by lymph channels, so that metastasis in one gland predisposes positive findings in additional glands. However, our data are consistent with independence of affected glands, independence of locations of lesions, and independence of readings with lesion locations.

In conclusion, reviewing early, late, and subtraction pinhole images and SPECT images together maximizes parathyroid lesion detection accuracy. Test sensitivity is lower for MGD than for SGD and is adversely affected by decreasing lesion weight.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: MGD = multigland disease • ROC = receiver operating characteristic • SGD = single-gland disease

Author contributions: Guarantors of integrity of entire study, K.J.N., C.J.P.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, K.J.N.; clinical studies, G.G.T., J.N.R., B.D.K., K.S.H., L.A.S.; statistical analysis, K.J.N.; and manuscript editing, all authors

Authors stated no financial relationship to disclose.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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M. B. Tomas, P. V. Pugliese, G. G. Tronco, C. Love, C. J. Palestro, and K. J. Nichols
Pinhole Versus Parallel-Hole Collimators for Parathyroid Imaging: An Intraindividual Comparison
J. Nucl. Med. Technol., December 1, 2008; 36(4): 189 - 194.
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