| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
BRIEF REPORT |
Divisions of Endocrinology (F.M.S., P.H.Z., E.K.T., R.Y.A.d.C., M.A.A.P.) and Nuclear Medicine (J.J.C., J.S., L.K.C., M.I., M.C.P.G., J.C.M.), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, CEP 05403-000 São Paulo, Brazil; and Department of Preventive Medicine (J.E.-N.), Faculdade de Medicina da Universidade de São Paulo, CEP 01246-903 São Paulo, Brazil
Address all correspondence and requests for reprints to: Maria Adelaide Albergaria Pereira, M.D., Division of Endocrinology and Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Avenida Dr Enéas de Carvalho Aguiar, 255, 7th floor, CEP 05403-000 São Paulo (SP), Brazil.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Methods: Forty-two consecutive patients with thyroid nodules with indeterminate cytological results participated in this study. Abnormal 18F-FDG PET uptake was assessed visually and by measuring the maximum standardized uptake value (SUVmax) in thyroid topography. All these results were compared with the final pathological results.
Results: The presence of focal uptake correlated with a greater risk of malignancy (P = 0.018). All 11 malignant nodules had focal uptake (sensitivity of 100%). Of the 31 patients with benign nodules, there were 19 with positive uptake (specificity of 38.7%). The pre-PET probability of cancer was 26.2% (11 of 42), and this probability increased to 36.7% after PET for those patients whose exam showed focal uptake (11 of 30). The preoperative use of 18F-FDG PET would result in a significant reduction (39%, 12 of 31) in the number of thyroidectomies performed in patients with benign lesions. SUVmax could not improve this degree of accuracy. There was no correlation between thyroid nodule size and SUVmax value (P = 0.96). Patients with carcinomas were younger than patients with benign lesions (P = 0.048). There was no other clinical, laboratory, or ultrasonographic variable related to malignancy.
Conclusions: 18F-FDG PET provides high sensitivity to malignant lesions and may be a potentially useful tool in the evaluation of thyroid nodules with indeterminate cytological findings. For these nodules the number of unnecessary thyroidectomies in a hypothetical algorithm using 18F-FDG PET would be reduced by 39%.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In a university hospital in Brazil, 42 patients (38 female) with indeterminate cytological results underwent hemithyroidectomy or total thyroidectomy and had their 18F-FDG PET findings compared with their histopathological results (Table 1
). Incidentally found papillary microcarcinomas were not included in the analysis. Exclusion criteria were uncontrolled diabetes mellitus, other known malignancies, pregnancy, and abnormal TSH levels. The study was approved by the Ethical Board of the Clinical Hospital of São Paulo University, and written informed consent was obtained from all patients.
|
The mean age was 45.3 ± 16.3 yr (range 18–80 yr). All patients underwent thyroid ultrasonography, 50% of them having just one nodule. The nodules had a mean maximum diameter in histopathological exam of 3.0 ± 1.8 cm (range 0.4–8.5 cm). The interval between fine-needle aspiration biopsy and 18F-FDG PET was at least 17 d.
18F-FDG PET imaging
All patients fasted for at least 6 h. Their fasting glucose level was less than 160 mg/dl. PET imaging acquisition started after a 60-min uptake period after iv administration of 296–444 MBq (8–12 mCi) of 18F-FDG. The patients were instructed to rest comfortably between injection and scanning. Images in two dimensions were captured by a GE Advance PET scanner (General Electric Medical Systems Advance, Milwaukee, WI). High-resolution images were taken with attenuation correction in two or three bed positions, from the base of the skull to the middle thorax.
PET images were displayed as projections and in transaxial, coronal, and sagittal tomographic sections. Visual inspection of the images was performed independently by two experienced observers. These observers were not aware of the location of the nodule, ultrasonography, and histopathological examination. 18F-FDG PET-positive results were defined as the presence of any focal 18F-FDG uptake in thyroid topography, standing out from the thyroid bed background. There was 100% agreement between the two observers who analyzed these results.
Regions of interest (ROIs) were selected for quantification of 18F-FDG uptake from the visible lesions. When the thyroid nodule could not be seen, large ROIs that included the thyroid itself were selected. Maximum standard uptake values (SUVmax) were calculated.
Statistical analysis
A computer program (SPSS for Windows, version 13.0; SPSS Inc., Chicago, IL) was used for two-tailed statistical analysis. The level of significance was set at 0.05. Correlations were determined using the Spearman test. Analyses were also carried out using the Mann-Whitney test, independent samples t test, and Fisher’s exact test, where appropriate, as shown in Results.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
). Of the 11 patients with well-differentiated thyroid carcinomas, eight had papillary, two had follicular, and one had a well-differentiated thyroid carcinoma not otherwise specified. The presence of focal thyroid uptake was associated with increased risk of malignancy (Fisher’s exact test, P = 0.018). All malignant nodules had focal uptake (sensitivity of 100%). Of the 31 patients with benign nodules, 12 (39%) had negative uptake (Table 2). The pre-PET probability of cancer of 26% (11 of 42) rose to 37% (11 of 30) after PET. SUVmax levels were not significantly greater in malignant than benign thyroid nodules (Mann-Whitney test, P = 0.069) and could not improve the accuracy of 18F-FDG PET beyond that obtained by the analysis of focal uptake presence. All nodules without 18F-FDG focal uptake had a level of SUVmax of less than 3.7, except one patient with a diffuse thyroid 18F-FDG uptake, but no focal uptake, that had a level of SUVmax of 3.9.
|
Four patients with benign thyroid lesions and positive 18F-FDG PET had incidental papillary microcarcinomas in the same lobe (maximum diameters of 0.5, 0.5, 0.2, and 0.1 cm). All these cases were considered as false-positive results by the analysis. Unexpected additional findings were found in two of the 42 patients (4.8%): absence of 18F-FDG uptake in one lobe of the cerebellum (a cystic neoplasia in computed tomography) in patient number 11 (Table 1) and focal uptake in mediastinum in patient number 1 (the thorax computed tomography with iv contrast was normal).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
). From more than 100 patients with malignant thyroid nodules evaluated in the literature, the only reported false-negative results are one case in a study that did not use a modern PET camera (9) and seven nodules from the study by Mitchell et al. (12), five being incidental microcarcinomas, one a papillary carcinoma measuring 3.5 cm x 2.6 cm in diameter (SUVmax of 2.3), and one a renal carcinoma metastatic to thyroid (SUVmax of 2.3). This study, done by PET-computed tomography, was the only one that included incidental microcarcinomas in the analysis. Of note, if the diagnostic criteria adopted by Mitchell et al. were to be changed from an SUVmax greater than 5.0 to an SUVmax greater than 0 (implying some degree of nodule uptake), then the two major carcinomas would have to be considered true-positive results, although the specificity among thyroid nodules with indeterminate cytological results would be considerably reduced (Table 2).
In our study, 39% of the patients with benign thyroid nodules had no focal 18F-FDG uptake. Other significant studies in literature had variable results (Table 2). In studies by Kresnik et al. (2) and De Geus-Oei et al. (1), 56 and 66%, respectively, of the patients with benign nodules had no focal FDG uptake when 18F-FDG PET was used in the preoperative evaluation of thyroid nodules with indeterminate cytological results. It should be emphasized, however, that in the study by Kresnik et al. (2), patients were from an iodine-poor area, and that in the study from De Geus-Oei (1), only patients with palpable thyroid nodules were selected and that their size and ultrasonographic characteristics were not reported. On the other hand, in the study by Kim et al. (3), all benign thyroid nodules were 18F-FDG avid and the only characteristic associated with SUVmax value was nodule size. In our study, however, the maximum nodule diameter was not related to SUVmax value or focal uptake presence in the thyroid bed. Neither was any relationship apparent when the subgroup of benign and malignant thyroid nodules was analyzed.
The reasons for these differences are unclear and may be related to a different pattern of gene expression between benign nodules in different regions of the world because malignant nodules are consistently FDG avid in all studies. Variations in technique and selection of patients could also be a reason. Prior studies reported increased glucose transporter-1 protein immunostaining (13) and gene expression (14) in thyroid cancer in relation to benign lesions, supporting the view that 18F-FDG PET may be a useful tool when evaluating thyroid nodules.
Our data also support the view introduced by De Geus-Oei (1) that focal uptake presence should be the cornerstone in any analysis of 18F-FDG PET used in the evaluation of thyroid nodules, as shown in Table 2, although the specificity of our findings in our study was only 39%. The value of SUVmax depends on acquisition, reconstruction and ROI parameters and the particular PET scanner used for the exam (1, 15). This introduces many factors that may lead to possible bias in the SUVmax measurement making it difficult to apply in different centers. This may explain the different cutoffs of SUV found in different studies (1, 2, 12).
The finding in our study of a patient with negative thyroid focal uptake in a benign lesion but with an SUVmax of 3.9 (
3.7) was probably due to the coexistence of lymphocytic thyroiditis resulting in diffuse thyroid uptake in 18F-FDG PET (16). However, even in patients in whom thyroiditis coexists, it may be appropriate to recommend 18F-FDG PET because nine of the 11 patients with lymphocytic thyroiditis in histopathological examinations did not show an alteration in 18F-FDG PET sufficiently significant to impair the accuracy of this exam.
Finally, papillary carcinoma was the malignancy most frequently diagnosed in our study. This may be related to the elevated daily ingestion of iodine that is common in Brazil (17, 18), which could be responsible for substantially lowering the incidence of follicular as opposed to papillary thyroid carcinomas (19, 20).
In conclusion, 18F-FDG PET provides a high negative predictive value in the preoperative evaluation of thyroid malignancy in nodules whose cytological result is indeterminate but a positive predictive rate of only 37%. If we consider high sensitivity to be the most important characteristic of a test designed to determine which patients with indeterminate cytological findings should undergo surgery, then 18F-FDG PET can be a useful tool in the evaluation of these nodules. For these nodules the number of unnecessary hemithyroidectomies in a hypothetical algorithm using 18F-FDG PET would be reduced by 39%.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
First Published Online August 7, 2007
Abbreviations: 18F-FDG, 18F-fluorodeoxyglucose; PET, positron emission tomography; ROI, region of interest; SUVmax, maximum standard uptake value.
Received May 10, 2007.
Accepted July 31, 2007.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
