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Vrije Universiteit Medical Centre, Departments of Nuclear Medicine (L.H., O.S.H., G.J.J.T.), Clinical Epidemiology and Biostatistics (L.H., O.S.H., M.B., M.W.v.T.), Endocrinology (P.L.), and Institute for Research in Extramural Medicine (W.D.), 1007 MB Amsterdam, The Netherlands
Address all correspondence and requests for reprints to: Lotty Hooft, M.Sc., Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail l.hooft{at}azvu.nl
Abstract
Positron emission tomography with 18F-fluorodeoxyglucose is
a relatively new nuclear imaging technique in oncology. We conducted a
systematic review to determine the diagnostic accuracy of
18F-fluorodeoxyglucose positron emission tomography in patients
suspected of recurrent papillary or follicular thyroid carcinoma.
Two reviewers independently selected, extracted, and assessed data from
relevant literature found in computerized databases and by reference
tracking. Prospective and retrospective studies with 10 human subjects,
or more, that evaluated the accuracy of ring positron emission
tomography, using 18F-fluorodeoxyglucose in follicular and papillary
thyroid cancer, were included. Studies on 18F-fluorodeoxyglucose
imaging using 
cameras, reviews, case reports, editorials, letters,
and comments were excluded. The methodological quality was assessed by
applying the criteria for diagnostic tests recommended by the Cochrane
Methods Group on Screening and Diagnostic Tests. A rating system was
used for qualitative analysis consisting of four levels of evidence
(1 = highest level; 4 = lowest level). Fourteen studies met
the inclusion criteria. All studies claimed a positive role for
positron emission tomography but, at evidence levels 3 or 4, precluding
quantitative analysis. Methodological problems included poor validity
of reference tests and a lack of blinding of test performance and
interpretation. The reviewed material was heterogeneous with respect to
patient variation and validation methodology. The most consistent data
were found on the ability of 18F-fluorodeoxyglucose positron emission
tomography to provide an anatomical substrate in patients with elevated
serum Tg and negative iodine-131 scans.
In conclusion, the results seem to support the potential of 18F-fluorodeoxyglucose positron emission tomography to identify and localize foci of recurrent cancer in the latter patient subset. However, implementation of positron emission tomography in a routine diagnostic algorithm requires additional evidence.
SINCE MOST PATIENTS with papillary or follicular thyroid cancer present at an early stage, surgical therapy is highly effective, and the 5-yr survival rate exceeds 85% (1). However, tumor recurrence can be associated with considerable morbidity (and even mortality). The aim of follow-up after primary surgery is the timely detection of local recurrence, lymphatic or distant relapse, assuming that early discovery of recurrences will improve the outcome after treatment (2). Besides physical examination, there is consensus about the use of serum Tg. Patients with detectable Tg levels need further tests to identify the anatomical substrate of recurrent disease. Usually, iodine-131 whole-body scintigraphy (131I WBS) will be the initial diagnostic procedure. However, if the findings are equivocal, many different diagnostic tests are available, including ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI), and scintigraphy using thallium-201 (201Tl), technetium-99m (99mTc)-MIBI or -tetrofosmin, and indium-111(111In)-octreotide. Despite the availability of all these radiological and nuclear medicine procedures, the clinical work-up of patients can be difficult because of negative, equivocal, and/or conflicting test results.
Positron emission tomography (PET), using 18F-fluorodeoxyglucose (FDG), is a relatively new and promising imaging modality to screen almost the entire body for neoplastic disease. It combines excellent scanner performance [sensitivity (Se), resolution] and a radioactive tracer with a favorable biodistribution and high affinity for cancer cells. At present, there is no consensus on the optimal place of FDG PET in treating patients with thyroid cancer.
The objective of this systematic review was to summarize the evidence on the diagnostic accuracy of dedicated (ring) FDG PET , focusing on its utility in two potential applications in the follow-up of patients with papillary and follicular thyroid carcinoma: 1) to identify anatomical substrates in patients with elevated serum markers (or other suspicion of relapse) after negative 131I WBS; and 2) to complete the work-up in patients with known neoplastic foci (e.g. before planned local therapy).
Materials and Methods
Literature search
We conducted a computer-aided search of the Medline, Embase, and Cancerlit databases up to October 2000 without any language restriction. A modified version of a recently developed search strategy identified primary studies on diagnostic tests (3). This strategy ran in Medline and Embase in conjunction with a specific search for PET, FDG, and thyroid cancer (4). To identify studies on thyroid cancer, we used the MeSH-terms "thyroid gland" or "thyroid diseases" or "thyroid neoplasms" or "thyroglobulin" in Medline and "thyroid gland" or "thyroid disease" or "thyroid tumor" or "adenoma" in Embase, and the text-words "thyroid$" or "thyroglobulin$" or "papillar$" or "follicular$" in both. In addition, we screened the Cochrane library 1999, issue 2, using the search terms "thyroid cancer", "thyroid carcinoma", and "positron emission tomography". We also checked references given in relevant identified publications and reviews.
Study selection
Two unblinded reviewers (O.S.H. and L.H.) independently selected
the studies. Differences were resolved by consensus. They applied the
inclusion and exclusion criteria to select the relevant studies from
the titles, abstracts, and keywords of the references retrieved by the
literature search. Studies were included if they were prospective or
retrospective, with 10 human subjects or more, and evaluated the
accuracy of dedicated (ring) PET using FDG in patients suspected of
recurrent follicular and papillary thyroid cancer. Studies on FDG
imaging using cameras, reviews, case reports, editorials, letters,
and comments were excluded.
Methodological quality assessment
The same two unblinded reviewers independently assessed the methodological quality of the included studies using the criteria list for diagnostic tests recommended by the Cochrane Methods Group on Screening and Diagnostic Tests (5). The list consists of criteria for internal validity of studies (A-items), described below, and criteria relevant to the applicability of the study results or external validity (B- and C-items). A complete criteria list is available, on request, by contacting the first author.
Eight internal-validity criteria were considered.
Reference standard (criterion no. 1). Diagnostic accuracy is best determined by comparing test results with an appropriate so-called gold reference standard. To correct for potential systematic errors of measurements, it is essential that each patient (criterion no. 2) is submitted to the reference test, applied in a standardized manner (criterion no. 3). Ideally, histology and extended follow-up (e.g. 3 yr, given the often slow progression of thyroid cancer) would be the reference tests of choice. However, this is unrealistic in most clinical settings, especially at the level of individual lesions in patients with known neoplastic foci elsewhere. Therefore, we decided to accept the following reference tests to identify and localize recurrent cancer: 1) histology/cytology; 2) focal 131I-uptake; 3) pathognomonic bone scan or MRI for bone metastases; 4) CT/MRI for brain metastases; and 5) progression of radiologically documented lesions suspect for malignancy. With intrapulmonary lesions unconfirmed by histology or 131I, and of which no radiological follow-up was reported, congruence of PET and CT was also classified as recurrent disease. With PET-CT discrepancies, follow-up was needed. We regarded US, CT, or MRI of the neck as invalid without tissue confirmation, given that fine-needle aspiration is feasible. The minimally required duration of follow-up was 12 months.
Independence of interpretation (criterion no. 4). This criterion refers to blinding of interpretations of the index test(s) and reference test(s) to avoid review bias. It is likely that the interpretation of an index test could be influenced by knowledge of the reference test results (or vice versa). We considered this requirement fulfilled in the case of pathology examination.
Uniform application of reference test (criterion no. 5). This criterion helps to avoid work-up bias. When the results of a diagnostic test influence whether patients undergo confirmation by the reference test, the properties of a diagnostic test will be distorted.
Comparison of different tests in a valid design (criterion no. 6). When FDG PET was compared with other imaging procedures, we considered the design valid when all (index) tests were performed and interpreted, independently of each other, on each patient. It is likely that the interpretation of an index test can be influenced by knowledge of the other index test results.
Study design (criterion no. 7). Each study was characterized as prospective or retrospective.
Missing data (criterion no. 8). It is essential to include a description regarding missing data, because the patients who are unavailable may have very different outcomes from those available for assessment. This is a threat for the validity of the study results.
Not all eight items reflecting the internal validity were used to assess the methodological quality of these studies. Comparison of different tests in a valid design (criterion no. 6) is obviously only relevant in studies where FDG PET was compared with other imaging tests, such as 99mTc-MIBI.
If the original paper did not provide enough data on one or more of the A-, B-, and C-items, we requested additional information from the corresponding authors.
Data extraction
Two reviewers (O.S.H. and L.H.) independently extracted the following data:
Appropriate clinical setting and patient spectrum. The value of a diagnostic test is established only in a study that closely resembles clinical practice. An appropriate spectrum should represent patients that would normally be tested for the target disorder. Therefore, the description of the study population is essential. The extracted data included age distribution, sex distribution, number of patients, tumor type, tumor stage, and (methods and) levels of serum Tg measurements.
Description of imaging procedure. This criterion required that the imaging protocol be described in sufficient detail to enable its application in one’s own practice. For FDG PET, this was fulfilled if the following items were discussed: 1) the patient preparation (fasting period); 2) timing and duration of acquisition; 3) dose FDG (megabecquerels); 4) attenuation correction; and 5) scanned trajectory.
Analysis
We initially tried to carry out a quantitative metaanalysis; however, most studies did not supply enough valid data to enable calculation of Se and specificity (Sp) to allow statistical pooling. Furthermore, the spectrum of patients was too heterogeneous. Consequently, we analyzed three subgroups of patients: 1) with negative 131I WBS and raised serum markers, or 2) other clinical suspicion of relapse; and 3) with known neoplastic foci to complete the work-up. We extracted data on the proportion of patients with positive and negative PET scans in these groups, and we classified findings according to the defined set of criteria, i.e. true positive if confirmed by one of the valid reference tests (defined in the Methodological Quality Assessment paragraph), and false positive if confirmed by histopathology. Patients with unconfirmed PET lesions (within an FU of 12 months) and raised serum markers (indicative of recurrence) were classified as unclear (i.e. the PET finding was not clinically useful). Patients with discrepancy of PET and reference test (within an FU of 12 months) and low serum markers were classified as false positive. We classified negative PET findings as being true if confirmed by histopathology. Patients with congruent negative findings on PET and one of the valid reference tests (criterion no. 3, reference tests 2–5 above), combined with an FU of 12 months, were also classified as true negative. Patients with discrepancy of PET and one of the valid reference tests were classified as false negative. In all other, PET findings were classified as unclear.
In a qualitative analysis, the conclusion on the value of FDG PET in
thyroid carcinoma was based on the strength of scientific evidence.
Levels of evidence (6) were generated from the analytic
framework adapted from the Center for Evidence-Based Medicine of the
National Health Service Research and Development in Oxford (see Table 1
).
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Literature search and study selection
The Medline-search identified 86; and the Embase-search, 97 publications. Because 65 studies were found in both databases and Embase identified one article twice, the total number of studies was 117. No additional studies were obtained through Cancerlit, the Cochrane library, or reference tracking. On the basis of title, abstract, and keywords, 97 studies were excluded. A full review of the remaining 20 studies resulted in the exclusion of another 6, because these articles were (partial) duplications (7, 8, 9, 10, 11, 12). In these cases, we used the publication with the largest study population. However, the 1999 Grünwald et al. study (12) was excluded because its multicenter and retrospective nature entailed that many specific details were lacking, which were available in the original articles (13, 14, 15 and personal communication) and highly relevant for a systematic review. The final review comprised 14 studies (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26). The study of Wang et al. (27) focused on the prognostic value of FDG PET, which was beyond the scope of this review and was therefore not included.
Methodological quality assessment
The reviewers disagreed on 60 out of 398 scores (15%; 14 studies), and on 30 out of 166 internal validity scores (18%). All disagreements were resolved through consensus. Thirty-one scores (14A, 10B, and 7C; 8%) were corrected after applying the additional information obtained through personal communication: 6 of the 14 corresponding authors responded (13, 15, 16, 17, 18). These data did not affect final assessment of the methodological quality of the studies.
Most studies lacked information on one or more internal validity items.
In particular, only small groups of patients were submitted to valid
reference test(s); the results in patients with negative FDG PET were
often not confirmed in a valid way; most interpretations of FDG PET and
the reference test(s) were probably not performed independently of each
other; the selection of patients for the assessment by the reference
test was often not independent of the FDG PET results; and in most
studies, no description regarding missing data were included (Table 2).
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Study characteristics
The 14 reviewed articles were published between 1996 and 2000 (7
had a prospective study design; 5 studies were retrospective; and for
2, the design was unclear) (Table 3). Ten
studies described the inclusion criteria used for selection of the
study population, and only 3 described the exclusion criteria. Most
studies did not describe whether exclusion of patients was based on
indeterminate PET results. Two studies were incomplete regarding both
criteria (21, 22). Only the Dietlein et al.
article (14) mentioned that it included patients
consecutively presenting in the clinical department. On request, 5
other authors stated that they had done so (Table 3).
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Sample sizes ranged from 10–58 subjects; and the mean age, from
41–67. Information on age and/or gender was missing in 4 of the 12
studies (13, 16, 18, 24). Six studies provided
baseline data on the initial tumor stage of the patients (14, 15, 16, 18, 21, 23), revealing that the majority concerned patients
at high risk of recurrence (Table 3
). Seven of the 14 studies properly
described previous test information known to the physician
(15, 16, 17, 18, 19, 23, 24). Data on comorbid conditions and the
period between first diagnosis and PET was only described in 3 studies
(14, 22, 23).
The ability of FDG PET to identify and localize recurrent disease
The results of the studies, as reported, are summarized in Table 3, with Se and Sp ranging from 70–95% and 77–100%, respectively.
However, these data only were available from seven studies. Indications
for PET scanning and studied patient spectra were very heterogeneous
(Tables 3 and 4). As stated, we assessed
the utility of FDG PET at three positions in the clinical
work-up. FDG-PET in negative 131I
WBS and elevated serum markers. All 14 reviewed studies provided
data on FDG PET in patients with negative 131I
WBS. According to their inclusion criteria, 6 specifically addressed
the value of PET in patients with negative 131I
WBS (15, 19, 22, 23, 25, 26). Three of these studies
(15, 25, 26) focused on patients with elevated serum
markers, i.e. Tg or Tg-antibodies. Of the provided Tg
values, 50% exceeded 40 ng/ml, and 30% were higher than 100 ng/ml.
However, many different Tg kits were used, and Tg data were provided
with and/or without TSH stimulation.
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). According
to our criteria, adequate validation on patient level was obtained in
only 50% (68/131) of the cases, 90% of which proved to be recurrent
disease. As far as we could extract from the data, histopathological
confirmation was obtained in 51–57 of these 68 cases (Table 5). On a
patient basis, PET missed confirmed recurrences (according to our
criteria) in 6 patients, with histopathological documentation in 3. A
lesion-based (staging) accuracy could not be deduced from these studies
because of methodological heterogeneity and limitations.
FDG-PET in negative 131I WBS without
elevated serum markers. The reported yield of PET in cases with
negative 131I WBS and without elevated serum
markers is summarized in Table 6.
Usually, the clinical indication for PET in this group was not
described in detail but appeared to comprise patients with clinical
suspicion of relapse, e.g. equivocal imaging tests. PET
scans were negative in 34 of 50 patients (68%). Using follow-up (1 yr)
and histology as reference tests, this was a false negative result in
one case. False positivity, as documented by histopathology,
seemed to be more frequent than in the group with raised serum markers.
However, the prevalence of disease in the latter probably was much
higher. Even though lesion-based accuracy could not be deduced from
these studies, the usefulness of FDG PET may vary from organ to organ.
Some authors suggest that the technique would mainly be beneficial in
patients with suspected regional lymph node metastases (14, 22); others suggest a higher detection limit (worse detection)
of PET in the lungs (14). FDG PET
in patients with known neoplastic foci. Six of the 14 reviewed
studies seemed to contain data on FDG PET in patients with otherwise
established recurrent disease (Table 4). According to the inclusion
criteria, only 1 study specifically addressed this patient group
(17). In none of these articles was it clearly defined for
which clinical problems, if any, the PET scan had been performed. Some
studies may have been performed to explore the relationship between
131I and FDG uptake (the flip-flop phenomenon,
13). The data usually allowed comparison only between the
results of 131I WBS and FDG PET on a patient
level. Analysis on a lesion level was largely anecdotal
(16). We found that it was even difficult to identify
patients in whom positive 131I findings
represented an established recurrence, rather than uptake in benign
remnant thyroid tissue (21).
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131I dose at WBS. As shown in Tables 5 and 6, the
conditions of 131I scanning were not consistent
in different studies. Especially in patients with elevated tumor
markers without known tumor substrates, this may affect the results.
Low-dose 131I scanning (2–5.5 mCi in these
studies) may fail to disclose 131I-accumulating
tumor deposits; Pacini et al. (1987) reported that high-dose
131I may reveal metastases in 12% of patients
with a negative low-dose scan (28). In the presently
reviewed studies, Wang et al. (23) reported
this discrepancy in 7/13 patients subjected to high-dose
131I scanning after a negative diagnostic scan.
The present data do not allow quantification of this effect, however.
In the patients assessed with high-dose 131I WBS
and elevated serum markers, 79% (45/57) of the PET scans provided at
least 1 site suspect of tumor. TSH levels.FDG uptake, and therefore detection, might depend on serum TSH
levels. It is unclear whether discrepant results [i.e.
studies showing positive relation between TSH levels and FDG uptake
(29, 30) vs. those showing similar detection
rate under TSH stimulation and TSH suppression (13, 17, 18)] relate to methodological differences or to biological
variation. Of the studies in this review, none performed a head-to-head
evaluation of this potential effect, and only one (23)
supplied outcome measures stratified by TSH level with no apparent
differences. It was unclear how patients had been selected for either
modality, however.
FDG PET compared with other imaging procedures
Only 3 studies (16, 18, 21) compared FDG PET with other imaging procedures. Grünwald et al. (18) compared FDG PET with 99mTc-Sestamibi (MIBI) and reported superior outcomes of FDG PET for the detection of recurrent thyroid cancer. Regarding individual tumor sites, FDG PET and MIBI had congruent positive results in 65%, FDG-positive/MIBI-negative in 25%, and FDG-negative/MIBI-positive in 10%. Lind et al. (21) compared FDG PET with TETRO and concluded that FDG PET gives better image quality and demonstrates more lesions, compared with 99mTc-Tetrofosmin (135 FDG positive vs. 61 TETRO positive lesions). However, it was not possible to determine overall accuracy of FDG PET and TETRO in this group of patients because the FDG/TETRO-positive and 131I-negative lesions (61 FDG positive vs. 20 TETRO positive lesions) were not verified. Brandt-Mainz et al. (16) investigated the 99mTc-Furifosmin and found an Se of 33% (Sp of 100%) on a patient-by-patient level, and of 34% (Sp of 100%) on a lesion-by-lesion level. For FDG PET, an Se of 72% (Sp of 100%) was found on a patient-by-patient basis, and of 91% (Sp of 100%) on a lesion-by-lesion basis.
Qualitative analysis
Two of the 14 studies that evaluated the diagnostic accuracy of
FDG PET for the detection of recurrent disease were considered of level
3 evidence (14, 22), because both the PET-scan and the
reference tests were not performed in all patients (Tables 2 and 3).
The other 12 studies provided level 4 evidence (13, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26), which was scored when the PET-scan and the reference
tests were not performed and interpreted independently and blindly from
each other, and irrespectively of the spectrum or the number of
patients that received both the PET-scan and reference test(s). In most
studies, only the positive PET findings were confirmed. To evaluate the
patients with a negative PET or a negative reference test, a relevant
duration of a follow-up period is required. Follow-up was performed in
7 studies, but only a small percentage was followed up, except for 2
studies in which 58% (24) and 76% (22) were
evaluated.
Discussion
This systematic review included 14 studies that assessed the value of the diagnostic imaging technique FDG PET in papillary and follicular thyroid carcinoma. FDG PET is clearly able to solve clinical problems in selected patients with (suspected) recurrent thyroid cancer; and the studies showed promising results in this setting but cannot be viewed with confidence, because of methodological problems. These problems are considerable, given that 50% of the criteria for internal validity were not met.
Studies investigating the diagnostic accuracy of FDG PET, or any other imaging technique, in thyroid cancer encounter specific problems. Most studies have small sample sizes, compatible with the low incidence of the disease. The validity of reference tests is a difficult issue, especially in defining the true extent of disease. From a scientific point of view, histopathological data and prolonged follow-up, preferably without interventions, would be the best combination. This is especially problematic if lesion-by-lesion analysis is necessary in patients with known recurrent disease. Further, in often slow growing tumors like thyroid cancer, prolonged follow-up, e.g. 3 yr, would be necessary. These requirements are not compatible with the clinical context in which these studies were clearly conducted; and, as a result, a variety of validation tests were used. For the purpose of this review, we reasoned that histopathological proof of lesions in the neck area should be clinically feasible. This is not the case for many pulmonary lesions, because without follow-up, this usually requires surgical evaluation. We therefore accepted congruence of CT and PET as confirmed disease, but we also performed an Se analysis. This revealed that the assumption did not dramatically alter the conclusion that PET seemed to have been helpful in many patients with negative 131 I scans and raised serum markers.
This yield of PET, i.e. in terms of localizing recurrent disease in patients with elevated serum markers and negative findings at 131I WBS, is reported to be very high. These data apply to the included spectrum of patients, i.e. with (very) high serum markers (indicative of recurrent disease). Because serum marker levels and tumor load are positively related, these findings cannot be extrapolated to situations with lower serum markers. In some studies, it is also unclear whether data refer to consecutive patients presenting in a typical clinical setting (rather than in the PET center) and in what time frame various tests have been carried out. As a result of these factors, Sp is probably overestimated, and the number of patients needed to have a PET-scan to localize recurrence may be underestimated.
Apart from showing the presence of disease, PET may also play a role in determining the actual tumor spread, with potential important implications for the choice of therapy. This includes patients with and without known neoplastic foci (before PET). In TNM staging, the entire body is subject of investigation. Depending on the predilection sites of the cancer at hand, sequences of radiological methods (plain X-rays, bone scintigraphy, US, CT, MRI) focusing on body parts (like neck, lung, bone in thyroid cancer) are necessary to define the extent of disease. Consensus on the battery of tests (including methods and duration of follow-up) to validate findings of whole-body techniques like PET is urgently needed. On the other hand, standardizing conventional work-up would simplify the assessment of the additional value of PET. Data on the performance of FDG PET, relative to other diagnostic methods in specific body areas, are largely anecdotal, and they merely suggest that the detection of lung metastases is not perfect (14), as has been found in other malignancies.
Apart from clinical consensus, basic PET acquisition parameters also need to be clarified: should FDG PET be performed during thyroxin withdrawal or not? The present data are confusing. This lack of knowledge also impairs the understanding of the inverse relation between FDG and 131I (so-called flipflop phenomenon) reported in 31–74% of the patients (13, 14, 18). Again, it is unclear whether these differences relate to biological or methodological issues (e.g. variability of 131I WBS dose). Finally, if the claims are true that FDG uptake has prognostic relevance (27), this still needs to be translated into the clinical approach of these patients. Mixed patterns of 131I and FDG uptake within patients, and even within metastases, have been documented (13). To date, it is not evident what the impact of altered therapy decisions would be on patient outcomes in curative and palliative settings.
Instead of focusing only on Se and Sp estimates, one might investigate whether application of FDG PET would improve patient outcomes, e.g. reduce the number of incorrect clinical decisions (compared with a defined conventional strategy). Because mortality is not the only issue in thyroid cancer, outcome measures should also be defined in terms of patient burden: inconclusive or negative diagnostics tests, invasive investigations, ineffective 131I-therapies, thyroxin withdrawal, negative surgical explorations, recurrence outside the field of local therapy within a specified time lapse, and quality of life. Then, follow-up duration and methodology should be specified. In the present evaluation, we considered 12 months as a minimum period of follow-up. We reasoned that unconfirmed lesions within that time frame are unlikely to affect clinical management, and that recurrent disease within that period after presumed radical local therapy would generally be estimated as a poor result of initial staging. Such studies may have to focus on clinical situations where actual staging (establishing the extent of disease) is crucial for therapy choice.
In conclusion, the results seem to support the potential of FDG PET to provide anatomical substrate of raised serum markers in patients with a negative 131I scan. However, the present evidence does not allow implementation of PET in a routine diagnostic algorithm.
Footnotes
Abbreviations: A, B, and C, Criteria list A-items, B-items, and C-items, respectively; CT, computerized tomography; FDG, 8F-fluorodeoxyglucose; FU, follow-up; 131I WBS, iodine-131 whole-body scintigraphy; MIBI, 99mTc-hexakis-2-methoxyisobutylisonitrile; MRI, magnetic resonance imaging; PET, positron emission tomography; Se, sensitivity; Sp, specificity; TETRO, 99mTc-Tetrofosmin; US, ultrasound.
Received September 13, 2000.
Accepted March 13, 2001.
References
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