Article

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

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Abstract

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131I) and a negative FDG PET, in four cases 131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant "staging", differences between 131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131I-positive/FDG-negative, 131I-negative/FDG-positive and 131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

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... Tg was elevated (5590ng/ml) and increased further after thyrogen administration (6616 ng/mol -Reference range <10.0ng/ml). 18 F FDG PET-CT scan showed hypermetabolic thyroid tissue (SUV 16.1), with multiple FDG avid lesions in the right lower cervical (SUV 7.1), supraclavicular (SUV 13.1), left parasternal (SUV 5.1), right paratracheal (SUV 11.1), right hilar (SUV 11.2), and subcarinal nodes (SUV 16.9). Further hypermatabolic lesions included two pleural based lesions in the right upper and lower zones and a right lung parenchymal lesion ( Figure 2). ...
... (16) In cases of increased Tg levels but negative WBIS, restaging is accomplished by using other diagnostic imaging modalities. Several studies have investigated the role of 18 F FDG PET-CT in detecting recurrent or metastatic DTC. ( 17,18,19,20) 18F FDG PET-CT is at present the best reference imaging study in evaluation of DTC patients with negative Iodine 131 WBS and elevated Tg levels as well as in cases of undetectable Tg with clinical suspicion of recurrence or metastases. 18 F FDG PET-CT has demonstrated clinical utility in evaluating non-iodine-avid lesions, with sensitivity approaching 90%. ...
... Several studies have investigated the role of 18 F FDG PET-CT in detecting recurrent or metastatic DTC. ( 17,18,19,20) 18F FDG PET-CT is at present the best reference imaging study in evaluation of DTC patients with negative Iodine 131 WBS and elevated Tg levels as well as in cases of undetectable Tg with clinical suspicion of recurrence or metastases. 18 F FDG PET-CT has demonstrated clinical utility in evaluating non-iodine-avid lesions, with sensitivity approaching 90%. (21,22) This peculiar phenomenon has been described by Feine et al (23) as the "flip-flop" mechanism, where the dedifferentiated tumors lose iodine trapping capability, but have increased glucose metabolism and vice versa. ...
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Metastases of differentiated thyroid cancer (DTC) can lose affinity to radioiodine with the passage of time, with resultant difficulty in management. Thyroid tumors are known to express somatostatin receptors and therefore 111In-pentetreotide, somatostatin analogue, can visualize tumors with high concentration of somatostatin receptors. We report a case of I-131 whole body scan (WBS) negative recurrent metastatic papillary thyroid carcinoma with positive 18F FDG PET-CT and 111In-pentetreotide scan. Somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide may be useful both in the staging and monitoring of patients with non-iodine avid carcinoma of the thyroid. 111In-pentetreotide scan positive patients are potential candidates for somatostatin receptor-targeted therapy.
... Amet hod that has become popular for detecting a variety of cancers is 18 F-FDG PET (1). Clinical experience with FDG PET in patients with differentiated thyroid cancer has recently been reported (2)(3)(4)(5). Several investigators reported that FDG PET and 131 I whole-body scanning played complementary roles in the detection of recurrent or metastatic differentiated thyroid cancer (2,3,6). ...
... Clinical experience with FDG PET in patients with differentiated thyroid cancer has recently been reported (2)(3)(4)(5). Several investigators reported that FDG PET and 131 I whole-body scanning played complementary roles in the detection of recurrent or metastatic differentiated thyroid cancer (2,3,6). Highly differentiated thyroid cancer was positive for 131 I uptake and negative for FDG uptake, whereas poorly differentiated cancer was negative for 131 I uptake and positive for FDG uptake (2,3,5). ...
... Several investigators reported that FDG PET and 131 I whole-body scanning played complementary roles in the detection of recurrent or metastatic differentiated thyroid cancer (2,3,6). Highly differentiated thyroid cancer was positive for 131 I uptake and negative for FDG uptake, whereas poorly differentiated cancer was negative for 131 I uptake and positive for FDG uptake (2,3,5). On the other hand, Grünwald et al. (4) reported that FDG PET was more sensitive than 99m Tc-sestamibi, probably because of better spatial resolution with respect to tomographic imaging and differences in the tracer uptake mechanism. ...
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There are several reports about the usefulness of 18 F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with 131 I and 201 Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from 131 I and 201 Tl scintigraphy. Methods: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30 –77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both 201 Tl uptake and FDG PET uptake. Results: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with 131 I uptake in only 18 lesions (38%). FDG uptake was concordant with 201 Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for 201 Tl uptake, and two lesions were positive for FDG uptake and negative for 201 Tl uptake. A significant correlation was seen between the TBR of 201 Tl and that of FDG (r 0.69; P 0.05). Conclusion: These data indicate that for detecting metastatic lesions, FDG PET and 131 I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of 201 Tl scintigraphy. Thus, the combination of 131 I scintigraphy and FDG PET (or 201 Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.
... Patients with elevated hTg levels but negative 131 I WBS, are not usually treated with high-dose 131 I. Accurate localization of metastatic lesions is therefore very important since they need to be removed surgically or treated with external radiotherapy. Non-specific radiopharmaceuticals, such as 201 Tl chloride, 99m Tc methoxysiobutyl isonitrile ( 99m Tc MIBI) and positron emission tomography (PET) with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) have been shown to be valuable [7][8][9][10][11][12][13][14][15][16][17][18][19]. This study was designed to assess the clinical usefulness of 99m Tc MIBI scintigraphy and FDG-PET in the followup of patients with differentiated thyroid cancer who present with increased hTg levels and negative 131 I scans. ...
... The cationic charge and lipophilicity of 99m Tc MIBI, the mitochondrial and plasma membrane potentials of the tumor cells, and the cellular mitiochondrial content are all considered to play significant roles in the mechanism of tumor Tc-MIBI scintigraphy uptake of this agent [20]. FDG-PET has also been found to be a valuable imaging modality in detecting metastatic lesions in patients with DTC who present with elevated hTG and negative 131 I WBS levels [11,13,21]. For the detection of metastatic DTC, studies have found that 99m Tc MIBI [7] and FDG [11,21] accumulated more often in lesions in which 131 I had failed to accumulate. ...
... FDG-PET has also been found to be a valuable imaging modality in detecting metastatic lesions in patients with DTC who present with elevated hTG and negative 131 I WBS levels [11,13,21]. For the detection of metastatic DTC, studies have found that 99m Tc MIBI [7] and FDG [11,21] accumulated more often in lesions in which 131 I had failed to accumulate. It was suggested that FDG uptake and concomitant loss of 131 I uptake is a sign of dedifferentiation of the cancer cells [11,15,21,22]. ...
... whole body scan, with a high sensitivity of 80% to 90% [4][5][6][7][8]. It is postulated that these less or de-differentiated thyroid cancer cells, which are more aggressive in their clinical behavior, have a high glucose metabolism and FDG uptake [4,[9][10][11][12]. ...
... Recent studies have demonstrated the usefulness of FDG PET-CT in thyroid cancer patients with elevated serum Tg but negative 131 I whole body scan [4,[9][10][11][12]. According to the study performed by Feine and coworkers [9], FDG PET-CT has a sensitivity of 94% in detecting recurrent or metastatic lesions. ...
... According to the study performed by Feine and coworkers [9], FDG PET-CT has a sensitivity of 94% in detecting recurrent or metastatic lesions. In another study performed by Grunwald et al [11], they showed that FDG PET-CT was more sensitive than 131 I and 99m Tc/ 201 Tl scan, with a sensitivity of 75% versus 50% and 53% respectively. ...
Article
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F-FDG (FDG) PET-CT in detecting recurrent or metastatic lesions in patients with well-dif- ferentiated thyroid cancer who have elevated serum thyroglobulin level but negative 131 I whole body scan.
... F-18 FDG PET can be useful for localizing distant metastases, especially when the metastases have no radioiodine avidity, such as poorly differentiated thyroid carcinoma. Several investigators have reported that F-18 FDG PET and I-131 WBS played complementary roles in detection of recurrent or metastatic DTC due to a flip-flop phenomenon [13][14][15][16]. According to this phenomenon, DTC with good differentiation usually takes up radioiodine but does not take up FDG, whereas DTC with poor differentiation takes up FDG but does not take up radioiodine [13][14][15][16]. ...
... Several investigators have reported that F-18 FDG PET and I-131 WBS played complementary roles in detection of recurrent or metastatic DTC due to a flip-flop phenomenon [13][14][15][16]. According to this phenomenon, DTC with good differentiation usually takes up radioiodine but does not take up FDG, whereas DTC with poor differentiation takes up FDG but does not take up radioiodine [13][14][15][16]. In the current study, F-18 FDG PET/CT detected pulmonary metastases in 33/36 patients (91.7 %). ...
Article
Purpose To evaluate differences in clinical, radiological and laboratory findings between pulmonary metastasis with and without radioiodine avidity in thyroidectomized differentiated thyroid cancer (DTC) patients with pulmonary metastasis who underwent high-dose I-131 treatment. Methods A total of 105 DTC patients with pulmonary metastasis (age, 48.7 ± 16.8 years; women/men, 78/27) were included. Clinical characteristics, chest computed tomography (CT), F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET)/CT and thyroid-stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) level were compared between patients with and without radioiodine uptake in metastatic lung lesions. The response to I-131 treatment was evaluated with follow-up study. Results Eighty-nine patients (84.8 %, whole-body scan positive [WBSP] group) showed radioiodine uptake at pulmonary metastasis on post I-131 treatment whole-body scan (WBS) and 16 patients (15.2 %, WBS negative [WBSN] group) did not show uptake at pulmonary lesions on the WBS. Ninety percent and 87 % of the WBSP group had visible metastatic lesions on CT and F-18 FDG PET/CT; however, all of the patients in the WBSN group showed lesions on CT and F-18 FDG PET/CT. In seven (6.7 %) of 105 patients, CT and F-18 FDG PET/CT could not detect pulmonary lesions, which were diagnosed by post I-131 treatment WBS. Complete disease remission was achieved in six (5.7 %) patients and all of them were in the WBSP group. Conclusions Metastatic lesion was not visualized on chest CT or F-18 FDG PET/CT in 6.7 % of DTC patients with pulmonary metastasis and the lesion was visualized only on post I-131 treatment WBS. Complete remission was achieved in 5.7 % of DTC patients with pulmonary metastasis and the cured metastases were non-visualizing or micronodular lesions on chest CT and demonstrated radioiodine avidity on post I-131 treatment WBS.
... In DTC patients with high Tg levels superior sensitivities and specificities of 18 F-FDG-PET as well as 18 F-FDG-PET/CT have been observed than in those with low Tg concentration (6,8,25). The most appropriate indication for 18 F-FDG-PET/CT seems to be a high Tg during follow-up, combined with a negative WBS (1,29). ...
... Zoller et al. demonstrated a slight increase in lesion detection on 18 F-FDG-PET, from 83% to 88%, in the presence of increased TSH levels (29). However, contrasting results were found by other groups (8,23). Therefore, only 18 F-FDG-PET and 18 F-FDG-PET/CT under TSH-stimulation (≥ 5 mU/l) were included in the present analysis. ...
Article
Unlabelled: The clinical significance of (18)F-FDG-PET/CT in the follow-up of patients with differentiated thyroid carcinoma was evaluated and the results were compared with those of (18)F-FDG-PET, (131)I-whole-body scintigraphy including SPECT/CT (WBS) and ultrasound. In addition, it was the aim to investigate the impact of (18)F-FDG-PET/CT on the therapeutic management. Patients, methods: 327 patients (209 women, 118 men; mean age 53 ± 18 years) with differentiated thyroid cancer (242 papillary, 75 follicular, 6 mixed, 1 Hürthle cell and 3 poorly differentiated tumours) were analyzed retrospectively at four tertiary referral centres. 289 (18)F-FDG-PET/CT and 118 (18)F-FDG-PET studies were performed in these patients between 2007 and 2010. In addition, an overall clinical evaluation was performed, including cytology, histology, thyroglobulin level, ultrasound, WBS, and subsequent clinical course in order to compare the molecular imaging results. Finally, the change in therapeutic management due to findings of (18)F-FDG-PET/CT was investigated. Results: The sensitivity of (18)F-FDG-PET/CT was 92%, the specificity was 95%. Sensitivity and specificity of (18)F-FDG-PET alone were 67% and 93%, respectively. WBS showed a sensitivity of 65% and a specificity of 94%. The corresponding values of ultrasound were 37% and 94%, respectively. The sensitivity of (18)F-FDG-PET/CT in the group of patients with a negative WBS (n=194) amounted to 96%. When (18)F-FDG-PET/CT and WBS were considered in combination, tumour tissue was missed in only 2 out of 133 patients; when (18)F-FDG-PET and WBS were combined, tumour tissue was missed in 1 out of 24 patients. (18)F-FDG-PET/CT resulted in management change in 43% (n=57/133) with a decision on surgical approach in 20% (n=27/133). Conclusions: (18)F-FDG-PET/CT is superior to (18)F-FDG-PET alone in patients with differentiated thyroid cancer and has a direct impact on the therapeutic management of patients with suspected local recurrence or metastases, particularly in those with negative WBS.
... Finally, as reported in a meta-analysis by Maxon and Smith, about one fourth of the recurrences and metastases from DTC do not concentrate 131 I [11], thus suggesting the need to find, in such cases, alternative diagnostic tools. Therefore, several alternative procedures have been evaluated in the management of DTC patients including 201 Tl chloride and 99m Tc-methoxyisobutyl isonitrile ( 99m Tc-MIBI) scans [12][13][14][15][16][17][18][19][20][21] and, more recently, positron emission tomography with fluorodeoxyglucose [19][20][21]. ...
... Finally, as reported in a meta-analysis by Maxon and Smith, about one fourth of the recurrences and metastases from DTC do not concentrate 131 I [11], thus suggesting the need to find, in such cases, alternative diagnostic tools. Therefore, several alternative procedures have been evaluated in the management of DTC patients including 201 Tl chloride and 99m Tc-methoxyisobutyl isonitrile ( 99m Tc-MIBI) scans [12][13][14][15][16][17][18][19][20][21] and, more recently, positron emission tomography with fluorodeoxyglucose [19][20][21]. ...
Article
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Tc-methoxyisobutyl isonitrile (MIBI) has been reported to show considerable clinical utility in the study of many neoplastic diseases. The aim of our study was to investigate the possible role of Tc-MIBI in the initial follow-up of patients with differentiated thyroid cancer (DTC) for detecting residual thyroid uptake and/or loco-regional/distant metastases. Eighty-two patients with DTC (61 women, 21 men; mean age: 49 years) were studied after total or near-total thyroidectomy (not earlier than 3 months after thyroidectomy but before they underwent radioiodine therapy). About 20 min after the intravenous administration of 370 MBq of Tc-MIBI, planar images (and, if necessary, tomographic images, single photon emission tomography) of the cervical and thoracic regions were recorded and compared with posttherapy radioiodine scanning and thyreoglobulin serum levels. MIBI scans detected thyroid remnants in 53 of 82 patients (65%) and metastatic foci in 10 of 11 (91%) patients, in whom a standard activity of 1110 MBq of I administered following MIBI scan had shown the presence of thyroid remnants or metastatic foci, respectively. One metastatic patient was false negative for both MIBI scan and post-I dose whole body scan. Our data indicate that an MIBI scan has a high sensitivity in detecting metastatic lesions from DTC. Therefore, an MIBI scan after thyroidectomy and immediately before radioiodine treatment may be clinically useful for choosing the best therapeutic approach in terms of either ablative or therapeutic I activity for both thyroid remnants and/or DTC metastases and for evaluating surgical reappraisal of metastatic lymph nodes.
... Local glucose use, as measured by FDG PET imaging, is an indicator of malignancy. In thyroid carcinoma, FDG uptake is correlated with the grade of malignancy (14), and most malig nant lesions are only FDG positive (poorly differentiated tumors) or radioiodine positive (well-differentiated tumors) (14,15). In the patient described here, FDG uptake in metastatic lesions did not vanish during redifferentiation therapy but was unchanged in lung and mediastinum and increased in the left shoulder. ...
... Local glucose use, as measured by FDG PET imaging, is an indicator of malignancy. In thyroid carcinoma, FDG uptake is correlated with the grade of malignancy (14), and most malig nant lesions are only FDG positive (poorly differentiated tumors) or radioiodine positive (well-differentiated tumors) (14,15). In the patient described here, FDG uptake in metastatic lesions did not vanish during redifferentiation therapy but was unchanged in lung and mediastinum and increased in the left shoulder. ...
Article
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We report on a patient with a follicular Hurthle cell carcinoma in whom distant metastases were initially radioiodine negative or only weakly positive. Redifferentiation therapy with 13-cis retinoic acid induced a significant radioiodine uptake in metastatic tissue. Thyroglobulin (Tg) immunostaining and autoradiography of a bone metastasis in the right femur, which was initially radioiodine negative, proved Tg synthesis, combined with iodine incorporation into tumor cells. Glucose metabolism in metastases was partially increased and partially unchanged after redifferentiation therapy. The distinct increase of serum Tg after retinoic acid treatment was interpreted as a functional sign of redifferentiation.
... Papi, et al. [34] reported that a palpable thyroid nodule was found in 72% of patients with metastasis to the thyroid gland. Metastatic thyroid cancers can be found with 18 FDG-PET [35][36][37][38]. ...
... However, special subgroups of patients demonstrate a less favorable course of disease with much lower survival rates where poor radioiodine accumulation is usually associated [4] and presence of distant metastasis [5]. Patients with DTC may have only iodine-negative tumor lesions or both iodine-negative and iodine-positive tumor tissue [4,6]. Consequently, the presence of iodine-negative tumor tissue decreases the accuracy of iodine scintigraphy. ...
Article
Purpose: To investigate the impact of quantitative FDG-Metabolic activity of non-iodine avid Loco-regional recurrence [LRR; thyroid recurrence and/or cervical node metastasis] on therapy selection in thyroid cancer patients with elevated thyroglobulin [TG]. Methods: Forty thyroid cancer [33 papillary and 7 follicular] patients who underwent FDG PET/CT were studied [with TSH>30 mU/L]. Those with only LRR were classified according to maxSUV [cut-off level 5] into high and low metabolic activity lesions [HMA &LMA]; their therapy outcome was compared with histopathologic findings and/or follow-up routine evaluation. Results: Only LRRs was found in 20 patients [17 papillary and 3 follicular] with diagnostic accuracy of FDG PET/CT of 100%. 14/20 patients belonged to HMA where surgical neck exploration was done while in the remaining 6 patients with LMA empirical high dose of radioactive iodine-131 was given based on the assumption of the presence of a mixture of undifferentiated and differentiated thyroid cancer cells; though their post-therapy scan was negative but declined TGlevels were elicited in their follow-up [base-line 27.7±2.4 and at follow-up 6.8±1.4 ng/ml; P 0.02]. Conclusion: Max-SUV based classification of non-iodine avid LRR might improve the diagnostic accuracy FDG PET/CT in a therapeutically relevant way in DTC-patients by precisely localizing them with subsequent surgical guidance in HMA lesions while those with LMA could benefit from further RA-131 therapy.
... The established role of FDG PET in WDTC is to search for occult metastases in patients with elevated thyroglobulin levels suggesting persistent or recurrent disease, despite nonlocalizing 131 I scintigraphy. FDG PET has particular value when thyroglobulin levels are high and/or when distant metastases are suspected (63,(127)(128)(129)(130)(131). 131 I SPECT/ CT, FDG PET, and 99m Tc-methylene diphosphonate bone scans were compared in patients with suspected thyroid cancer bone metastases. ...
Article
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Nuclear medicine imaging of endocrine disorders takes advantage of unique cellular properties of endocrine organs and tissues that can be depicted by targeted radiopharmaceuticals. Detailed functional maps of bio-distributions of radiopharmaceutical uptake can be displayed in 3D-tomographic formats, using single photon emission computed tomography (SPECT), that can now be directly combined with simultaneously acquired cross-sectional anatomic maps derived from computed tomography (CT). The integration of function depicted by scintigraphy and anatomy with CT has synergistically improved the efficacy of nuclear medicine imaging across a broad spectrum of clinical applications, that include some of the oldest imaging studies of endocrine dysfunction.
... Recent studies have shown that de-differentiating follicular thyroid cells reduce the expression of the NIS and increase glucose metabolism. [11][12][13][14] Interestingly, the glucose metabolism can be tracked by a radioactive glucose analogue (i.e. 18 F-fluorodeoxyglucose [ 18 F-FDG]). ...
Article
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Nuclear medicine techniques were first used in clinical practice for diagnosing and treating thyroid diseases in the 1950s, and are still an integral part of thyroid nodules work-up. Thyroid imaging with iodine or iodine-analogue isotopes is the only examination able to prove the presence of autonomously functioning thyroid tissue, which excludes malignancy with a high probability. In addition, a thyroid scan with technetium-99m-methoxyisobutylisonitrile is able to avoid unnecessary surgical procedures for cytologically inconclusive thyroid nodules, as confirmed by meta-analysis and cost-effectiveness studies. Finally, positron-emission tomography alone, and positron-emission tomography combined with computed tomography scans with 18F-fluoro-2-deoxy-d-glucose are also promising for diagnosing thyroid diseases, but further studies are needed before introducing them to clinical practice.
... The flip-flop phenomenon is the observation that thyroid cancers and their metastases show either some iodine uptake combined with low FDG uptake, or no uptake of 131 I combined with high FDG uptake [75]. The expression flip-flop refers to the alternating pattern of 131 I and FDG uptake observed in well-differentiated PTCs or FTCs that have high I uptake and low FDG uptake, in comparison with PDTCs and ATCs, that have low I uptake and high FDG uptake (Fig. 9 ). ...
Article
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Papillary and follicular thyroid carcinomas (well-differentiated forms) are the most common follicular cell-derived thyroid malignancies, while poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas (also poorly differentiated) are the less common ones. Papillary carcinomas are morphologically and genetically different from follicular carcinomas: the former are associated, in up to 70 % of cases, with BRAF or RAS point mutations or RET/PTC rearrangements; the latter carry the RAS point mutation or the PAX8/PPARgamma rearrangement. The poorly differentiated forms have abnormalities in the TP53 and the CTNNB1 genes. The best way to image thyroid cancer cells is to exploit the capability of normal follicular thyroid cells to concentrate iodine 131I through the sodium–iodine symporter. Iodine is necessary for the production of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Unfortunately, the cells of poorly differentiated carcinomas lose the capability to concentrate iodine; at the same time, their basal metabolism increases to satisfy the energy demands of highly proliferating cells. These cells require more glucose and a glucose analog, namely 18F-2-fluoro-2-deoxy-d-glucose (18FDG), is used in place of glucose to study their metabolism. The increased intake of glucose is mediated by a transmembrane transporter called glucose transporter-1 located on the cell membrane. The alternation of 131I and 18FDG uptake observed in thyroid tumors and their metastases is known as the “flip-flop” phenomenon. This review looks at the cellular and molecular mechanisms underlying thyroid cancer and thyroid cancer imaging.
... Inúmeras investigações vêm demonstrando a importância da tomografia por emissão de pósitron (PET) com flúor-18 fluorodesoxiglicose (FDG-18 F) na detecção de recidiva local ou metástase de CDT. Este método é particularmente útil na detecção das células tumorais menos diferenciadas que apresentam elevada taxa de consumo de glicose e não captam iodo (5)(6)(7). O recente advento do equipamento híbrido de PET e CT oferece alta precisão na localização anatômica das lesões neoplásicas funcionalmente alteradas, pois avalia tanto o metabolismo quanto a anatomia do corpo inteiro num único exame. As imagens de co-registro PET-CT são particularmente úteis na região cervical, onde algumas estruturas normais com captação fisiológica da glicose marcada (tecido linfóide da naso/orofaringe, atividade muscular e da gordura marrom) podem dificultar a detecção da lesão hipermetabólica tumoral. ...
Article
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OBJETIVO: Avaliar o papel da PET-CT com FDG-18F na detecção de recidiva e/ou metástase de carcinoma diferenciado da tireóide (CDT) em pacientes com níveis elevados de tireoglobulina (TG) e PCI negativa. PACIENTES E MÉTODO: Os achados da PET-CT de 25 pacientes foram comparados com a avaliação histopatológica e os métodos convencionais de imagem (MC). RESULTADOS: A PET-CT foi positiva em 16 pacientes com resultado verdadeiro-positivo em 14 e falso-positivo em 2 casos (valor preditivo positivo 87,5%). Nove pacientes tiveram PET-CT negativa; dois evoluíram com níveis indetectáveis de TG. Doença residual foi observada na PCI pós-dose terapêutica de uma paciente. Seis pacientes não apresentaram evidências de tumor durante o seguimento (média 16 meses). PET-CT foi concordante com MC em 52%, parcialmente concordante em 12% e discordante (6 falso-negativos e 3 falso-positivos dos MC) em 36%. Foi observada uma tendência de aumento da proporção de PET-CT positiva com o aumento de TG. CONCLUSÃO: A PET-CT com FDG-18F é útil na detecção de recidiva e/ou metástases de CDT com níveis de TG elevados mas PCI negativa. Apresenta alto valor preditivo positivo e é superior aos MC, sendo mais efetiva quanto maior o nível de TG.
... 2,3 Furthermore, it seems important to diagnose and remove iodine-negative tumor tissue as early as possible because the prognosis of this tumor subgroup is considerably worse than the most of DTC. 4 In these patients, [ 18 F]-fluorodeoxyglucose positron emission tomography/CT ( 18 FDG-PET/CT) has been shown to improve detection and localization of tumor foci. [5][6][7][8] In a recent meta-analysis, the reported overall sensitivity of 18 FDG-PET/CT for localization of recurrent papillary thyroid cancer was 77% to 82% and the corresponding calculated specificity was 85%. 9 Tg levels generally correlates to the tumor burden regardless of whether levels are measured during levothyroxine (T4) treatment (ie, unstimulated Tg) or after thyroidstimulating hormone (TSH) stimulation. ...
Article
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The purpose of this study was to assess the relationship between [(18) F]-fluorodeoxyglucose ((18) FDG)-positron emission tomography/CT ((18) FDG-PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated thyroid carcinoma (DTC). Forty-two patients with recurrent DTC and negative Tg antibodies were included in the study. All patients underwent (131) I therapy due to an increasing serum Tg with a corresponding negative (131) I posttreatment whole body scan. The (18) FDG-PET/CT scans were then performed on all patients, serum Tg was measured concurrently, and respective results were compared. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of the (18) FDG-PET/CT examination were 93%, 84%, 93%, 84%, and 90%, respectively. The sensitivity of (18) FDG-PET/CT significantly increased in patients with serum Tg levels ≥4.6 ng/mL (96%) in comparison with patients having lower levels (25%; p < .001). Nonetheless, 3 of 27 patients (11%) with a true-positive (18) FDG-PET/CT still had a Tg <4.6 ng/mL. Although (18) FDG-PET/CT scans are more likely to be positive with pretest Tg levels ≥4.6 ng/mL, 11% of patients with DTC with a lower serum Tg level will still have a positive scan. Our findings are in contrast with the American Thyroid Association (ATA) guidelines, which only recommend to perform (18) FDG-PET/CT in patients with Tg levels >10 ng/mL.
... The FDG uptake showed an inverse proportionality to iodine uptake and to tumour differentiation. Grunwald et al. interpreted increased glucose metabolism as a sign of higher malignancy [278]. ...
Article
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Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved.
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Several major advances and paradigm shifts have occurred in the surveillance of differentiated thyroid cancer (DTC) over the last two decades. Ultrasensitive thyroglobulin assays and cervical ultrasonography have emerged as the most sensitive techniques for detecting residual or recurrent disease. Diagnostic whole-body scans, once a mainstay in DTC surveillance, are now used more selectively. Recombinant human TSH (rhTSH) has largely supplanted thyroid hormone withdrawal (THW) for stimulated testing, resulting in significantly improved quality of life. Additional tools for detecting disease after initial treatment include cross-sectional imaging and positron emission tomography. Each test has unique strengths, limitations, and specific indications. The intensity of surveillance, and the methodologies employed, should be based on initial and subsequent risk stratification. Strategies must be modified in the presence of thyroglobulin antibodies and in patients who have not undergone total thyroidectomy or radioiodine ablation. Given the excellent survival and low rate of structural recurrence in DTC patients as a whole, it is essential to consider the potential harms of overaggressive surveillance, including the physical, psychosocial, and financial burdens. Recent data suggest that the intensity of surveillance may be safely decreased in select patients.
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The incidence of malignant melanoma is increasing more rapidly than any other kind of cancer; since 1973 it has risen by 4–6% per year in the United States. While in 1935 the risk of an American developing malignant melanoma during his lifetime was 1:1,500, by 1991 the risk was 1:105, and it is estimated that it will be 1:75 by the year 2000 (Boring et al. 1994; Harris et al. 1995). Among women between the ages of 20 and 29 it is the most frequent type of tumor (Friedman et al. 1991; Katsambas and Nicolaidou 1996; Kof 1991; Johnson et al. 1994; and Schneider et al. 1994).
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Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, comprising 80% of all thyroid carcinomas. From 1973 to 2002, the incidence of all thyroid cancers increased 2.4-fold, and the increase was virtually entirely due to an increase in papillary carcinomas. Over this 30-year period, the incidence of PTC increased more by 5 per 100,000, a 2.9-fold increase. Despite the increasing incidence of PTC, the mortality from thyroid cancer has remained stable over the years. Many thyroid cancers are found as nonpalpable, incidentally discovered nodules. In fact, papillary thyroid microcarcinoma (PTMC), defined by the World Health Organization as thyroid cancer less than or equal to 1 cm, accounts for 49% of the increase in PTC. Furthermore, 87% of the increase in PTC is due to cancers less than or equal to 2 cm in size. One explanation for the increased incidence of PTC is an increase in diagnostic scrutiny due to advances in ultrasonography and fine needle aspiration (FNA) biopsy; however, since the increase occurs across all tumor sizes, other factors may also play a role.
Article
The diagnostic imaging procedures that have a role in detection of malignant thyroid tissue are radioiodine (131I) diagnostic whole-body scintigraphy (WBS), neck ultrasound, and CT and MRI for evaluation of the mediastinal area. Despite excellent morphologic characterization of metastatic nodal recurrences, MRI cannot reliably make a differentiation between benign and malignant lymph nodes. Although it detects enlarged metastatic lymph nodes, there are also many small nodal metastases that are usually missed. In one-third of patients with well differentiated thyroid carcinoma, there are carcinomas with dedifferentiated tumor cells: metastatic tissue may not concentrate radioiodine well; thus 131I-WBS is negative despite elevated thyroglobulin (Tg) levels. Although MRI helps in detection of these non-iodine avid metastases, FDG PET/CT can perform more effectively. Due to its high glycolytic rate, changes in glucose transport systems and hexokinase activity, [18F] fluorodeoxyglucose (FDG) accumulates in malignant tissue and is useful for identification of distant metastases in these patients. Iodine positive metastases are often negative with FDG-PET imaging while iodine negative metastases exhibit increased FDG-uptake. If a metastatic lesion is identified by FDG positron emission tomography/ computed tomography (PET/CT), the usual approach is to first send the patient to surgery for removal of neoplastic tissue, if possible. This is followed by re-treatment with 131I therapy after tumor redifferentiation with retinoic acid. In a limited number of patients, iodine negative thyroid cancer may express somatostatin receptors and radiopeptide therapy may be utilized. FDG PET/CT is a hybrid imaging diagnostic tool which helps in detection of non-iodine avid metastases. It has a role in exact localization of recurrences which will assist in the decision to remove the malignant tissue surgically.
Article
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Differentiated thyroid cancer is usually a curable disease, for which treatment modalities such as surgery, radioiodine, and thyroid hormone have been used for the last 50 years, yet little consensus has been established due to the lack of prospective randomized controlled therapeutic trials. After an initial surgery, the patients' outcome can be predicted by staging classification on the basis of several parameters such as the age of the patient, tumor size, tumor grade or differentiation, presence of local invasion, and regional or distant metastases. However, regardless of the pathologic stage, most patients(except those with micopapillary or minimally invasive follicular carcinomas who underwent only a lobectomies) are supposed to receive radioiodine therapy for ablation of any remnant thyroid tissue, which increases the sensitivity of serum Tg and 131I whole body scan used to detect recurrence or metastasis during a long-term follow-up. Until recently, a high dose of 131I has been preferred, however, low dose therapy(30mCi) is a new trend nowadays, which decreases the incidence of both acute and late complications of radioiodine with the same ablation rate. All patients take thyroid hormone after surgery and radioremnant ablation to suppress the level of serum TSH, which is thought to stimulate tumor cell growth.The T4 dose should be adjusted according to the age of the patient, other medical conditions and the risk of recurrence. During the follow-up, the serum Tg level with anti-Tg antibody and the TSH level and 131I whole body scan should be checked regularly. Recently the serum Tg level stimulated by T4 withdrawal or rhTSH injection is suggested to be the most sensitive marker for the detection of recurrence or metastasis. When the stimulated Tg is undetectable (< 2ng/mL), residual or metastatic cancer can be nearly excluded; when it is higher than 10ng/mL, a high dose 131I therapy and posttherapy 131I whole body scan are needed. In cases where the localization fails(Tg-positive/131I scan-negative cases), other imaging studies such as high-resolution ultrasonography of the neck, spiral CT of chest, bone X-ray or 99mTc-MDP bone scan and 18F-FDG PET scan can be useful. 18F-FDG PET is especially sensitive to detect poorly differentiated thyroid cancers that have lost the ability to uptake radioiodine.
Article
Objectives To compare the diagnostic performance of ultrasound, contrast-enhanced computed tomography (CT) and 18F-FDG positron emission tomography (PET)/CT for detecting recurrent differentiated thyroid cancer in the neck. Methods Twenty patients who had undergone previous surgery for differentiated thyroid cancer (19 papillary carcinomas; 1 medullary carcinoma) and presented with pathologically proven recurrence in the neck were included. All patients had undergone ultrasound, CT and PET/CT in the 2 months before further surgery. In each patient, ultrasound, CT and PET/CT images were retrospectively reviewed to determine the presence of loco-regional recurrence by level-by-level analysis. Imaging results were correlated with the histological evaluation of the neck dissection as a standard of reference. Results Recurrences were found at 52 out of 110 cervical nodal levels surgically explored. The sensitivity, specificity and accuracy were 69.2 %, 89.7 % and 80.0 % for ultrasound; 63.5 %, 94.8 % and 80.0 % for CT; and 53.8 %, 79.3 % and 67.3 % for PET/CT, respectively. ROC analysis revealed higher diagnostic performance with ultrasound than with PET/CT for detecting recurrent tumour. Conclusions Although no significant difference was found among the three techniques, the sensitivity and specificity of ultrasound and CT were higher than those of PET/CT for the evaluation of cervical recurrence in patients with differentiated thyroid cancer. Key Points • Ultrasound, CT and 18 F-FDG PET/CT can all detect recurrent thyroid cancer. • Ultrasound and CT have higher sensitivity and specificity. • Ultrasound, CT and 18 F-FDG PET/CT frequently demonstrated discordant findings
Article
Aim: To evaluate the utility of (18F)FDG-PET for patients diagnosed of differentiated thyroid carcinoma who present risk of disease and invaluable levels of thyroglobulin (Tg) by the presence of antibodies antithyroglobulin (AbTg). Material and methods: Retrospective study of 7 women of 40 years old and histological diagnosis of differentiated thyroid cancer (7 papillary tumours) that were sent to our department for the accomplishment of (18F)FDG-PET study because of suspicion of disease, due to I-131 negative and high levels of AbTg, between the year 2002 and 2007. 11 PET scans were obtained after the intravenous injection of 370-434 MBq of (18F)FDG in normoglycemia conditions and previous administration of muscle relaxant, hydration and diuretic. The results of (18F)FDG-PET scans were confirmed by pathologic examination or clinical outcome and radiographic examination for more than 24 months. Results: The prevalence of recurrence in our population was 57.14%. All patients presented levels of Tg lower than 3 ng/dl and AbTg superior to 200 Ul/ml. Three patients had precedent thyroiditis. Out of 11 scans performed 3 of them were negative and 8 cases were found positive. It ruled out the existence of disease in three patients and localized the presence of recurrence in 4 patients. Conclusion: (18F)FDG-PET CONCLUSION: 18F-FDG-PET is a useful diagnostic tool for the detection of recurrence as well as to rule out the existence of disease with a high accuracy, in patients with differentiated thyroid carcinoma with I-131 whole body scan negative but with pathological elevation of antithyroglobulin antibodies.
Article
Aim: To evaluate the utility of (18F)FDG-PET for patients diagnosed of differentiated thyroid carcinoma who present risk of disease and invaluable levels of thyroglobulin (Tg) by the presence of antibodies antithyroglobulin (AbTg). Material and methods: Retrospective study of 7 women of 40 years old and histological diagnosis of differentiated thyroid cancer (7 papillary tumours) that were sent to our department for the accomplishment of(18F)FDG-PET study because of suspicion of disease, due to ¹³¹I negative and high levels of AbTg, between the year 2002 and 2007. 11 PET scans were obtained after the intravenous injection of 370-434 MBq of (18F)FDG in normoglycemia conditions and previous administration of muscle relaxant, hydration and diuretic. The results of (18F)FDG-PET scans were confirmed by pathologic examination or clinical outcome and radiographic examination for more than 24 months. Results: The prevalence of recurrence in our population was 57.14%. All patients presented levels of Tg lower than 3 ng/dl and AbTg superior to 200 UI/ml. Three patients had precedent thyroiditis. Out of 11 scans performed 3 of them were negative and 8 cases were found positive. It ruled out the existence of disease in three patients and localized the presence of recurrence in 4 patients. Conclusion: (18F)FDG-PET CONCLUSION: 18F-FDG-PET is a useful diagnostic tool for the detection of recurrence as well as to rule out the existence of disease with a high accuracy, in patients with differentiated thyroid carcinoma with ¹³¹I whole body scan negative but with pathological elevation of antithyroglobulin antibodies.
Article
The majority of thyroid carcinomas present rather well-defined clinical challenges and therapeutic options. Rare forms of thyroid cancer are generally unfamiliar to clinicians and require creative approaches. This chapter attempts to introduce unusual variants of differentiated epithelial thyroid carcinoma, undifferentiated thyroid cancers, and extraordinary primary thyroid cancers with limited clinical epidemiology. The initial sections will discuss the presentation and clinicopathologic features of these neoplasms, many of which are controversial. The final section will suggest strategies for therapeutic management.
Article
Positron emission tomography (PET) has evolved into a technique that can accurately determine the distribution of positron-emitting radionuclides. The addition of a coincidence detection mode to a standard dual-head detector system has resulted in the option of single-photon and annihilation coincidence detection. This new device for imaging fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in neoplasms became commercially available in 1994. Besides conventional low-energy imaging in the collimated single-photon mode, it offers a relatively inexpensive opportunity to perform uncollimated PET by switching to the coincidence acquisition mode. This review summarises the clinical value of 18F-FDG detection with a dual-head coincidence camera in oncology. The results are compared with the overall results obtained using dedicated PET scanners. With respect to head and neck tumours, 18F-FDG coincidence mode gamma camera imaging (CGI) yields results that are in agreement with those obtained with dedicated PET scanners. With regard to other malignancies, such as lung cancer, lymphoma and brain tumours, data in the literature are too scarce to draw any definite conclusions. In general, the results of 18F-FDG CGI in tumours >15 mm seem to be comparable to those obtained with dedicated PET scanners, whereas in tumours 18F-FDG CGI is approximately 80%. Using attenuation correction, the diagnostic yield of 18F-FDG CGI may increase. However, further clinical investigation is required to definitely establish its value in staging primary disease, therapy monitoring and assessment of tumour recurrence in clinical oncology.
Article
Functional and methodological features of positron emission tomography (PET) are described, with special emphasis on the fluorine-18- fluorodesoxyglucose (18FDG) isotope and its applications in the follow-up of differentiated thyroid cancer (DTC). According to the medical literature, the main role of 18FDG-PET is to detect DTC recurrences in patients with negative 131I scanning and elevated thyroglobulin levels. The hypothetical advantages of rTSH treatment prior to 18FDG-PET, and of combined computed tomography (CT)/FDG-PET imaging in the detection of recurrences are examined. The possible value of 18FDG-PET in the evaluation of thyroid nodules, and of PET in the evaluation of thyroid incidentaloma, are discussed.
Article
(18)Fluorine-fluorodeoxyglucose (FDG) positron-emission tomography (PET) has emerged as a useful method in various fields of oncology. The aim of the present study was to evaluate the clinical significance of this technique in differentiated thyroid carcinoma and to compare the results with other imaging modalities, particularly with whole-body (131)iodine scintigraphy (WBS) and hexakis (2-methoxyisobutylisonitrile) (99m)technetium (I) scintigraphy (MIBI). Whole-body PET imaging using I;DG was performed in 54 patients. There were 39 patients with papillary tumors and 15 patients with follicular tumors (including 3 Hurthle-cell carcinomas). Primary tumor stage (pT) was pT1 in 5 cases, pT2 in 19 cases, pT3 in 2 cases, pT4 in 24 cases, and unknown in 4 cases, respectively. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, sonography, computed tomography, magnetic resonance imaging, and subsequent clinical course, to allow a comparison with functional imaging results. Compared with WBS, FDG-PET gave different results in the majority of cases with recurrence/metastases (11 FDG-true-positive/WBS-negative tumor sites and 8 WBS-true-positive/FDG-negative tumor sites). In 7 patients with recurrence/metastases, FDG-PET and WBS gave corresponding results (10 sites). In 28 patients, FDG-PET and WBS were normal (including 2 false-negative cases). MIBI was performed in 44 cases. FDG-PET was better correlated to MIBI (congruent positive results in 13 tumor sites) than to WBS. Compared with MIBI, FDG-PET was superior in 5 cases (including 3 patients with distant metastases). Two FDG-negative/MIBI-positive tumors were. observed. Different tracer uptake mechanisms have to be considered regarding ''nonspecific'' tumor imaging with FDG-PET or MIBI. Nevertheless, since spatial resolution with respect to tomographic imaging is inferior with single photon emission computer tomography (SPECT) using MTBI, the observed higher sensitivity of PET might be due to the higher spatial resolution of this method. As far as grading could be obtained, FDG-PET seemed to be more sensitive than WBS in high-grade tumors, whereas WBS was positive predominantly in low-grade carcinomas, although statistical significance could not be reached. The results prove the clinical usefulness of FDG-PET and MIBI for detection of (131)iodine-negative tumor tissue in differentiated thyroid cancer.
Article
This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. Material and methods Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH ≥ 30 μIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy 99mTc-Mibi was done in 14 patients and morphologic imaging in 26 by CT scan. Results Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. Conclusions These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.
Article
Thyroid cancer is the most common endocrine malignancy. It is divided in several types with papillary, folliculary and Hürthle cell cancer (also called differentiated thyroid cancer) originating from the follicular epithelial cells as the most common types (>90%). Other types are medullary thyroid carcinoma (a neuroendocrine tumor origi­nating from the calcitonin producing C-cells) (3-10%) and anaplastic carcinoma (often a dedifferentiated form of the other types) (2-10%) (Schlumberger and Pacini 2003). There is a different treatment for each of these types of thyroid cancer. In differentiated thyroid cancer the initial therapy is total thyroidectomy with or without lymph node dissection, followed by adjuvant radioactive iodine therapy. Radioactive iodine therapy with 131I can be used successfully due to the active uptake of iodine in tumor cells of thyroid origin. However, this property can be lost during dedifferentiation, which limits the use of this therapy in anaplastic carcinoma. Medullary thyroid cancer cells show no iodine uptake at all and curative options are therefore mainly limited to surgical resection of primary tumor and metastases (Sherman et al. 2005).
Article
Struma ovarii is an ovarian teratoma mainly composed of thyroid tissue, which can become malignant with possible peritoneal dissemination or even distant metastases. Therapeutic management follows protocols used for thyroid cancer. We report the first use of (18)F-fluorodeoxyglucose positron emission tomography (PET) in the follow-up of malignant struma ovarii with persistently elevated serum thyroglobulin level and negative diagnostic iodine 131 whole body scan after thyroidectomy and four courses of 131 iodine. Hilar and mediastinal lymph node uptake was detected but histological verification concluded that there was a false-positive localization corresponding to sarcoidosis lesions without malignant aspect.
Article
Background: There has been considerable difference in the mode of the imaging procedure and approach for the workup and post-surgery surveillance of thyroid cancer. Determination of serum thyroglobulin is recommended in the follow-up for monitoring the patients with differentiated thyroid carcinoma. Herein, the precise clinical role of individual imaging modalities is discussed, including ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI) and scintigraphic procedures for the diagnosis of recurrent or metastatic thyroid cancer. Method: A review is presented of the scientific papers published in the literature between 1982 and 2007. Relevant articles for this review were identified by searching PubMed using the following search terms: thyroid cancer, ultrasound, computerized tomography, magnetic resonance imaging and scintigraphy. The papers were analyzed and categorized in tabular form by date, subject, author and the type of scientific paper (e.g., randomized controlled trial, meta-analysis, clinical cases and review articles). Conclusion: Sonographic features of malignancy include microcalcifications, solid mass, absence of halo and internal blood flow, and these are helpful to predict thyroid malignancy in a nodule. Ultrasound is used for guiding fine needle aspiration to improve the accuracy of cytological analysis. However, biopsy is often necessary for a definitive diagnosis. This modality is also useful for postoperative neck evaluation of patients with elevated serum thyroglobulin levels to search for local recurrence or regional lymph node metastasis, which are the most common sites of recurrence. Tumor extension to the neighboring musculature, trachea, larynx and retropharyngeal, parapharyngeal and retrotracheal nodes are better defined by other anatomical imaging methods, such as CT or MRI. Anatomical imaging procedures are highly sensitive but not specific for postoperative evaluation of these patients and have few implications for deciding on subsequent I-131 therapy in patients with differentiated thyroid carcinoma. In addition to radioiodine scan, which has been the cornerstone of managing patients with differentiated thyroid cancer, nuclear imaging (scintigraphy) with technetium-99m sestamibi and tetrofosmin have all been used for determination of recurrent or metastatic differentiated thyroid cancer. Meta-iodo-benzylguanidine labeled either with I-123 or with I-131, 99mTc sestamibi and tetrofosmin and In-111 labeled somatostatin receptor analogues have been used for determination of recurrent or metastatic disease of medullary thyroid cancer. Over the last decade, positron emission tomography using 18-F-fluorodeoxyglucose has emerged as a useful tool in detecting non-iodine avid dedifferentiated and/or poorly differentiated thyroid cancer and plays a principal role in such settings.
Article
Context/Objective: Approximately 15% of thyroid cancer patients develop subsequent metastases. The clinical course of patients with metastatic thyroid carcinoma is highly variable. We hypothesized that the metabolic activity of metastatic lesions, as defined by retention of 2-[ 18 F] fluoro-2-deoxyglucose (FDG), would correlate with prognosis. Design/Patients: The initial FDG-PET scans from 400 thyroid cancer patients were retrospectively reviewed and compared with overall survival (median followup = 7.9 years). We examined the prognostic value of clinical information such as: gender, age, serum thyroglobulin (Tg), AJCC stage, histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions, and the glycolytic rate of the most active lesion (SUV max). Results: Age, initial stage, histology, Tg, radioiodine uptake, and PET outcomes all correlated with survival by univariate analysis. However, only age and PET results continued to be strong predictors of survival under multivariate analysis. The initial AJCC stage was not a significant predictor of survival by multivariate analysis. There were significant inverse relationships between survival and both the SUV max and the number of FDG-avid lesions. Conclusions: FDG-PET scanning is a simple, expensive, but powerful means to re-stage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low (FDG-negative) or high (FDG-positive) risk of cancer associated mortality. We propose that the aggressiveness of therapy for metastases should match the FDG-PET status.
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In an extensive review of this subject, 1095/3083 (35.5%) patients with papillary carcinoma and 102/797 (12.8%) patients with follicular carcinoma were found to have lymph node metastases at the time of initial diagnosis of their cancer (1). In children, the prevalence may be as high as 70% (2). Of patients thought to be disease free after their initial treatment, 252/2684 (9.4%) with papillary and 43/641 (6.7%) with follicular carcinoma subsequently developed nodal metastases (1).
Article
The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in acute and chronic osteomyelitis and inflammatory spondylitis. The study population comprised 21 patients suspected of having acute or chronic osteomyelitis or inflammatory spondylitis. Fifteen of these patients subsequently underwent surgery. FDG-PET results were correlated with histopathological findings. The remaining six patients, who underwent conservative therapy, were excluded from any further evaluation due to the lack of histopathological data. The histopathological findings revealed osteomyelitis or inflammatory spondylitis in all 15 patients: seven patients had acute osteomyelitis and eight patients had chronic osteomyelitis or inflammatory spondylitis. FDG-PET yielded 15 true-positive results. The tracer uptake correlated with the histopathological findings in each case. Bone scintigraphy performed in 11 patients yielded ten true-positive results and one false-negative result. Follow-up carried out on two patients revealed normal or clearly reduced tracer uptake, which correlated with a normalisation of clinical data. In early postoperative follow-up it was impossible to differentiate between postsurgical reactive changes and further infection using FDG-PET. It is concluded that acute and chronic osteomyelitis of the peripheral as well as the central skeleton can be detected using FDG-PET. Osteomyelitis can be differentiated from soft tissue infection surrounding the bone. Unlike computed tomography and magnetic resonance imaging, FDG-PET is not affected by metal implants used for fixing fractures. FDG-PET demonstrated promising initial results with respect to treatment monitoring. Nevertheless, in the early postoperative phase FDG-PET seems to be of limited value owing to unspecific tracer uptake.
Article
=222) and the group with negative radioiodine scan (n=166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n=117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.
Article
Exact localization of recurrent iodine-negative thyroid cancer is mandatory, since surgery is the only curative therapy option in patients with iodine-negative tumor tissue. The aim of this study was to evaluate the impact of (18)F-FDG-PET/CT as a routine diagnostic tool on clinical management in patients with suspected thyroid cancer recurrence and elevated serum thyroglobulin (Tg) but negative radioiodine whole body scan. After total thyroidectomy followed by radioiodine ablation, 30 consecutive patients with differentiated thyroid cancer, elevated serum thyroglobulin levels and negative whole body radioiodine scan underwent (18)F-FDG-PET/CT. Results were verified by histology, ultrasound, or clinical follow-up. Diagnostic accuracy was determined for the whole study population and for subgroups with serum thyroglobulin below and above 10 ng/ml, respectively. Impact of PET/CT on clinical management was assessed. PET/CT identified FDG accumulating lesions in 19 of 30 patients. 17 were true-positive and 2 false-positive. In the true-positive group, 11 of the 17 patients had loco-regional disease, 3 had distant metastases only and 3 patients had both loco-regional and distant metastatic involvement. (18)F-FDG-PET/CT was true-negative in 3 patients and false-negative in 8 patients. Overall sensitivity, specificity and accuracy were 68.0, 60.0, and 66.7%, respectively. In the subgroup of patients with serum thyroglobulin above 10 ng/ml (n = 21) the sensitivity, specificity and accuracy were substantially higher with 70.0, 100.0, and 71.4%, respectively. Clinical management was changed for 17 (57%) of 30 patients, guiding to a curative surgical intervention in 9 patients (30%). (18)F-FDG-PET/CT enables detection and precise localization of loco-regional recurrence and distant metastases of differentiated thyroid cancer in patients with elevated serum thyroglobulin but negative radioiodine with significant impact on patient management and can therefore be recommended as a routine diagnostic tool.
Article
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The first aim of this study was to compare the detectability of metastasis of postoperative differentiated thyroid cancer (DTC) among (131)I whole body scintigraphy (IWBS), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), and diffusion-weighted magnetic resonance imaging (DWI). The second aim was to clarify the association between the image pattern and prognosis. We evaluated 70 postoperative DTC patients on both a patient basis and an organ basis (lymph nodes, lung, bone), and we analyzed the correlation between the image pattern and the prognosis. For the patient-basis analysis, the detectability by IWBS, PET/CT, and DWI was 67.1%, 84.2%, and 57.6%, respectively. IWBS provided complementary information to that provided by PET/CT in 11 of 70 (15.7%) cases. For the organ-basis analysis, IWBS was the best detector for lymph node metastasis (72.4%). PET/CT was superior to IWBS for detecting metastasis of bone (85.7% vs. 71.4%) and lung (94.1% vs. 62.7%). For the correlation analysis, PET and DWI positivity were the factors predicting a poor prognosis. PET/CT was the best modality for detecting metastases in postoperative DTC patients, although IWBS provided complementary information. Because PET/CT and DWI gave similar information (e.g., positivity) suggesting poor prognoses, the combination of IWBS and DWI might be the method of choice for monitoring postoperative DTC.
Article
While iodine scanning is the mainstay of functional imaging in differentiated thyroid cancer, there is now a significant body of literature regarding positron emission tomography with 2-fluoro-2-deoxy glucose in thyroid cancer. This clinical review will examine the evidence supporting the use of 2-fluoro-2-deoxy glucose-positron emission tomography throughout the diagnosis and management of thyroid cancer, and provide suggestions for its clinical use and potential future roles. © 2010 The Authors. ANZ Journal of Surgery
Article
The aim of this study was to evaluate the local efficacy of I-131 for F-18 fluorodeoxyglucose positron emission tomography (FDG PET)-positive lesions. Whole-body FDG PET/CT was performed on 37 patients (55 cases: 16 men, 21 women; age range: 24-82 years; mean age ± standard deviation: 60.5 ± 16.0 years) with differentiated thyroid cancer after total thyroidectomy. The metastatic or recurrent lesions were divided into 5 categories: primary tumor bed, lymph node, lung, bone, and other. The well-defined lesions were measured on CT, and the sizes were compared before and after radioactive iodine therapy. The analysis was performed on 37 patients with 44 lesions (lymph node:24, lung:16, bone:4). Sixteen lesions (70%) were increased and 7 (30%) showed no change or reduction when there was positive accumulation on FDG PET/CT and negative accumulation on I-131 (F(+)I(-)) group. In the positive accumulation for both FDG PET/CT and I-131 (F(+)I(+)) group, 5 lesions (63%) were increased and 3 (37%) showed no change or reduction. There was no significant difference for the tendency to increase in size between the F(+)I(-) and the F(+)I(+) groups. Lesions which show positive accumulations on FDG PET/CT have a greater tendency to increase in size. FDG-avid lesions are resistant to radioactive iodine therapy with or without I-131 uptake.
Article
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BRAF V600E is a potential marker of poor prognosis in papillary thyroid cancers (PTC). In a previous report, we showed that recurrent PTC with no radioiodine ((131)I) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene. The aim of the present study was to assess BRAF status in a large series of recurrent PTC patients, considering paired primary and recurrent cancers. The BRAF genotype was correlated with the ability to concentrate (131)I and/or 2-[(18)F]fluoro-2-deoxi-d-glucose ((18)F-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome. We studied 50 PTC patients with recurrent cervical disease submitted to a re-intervention, followed up in median for 9 years. BRAF analysis was conducted by direct sequencing and mutant allele-specific PCR amplification. In 18 cases, molecular analysis was also assessed in the primary cancer. Out of 50 patients, 30 underwent (18)F-FDG-positron emission tomography-computed tomography. BRAF V600E-positive recurrent patients were found (131)I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both (131)I-negative and (18)F-FDG positive. In paired primary and recurrent PTC, BRAF V600E was observed in 79% of the primary cancers and 84% of their recurrences. Three patients with (131)I-negative and BRAF V600E-positive recurrent cancers deceased during follow-up. BRAF mutations are more common in thyroid recurrences with no (131)I uptake than in (131)I-positive cases. They are correlated with the ability to concentrate (18)F-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.
Article
Positron emission tomography (PET) combined with cross-sectional computed tomography (CT) is increasingly used for staging and surveillance of cancers in the head and neck region. Ultrasonography (US) is an alternative imaging technique that provides diagnostic information while enabling simultaneous image-guided biopsies. A comparison of these diagnostic modalities in cancer detection is warranted. All patients with malignant neoplasms in the head and neck region who were evaluated by both PET/CT and US were reviewed. Diagnostic accuracy rates of PET/CT and US were determined according to whether cytologically or histologically confirmed cancer was present in US-guided fine-needle biopsy or surgical specimens. From October 2004 to December 2007, 42 patients with an ultimately confirmed tissue diagnosis of a head and neck malignancy underwent both neck US and PET/CT. The sensitivity and specificity of US in predicting malignancy in the head and neck was 96.8% and 93.3%, respectively, in those 42 individuals. The positive predictive value (PPV) was 96% and the negative predictive value (NPV) was 93%. In comparison, PET/CT in this group demonstrated a sensitivity of 90.3%, specificity 20%, PPV 70%, and NPV 50%. PET/CT and US, especially when combined with US-guided fine-needle biopsy, are complementary tools in the detection of cancers of the head and neck. The highly sensitive and specific nature of US, combined with its low cost, low morbidity, availability as an in-office examination, and ability to guide biopsies, warrant consideration of its routine use in the management of head and neck and thyroid cancer patients.
Article
For more than a decade, positron emission tomography (PET) has had an important role in the management of thyroid cancer patients. It may be involved in initial, sometimes inadvertent, diagnosis; in postoperative evaluation; in detection of occult metastases; in the evaluation of thyroid nodules; and in prognostication of metastatic disease. In this review we will update the advances in the application of PET scanning to optimal patient management. The majority of the published studies to date have used 18F-fluoro-deoxyglucose (FDG) as the PET isotope, and unless specifically noted, all references to PET scanning will imply that this tracer has been used.
Article
An 18F-fluorodeoxyglucose (FDG) whole-body PET scan was performed on a thyroid cancer patient with long-standing rheumatoid arthritis who presented with pulmonary nodules. A recent diagnostic radioiodine whole-body scan was negative. However, the 18F-FDG scan demonstrated intense uptake in the chest lesions as well as in several joints affected by rheumatoid arthritis. Fine-needle aspiration of a pulmonary nodule revealed inflammatory reaction and absence of malignant cells, fungus and tuberculous infection. A repeat chest CT scan after 7 mo of steroid therapy showed a marked decrease in the size and number of nodules. In thyroid cancer patients, 18F-FDG uptake in the lung may not necessarily represent pulmonary metastases. This case illustrates a benign, unrelated pathology namely, rheumatoid arthritis-associated lung disease.
Article
Positron emission tomography (PET) has been retrospectively reported to be a sensitive method for detecting malignant melanoma metastases. One hundred consecutive patients with high risk melanoma (tumor thickness > 1.5 mm) were prospectively evaluated (52 at primary diagnosis, comprising Group A, and 48 during follow-up, comprising Group B) by whole-body PET and conventional diagnostics (CD). In Group A, the sensitivity of PET was 100% and the specificity was 94%, whereas CD did not identify any of the 9 lymph node metastases and demonstrated a lower specificity (80%). In Group B, 121 lesions were detected, 111 by PET and 69 by conventional imaging. On the basis of patients, the sensitivity, specificity, and accuracy of PET were 100%, 95.5%, and 97.9%, respectively (91.8%, 94.4%, and 92.1%, respectively, on the basis of single metastases). Prospectively, CD did not identify all patients with progression (sensitivity, 84.6%) and detected significantly fewer metastases (sensitivity, 57.5%) with much lower specificity (68.2% on the basis of patients, 45% on the basis of single lesions); therefore, the accuracy of CD was 77.1% on the basis of patients and only 55.7% on the basis of single metastases. Results also depended on specific sites: while PET yielded a higher sensitivity in detecting cervical metastases (100% vs. 66.6%) and abdominal metastases (100% vs. 26.6%), computed tomography proved to be superior in detecting small lung metastases (87% vs. 69.6%). PET is a highly sensitive and specific technique for melanoma staging. With the exception of the brain, one single whole-body 18F-fluorodeoxyglucose-PET scan could replace the standard battery of imaging tests currently performed on high risk melanoma patients.
Article
Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a new imaging modality used in the follow-up of patients with differentiated thyroid cancer if the results of (131)I scintigraphy are negative in spite of an elevated thyroglobulin level. The aim of this retrospective analysis was to estimate the value of FDG-PET regarding the operability of patients with positive findings. From January 1994 to October 1997, we investigated 60 patients with differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on after positive findings. Most of these lesions were suspected of having lymph-node involvement or local recurrences in the thyroid bed. One patient showed a solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13 patients confirmed the suspected involvement of thyroid cancer. The false-positive findings were caused by inflamed lymph nodes in two cases and benign thymus tissue in one case. We conclude that PET is a useful diagnostic tool to guide early surgical therapy in patients with (131)I negative differentiated thyroid carcinoma.
Article
In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastatic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine- 131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml, range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 microIU/ml, range 31-116 microIU/ml, median 74.6 microIU/ml). In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01. These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.
Article
To investigate the usefulness of positron emission tomography (PET) in detecting I-131 nonvisualized metastatic foci of well-differentiated thyroid carcinoma (WDTC), 2 patients with papillary and follicular thyroid carcinoma respectively, were studied with I-131 total body scan, thallium-201 scan, Tc99m bone scan and [18F]-2-deoxy-2-fluoro-D-glucose (FDG) PET. Case 1 showed no metastatic lesion in I-131 (up to 150 mCi) total body scan, 1 anterior mass in thallium-201 scan, none in Tc99m bone scan and 7 including the main anterior mediastinal mass in FDG-PET. Case 2 showed 2 metastatic lesions in I-131 (150 mCi) total body scan, 11 bony metastatic lesions in Tc99m bone scan and 13 in FDG-PET. However, lower extremities were not scanned in FDG-PET. Tumor/background ratio of 1.5 or above is needed to be visualized grossly. The FDG-PET tumor/background ratios are higher than those of thallium-201 except in one site. In conclusion, I-131 scintigraphy is still the first line method to use in detecting WDTC recurrence and metastasis, as I-131 has the advantage of being both a therapeutic and imaging agent. For I-131 nonvisualized metastasis of WDTC, thallium scintigraphy and FDG-PET may be considered. Even though FDG-PET has better sensitivity, resolution imaging and spatial localization, this has to be balanced with its higher cost when compared with thallium scintigraphy.
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With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology.
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Three patients with multiple metastases of thyroid carcinoma were studied with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and iodine-131 (131I) imaging. Metastases that accumulated only FDG, only 131I, or both FDG and 131I could be demonstrated. Metabolic heterogeneity was seen between different metastases in all patients. The accumulation of FDG may also differ between different metastases of the same patient. The uptake of FDG in metastases was shown to increase parallel with their progression. Metastases of thyroid carcinoma that have ceased to accumulate 131I after treatment with radioiodine may still be demonstrated with FDG. Metastases that accumulate FDG, but not 131I, may behave more aggressively than metastases that accumulate 131I, but not FDG.
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Dedifferentiation of well-differentiated thyroid carcinoma is a well-known phenomenon that may lead to the disappearance of radioiodine uptake in tumors and the inability to treat patients with radioiodine. We report a patient in whom the 131I uptake progressively diminished to such low levels after a cumulative dose of 31.5 GBq that further 131I administration was considered nonbeneficial. Thereafter, metastases in the lungs and skeleton progressed. Because of the absence of any other therapeutic options, nearly 2 yr later we decided to reperform 131I measurements and scanning under hypothyroid conditions. All known metastatic lesions this time showed intense 131I uptake, more than 10-fold the previously measured values. High-dose 131I treatment was restarted.
Article
Technetium-99m-sestamibi has been reported to localize in various tumors. Scintigraphic results for a patient with recurrent Hurthle cell carcinoma of the thyroid whose tumor was imaged with both 99mTc-sestamibi and 201TI, but not with 131I, are presented.
Article
Serum thyroglobulin (Tg) should be undetectable in patients successfully treated for thyroid carcinoma. We have examined the course of disease in 19 patients with raised serum Tg (greater than 5 micrograms/l) on initial measurement but no other evidence of residual, recurrent or metastatic cancer. 416 patients from several centres were followed for periods between 1 and 9 years. Serum Tg was measured at 6-12-month intervals. All had differentiated thyroid cancer, treated by partial or total thyroidectomy and/or 131I ablation, and were receiving suppressive thyroxine therapy. Serum Tg was measured and clinical, X-ray and scan assessment made of presence or absence of residual, recurrent or metastatic cancer. Of 416 patients initially assessed, only 19 had Tg greater than 5 micrograms/l but no clinical or radiological evidence of disease. At follow-up, 11 patients had developed overt signs of malignancy; one had been treated with 131I with a subsequent fall in Tg; five had Tg between 5 and 20 micrograms/l with incompletely suppressed TSH levels; two subjects remained with slightly elevated Tg and undetectable TSH. Patients with elevated Tg require careful follow-up even in the apparent absence of disease. Moderate elevation of serum Tg may be due to inadequate thyroxine suppression therapy, assessed by detectable TSH values measured in a sensitive assay.
Article
The goiter prevalence in iodine-deficient regions is up to 25%-54%. The most frequent disease in these endemic areas is non-toxic goiter, which is, however, oftentimes connected with autonomously functioning thyroid tissue leading to borderline or overt hyperthyroidism. Other thyroid diseases like cancer, thyroiditis and hypothyroidism play only a minor role in a thyroid clinic, while cases of Graves' disease may be observed more frequently. The most cost-effective tools to evaluate thyroid patients are the hand, ear and mouth of the thyroid clinician. The differential diagnosis of thyroid disorders may be evaluated by a battery of diagnostic tools like in-vitro tests and high performance imaging modalities. Once the diagnosis is established, the appropriate therapeutic procedures (drugs, radioiodine, surgery) have to be chosen. This review should be considered as a guideline for the diagnosis and treatment of thyroid diseases. In addition, special problems concerning elderly patients and pregnant women are discussed, including the differential diagnosis of thyroid diseases.
Article
Fourteen human thyroid tumors were studied with 18F-fluorodeoxyglucose (FDG) imaging. The proliferative activity and DNA ploidy of the tumors was assessed by DNA flow cytometry. FDG accumulated in a Hürthle cell carcinoma, an anaplastic carcinoma and a thyroid lymphoma, but only slightly or not at all in the three papillary carcinomas studied. Three of the eight benign tumors also accumulated FDG, but two of these were selected for imaging because of a large number of proliferating cells in DNA flow cytometry. Two carcinomas with increased nuclear DNA content retained FDG, but a histologically benign follicular adenoma with DNA aneuploidy did not. We conclude that in addition to malignant thyroid tumors, histologically benign tumors may also accumulate FDG, and therefore the value of FDG scanning in the preoperative diagnosis of thyroid malignancy is limited.
Article
Consideration of the behaviour of differentiated thyroid tumours and retrospective analysis of patients who have been treated with 131I and followed up for a long time provide information which can be used to formulate a rational policy with regard to 131I therapy after thyroidectomy. There is a good case for ablating any residual thyroid tissue with 131I in patients with follicular tumours because these tumours are potentially functioning and some of them may already have metastasized by the time the patients seek medical advice. This approach will facilitate both the detection and treatment of any functioning metastases that may already be present or may develop subsequently. A whole body scan should be performed after thyroid ablation because a number of patients with differentiated tumours will be found to have occult metastases (Henk et al., 1972). The arguments in favour of 131I therapy in patients with papillary tumours are less cogent. The prognosis for these patients is good provided they are under the age of 40, but the recurrence rate is not insignificant and recurrences when they do occur are likely to be located in the remaining thyroid tissue. It would seem reasonable to recommend 131I ablation for all patients over the age of 40 and to consider ablation for those patients whose tumours contain a substantial follicular component. Young patients with papillary tumours showing little or no follicular structure probably require no treatment other than surgery.
Article
A 49-yr-old white woman with diffuse sclerosing variant of papillary carcinoma of the thyroid revealed abnormal [18F]FDG accumulation within cervical lymph node metastases prior to thyroidectomy. The abnormal cervical foci of glucose metabolism corresponded to similar areas of abnormal [99mTc]pertechnetate and radioiodine accumulation on presurgical scans. The primary thyroid tumor within the thyroid gland was not delineated as a focal defect on any of the three imaging studies. The relative thyroid-to-background soft-tissue ratio in the [18F]FDG study, however, appeared higher than usual. As with 131I and [99mTc]pertechnetate, this case demonstrates that [18F]FDG PET can detect cervical lymph node metastases in the preoperative thyroid cancer patient.
Article
Whole-body PET scanning was performed using 18F-fluorodeoxyglucose (FDG) in two patients with hilar lymphadenopathy in whom the clinical differential diagnosis was between sarcoidosis and lymphoma. Both patients were later proven to have sarcoidosis. Uptake of 18FDG was seen in both intra- and extrathoracic lesions as well as in associated erythema nodosum. One patient underwent a repeat scan after steroid therapy where a marked decrease in hilar uptake was seen. Fluorine-18-fluorodeoxyglucose uptake is observed in lymph nodes with sarcoid involvement. Further investigation is necessary to assess if quantitative differences exist between sarcoid and malignant lymphadenopathy.
Article
To determine the significance of serum thyroglobulin (Tg) level in terms of presence or absence of thyroid cancer, we evaluated available serum Tg data on and off T4 therapy in 180 patients with differentiated thyroid cancer who have now been followed up to 18 yr. The presence of cancer was established by radioiodine scans, x-rays, and clinical examination. Thirty-two patients with detectable serum Tg autoantibodies were excluded from this analysis. Tg was measured by RIA with a sensitivity of 1 ng/mL. Patients who had all stages of cancer, but who had no evidence of active disease after treatment, were grouped according to operative and 131I ablative therapy. In patients with a partial thyroidectomy with or without ablation, the presence of Tg did not indicate the presence of cancer since levels were often above either a 5 ng/mL or a 10 ng/mL cutoff. The presence of residual normal thyroid tissue decreases the diagnostic value of serum Tg assay. In patients who underwent near total (NTT) or total thyroidectomy (TT) and 131I ablation, 3 of 55 (5.5%) patients had Tg greater than 5 ng/mL and 1 of 55 (1.8%) patients had Tg greater than 10 ng/mL during therapy, whereas off therapy 13 of 57 (22.8%) patients had Tg greater than 5 ng/mL and 6 of 57 (10.5%) patients had Tg levels greater than 10 ng/mL. In this group of patients, a Tg level less than 10 ng/mL during suppressive therapy indicated the absence of apparent tumor in 54 of 55 (98.2%) of patients. Whereas sensitivity of the assay was increased by withdrawal of hormone, "false positives" increased especially at lower (3-6 ng/mL) cut-off levels. No cut-off value properly categorized all patients. These data suggest, that even in patients who underwent 131I ablation and total thyroidectomy and were thought to be cured, small foci of thyroid tissue which are undetectable by standard 2 mCi 131I scans may exist and produce some Tg. However, these residual cells do not appear to cause an adverse prognosis in most patients. In patients with recurrent or continued disease, during T4 treatment, Tg levels ranged between 2-21,000 ng/mL and 5 of 11 patients had a Tg less than 5 ng/mL. Off treatment, Tg levels ranged between 6-10,700 ng/mL and 3 of 13 patients had a Tg less than 10 ng/mL. In 4 patients Tg levels were less than 10 ng/mL on treatment but greater than 10 ng/mL off therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Nine patients with suspicious thyroid nodules were studied with positron emission tomography (PET) following the administration of [18F]-2-deoxy-2-fluoro-D-glucose (FDG) prior to surgical excision. Three patients were ultimately determined to have papillary carcinoma, four were shown to have follicular adenomas, and two were proven to have multinodular goiters with dominant nodules. All three malignancies and four of the six benign lesions were easily detected visually as areas of increased FDG uptake. While visual analysis alone did not discriminate between the benign and malignant lesions, all three malignancies had dose uptake ratios (DURs) for FDG in excess of 8.5 while the DURs for benign lesions ranged between 1.9 and 6.3. The mean FDG DUR for the three papillary carcinomas (10.9 +/- 3.9; mean +/- SD) was significantly greater (p = 0.0019) than that of the six benign lesions (3.2 +/- 1.7). There was no significant difference between the FDG DUR for the follicular adenomas and the dominant nodules of multinodular goiters. Further research is needed to confirm the usefulness of PET in the differential diagnosis of thyroid nodules, and, in particular, whether or not PET can discriminate between benign and malignant follicular neoplasms.
Article
Because of the limitations of periodic 131I whole-body scans, including suspension of substitution therapy, questionable sensitivity and low yield in detecting metastases in patients who have undergone thyroidectomy, serum thyroglobulin and 131I whole-body scans were evaluated for sensitivity in detecting local, regional or distant metastases in 261 patients with differentiated thyroid carcinoma after total thyroidectomy and ablation. A noncompetitive immunoradiometric assay was used for serum thyroglobulin determination. An 131I whole-body scan was obtained after replacement therapy had been suspended for 6 wk or when TSH reached levels higher than 50 microU/ml. In patients who underwent radiological procedures with iodinated contrast media, the waiting period before the 131I whole-body scan was no less than 10 wk. Of the 58 patients with proven metastases who were followed for 12 yr (mean 7 +/- 3.3 yr), 51 (88.4%) had high serum thyroglobulin assays performed while under full replacement therapy and 32 (55%) showed clear 131I whole-body scan localization. There were no instances of positive whole-body scans and negative serum thyroglobulin. In patients treated with 131I, serum thyroglobulin assay was an excellent method to assess treatment. Patients with metastatic disease and negative whole-body scans with or without serum thyroglobulin exhibited a trend toward higher mortality. This trend may also indicate that the lack of 131I trapping and low thyroglobulin is a sign of metabolic dedifferentiation of otherwise histologically differentiated thyroid tumors.
Article
A patient developed a pulmonary metastasis from papillary thyroid carcinoma. This tumor concentrated relatively little 131I, but sufficient 18F-fluoro-2-deoxy-D-glucose (FDG) to be quantified and imaged by positron emission tomography. The uptake of FDG was lower on positron emission tomographic images after T4 therapy and when the serum TSH concentration was reduced to the low normal range. It may be possible to use decreases in FDG uptake by thyroid cancers, which represent declines in metabolism by the tumors, to indicate the optimum doses of T4 treatment for patients with these neoplasms. In addition, the ratio of tumor to background radioactivity was higher for FDG than for the flow agent 201Tl, so that studies with FDG may be a useful scintigraphic method for locating thyroid cancers when radioiodine imaging is unsatisfactory.
Article
A prospective study was conducted to evaluate the use of iodine-131 sodium scintigraphy, thallium-201 chloride scintigraphy, and quantitative serum thyroglobulin estimation in the detection of differentiated thyroid carcinoma after thyroidectomy and iodine-131 sodium ablative therapy. Thirty-one patients with a median age of 45.6 years (range, 20-73 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (> 50 mU/ml), 53 pairs of iodine-131 and thallium-201 scans were performed. Concomitant serum thyroglobulin levels were available for 32 pairs of scans. The presence or absence of thyroid cancer was established by clinical, radiologic, and/or biopsy findings. The concordance between iodine-131 and thallium-201 scan findings in the presence of disease (25 scan sets) was 36%. The concordance in the absence of disease (28 scan sets) was 82%. Iodine-131 scanning was found to be significantly better (P < 0.05) than thallium-201 scanning, in terms of sensitivity (0.8 versus 0.6), specificity (0.96 versus 0.82), accuracy (0.89 versus 0.72), and the predictive value of a positive test (0.95 versus 0.75). The measurement of serum thyroglobulin had a low sensitivity (0.3) in the study but had a specificity of 1.0. It was concluded that iodine-131 sodium scintigraphy is superior to thallium-201 scintigraphy and serum thyroglobulin estimation for the detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities provides a higher diagnostic yield. Thallium-201 scintigraphy was especially useful in cases in which iodine-131 scintigraphy was negative and quantitative thyroglobulin levels were elevated.