Negative Whole-body Scan Research Articles

SAT551 Significantly Elevated Thyroglobulin Levels with Negative Whole-Body Scan and PET/CT After Treatment of Thyroid Cancer: A Case Report

Abstract Disclosure: A. Bassatne: None. J.T. Chaiban: None. Background: Thyroglobulin (Tg) levels are used to monitor recurrence or persistence of disease after treatment of differentiated thyroid cancer. Some cases may have persistently elevated Tg and negative whole-body scans (WBS). We present a case of substantially elevated Tg levels despite negative WBS and PET/CT after thyroidectomy and radioactive iodine (RAI) treatment in a patient with papillary thyroid carcinoma (PTC). Clinical Case: A 66 years old lady was referred to the endocrinology clinic almost 5 years ago after incidental findings of calcified thyroid nodules on CT. Thyroid US confirmed 2cm aggregate calcified nodules. FNA revealed PTC for which she underwent thyroidectomy. Pathology showed a unifocal 3.5 cm left lobe conventional PTC without angioinvasion nor extrathyroidal extension, 3/13 positive lymph nodes (LN) on the lateral dissection of the left neck as well as multiple small LN on the central dissection. 6 days postop, her Tg was still significantly high at 40.5ng/mL (Ref 1.2-35 ng/mL) and then increased to 397ng/mL after thyrogen preparation for RAI ablation, antithyroglobulin antibodies were negative. WBS post RAI was negative except for the physiologic neck uptake. Almost a year later, a diagnostic WBS after thyrogen stimulation was still negative but the stimulated Tg increased again to 235 ng/mL with negative thyroglobulin antibodies. Tg result were confirmed by LC-MS method. Heterophile Antibodies were negative. Patient confirmed that every single time she followed at least 2 weeks of low iodine diet in preparation for the WBS. Unfortunately, we were not able to get a 24 hour urine collection for iodine. A PET/CT was reassuring. CT neck/chest did not show any suspicious metastases. TSH was maintained at an adequately suppressed level all through and Tg levels were ranging around 6-8 ng/mL. After another year, a stimulated Tg was 302.4 ng/mL with a TSH of 198 mcU/mL (Ref 0.35-5.0 mcU/mL). At that time, a repeat WBS was negative and a repeat PET/CT demonstrated an interval development of a small thyroid focus thought to be consistent with recurrence of malignancy. However, a CT of neck/chest did not reveal any abnormal thyroid findings or metastases. Patient received 100 mCi of RAI after thyroid hormone withdrawal. Subsequent WBS was negative. Currently her Tg levels are stable at around 8-9ng/mL for the past 6 months with a suppressed TSH. Patient had another PET/CT through her breast surgeon to follow on a previous breast lesion and no thyroid abnormality was noted. Conclusion: Elevated Tg levels despite negative imaging may be seen in patients with PTC as illustrated in this case. We are reporting it due to the extent of elevation of Tg levels seen on more than one occasion in the absence of structural recurrence. Evaluation and treatment of such patients remain controversial. Presentation Date: Saturday, June 17, 2023

The role of 18 F-FDG-PET/CT in the management of differentiated thyroid cancer.

In previous literature, 18 F-FDG-PET/ CT imaging significantly impacted differentiated thyroid cancer (DTC) therapy. Low thyroglobulin (Tg) levels and negative Iodine-131 (131I) whole-body scan (WBS), along with negative 18 F-FDG-PET/ CT, suggested a lesser likelihood of active illness. Positive 18 F-FDG-PET/CT findings, however, were associated with a variety of signs of local recurrence and regional or distant metastases in patients with suspected WBS. We aim to evaluate the utility of 18 F-FDG-PET/CT in managing DTC patients with negative 131I post-therapy WBS and elevated Tg. We retrospectively reviewed 55 patients with DTC (76% papillary and 24% follicular). Patients underwent total thyroidectomy or several radioactive iodine (RAI) treatments or both. WBS was performed 5-7 days after RAI treatment. Inclusion criteria were elevated serum Tg, negative anti-Tg auto-antibodies (AbTg) during long-term follow-up, presence of 18F-FDG-PET/CT images, and negative or suspicious WBS. 54% of 18 F-FDG-PET/CTs detected at least one lesion, mainly, cervical lymph nodes (49.9%), mediastinal lymph nodes (40.4%), local recurrence (34%), and bone or tissue metastasis (36.2%). The three major sites of metastasis were lung, bone, and liver. 18 F-FDG-PET/CT identified recurrence or metastasis in 45% of patients with high serum Tg and negative WBS, modifying therapeutic management in half the patients for suitable treatment modality (surgery vs. tyrosine kinase inhibitor). The findings redemonstrate that elevated Tg with negative or suspicious WBS necessitates 18 F-FDG-PET/CT for localization of recurrence. 18 F-FDG-PET/CT is useful in managing locally recurrent or metastatic DTC with high Tg levels. It influences treatment and accurately assesses disease severity.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

Impact of 18F-FDG PET/CT on treatment of patients with differentiated thyroid carcinoma, negative 131I whole body scan and elevated serum thyroglobulin.

Objective(s): 18F-FDG PET/CT is increasingly performed in patients with differen-tiated thyroid cancer. The aim of this study was to assess the clinical impact of 18F-FDG PET/CT on the management of patients with differentiated thyroid carcinoma who had elevated serum thyroglobulin (Tg) and negative 131I whole body scan (WBS). Methods:67 patients with differentiated thyroid carcinoma were included in this study. The findings of 18F-FDG PET/CT imaging were compared with histo-pathology, follow up imaging, or clinical follow-up results. The diagnostic accuracy of 18F-FDG PET/CT was evaluated for the entire patient group and for those patients with stimulated serum thyroglobulin levels of less than 5, 5–10, and more than 10 pmol/L as well as for local recurrences and metastases sites. The impact of 18F-FDG PET/CT on therapeutic management was also evaluated. Results:30/67 patients had positive findings on 18F-FDG PET/CT; 28 were true-positive and 2 were false-positive. 18F-FDG PET/CT results were true-negative in 36 patients and false-negative in 1 patient. The overall sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were, 96.5%, 94.5%, 95.5%, 93.3%, and 97.2% respectively. Positive 18F-FDG PET/CT findings were directly correlated with stimulated serum thyroglobulin levels, 7.1% had Tg between 5–10, and 92.9% had Tg greater than 10 pmol/L. 18F-FDG PET/CT had a high or moderate impact on treatment management in 28 (41.8%) of patients.Conclusion: 18F-FDG PET/CT is able to improve diagnostic accuracy and have management impact in a therapeutically relevant way in patients with differentiated thyroid carcinoma who present with rising thyroglobulin level, negative 131I WBS, and clinical suspicion of recurrent disease.

A Case of Diffuse Sclerosing Variant of Papillary Thyroid Cancer: An Aggressive Variant Presenting With Recurrent Locoregional Nodal Disease

Diffuse sclerosing variant (DSV), a subtype of papillary thyroid carcinoma (PTC), has been considered more aggressive than classical PTC given that it usually presents with extrathyroidal invasion and lymph node metastasis at the time of diagnosis. Data about the risk of recurrence and prognosis is still debatable. Hence, we report a 29-year old woman with recurrent DSV-PTC that presented with pulmonary metastasis after multiple surgical interventions, radioactive iodine (RAI) therapy and a negative whole-body scan (WBS) ten months prior to this finding.A 29-year old woman without history of systemic illness, family history of thyroid cancer or neck radiation exposure, developed diffuse goiter at age 23. A thyroid and neck ultrasound revealed an enlarged heterogeneous thyroid gland with innumerable small bright echogenicities scattered throughout and bilateral neck adenopathy. No thyroid nodules were seen. Anti-thyroglobulin antibodies (anti-Tg Ab) were positive. A fine needle aspiration biopsy (FNAB) was positive for PTC with cytologic features suggestive of DSV. Subsequently, total thyroidectomy was performed, and 15 lymph nodes were positive for PTC. Thyroid suppression therapy was started maintaining goal of TSH <0.1ng/dL. Patient had a second neck dissection one month later, where 7 lymph nodes were positive for PTC. Pathology revealed chronic lymphocytic thyroiditis with bilateral multifocal PTC and staging pT3N1b. Two months after thyroidectomy, RAI therapy was provided with 153.6mCi of I-131. Post RAI therapy WBS and SPECT/CT demonstrated persistent metastasis to lymph nodes. After this finding, a third left neck dissection was done with additional lymph nodes resection positive for PTC. A second RAI therapy with 138mCi of I-131 was administered the following year. Continued surveillance suggested recurrence of PTC due to new suspicious nodules on neck along with increased anti-Tg Ab level from 44.64 to 95 IU/mL. FNAB confirmed PTC of five different locations of the thyroid bed. She had two additional neck dissections. Metastasis of lymph nodes was confirmed at multiple levels in the right neck and central compartment. Ten months after being without evidence of PTC recurrence in previous WBS and FDG-PET/CT, she started to develop hemoptysis. A neck and chest CT scan demonstrated innumerable bilateral hyperdensities consistent with pulmonary metastasis. At this time, TSH continued suppressed in 0.06 mIU/mL but, anti-Tg Ab had increased to 160 IU/mL.DSV-PTC has been shown to be at an advanced stage upon diagnosis. Furthermore, it has been documented that distant metastasis could also be present at this time with pulmonary metastasis being the most common. Nonetheless, some authors suggest that the advanced presentation could be due to delayed diagnosis rather than DSV intrinsic behavior. Besides its aggressive nature, DSV-PTC risk of recurrence remains controversial.

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.

Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq.

BackgroundAfter initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.MethodsTotal 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.ResultsIn patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.ConclusionTherefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

A Review of TENIS Syndrome in Hospital Pulau Pinang.

Introduction:The treatment for differentiated thyroid cancers (DTCs) has always been radioactive iodine 131I therapy after definitive surgical management. Clinicians are faced with therapeutic challenges when dealing with patients having thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome (elevated serum thyroglobulin [Tg] levels but negative whole-body scans [WBSs]).Objective:The aim of the study was to determine the prevalence of TENIS syndrome in our local setting and to evaluate the use of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) in the management.Methodology:The data from DTC patients treated in the Department of Nuclear Medicine, Hospital Pulau Pinang from December 1, 2010, to November 30, 2016, with negative WBS and elevated Tg were reviewed. These patients should have undergone 18F-FDG PET-CT to be included in the study.Results:Only forty (10.4%) out of a total of 386 patients treated in Hospital Pulau Pinang during the study fulfilled the inclusion criteria. There were 28 women (70%) with median age of 59 years old. Thirty-four patients (85%) had papillary thyroid cancer (PTC) and six patients had follicular thyroid cancer. The use of 18F-FDG PET-CT revealed 23 patients (57.5%) with 18F-FDG avid metastases suggesting dedifferentiation of thyroid cancers. Based on this study, the probability of detecting FDG-avid disease is higher (P = 0.03) if 18F-FDG PET-CT was performed when Tg ≥15 ng/mL.Conclusion:TENIS syndrome constitutes a significant number of cases in our setting. Our data suggest a cutoff Tg ≥15 ng/mL for performing 18F-FDG PET-CT for these patients would be more beneficial than the currently American Thyroid Association recommended cutoff of 10 ng/mL.

A rare case report of very low thyroglobulin and a negative whole-body scan in a patient with a solid variant of papillary thyroid carcinoma with distant metastases

Rationale:The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in postsurgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-iodine distribution on a whole-body scan (WBS). Recent studies have defined patients who subsequently have no evidence of disease as those who have a stimulated Tg level <1 ng/mL with no other radiological or clinical evidence of disease.Patient Concerns:A woman patient with solid variant papillary thyroid carcinoma (SVPTC) had undergone twice thyroidectomy with lymph node dissection and radioactive therapy. Recently, she was found to have lung and brain metastases despite a very low serum Tg level and a negative WBS. Nowadays, the patients have suggested targeted treatment, such as tyrosine kinase inhibitors, may be worthy of consideration to prevent the related events.Diagnoses:She was diagnosed as PTC.Interventions:She had undergone twice thyroidectomy with lymph node dissection and radioactive therapy.Outcomes:She was found to have lung and brain metastases despite a very low serum Tg level and a negative WBS.Lessons:We aim to suggest that patients with SVPTC should be treated cautiously because they may have a higher frequency of distant metastases and a less favorable prognosis compared with patients with classical papillary thyroid cancer.

Can the American Thyroid Association Risk of Recurrence Predict Radioiodine Refractory Disease in Differentiated Thyroid Cancer

Objective: The aim of this study was to compare the TNM staging system and the American Thyroid Association (ATA) recurrence risk classification in predicting radioiodine refractory disease (RRD) in differentiated thyroid cancer (DTC) and to analyze the correlation of stimulated thyroglobulin (Tg) levels and rate of Tg elevation with the standardized uptake value on ¹⁸F-fludeoxyglucose (FDG) PET/CT scan. Methods: RRD was indicated through the retrospective analysis of consecutive ¹⁸F-FDG PET/CT scans in DTC with stimulated Tg >10 ng/ml and negative ¹³¹I NaI whole-body scans (WBS). Tg elevation velocity was compared to the likelihood of a positive scan. The ATA recurrence risk and TNM staging system were compared to see which of them better predicted the subsequent development of RRD. Results: Fifty-eight of 636 subjects developed RRD: 52 papillary and 6 follicular thyroid cancer. The median time between diagnosis and a negative WBS was 24 months (range 12-240). RRD developed in 11 low-risk, 32 intermediate-risk and 15 high-risk patients. A better response to therapy was seen in the low-risk versus the intermediate- and high-risk groups. ¹⁸F-FDG PET/CT scans had a diagnostic accuracy of 94.8%, sensitivity of 97.7%, specificity of 85.7%, positive predictive value of 95.6% and negative predictive value of 92%. There was no correlation between the Tg level or rate of rise and a positive scan. Overall, PET-CT upstaged 18 (31%) cases, leading to a change in management in 20 (35%) cases. Conclusion: The TNM and ATA staging systems show no significant difference in predicting the development of RRD. RRD is less likely in stage I, II and low-risk patients. There is no correlation between the level or rate of Tg rise and a positive ¹⁸F-FDG PET/CT scan.

Differentiated thyroid carcinoma: Incremental diagnostic value of 131I SPECT/CT over planar whole body scan after radioiodine therapy.

The purpose of this prospective study was to determine the incremental diagnostic value of single photon emission computed tomography/computed tomography with iodine-131 over planar whole body scan in the staging of patients with differentiated thyroid carcinoma. A total of 365 patients (270 female, 95 male) with differentiated thyroid carcinoma were treated with radioiodine therapy for thyroid remnant ablation with radical intent after thyroidectomy between January 2013 and November 2014. In addition to planar whole body scan, single photon emission computed tomography/computed tomography of neck and chest were performed. Each radioactive focus at whole body scan was classified as positive or equivocal with respect of specific territories: thyroid bed, cervical lymph nodes and distant metastases.Whole-body scan detected focal uptake in 353 patients and no uptake in 12. The location was considered equivocal in 100. Single photon emission computed tomography/computed tomography detected focal uptake in 356 patients and no uptake in nine. In three patients with negative wholebody scan, single photon emission computed tomography/computed tomography provided information about residual activity in the thyroid bed. By single photon emission computed tomography/computed tomography the location was equivocal in 18 patients only. Single photon emission computed tomography/computed tomography was helpful in 82 out of 100 patients with equivocal findings by whole body scan allowing a correct identification of the uptake sites. In a great number of equivocal whole body scan, due to high remnant activity, single photon emission computed tomography/computed tomography was able to differentiate between thyroid remnant and lymph nodes uptake. In 22 out of 100 patients with doubtful whole body scan, single photon emission computed tomography/computed tomography correctly identified nodal or distant metastases, and in 2/100 patients, focal uptake classified as metastatic by whole body scan was reclassified as para-physiological by single photon emission computed tomography/computed tomography. The TNM classification changed in 13 out of 22 patients. Single photon emission computed tomography/computed tomography improves detection and localization of the iodine-131 uptake after thyroidectomy in patients with differentiated thyroid carcinoma and it is more accurate than whole body scan to evaluate lymph nodes and to identify and characterize distant metastases. Single photon emission computed tomography/computed tomography aids assessment of lower/upper stage in a significant number of patients with differentiated thyroid carcinoma and it can affect therapy decision-making and patient management.

The usefulness of fluorine-18 fluorodeoxyglucose PET in the detection of recurrence in patients with differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan.

PET/computed tomography (CT) using fluorine-18 fluorodeoxyglucose (F-FDG) has been used in the diagnosis of recurrence and metastases of differentiated thyroid cancer (DTC) in cases of negative whole-body scan (WBS) despite elevated concentrations of stimulated thyroglobulin (Tg). To assess the utility of PET/CT in the detection of recurrence among patients with DTC with increased Tg levels and negative results of WBS. PET/CT results were retrospectively analyzed in patients with DTC with increased Tg and negative results of WBS as well as negative cervical ultrasonography and chest radiography. PET-CT was performed 1-2 weeks after recent diagnostics under conditions of endogenous or exogenous thyroid-stimulating hormone stimulation. PET/CT was performed using a Discovery ST scanner 1 h after an intravenously F-FDG injection (activity 4-5 MBq/kg). To determine the cutoff value of Tg, receiver operating characteristic curves were analyzed. Sixty-nine patients with DTC (48 women, 21 men) aged 22-83 years (mean 50.9±17.5 years) were qualified. In 44 patients (63.8%), PET/CT indicated lesions of DTC. Thirty (43.5%) patients had F-FDG positive findings. In the remaining 14 patients (20.3%), lesions were found in CT only. Patients with a positive PET/CT scan had significantly higher Tg values than patients with a negative PET/CT (mean 143.8 vs. 26.5 ng/ml, P=0.03). The cutoff value of Tg concentration measured with the receiver operating characteristic analysis was 32.9 ng/ml. PET/CT is a useful tool in the detection of recurrence among thyroid cancer patients in cases of conflicting results of standard procedures, particularly for those with high Tg levels and negative WBS. The probability of obtaining a positive PET-CT result increases with the level of Tg.

The role of FDG-PET in localization of recurrent lesions of differentiated thyroid cancer (DTC) in patients with asymptomatic hyperthyroglobulinemia in a real clinical practice.

Available methods, including serum thyroglobulin (Tg) measurement and whole-body scan (WBS) performed after radioiodine administration, allow for a precise diagnostics in differentiated thyroid cancer (DTC). However, some asymptomatic patients demonstrate negative WBS despite a high Tg serum concentration. In these subjects, fluorodeoxyglucose-positron emission tomography (FDG-PET) should be considered. The primary aim of our study was to evaluate a diagnostic value of FDG-PET in asymptomatic hyperthyroglobulinemia. The secondary one was to determine a prognostic value of a negative FDG-PET result in DTC patients with elevated Tg level. One hundred and ten FDG-PET/CT scans were retrospectively analyzed, 85 scans were done under TSH stimulation and 25 on LT4 suppressive therapy. Follow-up ranged between 4 and 9 years. The first FDG-PET/CT detected cancer foci in 49 subjects with a global sensitivity of 45%. When the sensitivity was evaluated with reference to TSH stimulation and suppression, its values were 50 and 28% respectively. In 42 patients, FDG-PET failed to diagnose the reason for elevated Tg level. During further follow-up, in 17 of them, DTC recurrence was detected by other methods (CT, MRI, US). Fourteen subjects with asymptomatic hyperthyroglobulinemia were free of DTC progression for at least 4 years. FDG-PET in DTC patients with asymptomatic hyperthyroglobulinemia constitutes a valuable diagnostic tool. Negative FDG-PET demonstrated a limited prognostic significance, as only every third patient did not show DTC progression. Moreover, negative FDG-PET does not justify less strict DTC monitoring, because it is related to 40% risk of relapse during the 5-year follow-up.

Value of Dedicated Head and Neck 18F-FDG PET/CT Protocol in Detecting Recurrent and Metastatic Lesions in Post-surgical Differentiated Thyroid Carcinoma Patients with High Serum Thyroglobulin Level and Negative 131I Whole-body Scan.

Objective(s):In clinical practice, approximately 10-25% of post-surgical differentiated thyroid carcinoma (DTC) patients with high serum thyroglobulin (Tg) and negative 131I whole-body scan (WBS) have poor prognosis due to recurrent or metastatic lesions after radioactive iodine treatment. The purpose of this study was to evaluate the value of 18F-FDG PET/CT scan in DTC patients with high serum Tg level and negative 131I WBS.Methods:69 post-surgical DTC patients with high serum Tg level and negative post ablation 131I WBS were enrolled in this study. All DTC patients underwent head and neck ultrasound, CT scan and whole-body 18F-FDG PET/CT, based on the dedicated head and neck protocol.Results:Overall, 92 lesions were detected in 43 (62.3%) out of 69 patients with positive 18F-FDG PET/CT scan, compared to only 39 lesions detected on CT scan in 26 (37.7%) out of 69 patients. The sensitivity, accuracy and negative predictive value of 18F-FDG PET/CT were 88%, 87% % and 76%, respectively, which were significantly higher than those of CT scan (67.2%, 54.3% and 48.8%, respectively) (P<0.01). Specificity and positive predictive value of 18F-FDG PET/CT (90.5% and 95.2%, respectively) were similar to those of CT scan (95.2% and 96.2%, respectively) (P>0.05). The maximum standardized uptake value (SUVmax) threshold was 4.5 with a good diagnostic value (sensitivity of 92.3% and specificity of 100%). The dedicated head and neck 18F-FDG PET/CT protocol altered the treatment plan in 33 (47.8%) out of 69 DTC patients with high serum Tg level and negative 131I WBS.Conclusion:Dedicated head and neck 18F-FDG PET/CT protocol showed a higher diagnostic value, compared to CT scan and played an important role in detecting recurrent or metastatic lesions in post-surgical DTC patients with high serum Tg level and negative 131I WBS.

Diagnostic value of 18F-FDG PET/CT in patients with TENIS syndrome: correlation with thyroglobulin levels

The aim of the study was to disclose the place of (18)F-FDG PET/CT to predict recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Seventy-one patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels underwent PET/CT. They were followed up for 6-50 months (median 23) for the occurence of recurrent disease as detected by either clinical findings, other imaging modalities or histopathological examination. The place of PET/CT findings at baseline to predict the presence of recurrent disease was evaluated. Correlation between PET/CT findings and Tg levels was examined and a threshold for Tg level above which the predictive value of PET/CT was highest was determined. PET/CT was positive for recurrent disease in 38 (53.5%) patients. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of PET/CT to predict the occurence of recurrent disease at follow-up were 68.8, 78.3, 86.8, 54.5 and 71.9%, respectively. The sensitivity, accuracy and PPV of PET/CT increased with increasing Tg levels. The highest diagnostic accuracy of PET/CT, with a sensitivity of 76.2% and a specificity of 100% to detect recurrent disease appeared to be at a Tg level greater than 29 ng/mL. Our findings suggest that (18)F-FDG-PET/CT is a valuable tool to predict the occurence of recurrent disease in patients with DTC, negative WBS and elevated Tg levels. PET/CT positivity has been shown to be strongly and positively correlated with Tg levels in this patient subset.

Long-Term Follow-Up of Patients With Differentiated Thyroid Cancer Who had Negative 131I Whole-Body Scan at First Evaluation After Treatment

The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).

18-Fluorodeoxyglucose Positron Emission Tomography in the Early Diagnostic Workup of Differentiated Thyroid Cancer Patients with a Negative Post-Therapeutic Iodine Scan and Detectable Thyroglobulin

Surgery and high-dose radioactive iodine ((131)I) treatment are the cornerstones in the treatment of differentiated thyroid cancer. Patients without (131)I uptake on the post-therapeutic whole body scan (WBS), but with detectable thyroglobulin (Tg) during thyroxine withdrawal (Tg-off), are evaluated with an 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) for tumor localization within three months. The yield of (18)F-FDG-PET imaging and clinical usefulness of a Tg-off cutoff value to predict a positive scan were assessed. From 2002 to 2011, 52 patients with a negative WBS and concurrent detectable Tg-off were evaluated. Thirty-five PET scans were performed during initial treatment, 17 after recurrent disease. Thirty-two patients were on substitution therapy, 17 were evaluated with endogenous thyrotropin elevation, and 3 after recombinant human thyrotropin stimulation. To determine the Tg-off cutoff value, a receiver operating characteristic curve was used. Nine (17%) (18)F-FDG-PET scans were true positive, 3 (6%) false positive, 36 (69%) true negative, and 4 (8%) false negative (sensitivity 69%, specificity 92%). In 13%, a true-positive scan resulted in a change in the clinical management. The area under the receiver operating characteristic curve is 0.82 [CI 0.64-0.99] (p<0.01), and the Tg-off cutoff value is 38.00 ng/mL (sensitivity 67%, specificity 95%). Ninety percent of (18)F-FDG-PET true-positive patients had a Tg-off >2.00 ng/mL. An (18)F-FDG-PET within three months after a negative WBS with detectable Tg-off showed additional tumor localization in 17% of the patients, leading to a change in clinical management in 13%. A clinically useful Tg-off cutoff value was not found, but 90% of positive (18)F-FDG-PET scans occurred in patients with a Tg-off >2.00 ng/mL.

Therapeutic Implications of Diffuse Hepatic Uptake Following I-131 Therapy for Differentiated Thyroid Cancer

To determine if diffuse hepatic uptake (DHU) of radioactive iodine (I-131) following radioactive iodine treatment has prognostic implications in otherwise scan-negative patients. This is a retrospective review of patients treated for differentiated thyroid cancer (DTC) at Beth Israel Deaconess Medical Center between January 1990 and June 2006. This group included patients receiving therapy to ablate presumed remnant tissue, as well as treatment for persistent disease as measured by thyroglobulin or imaging. All patients included in the study had no remnant uptake and otherwise negative posttherapy scans. A total of 57 patients with 63 scans met these criteria. The scans were then scored for DHU on a scale of 0 to 5, with 0 being no uptake and 5 being intense uptake relative to background. Sixteen of 63 treatments were remnant ablations. Ten of 57 patients had positive thyroglobulin antibodies. Average DHU was similar in the ablation and therapeutic groups (1.9 vs. 2.3, P = .3). There was no correlation with either I-131 dose or the presence of thyroglobulin antibodies. There was a difference for DHU in the rate of disease-free survival, (undetectable thyroglobulin and no clinical or radiographic evidence of metastasis); 50% of patients with hepatic uptake scores of 0-2 were disease-free compared to 15% with scores of 3-5 (P<.01). The average length of follow-up for disease-free patients was 4.6 years. In patients with DHU with otherwise negative whole-body scans following I-131 treatment, more intense hepatic uptake is associated with lower likelihood of complete response to I-131 treatment.

Value of the negative PET-FDG in the middle term follow-up of differentiated thyroid cancer in patients with negative 131I-Na scan and elevated thyroglobulin serum levels

ObjectiveThis study has aimed to analyze the evolution of patients diagnosed with differentiated thyroid carcinoma (DTC) with a negative 131I-Na whole body scan (WBS), high levels of serum thyroglobulin (Tg) and negative 18F-fluorodeoxyglucose positron emission tomography (PET-FDG) study. Material and methodsTwenty-three patients diagnosed and treated for DTC were studied retrospectively. Patients were aged between 23 and 83 and had shown, between January 2001 and December 2002, negative WBS, Tg values in a range of suspected recurrence or metastasis (Tg>2ng/mL with thyroid hormone withdrawal) and a negative PET-FDG study. The patients were monitored clinically, radiologically and analytically for a minimum period of 4 years. After this, a new evaluation was made of their state of disease with a control WBS, also observing the evolution of Tg. All WBS were performed with a 185MBq diagnostic dose of 131I-Na. ResultsIn 18/23 patients, Tg decreased and in 5 it increased. Four patients (17%) were free of active disease (negative WBS Tg<2ng/mL). A total of 16 patients (70%) were free of disease according to the WBS but had elevated Tg. Three patients (13%) had disease and high levels of Tg, two of them with positive WBS and the third with positive 99mTc-MIBI scan and CT. ConclusionsMost patients with a negative WBS, high Tg serum levels and negative PET-FDG had good evolution, with descending Tg levels, normal levels even being reached in a significant percentage of them.