Elevated Serum Thyroglobulin Levels Research Articles

Prospective evaluation of 68 Ga-NODAGA-RGD PET-CT in patients of carcinoma thyroid with thyroglobulin elevated negative radioiodine scintigraphy (TENIS) with a head-to-head comparison with FDG-PET/CT.

This study aimed to examine the expression of RGD binding integrins in patients of elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (TENIS) employing 68 Ga-NODAGA-RGD PET-CT. This was a prospective study involving 30 proven cases of TENIS with histopathological diagnosis of differentiated thyroid carcinoma post-surgery. In addition to observing the lesional concentration on 68 Ga-NODAGA-RGD PET-CT, a 4-point visual grading system (grade I-IV), was undertaken to estimate the degree of radiotracer avidity, for potential of theranostics. On 18 F-FDG-PET/CT, the uptake was seen in 182 lesions out of a total of 200 (91%). 68 Ga-NODAGA-RGD PET-CT showed expression in a total of 110/200 (55%) lesions. On patient-specific analysis, 68 Ga-NODAGA-RGD PET-CT was positive for the disease in 21/30 patients (70%) and negative in 9/30 (30%) patients. The overall patient-specific sensitivity and specificity of 68 Ga-NODAGA-RGDPET-CT were 75% and 100%, respectively. 18 F-FDG PET-CT was positive for the disease in 26/30 patients (86.66%) and negative in 4/30 (13.33%) patients. The overall patient-specific sensitivity and specificity of 18 F-FDG-PET/CT were 92.86% and 100%, respectively. The 4-point visual grading system revealed 14/200 (7%) lesions demonstrating Grade I uptake, 49/200 (24.5%) lesions grade II uptake, 17/200 (8.5%) lesions grade III uptake and 40/200 (20%) lesions grade IV uptake. The results suggested that RGD-binding integrin is expressed in a sizeable fraction of metastatic lesions of TENIS cases, albeit demonstrating a varying degree of uptake. Out of the soft tissue, lung, and bone lesions, metastatic bone lesions showed more RGD affinity than other sites. The patients with substantial RGD uptake on a 4-point visual grading system may be potential targets for RGD-based therapy.

Radioiodine ablation after thyroidectomy could be safely abandoned or postponed in selected stage I papillary thyroid carcinoma patients of low-risk group: an observational prospective study

Background. The European Thyroid Association consensus for the management of differentiated thyroid cancer (2006) suggested to avoid radioactive iodine (RAI) after thyroidectomy in patients with unifocal microcarcinoma (≤ 1 cm) with no extension beyond the thyroid capsule and without lymph node metastases. As the new data was collected and the risk stratification was revised, in 2022 the same recommendation was expanded to the patients with microcarcinoma and central neck lymph node involvement. The American Thyroid Association guidelines (2015) advocated no RAI ablation after hemi- or total thyroidectomy for thyroid cancer less than 1 cm with 5 and less micrometastases up to 2 mm in central neck lymph nodes as this strategy has no negative impact on the disease prognosis. In low-risk patients, no sufficient evidence of the obligatory postsurgical radioiodine ablation has been yet demonstrated. The aim of our study was to reveal whether RAI after thyroidectomy can be abandoned or postponed until the disease progression is confirmed in low-risk patients. Materials and methods. Two groups of patients (30 per group, 60 in total) with papillary microcarcinoma Т1N1a (5 and less level VI micrometastases up to 2 mm) were observed during a 5-year follow-up. In the first group, patients received 100 mCi (3.75 GBq) I131 shortly after total thyroidectomy while in the second group, postponed RAI was applied when progression signs were observed (elevated serum thyroglobulin level and US/CT suspected findings) after thyroid surgery. Results. After 5 years, no significant difference between groups was observed regarding post-RAI local recurrences (one in the first group and two in the second group) and/or distant metastases (t-test, p = 0.58). All cases of neck recurrences were treated with subsequent surgical excision, with no new data of progression within the specified follow-up. Conclusions. RAI adjuvant therapy for papillary thyroid carcinoma Т1N1a may not be necessary for patients with small number of level VI micrometastases. Local and distant metastases revealed during the careful follow-up by thyroglobulin level elevation and when using visualization techniques can be effectively treated with postponed RAI therapy and/or surgery.

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.

Importance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in detection of post-thyroidectomy recurrence in differentiated thyroid cancer with negative radio-isotope iodine scan, yet, elevated serum thyroglobulin level

BackgroundThyroid cancer considered the 6th common cancer in female and represents approximately 1% of all cancers. Thyroid cancer is generally characterized by good prognosis, long term survival and low aggressiveness. Its prognosis is related to tumor dimensions, extra capsular extensions, the age at diagnosis and distant metastases sites. Combination between positron emission tomography and computed tomography allow anatomic, functional & molecular information.AimTo demonstrate Fluorine 18 fluorodeoxyglucose positron emission tomography)/computed tomography role for evaluation of post-thyroidectomy recurrence either local or distant metastatic lesions in differentiated cancer thyroid patients with negative radio-isotope iodine scan, yet showing elevated serum thyroglobulin level.ProcedureA prospective study included twenty patients with previous history of differentiated thyroid cancer. All patients after history taking and revising the medical sheet underwent Serum Thyroglobulin level & I-131 whole body scan examinations and then Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography study. The findings of Positron Emission Tomography/Computed Tomography imaging compared with results of histopathology or follow-up clinical results as a gold standard.ResultsFluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography based analysis showed that nineteen true positives and one was true negative as confirmed by the gold standard (Histopathology and clinical follow-up). Thirteen patients had either local recurrence or lymph node metastases without distant metastatic disease, six patients had different distant metastasis. Fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography based analysis showed that nineteen true positives and one was true negative as confirmed by the gold standard (histopathology and clinical follow-up). The accuracy and sensitivity of Fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (95%) were significantly better than those of the Computed Tomography alone (84.2% and 80%, respectively).ConclusionsFluorine 18 Fluorodeoxyglucose positron emission tomography/computed tomography provided a critical role in assessment and management of patients with suspected differentiated thyroid recurrence, presenting with high serum thyroglobulin level and negative radio-isotope iodine scan. It enhances diagnostic accuracy through giving exact anatomical localization of recurrent and/or metastatic tumor foci.

Clinical predictors of I-131 therapy failure in differentiated thyroid cancer by machine learning: A single-center experience.

Well-differentiated thyroid carcinoma is predominantly a slow-growing malignancy, amendable to treatment, and has an excellent prognosis following thyroidectomy and radioiodine (RAI) therapy. However, patients who fail the initial RAI treatment attempt may require repeated RAI or other treatments and with this, comes an associated impact on patient quality of life. Therefore, the anticipation of patients in whom there is a higher risk of RAI failure may help in patient risk stratification and subsequent management. We conducted a retrospective review to determine the factors associated with initial RAI therapy failure in well-differentiated thyroid cancer patients. Using scikit-learn from Python, we implemented a machine-learning algorithm to determine the clinical patient factors associated with a higher likelihood of treatment resistance. We found that clinical factors such as tumor focality (P = 0.026) and lymph node invasion at surgical resection (P = 0.0135) were significantly associated with initial treatment failure following RAI. Elevated serum thyroglobulin (Tg) and Tg antibody levels following surgery but before RAI were also associated with treatment resistance (P < 0.0001 and P = 0.011 respectively). Less expected factors such as decreased time from surgery to RAI were also associated with treatment failure, however not to a statistically significant degree (P > 0.064). Clinical outcomes following RAI can be stratified by identifying factors that are associated with initial treatment failure. These findings can help restratify patients for RAI treatment and change patient management in certain cases. Such stratification will ultimately help to optimize successful treatment outcomes and improve patient quality of life.

Serum thyroglobulin level in newly detected thyrotoxicosis and its role in differential diagnosis of thyrotoxicosis

Background: Elevated serum thyroglobulin (Tg) level is commonly observed in various forms of thyrotoxicosis; the levels vary according to different etiologies. This study aimed at identifying the value of serum Tg level in the differential diagnosis of common etiologies of thyrotoxicosis. Methods: This cross-sectional study was conducted at the endocrine outpatient department of a tertiary hospital in Bangladesh from March 2015 to May 2017. In this study, 200 subjects with newly detected untreated thyrotoxicosis were evaluated. Serum Tg was assayed by chemiluminescent immunometric assay. Results: Serum Tg level was raised in 48% of subjects. Subjects aged ≥40 years, and those having a family history of thyroid disorders had relatively higher thyroglobulin levels. The frequency of subjects with an elevated Tg was highest in subacute thyroiditis (89.5%) followed by toxic nodular goiter (77.3%) and Graves’ disease (32.9%); the difference in the frequencies was statistically significant (p&lt;0.001). Median Tg was highest in the subjects with subacute thyroiditis (132.6 ng/ml) followed by toxic nodular goiter (99.55 ng/ml); those with Graves’ disease had the lowest Tg level (12.5 ng/ml); the differences in median Tg levels across the three groups were also statistically significant (p&lt;0.001). Conclusions: Serum thyroglobulin level may be useful for the etiological diagnosis of thyrotoxicosis.

Comparison of simultaneous 18F-2-[18F] FDG PET/MR and PET/CT in the follow-up of patients with differentiated thyroid cancer

18F-FDG PET/CT is the most accurate imaging modality in differentiated thyroid cancer (DTC) patients with either an aggressive histology, an absence of radioiodine uptake in neoplastic foci, or in the absence of imaging abnormalities in patients with an elevated serum thyroglobulin (Tg) level that progresses with time. We evaluated the diagnostic performance of FDG PET/MR in comparison with that of PET/CT. Following the injection of a single 18F-FDG activity, PET/MR and PET/CT were sequentially performed in 40 consecutive patients with DTC previously treated with total thyroidectomy and radioiodine ablation. All patients were then followed up for at least 6months. PET/MR was positive in 11 patients and PET/CT in 10. PET/MR detected 33 tumor foci and PET/CT 30. During the follow-up of the 12 patients with negative initial PET studies and with a detectable serum Tg, only one patient had a neck recurrence and the administration of an empiric high activity of 131I in the other 11 patients did not reveal any tumor focus. In the 17 patients with an initial serum Tg level < 2ng/mL, no recurrence occurred. This study confirms the high diagnostic accuracy of FDG PET studies in DTC patients with elevated serum Tg levels and shows that PET/MR brings similar information as compared to PET/CT imaging.

Outcome of 18f-Fluorodeoxyglucose Positron Emission Tomography (PET)-Directed Resections in Differentiated Thyroid Carcinoma (DTC): Experience in a Developing Country.

The aim of this study was to assess the accuracy of 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET scan) in localizing the disease in differentiated thyroid carcinoma patients undergoing re-operations. This is a retrospective analysis of a prospectively maintained data (December 2007 to December 2016). The patients included had elevated serum thyroglobulin (Tg) levels and negative iodine uptake (TENIS) and planned for re-operation with one or more accessible site of metastasis detected on FDG-PET scan. Clinical details, FDG-PET/CT findings, operative findings, histology, pre-, and post-operative Tg levels were recorded. Thirty-two patients were included. The mean age of the patients was 46.8 ± 15.8years (M:F = 1:1.6) and mean pre-operative Tg value was 247.6 ± 92.3ng/ml. FDG-PET disclosed a total of 77 hot spots in these 32 patients, 56 of which were surgically explored and resections performed. Patient- and lesion-based positive predictive value (PPV) of FDG-PET in detecting recurrent/metastatic DTC lesions was 87.5 and 71%, respectively. Remaining cases had granulomatous or nonspecific inflammatory lesions. A total of 12.5% of recurrent DTC patients explored could achieve biochemical cure. All these had disease confined to neck. Remaining patients continued to have high serum Tg level, though it fell substantially in majority of patients. False positive scans are frequent in regions with high prevalence of inflammatory diseases. Hence, FDG-PET directed re-operations should be taken up judiciously.

Role of PET/CT in detection of post-Thyroidectomy recurrence in differentiated cancer thyroid patients with negative radio-isotope iodine scan &amp; elevated serum thyroglobulin level

Abstract Aim of the Work To study of the role of PET/CT in in detection of post-thyroidectomy recurrence in differentiated cancer thyroid patients having negative radio-isotope iodine scan &amp; high serum thyroglobulin level. Materials and Methods The study incorporated 20 patients with previous history of differentiated cancer thyroid. All patients performed Serum Thyroglobulin level Estimation &amp; entire body scan I-131 (WBS) examination &amp; PET/CT study alluded from oncology specialist to Radiology Department. All patients in the study were subjected to history taking &amp;revising the medical sheet. Results PET/CT results will be compared with iodine radio-isotope scan &amp; serum thyroglobulin level and statistical analysis of the collected data will be performed to determine the diagnostic value of the PET/CT in detection of local recurrence or distant metastasis.

Heterophile antibody interference associated with natural killer cell therapy.

The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.

Oligometastatic Prostate Cancer: Molecular Imaging and Clinical Management Implications in the Era of Precision Oncology.

1338 Objectives: Differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple other negative conventional imaging studies represent a clinically difficult group of patients. 99m Tc-sestamibi is a non-conventional imaging study for DTC that was used in the 1980s-1990s to help evaluate DTC patients before being replaced with 18F-FDG. However, 18F-FDG PET scans may also be negative in these patients. This is a preliminary analysis of our study to evaluate the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tgs in patients with negative conventional imaging including negative 18F-FDG PET scans. Methods This prospective study included DTC patients who were at least 18 years old, had at least one prior 131I therapy, and had elevated Tg>5 ng/ml or positive anti-Tg antibodies (TgAb). In addition, all of the following imaging studies must have been clinically reported as negative for recurrence or metastasis within the last 12 months: neck ultrasound, diagnostic radioiodine scan, chest x-ray, CT of the chest/abdomen with/without contrast, and 18F-FDG PET/CT. If other imaging studies were performed, such as bone scans or brain imaging, these must also have been read as negative. This study was approved by the IRB at MedStar Health and all participants signed informed consent. Participants were injected with 925 MBq (25 mCi) of 99mTc-sestamibi intravenously and whole body images were acquired after ~1h with acquisition speed 4cm/min with parallel-hole low-energy collimator. Extra spot view, pinhole view, or SPECT/CT images were performed when necessary. Two blinded nuclear medicine physicians independently interpreted the 99mTc-sestamibi images, and graded each foci 1-5 (1 = definite physiological uptake or artifact; 2 = most likely physiological uptake or artifact; 3 = indeterminate; 4 = most likely recurrence or metastasis; 5 = definite recurrence or metastasis). Discordant findings were resolved by consensus. Foci graded 3-5 were categorized as positive result and was followed-up for confirmation. Results A total of four patients completed the sestamibi scan to date. One out of four patients (Patient1) was positive on the sestamibi scan for distant metastasis. In Patient 1, the sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponding to an occipital lytic bone lesion on the SPECT/CT (Figure 1). The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic thyroid cancer. Five months post-surgery the suppressed Tg was markedly reduced and stable at ~3.2ng/ml. Table 1 shows the sestamibi scan results, subsequent management and follow-up. With confirmation of the location of the metastatic foci in Patient 1, the two negative 18F-FDG PET/CT that were previously performed one year apart were reviewed again. The radiology reports did not document interpretation of the low-dose localization CT. In retrospect, the lytic skull metastasis was visible on both of the head CT, but could have been easily missed on the PET due to the normal intensive brain 18F-FDG activity. Conclusions In this preliminary analysis, 99mTc-sestamibi was able to identify the source of elevated Tg levels in one out of four DTC patients with biochemical recurrence and negative conventional imaging studies. 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT could not identify. Additional patients are being recruited. Research Support We are grateful for the generous donations from our patients.

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome.

AimsTo investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome.MethodsA cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus.ResultsEnlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus.ConclusionsThe angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake.

The high prevalence of reversible subclinical hypothyroidism with elevated serum thyroglobulin levels in chronic kidney disease patients .

We examined the thyroid function of non-dialysis-dependent chronic kidney disease (CKD) patients in Japan. Serum-free thyroxine, free triiodothyronine, thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) levels were evaluated in 37CKD patients. CKD was defined as sustained kidney damage for more than 3months and was classified as CKD 1+2 (n = 11), 3+4 (n = 10), or 5 (n=16), which were defined by glomerular filtration rates of ≥ 60, 15 - 59, or <15mL/min/1.73m2, respectively. The prevalence of primary hypothyroidism (TSH≥4.83 mU/L) in CKD 1+2, CKD 3+4, and CKD 5 was 9%, 20%, and 56%, respectively (p<0.05). Unexpectedly, elevated serum Tg levels (>30ng/mL), a marker of the reversible recovery of the thyroid function, were found in 67% of the CKD 5 patients (p < 0.05). The serum TSH and Tg levels became lower, without replacement therapy, after the initiation of hemodialysis and iodine restriction, and there was a significant correlation between the serum TSH and Tg levels in the CKD 5 patients (p < 0.05). The high prevalence of reversible hypothyroidism and the TSH-dependent elevation of the serum Tg levels was suggested in Japanese patients with advanced CKD. The excess ingestion and the impaired urinary excretion of iodine may be responsible for this reversible thyroid dysfunction. .

Elevated serum thyroglobulin levels as a marker of reversible hypothyroidism in patients with end-stage renal disease due to chronic glomerulonephritis

Difference in thyroid function depending on the etiology of end-stage renal disease (ESRD) was evaluated in 124 Japanese patients on haemodialysis (HD) due to either chronic glomerulonephritis (CGN...

Elevated serum thyroglobulin levels at the time of ablative radioactive iodine therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective cohort study.

Serum thyroglobulin is used as a surrogate marker for well-differentiated thyroid carcinoma recurrence. This study investigates whether thyroglobulin measured at the time of ablative radioactive iodine therapy predicts disease-free survival. A retrospective review was conducted of patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010 at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free survival of patients with a significantly elevated stimulated thyroglobulin level (27.5 µg/l or higher) at the time of ablative radioactive iodine therapy was compared to that of patients without a significantly elevated thyroglobulin level using univariate analysis. Patients with a thyroglobulin level of 27.5 µg/l or higher had an increased relative risk of disease recurrence of 4.50 (95 per cent confidence interval = 1.35-15.04). If lateral neck dissection was required at the time of surgery, patients also had an increased relative risk of macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47-16.55). An elevated thyroglobulin level of 27.5 µg/l or higher at the time of ablative radioactive iodine therapy is a prognostic indicator for macroscopic disease recurrence in well-differentiated thyroid carcinoma.

Early prognostic factors at the time of diagnosis of bone metastasis in patients with bone metastases of differentiated thyroid carcinoma.

Bone is the second most common site of distant metastases from differentiated thyroid cancer (DTC). Patients with bone metastases were associated with poor clinical outcomes; however, their clinical courses are heterogeneous. The aim of this study is to evaluate early prognostic factors of patients with bone metastases from DTC at the time of diagnosis of bone metastasis. This retrospective study included 93 patients with bone metastases from DTC. We defined 'Pre-RAIT group' as patients whose bone metastases were detected before initial RAIT. The 'post-RAIT group' was defined as patients whose bone metastases were detected after initial RAIT or during the follow-up period. Median age was 55.4years, and 55 patients (59%) had papillary thyroid cancer. Patients in the pre-RAIT group (n=32) demonstrated significantly poorer overall survival (OS) (HR=1.86, P=0.04) than those in the post-RAIT group. There was no significant difference in the OS according to the initial RAI avidity among all patients (P=0.18). RAI-avid bone metastases had better OS only in the pre-RAIT group (HR=0.23, P=0.01) but not in the post-RAIT group. In the post-RAIT group, older age (>45years), elevated serum thyroglobulin (Tg) level (>250ng/mL), and the presence of skeletal-related events (SREs) were significantly associated with poor OS. RAI avidity was not a significant prognostic factor in the post-RAIT group (P=0.33). Patients whose bone metastases were diagnosed before initial RAIT demonstrate a poorer prognosis. RAI avidity is an early prognostic indicator in the pre-RAIT group. Old age, higher serum Tg levels, and SRE are associated with poor survival outcomes in the post-RAIT group.

Iodine Uptake Patterns on Post-ablation Whole Body Scans are Related to Elevated Serum Thyroglobulin Levels After Radioactive Iodine Therapy in Patients with Papillary Thyroid Carcinoma.

Serum thyroglobulin (Tg) level is frequently elevated shortly after radioactive iodine (RAI) ablation therapy. The authors studied the relationship between the elevation of serum Tg after RAI therapy and iodine uptake pattern on post-ablation whole body scans (RxWBSs) in patients with papillary thyroid carcinoma (PTC). The study subjects were patients with PTC that had undergone first RAI therapy with thyroid hormone withdrawal after total thyroidectomy. Patients with a high level of serum anti-Tg antibody (TgAb, ≥60 U/mL), possible regional or distant metastasis as determined by pre-ablation or post-ablation studies, and negative iodine uptake of the anterior neck on RxWBS were excluded. Serum Tg was checked twice, that is, 7days after (post-ablation Tg) and on the day of RAI therapy (pre-ablation Tg). Ratio of pre-ablation Tg to post-ablation Tg (Tg ratio) was used to assess changes in serum Tg levels after RAI therapy. Patients were classified into two groups according to the presence of midline uptake above the thyroidectomy bed on RxWBS (negative (group 1) or positive (group 2) midline uptake). Variables were subjected to analysis to identify differences between the two groups. Two hundred and fifty patients were enrolled in this study; 101 in group 1 and 149 in group 2. Based on univariate analysis, post-ablation Tg (8.12 ± 11.05 vs. 34.12 ± 54.31; P < 0.001) and Tg ratio (7.81 ± 8.98 vs. 20.01 ± 19.84; P < 0.001) were significantly higher in group 2. On the other hand, gender, tumor (T) stage, lymph node (N) stage, size, multiplicity or bilaterality of primary tumor, dose of 131I, serum TgAb and thyroid-stimulating hormone (TSH) level (before or after RAI therapy) were not significantly different in the two groups. Variables with P values of <0.25 by univariate analysis were subjected to multivariate analysis, which showed post-ablation Tg (OR 1.060, 95% CI = 1.028-1.092; P < 0.001) and Tg ratio (OR 1.059, 95% CI = 1.028-1.092; P = 0.001) were significantly higher in group 2. Serum Tg level after RAI therapy was significantly higher in patients with midline uptake on RxWBS, compared with patients without midline uptake on RxWBS. Further investigations are needed to reveal the correlation between serum Tg elevation and clinical outcome according to the presence of midline uptake.

Prognostic Impact of Ultrasonography Features and (18)F-Fluorodeoxyglucose Uptake in Patients With Papillary Thyroid Microcarcinoma.

ObjectivesTo evaluate the prognostic impact of ultrasonography (US) features and 18F-fluorodeoxyglucose (18F-FDG) uptake in patients with papillary thyroid microcarcinoma (PTMC).MethodsThis study included 74 patients with a single PTMC diagnosed pathologically. Patients underwent total thyroidectomy, or near-total thyroidectomy and staging thyroid US and positron emission tomography (PET) were performed prior to surgery. US features of thyroid nodules were reviewed retrospectively and the maximum standard uptake value (SUV) of nodules was semiquantitatively analyzed on 18F-FDG PET/computed tomography (CT). Patients were followed-up for recurrence, which was defined as PTC on cytology results, elevated serum thyroglobulin (Tg) or anti-Tg antibody levels, or uptake on whole-body scintigraphy. We used univariate and multivariate analyses to evaluate whether poor prognostic outcomes were associated with US features or SUV values derived from PET/CT of nodules. In addition, subjects were divided into 2 groups for subgroup analyses: one with nodules equal to or larger than 5 mm and one with nodules smaller than 5 mm.ResultsAmong the 74 patients, there was no recurrence. Thus we evaluated the correlation between SUV value and US features with poor prognostic factors of PTMC which included extrathyroid extension, central and lateral lymph node (LN) metastasis. However no clinicopathologic factors were associated with extrathyroid extension, central LN metastasis, or lateral LN metastasis.ConclusionIn patients with PTMC, US features and SUV values on FDG-PET were not related to extrathyroid extension or LN metastasis. However, future studies with a larger sample size and longer follow-up should be performed to verify the results of this study.

Utility of (99m)Tc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels.

Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, 99mTc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of 99mTc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. 18F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. 18F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with 99mTc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease.

Somatostatin Receptor Imaging in Non–131I-Avid Metastatic Differentiated Thyroid Carcinoma for Determining the Feasibility of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE

The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin level was noted in one of the patients, and the other patient was lost to follow-up. Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is observed in a relatively low fraction of patients that could favor the feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking into account that no treatment exists in this group, somatostatin receptor-targeted imaging can be an alternative diagnostic modality in the therapeutic decision making with peptide receptor radionuclide therapy and monitoring. The documentation of elevated serum chromogranin A level in 3 patients with intense tracer uptake could suggest a possible neuroendocrine differentiation in the affected tissues leading to the expression of chromogranin A along with SSTR-avid expression. This observation needs to be explored in future studies. No definite conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy in this group at present, and more prospective research is required in this area.