Elevated Serum Thyroglobulin Research Articles

The impact of qualitative [18F]FDG PET/CT in predicting clinical outcomes of post-surgical differentiated thyroid cancer patients with elevated thyroglobulin and negative radioiodine whole-body scan

Background[18F]FDG PET/CT has been widely used as a diagnostic tool in detection and localization of recurrent non-avid radioiodine lesions in post-operative differentiated thyroid cancer (DTC) patients with elevated serum thyroglobulin but negative radioiodine whole-body scan (TENIS) syndrome. The aim of our study was to evaluate the role of [18F]FDG PET/CT in prediction on outcomes of these DTC patients.MethodsPost-operative DTC patients with TENIS syndrome were collected in the department of nuclear medicine, Hospital 108 from 2019 to 2023. Patients underwent [18F]FDG PET/CT with standard protocol following EANM guideline for tumor imaging version 2.0. The qualitative [18F]FDG PET/CT imaging characteristics were classified into three categories: (i) negative [18F]FDG PET/CT, (ii) minimal [18F]FDG PET/CT volume of lesions, (iii) extensive [18F]FDG PET/CT volume of lesions. Progression-free survival (PFS) and overall survival (OS) were the end point of the study. The prognosis of qualitative [18F]FDG PET/CT in predicting PFS and OS was illustrated by Kaplan–Meier survival analysis. The independent factors predicting PFS and OS were determined by univariate and multivariate analysis using logistic regression.ResultsThere were 164 consecutive patients, 51.2% female and 48.8% female. The most common histopathological type was papillary accounting for 91.5%. The median time of follow-up was 33.3 months, (range 6.57 – 82.5). There was 70 (36.6%) progressions and 12 (7.35%) deaths. Negative [18F]FDG PET/CT uptake patients had median PFS with median 57.1 months which was higher than that of minimal category (46.2 months), and extensive category (37.6 months) (p < 0,001). 1-year OS and 5-year OS in extensive PET/CT category was 97.8% and 86.2% respectively which were significantly lower than that of negative and minimal categories (p = 0.053). In multivariate analysis, age at the time of diagnosis, pulmonary, bone metastases and extensive [18F]FDG PET/CT volume of lesions were the independent factor predicting PFS. Bone metastasis was only the factor could predict OS in multivariate analysis.ConclusionsThe minimal and negative [18F]FDG PET/CT categories had better prognosis than extensive category in PFS and OS. Extensive [18F]FDG PET/CT category was an independent factor for predicting PFS. Bone metastasis was only the independent factor that could predict both PFS and OS.

Clinical and Histopathological Features of Thyroid Cancer with TERT Promoter Molecular Alterations in Isolation Versus with Concurrent Molecular Alterations: A Multicenter Retrospective Study

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis &gt;3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant

Abstract Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC. Presentation: 6/3/2024

The clinical significance of markedly elevated preoperative serum thyroglobulin levels

The clinical significance of markedly elevated preoperative serum thyroglobulin levels

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.

Efficacy of Empirical Radioiodine Therapy in Patients with Differentiated Thyroid Cancer and Elevated Serum Thyroglobulin without Evidence of Structural Disease: A Propensity Score Analysis.

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3-285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan-Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis.

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.

Additive value of 18FDG-PET/CT to positive 131I whole body scan in recurrent differentiated thyroid cancer patients with potential influence on treatment strategy: single Egyptian center experience

BackgroundYears ago the utility of of18F-fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) in differentiated thyroid cancer was confined mainly to cases with elevated serum thyroglobulin and negative 131I whole body scan. In this study, we try to assess the diagnostic performance of 18FDG-PET/CT in recurrent differentiated thyroid cancer patients with positive 131I whole body scan and in addition to evaluate the impact of 18FDG-PET/CT on the treatment strategy.ResultsThe 18FDG PET/CT detected tumor recurrence in 35 (81.3%) patients most of them (91.4%) were in stage IV, while the rest 8.5% was in stage III. No recurrence was detected among patients in stage II and III by 18FDG PET/CT.Regarding lesion-based analysis, sensitivity of 18FDG-PET/CT was superior to that of 131I post-therapeutic whole body scan (TxWBS) (78.2% vs. 69.4%, respectively), while both modalities had the same specificity (50%). 18FDG-PET/CT changed the treatment plan in 18 (41.6%) patients.Conclusion18FDG-PET/CT may be complementary to 131ITxWBS in high-risk DTC with impact on treatment strategy.

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.

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.

PET/CT in the management of differentiated thyroid cancer

The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (131I) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and 123I/131I whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate 131I may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (18F-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, 18F-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative 131I imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate 18F-FDG, and a reciprocal pattern of iodine and 18F-FDG uptake has been observed. Beyond 18F-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (124I), 18F-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points.

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.

The prostate-specific membrane antigen (PSMA)-targeted radiotracer 18F-DCFPyL detects tumor neovasculature in metastatic, advanced, radioiodine-refractory, differentiated thyroid cancer.

Prostate-specific membrane antigen (PSMA; also termed glutamate carboxypeptidase II (GCP II)) is abundantly expressed in prostate cancer. It has been shown recently that PSMA is expressed in neovasculature of differentiated thyroid cancer. In this study, we show that 18F-DCFPyl might detect neovasculature in advanced, metastatic differentiated thyroid cancer (DTC). We first stained the preserved lymph node samples of three patients with DTC who had undergone total thyroidectomy and neck dissection for cervical lymph node metastatic disease to identify PSMA expression, with the PSMA antibody (DAKO Monoclonal). Then, we performed 18F-DCFPyl imaging in two other advanced DTC patients with elevated serum thyroglobulin (Tg), indicative of residual disease. We compared the findings with contemporaneous FDG PET/CT scan, conventional Imaging (CT,MRI) and whole-body scan performed with I123/I131. All the three lymph node samples stained positive for PSMA expression in the neovasculature. In the first imaged patient, 18F-DCFPyl detected activity within the retropharyngeal CT contrast-enhancing lymph node. Compared to FDG PET/CT, the 18F-DCFPyl scan showed a greater SUV (3.1 vs 1.8). In the second imaged patient, 18F-DCFPyl showed intense uptake in the L3 vertebra (not seen on the post treatment 131I scan or the 18F-FDG PET/CT). MRI of the lumbar spine confirmed the presence of sclerotic-lytic lesion at the location, consistent with metastatic disease. Our exploratory study is proof of principle, that the prostate cancer imaging agent 18F-DCFPyl may prove useful for the localization of metastases, in patients with metastatic RAI-refractory DTC by detecting neoangiogenesis within the tumor.

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.

Role of adjuvant therapy with radioactive iodine in patients with elevated serum thyroglobulin after neck reoperation due to recurrent papillary thyroid cancer: a monoinstitutional comparative study.

Most patients with papillary thyroid cancer (PTC) and lymph node metastases (LNM) undergoing reoperation do not show apparent disease after this procedure, but serum thyroglobulin (Tg) continues to be elevated in part of them. This study evaluated adjuvant therapy with 131I in these patients. Patients with PTC and LNM diagnosed after initial therapy were selected. Patients undergoing reoperation and those without apparent disease after this procedure, but with nonstimulated Tg ≥1 ng/ml 6 months after reoperation, were included. The first 25 patients were submitted to therapy with 131I (groups A) and the subsequent 30 patients did not receive this therapy (group B). Groups A and B were similar. During further follow-up, 21 patients developed structural disease and 34 continued without detectable disease (eight achieved complete remission). The outcomes were similar in groups A and B. Patients with Tg reduction >50% after reoperation tended to have a lower risk of recurrence (22.7 versus 48.5%), notably distant metastases (0 versus 15.1%), and were more likely to achieve complete remission (28 versus 3%). Patients with LNM FDG-positive had a higher risk of recurrence (54.5 versus 11.7%) and were less likely to achieve complete remission (3 versus 29.4%) after reoperation. Our results suggest that therapy with 131I apparently does not prevent recurrences among patients who continue to have elevated Tg after neck reoperation. Further studies involving these patients are necessary, especially those who are at high risk of recurrence.