Effects of Chronic Suppression or Oversuppression of Thyroid-Stimulating Hormone on Psychological Symptoms and Sleep Quality in Patients with Differentiated Thyroid Cancer.

In differentiated thyroid cancer (DTC), the standard treatment includes total thyroidectomy and lifetime levothyroxine (LT4) replacement. However, long-term exogenous LT4 has become controversial due to the adverse effects of oversuppression. The study included 191 patients (aged 18-76 years) with a prospective diagnosis of non-metastatic DTC and 79 healthy individuals. The patients with DTC were stratified into three groups according to their TSH levels: suppressed thyrotropin if TSH was below 0.1 µIU/ml, mildly suppressed thyrotropin if TSH was between 0.11 and 0.49 µIU/ml, and low-normal thyrotropin if THS was between 0.5 and 2 µIU/ml. The Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Anxiety Sensitivity Index (ASI), Short Symptom Inventory (SSI), and Pittsburgh Sleep Quality Index (PSQI) were administered to all participants. It was found that the BDI, BAI, SSI and PSQI scores were worse in patients with DTC (p=0.024, p=0.014, p=0.012, and p=0.001, respectively). According to theTSH levels, the mean ASI was found to be higher in the suppressed and mildly suppressed thyrotropin groups (19±14.4 vs. 10.6±11.1; 16.4±14.9 vs. 10.6±11.1, p=0.024, respectively), the mean SSI was found higher in the suppressed group (61.0±55.5 vs. 35.1±37.0, p=0.046), and the mean PSQI was higher in all three groups (7.94±3.97 vs. 5.35±4.13; 7.21±4.59 vs. 5.35±4.13; 7.13±4.62 vs. 5.35±4.13, p=0.006) when compared with the controls. No significant difference was found between the groups. A positive correlation was detected in the duration of LT4 use and BDI and SSI, and a weak, negative correlation was detected between TSH levels and ASI and PSQI. Based on our study, it was found that depression, anxiety disorders, and sleep problems were more prevalent in patients with DTC, being more prominent in the suppressed TSH group. These results were inversely correlated with TSH values and positively correlated with the duration of LT4 use. Unnecessary LT4 oversuppression should be avoided in patients with DTC.

The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size.

The role of systemic inflammation has not been clearly defined in thyroid cancers. There have been conflicting reports on whether systemic inflammatory markers have predictive value for thyroid cancers. We aimed to evaluate the association between systemic inflammatory markers and clinicopathological factors in thyroid cancers and to assess their predictive value for thyroid cancers in detail. Five hundred thirty-one patients who underwent surgery for thyroid nodules were included. The patient population consisted of 99 individuals (18.6%) with benign thyroid nodules and 432 individuals (81.4%) with thyroid cancers. In 432 patients with thyroid cancers, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in the cases with tumors greater than 2 cm than in those with tumors less than 2 cm. (p = 0.027). NLR and platelet-to-lymphocyte ratio (PLR) were significantly higher in cases with lateral lymph node metastasis (LNM) than in those without LNM (p = 0.007 and 0.090, respectively). The nodule size was significantly higher in benign thyroid nodules than in thyroid cancers (p < 0.001). When the cases were stratified by tumor size, NLR was a significant predictor of thyroid cancers in cases with nodules greater than 2 cm (Exp(B) = 1.85, 95% CI = 1.15-2.97, p = 0.011), but not in those with nodules less than 2 cm. In thyroid cancers, preoperative NLR was associated with pathological prognosticators such as tumor size and lateral lymph node metastasis. When the size difference between thyroid cancers and benign thyroid nodules was adjusted, NLR could be a significant predictor of thyroid cancers.

Relationship Between Serum Inflammatory Factor Levels and Differentiated Thyroid Carcinoma.

BACKGROUND: Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tumors to explore their diagnostic values. MATERIAL AND METHODS: Altogether 487 thyroid tumor patients were recruited, their neutrophil (NE), white blood cell (WBC), monocyte (MO), lymphocyte (LY), platelet (PLT) counts, together with monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin (IL)-1ß, IL-2, IL-27, and tumor necrosis factor-α (TNF-α) levels were compared with controls. Afterward, the receiver operating characteristics (ROC) curve was plotted to further evaluate the values of these inflammatory markers in diagnosis. In addition, multivariable regression analysis was conducted to analyze all these inflammatory factors. RESULTS: Serum PLR, NLR, CRP, and IL-27 levels in thyroid adenoma (TA) and differentiated thyroid carcinoma (DTC) patients were higher than those in controls. Only the areas under the curve (AUC) for CRP and IL-27 were significant in the context of DTC. Besides, the AUC for IL-27 was significant between papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) groups, while that for NLR+PLR was also significant between PTC and healthy control groups. According to multivariable logistic regression analysis, IL-27 and CRP were associated with DTC. CONCLUSIONS: Inflammation plays an important role in TA and DTC progression. Preoperative IL-27 and CRP levels help to differentially diagnose DTC. Moreover, IL-27 assists in distinguishing FTC from PTC, and NLR+PLR is important for the differential diagnosis of PTC.

Serum Follistatin Is Increased in Thyroid Cancer and Is Associated With Adverse Tumor Characteristics in Humans.

CONTEXT: Obesity and classical growth factors are associated with thyroid cancer (TC). However, less is known regarding novel hormones such as follistatins and activins. We hypothesized that serum follistatin but not activins would be increased in TC. OBJECTIVE: This work aimed to assess circulating levels of follistatins, activins, and growth factors in patients with a history of TC vs patients with nonmalignant thyroid diseases. METHODS: A hospital-based, unmatched case-control study was conducted with 170 thyroidectomized patients due to well-differentiated TC and 106 thyroidectomized patients without history of malignancy. Anthropometric, biochemical, and histological parameters were recorded. Serum samples were collected in the steady state 45 days after surgery. Multivariate models were used to adjust for baseline differences of the unmatched variables. Serum levels of follistatin (FST), follistatin like-3, activin A, activin B, bioactive insulin-like growth factor-1, and stanniocalcin-2 were assayed with novel, highly specific ELISA kits. RESULTS: In unmatched univariate models, TC patients had higher FST serum levels compared to cancer-free individuals, independently of histological subtype. In multivariate models adjusting for covariates, individuals in the highest tertile of FST levels were associated with an increased risk for the presence of any type of TC or specific histological subtypes, including papillary, follicular and Hürthle-cell carcinoma, and medullary TC. Higher postoperative FST concentrations were found in patients with vascular invasion and distant metastases and associated with TNM staging at diagnosis. CONCLUSION: FST serum levels are increased in TC patients and correlate with advanced tumor aggressiveness. Future longitudinal studies are needed to confirm and extend our observations.

Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules.

BACKGROUND: Molecular testing is increasingly used to identify malignancy in thyroid nodules (especially indeterminate category). Measurement of cell-free DNA (cfDNA) levels from plasma has been useful in diagnosis of cancers of other organs/tissues; herein we analyze cfDNA levels in patients with thyroid nodules to explore the possibility of establishing a cutoff for identification of malignancy. METHODS: Patients underwent ultrasonography (USG) and USG-guided fine needle aspiration as well as surgery, where indicated. Cell-free DNA was extracted from plasma and quantified. In initial analysis (determination of cutoff), cfDNA levels were compared between Bethesda 2 and Bethesda 5 &6 to establish a cutoff value that could differentiate malignant from benign nodules. In the subsequent analysis, the aforementioned cutoff was applied (validation of cutoff) to those with indeterminate nodules to check ability to predict malignancy. RESULTS: Fine needle aspiration (n = 119) yielded patients with Bethesda 2 (n = 69) Bethesda 5 & 6 (n = 13) who underwent histopathological confirmation. Cell-free DNA levels in these 2 groups were 22.85 ±â€…1.27 and 96.20 ±â€…8.31 (ng/mL) respectively. A cfDNA cutoff of 67.9 ng/mL, with area under the curve of 0.992 (95% CI, 0.97-1.0) with 100% sensitivity and 93% specificity was established to identify malignant lesions. Indeterminate group (Bethesda 3 & 4) underwent surgery (malignant n = 24), (benign n = 13), and using the previously identified cutoff for cfDNA, we were able to identify malignant lesions with a sensitivity of 100% and specificity of 92.3%. There was a very strong agreement between cfDNA-based classification with histopathology-based classification of benign and malignant nodules (Cohen's kappa 0.94; P < 0.001). CONCLUSION: Plasma cfDNA estimation could help differentiate malignant from benign thyroid nodules.

Multiple Endocrine Neoplasia Type 2B Associated Mixed Medullary and Follicular Thyroid Carcinoma in A Chinese Patient with RET M918T Germline Mutation.

BACKGROUND: Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous morphological components and immunophenotypical features intermingled within the same lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated MMFC. METHODS: A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of calcitonin (Ctn; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/mL), and thyroglobulin (Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy, suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy, along with extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were performed. RESULTS: The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A, and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation manifested in the patient but was not detected in other family members. Follow up showed that the serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16 months after the surgery. CONCLUSION: Particular and diverse patterns of MMFC should be recognized with immunostaining features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological behavior and the treatment is mostly radical surgery.

Role of Thyroglobulin Doubling Time in Differentiated Thyroid Cancer and Its Relationship with Demographic-Histopathologic Risk Factors and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Parameters.

Background: Aim of this study was to investigate the relationship between thyroglobulin doubling time (TgDT) and basal risk factors and metabolic parameters derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in differentiated thyroid cancer (DTC). Materials and Methods: An analysis of 95 DTC patients who had rising serum thyroglobulin (Tg) levels under levothyroxine (LT4) suppression after radioiodine therapy was made. TgDT was calculated for 28/95 patients. The relationship between TgDT and basal demographic and histopathologic risk factors, preablative Tg, and antithyroglobulin antibody (ATg) levels and metabolic parameters was analyzed. Results: In 28 patients (15M, 13F, mean age: 52.6 ± 17.6) that TgDT could be calculated, 18F-FDG PET/CT was positive in 12 patients. Median TgDT was lower in 18F-FDG PET/CT positive patients compared to the negative cases (p < 0.05). Patients with skeletal metastasis or local recurrence had a shorter DT compared to the patients with lung metastasis. TgDT was correlated with peak standardized uptake value (SUVpeak) (p < 0.05). Maximum standardized uptake value (SUVmax) was correlated with tumor size (p < 0.05) and mean standardized uptake value (SUVmean) with tumor size and vascular invasion (p < 0.05). Median SUVmax and SUVmean were higher in follicular cancer or poor histological variants of papillary DTC compared to papillary cancer classical variant patients Conclusion: TgDT may be predictive of a positive 18F-FDG PET/CT in DTC. Skeletal metastasis and local recurrence are related to shorter TgDT. Greater tumor size, vascular invasion, and follicular cancer or poor variants of papillary carcinoma are related with higher SUVmax and SUVmean. Larger scale studies are needed to confirm results and to calculate a possible cutoff of TgDT for a positive 18F-FDG PET/CT study.

Distinguishing Patients With Distant Metastatic Differentiated Thyroid Cancer Who Biochemically Benefit From Next Radioiodine Treatment.

Background: Repeated radioiodine (131I) treatment (RT) are commonly performed in patients with 131I-avid distant metastatic differentiated thyroid cancer (DM-DTC), but more precise indications remain indeterminate. This prospective study was conducted to explore predictors for biochemical response (BR) to next RT. Methods: Totally thyroidectomized patients with 131I-avid DM-DTC demonstrated by initial post-therapeutic whole body scan (Rx-WBS) were consecutively recruited. Repeated RTs were performed at a fixed dose and a fixed interval, which was terminated once a decline in thyroid stimulating hormone-suppressed thyroglobulin (Tgon) could not be achieved or Rx-WBS was negative. BR was evaluated by change rate of Tgon level (ΔTgon%). Results: After exclusion of 27 ineligible courses, a total of 166 neighboring course pairs from 77 patients were established and utilized. Univariate and multivariate analyses showed that the maximum target/background ratio (T/Bmax) on the whole body scan and ΔTgon% derived from the former RT were independently associated to the latter one. In predicting biochemical remission, the positive predictive value (PPV) and negative predictive value (NPV) of T/Bmax at the cut-off value of 8.1 were 79.1% and 84.0%, respectively; whereas the PPV and NPV of ΔTgon% at the cut-off value of 25.3% were 70.8% and 77.1%, respectively. Notably, the PPV of combined T/Bmax ≥ 8.1 and ΔTgon% ≥ 25.3% increased to 87.7%; while the NPV of T/Bmax ≥ 8.1 or ΔTgon% ≥ 25.3% reached as high as 97.7%. Conclusions: This study revealed that combined use of the latest RT-derived T/Bmax and ΔTgon% may efficiently identify biochemical responders/non-responders to next RT, warranting management optimization of patients with 131I-avid DM-DTC.

MiRNA let-7 from TPO(+) Extracellular Vesicles is a Potential Marker for a Differential Diagnosis of Follicular Thyroid Nodules.

BACKGROUND: The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population hampers the development of new diagnostic tests. We hypothesize that the isolation of EVs with thyroid-specific surface molecules followed by miRNA analysis, may have improved diagnostic potency. METHODS: The total population of EVs was isolated from the plasma of patients with FA (n = 30) and FTC (n = 30). Thyroid peroxidase (TPO)-positive EVs were isolated from the total populations using immune-beads. The miRNA from the TPO(+)EVs obtained from the plasma of FA and FTC patients was assayed by RT-PCR. The diagnostic potency of the selected miRNAs was estimated by the receiver operating characteristic (ROC) analysis. RESULTS: TPO(+)EVs can be efficiently isolated by immunobeads. The analysis of Let-7 family members in TPO(+)EVs allows one to distinguish FA and FTC with high accuracy (area under curve defined by ROC = 0.77-0.84). CONCLUSION: The isolation of TPO(+)EVs, followed by RT-qPCR analysis of Let-7 family members, may present a helpful approach to manage follicular nodules in the thyroid gland.

Elevated serum concentrations of IGF-1 and IGF-1R in patients with thyroid cancers.

BACKGROUND: The rising incidence of thyroid cancer observed in the last few decades requires an improvement in diagnostic tools and management techniques for patients with thyroid nodules. AIMS: The aim of this study was to assess serum concentrations of IGF-1 and IGF-1R in patients diagnosed with thyroid cancers. METHODS: 36 patients diagnosed with papillary thyroid cancer (PTC), 11 subjects with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and 19 subjects with multinodular nontoxic goiter (MNG) were enrolled to the study. The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum IGF-1 and IGF-1R concentrations were measured using specific ELISA methods. RESULTS: Significantly higher concentrations of IGF-1 were found in patients with PTC as compared with controls but not that obtained from subjects diagnosed with MNG. The concentration of IGF-1R was significantly elevated in subjects with PTC and ATC as compared with healthy volunteers. Similarly, patients diagnosed with PTC or ATC presented significantly higher serum concentration of IGF-1R in comparison to the MNG group. CONCLUSIONS: Our results show that the IGF-1 - IGF-1R axis plays a significant role in the development of PTC and ATC and imply that serum concentrations of both cytokines may be considered as additional markers for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. These results indicate that IGF-1R serum concentrations allow us to differentiate between MNG and PTC or ATC. Moreover IGF-1R serum values appear to be better predictor of PTC and ATC than IGF-1 concentrations.

Utility of Stimulated Thyroglobulin in Reclassifying Low Risk Thyroid Cancer Patients' Following Thyroidectomy and Radioactive Iodine Ablation: A 7-Year Prospective Trial.

Context: Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence. Objective: To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation. Method: A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured. Results: Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period. Conclusion: Suppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.

Estimating the Growth Rate of Lung Metastases in Differentiated Thyroid Carcinoma: Response Evaluation Criteria in Solid Tumors or Doubling Time?

Background: Estimating the growth rate of lung metastases for the treatment of patients with metastases of differentiated thyroid carcinoma (DTC) is important. This study aimed to evaluate survival outcomes according to different criteria for estimating the growth rate of lung metastases. Methods: Patients with macronodular (≥1 cm) lung metastases of DTC who underwent total thyroidectomy and high-dose radioactive iodine therapy between 1995 and 2013 were enrolled. The time to progressive disease (PD) by the Response Evaluation Criteria in Solid Tumors (RECIST), average tumor volume doubling time of the two dominant target lung lesions (midDT), and thyroglobulin doubling time (TgDT) were measured in each patient, and their association with disease-specific survival (DSS) was evaluated. Results: Forty-four patients with target lung metastatic nodules with an initial maximal diameter of 1.3 cm (median) were followed-up for a median of 6.8 years after the diagnosis of lung metastases. Based on RECIST, 12 patients (27.3%) showed fast tumor progression, with time to PD <1 year. When assessed by midDT, nine patients (20.5%) had midDT ≤1 year, showing rapid tumor progression. Seven of 33 patients (21.2%) who were negative for thyroglobulin antibody had midDT <1 year. Growth rates assessed by all three criteria were significantly associated with DSS. However, midDT had the highest predictive value for DSS, with a proportion of variation explained of 33.6%. Five-year DSS was 29.6% in patients with midDT ≤1 year, 50.0% in patients with time to PD <1 year, and 42.9% in patients with TgDT <1 year. Conclusions: Among the different criteria for estimating the growth rate of metastases in patients with lung metastases of DTC, midDT was the most powerful for predicting DSS, in comparison with RECIST and TgDT. Performing at least three serial chest computed tomography scans during the first year from the diagnosis of lung metastases can facilitate early detection of patients with rapid tumor progression and provide objective guidance for initiation of systemic therapy.

Expressions of IL-17 and TNF-α in patients with Hashimoto's disease combined with thyroid cancer before and after surgery and their relationship with prognosis.

OBJECTIVE: This study aimed to investigate expressions and clinical significance of IL-17 and TNF-α after surgery in patients with Hashimoto's disease (HD) combined with thyroid cancer (TC). PATIENTS AND METHODS: From June 2010 to October 2012, 38 patients with HD combined with TC admitted to the oncology department of Tongji Hospital were selected as an experimental group, including three males and 35 females, aged 24-78 years. Forty adults undergoing physical examination during the same period were selected as a control group. All patients in the experimental group were given total endoscopic TC resection. Real-time fluorescence quantification (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of serum IL-17 and TNF-α before and 14 days after surgery. Patients with HD combined with TC were divided into high and low expression groups according to the median values of preoperative IL-17 mRNA and TNF-α mRNA. The relationship between IL-17, TNF-α, and prognosis of patients was analyzed through K-M survival curve. RESULTS: The concentrations of IL-17 and TNF-α in serum were also higher than those in control group 14 days after surgery (p < 0.05). qRT-PCT showed that the relative expressions of IL-17 and TNF-α in serum 14 days after surgery were higher than those in control group (p < 0.05). According to the relative expression median of mRNA in IL-17 and TNF-α before surgery, they were divided into high and low expression groups. It was found that the survival rate of high expression groups of IL-17 and TNF-α was lower than that of low expression groups (IL-17, p = 0.028; TNF-α, p = 0.014). CONCLUSIONS: The protein and mRNA of IL-17 and TNF-α in serum of HD patients with TC are higher than those of healthy control group. Expressions of IL-17 and TNF-α can be reduced by surgical resection of focal tissue. IL-17 and TNF-α may be used as potential prognostic indicators of HD patients with TC.

Definition of the Response to Initial Therapy with Radioiodine in Patients with Differentiated Thyroid Carcinoma: Basal or Stimulated Thyroglobulin?

Basal thyroglobulin (b-Tg) measured with second-generation assay or stimulated Tg (s-Tg) can be used to define the response to therapy of differentiated thyroid carcinoma. However, they do not always define the same category and guidelines do not establish "if" or "when" s-Tg needs to be obtained. We studied 304 patients without clinically apparent disease or disease detected by neck ultrasonography and without anti-Tg antibodies 9-12 months after therapy. Based on b-Tg, 196 patients had an excellent response and 108 had an indeterminate response. Based on s-Tg, a change in category occurred in 10.2% of the patients with an initial excellent response (all to indeterminate response) and in half the patients with an initial indeterminate response (44.4% to excellent response and 5.5% to biochemical incomplete response). One case of recurrence was observed among patients with an initial excellent response but whose response changed to indeterminate after s-Tg, while no disease was detected among those who remained in the initial category; however, this difference was not significant. In patients with an initial indeterminate response, no recurrence was detected among those whose response changed to excellent after s-Tg, while 11.1 and 33.3% of those who remained in the initial category or whose response changed to biochemical incomplete, respectively, had structural disease. This study suggest that, in low- or intermediate-risk patients, s-Tg better defines the response to therapy with 131I when it is classified as indeterminate based on b-Tg using second-generation assay. However, s-Tg is not necessary when b-Tg defines the response as excellent.

Diagnostic Capabilities of MRI Versus 18F FDG PET-CT in Postoperative Patients with Thyroglobulin Positive, 131I-negative Local Recurrent or Metastatic Thyroid Cancer.

BACKGROUND: The detection of recurrence or metastasis might be challenging in patients, who underwent total thyroidectomy and radioactive iodine therapy for Differentiated Thyroid Carcinoma (DTC), with increased serum Thyroglobulin (Tg) levels and negative 131I whole body scan (131I-WBS) results. AIMS: The purpose of this study was to compare the ability of Magnetic Resonance Imaging (MRI) and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F FDG PET-CT) to detect recurrence or cervical and upper mediastinal metastases in postoperative DTC patients who had negative 131I-WBS despite elevated serum Tg levels. STUDY DESIGN: This study has a retrospective study design. METHODS: We evaluated cervical and upper mediastinal MRI and 18F FDG PET-CT of 32 postoperative patients with DTC (26 patients with papillary thyroid carcinoma and 6 patients with follicular thyroid carcinoma). RESULTS: We evaluated 44 lesions in 32 patients. For all lesions, the Positive Predictive Value, (PPV) Negative Predictive Value (NPV), sensitivity, specificity, and accuracy of MRI were 81.4%, 76.4%, 84.6%, 72.2%, and 79.5% respectively. The PPV, NPV, sensitivity, specificity, and accuracy of 18F FDG PET-CT were 100.0%, 85.7%, 88.4%, 100.0%, and 93.1%, respectively. CONCLUSION: Although we could not replace 18F FDG PET-CT, MRI might be used as an adjunct to 18F FDG PET-CT for the evaluation of recurrent or cervical and upper mediastinal metastatic thyroid cancers; however, MRI is inadequate for the detection of metastases in small lymph nodes.

Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer: Study of External Dose Rate Attenuation Law and Individualized Patient Management.

BACKGROUND: Therapy with radioactive iodine (131I) is a well established treatment method for postsurgical differentiated thyroid carcinoma (DTC). A fixed discharge time is generally set, regardless of individual differences in residual body radioactivity (RBA). This study aimed to investigate the RBA of each patient to find the attenuation law and to identify underlying factors in order to predict the time point for a safe, scientifically sound discharge plan. METHODS: A total of 231 DTC patients undergoing 131I treatment were all treated with 3.7 GBq (100 mCi) of 131I. RBA was estimated by measuring the external body dose rate (EDR) at a distance of 1 m from the body surface between 0 and 72 hours after oral administration of 131I. Data from each patient were used to establish a time-EDR value (h-µSv/h) curve. Software was developed to predict the time when a patient's dose equivalent meets the national safety standard by including six time points between 40 and 60 hours. Several factors that might affect that time were analyzed. RESULTS: The EDR attenuation law in patients could be described with a double exponential decay model, and the cutoff value was set as 23.3 µSv/h, upon which the predictive software was developed. Student's t-test showed there was no statistical difference between predicted values and the actual measured values (p > 0.05). Correlation analysis found that serum thyroglobulin, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, 2- and 24-hour iodine uptake rate of the thyroid, scores of 99mTc-pertechnetate thyroid scan, scores of 131I whole-body scan, scores of ultrasound scan, and gastrointestinal residues were associated with attenuation speed. A further multiple linear regression analysis found that 24-hour iodine uptake (X1), residual thyroid grading by 131I whole-body scan (X2), blood free triiodothyronine (X3) and free thyroxine (X4) predominantly influenced the decline of the EDR. The regression equation was Y = 2.091X1 + 6.370X2 + 4.529X3 + 2.466X4 - 8.614 (F = 44.03, p < 0.01). CONCLUSIONS: An effective and convenient method was created to measure and predict the individual safety time for discharge. This could play a significant role not only for scientific hospital discharge planning, rational use of medical resources, and better individualized management, but also in public radiation protection.

Prognostic impact of elevated preoperative C-reactive protein on patients with differentiated thyroid carcinoma.

BACKGROUND: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS: A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS: Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). CONCLUSIONS: Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4.

Low trabecular bone score in postmenopausal women with differentiated thyroid carcinoma after long-term TSH suppressive therapy.

The effect of thyroid suppression therapy (TST) on trabecular bone scores (TBS) and bone mineral density (BMD) in thyroidectomized women with differentiated thyroid carcinoma (DTC) on long-term follow-up is presently not conclusive. PATIENTS AND METHODS: We carried out a study in 61 premenopausal and 84 postmenopausal Caucasian women with DTC. Serum biochemistry, bone markers, TBS, BMD, and bone fractures were evaluated 1-3 months post surgery and after a median follow-up of 10 years. RESULTS: In the final study, patients belonged to Group I Premenopausal (n = 14) who remained in this status; Group II Premenopausal who became postmenopausal (n = 47); Group III patients who were and continued as postmenopausal (n = 84). Baseline premenopausal patients had a normal TBS mean value of 1.39 ± 0.14 significantly higher than that found in postmenopausal 1.31 ± 0.12 (p = 001). In the final study, premenopausal patients continued to have a normal TBS of 1.46 ± 0.08 compared to the significantly lower value of postmenopausal patients 1.25 ± 0.11 (p = 0.0009). Lumbar BMD (L-BMD) loss after the long-term study was significant in Group II (0.99 g/cm2 ± 0.13 vs. 0.91 ± 0.12 g/cm2, p < 0.0001) and there was a slight, but not significant, bone loss in Group I (1.00 ± 0.12 vs. 0.98 ± 0.11, p = 0.1936) and in Group III (0.86 ± 0.12 vs. 0.84 ± 0.15, p = 0.1924) compared with baseline values. CONCLUSION: Longer-term suppression therapy in female patients with DTC did not increase significantly the risk of bone loss, although we found in postmenopausal patients deterioration of bone microarchitecture. TBS study should be considered in the evaluation of postmenopausal DTC patients on long-term DTC for the evaluation of the risk of fractures.

Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin.

Background The present study was designed to determine the value of pre-ablation stimulated thyroglobulin (s-Tg) in predicting distant metastasis (DM) at the time of ablation in children with differentiated thyroid cancer. Methods From August 2009 to December 2016, consecutive children with differentiated thyroid cancer undergoing remnant ablation were retrospectively analyzed. Serum s-Tg was measured with the high-sensitive electrochemiluminescence immunoassay during hypothyroidism at ablation just before the ablative radioactive iodine (131I) administration. Post-ablation, whole body planar scintigraphy was obtained 5 days after administration of ablation activity of 131I. Single photon emission computed tomography/low-dose computed tomography (SPECT/CT) was added for children whose planar findings were inconclusive. Receiver-operating characteristics (ROC) curve analysis was employed to find a cut-off level of pre-ablation s-Tg as a predictor of DM at the time of ablation. Results Fifty-seven children were included for the analysis. Metastases were noticed on post-ablation scintigraphy in 20 (35%) children: five post-operative residual neck lymph node metastases, four post-operative residual neck lymph node and lung metastases, three mediastinal lymph node and lung metastases and eight lung metastases. A significant difference in pre-ablation s-Tg levels was found in children with DM compared with those without DM, 603.5 vs. 5.7 ng/mL, respectively. A pre-ablation s-Tg level of 156 ng/mL was established as the optimal cut-off point to predict DM. Conclusions This study demonstrated that pre-ablation s-Tg could potentially act as a predictor of DM at the time of ablation in children with differentiated thyroid cancer. We also propose a specific pre-ablation s-Tg cut-off value of 156 ng/mL as an optimal threshold for practical use.