scholarly journals Increase of interferon-γ inducible α chemokine CXCL10 but not β chemokine CCL2 serum levels in chronic autoimmune thyroiditis

2005 ◽  
Vol 152 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Alessandro Antonelli ◽  
Mario Rotondi ◽  
Poupak Fallahi ◽  
Paola Romagnani ◽  
Silvia Martina Ferrari ◽  
...  
Keyword(s):  
Autoimmune Thyroiditis ◽  
Multinodular Goiter ◽  
Thyroid Volume ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Newly Diagnosed ◽  
Linear Regression Models ◽  
Chronic Autoimmune Thyroiditis ◽  
Hypothyroid Patients

Objective: To measure serum levels of CXCL10 and CCL2 prototype chemokines of the two major subclass (CXC and CC) in patients with newly diagnosed chronic autoimmune thyroiditis (AT), and relate the findings to the clinical phenotype. Design and methods: Serum CXCL10 and CCL2 were assayed in 70 consecutive patients with newly diagnosed chronic AT, in sex- and age-matched healthy volunteers (n = 37) and in 20 patients with non-toxic multinodular goiter, extracted from a random sample of the general population from the same geographic area. Results: CXCL10 serum levels were significantly higher in patients with thyroiditis than in controls or multinodular goiter patients, while comparable CCL2 levels were found between groups. CXCL10 levels were significantly increased in hypothyroid patients and in those with an hypoechoic pattern (P = 0.0004 and P = 0.0001, respectively) while serum CCL2 levels were significantly increased in patients older than 50 years and in those with hypothyroidism (P = 0.0001 and P = 0.03, respectively). No correlation between CXCL10 and CCL2 serum levels could be demonstrated. CXCL10 and CCL2 were studied separately in relation to clinical features of AT patients. Two separate multiple linear regression models for CXCL10 and CCL2 were performed, including age, thyroid volume, thyroid stimulating hormone (TSH), FT4, anti-thyroid peroxidase (AbTPO), hypoechoic pattern, and the presence of hypervascularity, demonstrating that ln of serum CXCL10 levels was associated with TSH independently of other possible confounders levels [regression coefficient (R.C.) 0.143 confidence interval (C.I.) (0.042–0.245); P = 0.0059], while serum CCL2 were significantly associated only with age [R.C. 5.412 C.I. (3.838–6.986); P < 0.0001]. Conclusion: Our results, obtained in a large cohort of newly diagnosed AT patients demonstrate increased CXCL10 especially in hypothyroid patients with a more aggressive disorder, and normal CCL2 serum levels in AT.

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis

2018 ◽  
Vol 127 (05) ◽  
pp. 281-288 ◽  
Author(s):  
Mario Štefanić ◽  
Stana Tokić ◽  
Mirjana Suver-Stević ◽  
Ljubica Glavaš-Obrovac
Keyword(s):  
T Cells ◽  
Autoimmune Thyroiditis ◽  
Thyroid Volume ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Expression Levels ◽  
Chronic Autoimmune Thyroiditis ◽  
End Stage ◽  
Hypothyroid Patients

Abstract Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.

Comparison of the sonography index of thyroid gland with serum level of Anti-thyroid peroxidase, Anti-thyroglobulin and thyroid function test in patients with Hashimoto thyroiditis

2021 ◽  
Author(s):  
Fatemeh Eftekharian ◽  
Gholamhossein Ranjbar Omrani ◽  
Mohammad Hossein Dabbaghmanesh ◽  
Reza Sahraei ◽  
Marzieh Bakhshayeshkaram ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Volume ◽  
Thyroid Function Test ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Thyroid Stimulating Hormone ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Antibody Titers

Abstract Background The purpose of this study was to determine the association of sonographic parameters with the serum levels of anti-thyroid peroxidase (TPO), anti-thyroglobulin (Tg), and thyroid hormones in patients with Hashimoto's thyroiditis. Methods 149 patients (118 females, 31 males; aged 18–60 years; mean age: 38.60 ± 8.03 years) who were diagnosed with Hashimoto's thyroiditis were enrolled in the study. Blood sample was taken to measure the serum levels of free T3 and T4, thyroid stimulating hormone (TSH), anti-TPO antibody titers, and anti-Tg antibody titers. The thyroid sonography of each patient was classified into one of the five grades by real-time ultrasonography (US) based on echogenicity, thyroid size, and thyroid pattern. We evaluated whether a correlation existed between thyroid characteristics on US and serum levels of thyroid hormones, anti-TPO and anti-Tg. Results Nodular structures were detected in 54 (36.2%) patients (38 micronodular and 16 macros nodular). Echogenicity was recorded as isoechoic in 15 (10.07%) and hypoechoic in 119 (79.87%) subjects. Euthyroid ‎subjects had significantly thicker isthmus than overt and subclinical hypothyroid patients (p = 0.018). Mean serum TSH, anti-Tg and anti-TPO titers was significantly higher in patients with micronodules than those with micronodules and subjects without nodules (P < 0.05). Isthmus thickness had a significant negative correlation with FT4 and FT3 (P = 0.046; r = 0.11& P = 0.017; r = 0.15, respectively). Thyroid autoantibodies had positive significant correlations with different parameters of the thyroid volume (P < 0.05). Conclusions Thyroid’s US findings in addition to serum levels of anti-Tg and anti-TPO titers would be useful in diagnosis and evaluation of the severity and extent of Hashimoto's thyroiditis, but further evaluations are needed. Trial registration: Trial registry identifier IR.SUMS.REC.1395.S161 (2015/11/30).

scholarly journals Clinical, Hormonal, and Ultrasound Characteristics of Patients with Newly Diagnosed Graves’ Disease And Different Thyroid Antibody Profiles

2019 ◽  
Vol 46 (2) ◽  
pp. 5-12 ◽  
Author(s):  
R. Mekova ◽  
M. Boyanov
Keyword(s):  
Thyroid Volume ◽  
Serum Levels ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Clinical Approach ◽  
Newly Diagnosed ◽  
Free T4 ◽  
Thyroid Antibody ◽  
Different Characteristics ◽  
Roche Diagnostics

Abstract Objective: Graves’ disease (GD) is characterized by elevated TSH-receptor antibodies (TRAb) and less often – thyroid peroxidase (TPOAb) and thyroglobulin antibodies (TgAb). Our aim was to examine the hormonal and ultrasound characteristics of patients with newly diagnosed GD with differing positive thyroid antibodies. Materials and Methods: This study included 249 patients with newly diagnosed GD (191 women, 58 men). 40.2% of them had Graves’ ophtalmopathy. The serum levels of TSH, free T4, free T3, TRAb, TPOAb, and TgAb were measured with third generation ECLIA assays (Roche Diagnostics, Switzerland). Thyroid ultrasound was performed with a Fukuda-Denshi 550 device (Fukuda Corp., Japan) and an Ultrasonix device (Ultrasonix Medical Corp., Canada). Statistical analyses were done using the SPSS 23.0 statistical package (Chicago, IL). Results: 64% of the patients were TPOAb+ and 36% − TgAb+. One third were only TRAb+, 1/3 had two positive antibodies (TRAb + second antibody) and 1/3 – all three positive antibodies. Patients with more positive antibodies tended to be younger, had higher fT4, TRAb levels, thyroid volume but rarely had nodules on US and accompanying GO. Positive TPOAb antibodies were found in younger patients, with higher fT4 and TRAb levels, higher thyroid volume and lower prevalence of nodules and GO. The same trends were found in patients with positive TgAb. Conclusion: The different characteristics of GD patients with varying thyroid antibody profiles may be due to a variation in the pathogenesis of the disease. An individualized clinical approach may be suitable in those cases.

scholarly journals Hypothyroidism in a physician’s practice: difficulties of diagnostics and treatment

2020 ◽  
pp. 206-212
Author(s):  
A. F. Verbovoy ◽  
Yu. A. Dolgikh
Keyword(s):  
Cardiovascular Disease ◽  
Body Weight ◽  
Autoimmune Thyroiditis ◽  
Clinical Manifestations ◽  
Drug Dose ◽  
Iodine Intake ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Chronic Autoimmune Thyroiditis ◽  
Cardiovascular Therapy

Hypothyroidism is the most common endocrine disease after diabetes mellitus. Its frequency depends on age, sex and iodine intake. The highest prevalence of hypothyroidism is observed in older women. Chronic autoimmune thyroiditis is the most common cause of this condition. The peculiarity of hypothyroidism is an erased clinical picture, diversity and nonspecific symptoms. This makes it difficult to diagnose the disease, leads to an erroneous diagnosis and later detection of thyroid insufficiency. This article discusses the various «masks» of hypothyroidism and peculiarities of clinical manifestations. The main «masks» are: cardiological, dermatological, urological, gastroenterological, endocrine and reproductive system disorders, neurological, psychiatric, hematological, rheumatological. Free thyroxine and thyroid-stimulating hormone are used to diagnose hypothyroidism, as well as antibody titer to thyroid peroxidase and thyroglobulin to detect chronic autoimmune thyroiditis. Levothyroxine preparations are used as a substitution therapy. The dose of the drug depends on the age of the patient and the presence of cardiovascular disease. Patients under 50 years of age without a severe concomitant cardiovascular disease are given 1.6 µg of levothyroxine per kg of body weight. In persons over 50 years of age with cardiovascular diseases, the drug dose is prescribed at the rate of 0.9 µg per kg of body weight. The therapy starts with small doses, slowly increasing it under the control of electrocardiography. At occurrence or strengthening of symptoms of angina a dose of levothyroxine is reduced to the previous one and the cardiovascular therapy is corrected. Evaluation of the effectiveness of the treatment is carried out on the level of thyroid hormone.

scholarly journals Combined Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Subclinical Hypothyroidism Patients with Autoimmune Thyroiditis

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Maurizio Nordio ◽  
Raffaella Pajalich
Keyword(s):  
Autoimmune Thyroiditis ◽  
Subclinical Hypothyroidism ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Chronic Lymphocytic Thyroiditis ◽  
Double Blind ◽  
Chronic Autoimmune Thyroiditis ◽  
Tsh Levels

Background. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis, is the most common form of thyroiditis affecting more than 10% of females and 2% of males. The present study aims to evaluate the beneficial effect of a combined treatment, Myo-Inositol plus selenomethionine, on subclinical hypothyroidism.Methods. The study was designed as a double-blind randomized controlled trial. Eligible patients were women diagnosed with subclinical hypothyroidism having Tg antibodies (TgAb) titer higher than 350 IU/mL. Outcome measures were Thyroid Stimulating Hormone (TSH) levels, thyroid peroxidase antibodies (TPOAb) and TgAb titer, selenium, and Myo-Inositol plasma concentration.Results. In the present paper, we demonstrated that the beneficial effects obtained by selenomethionine treatment on patients affected by subclinical hypothyroidism, likely due to the presence of autoantibody (TPOAb and TgAb), are further improved by cotreatment with Myo-Inositol.Conclusions. Indeed, due to its action as TSH second messenger, Myo-Inositol treatment reduces TSH levels closer to physiological concentrations.

scholarly journals Role of interlekin-35 as a biomarker in patients with newly diagnosed Hashimoto’s thyroiditis

2016 ◽  
Vol 50 (2) ◽  
pp. 55-61 ◽  
Author(s):  
Hakki Yilmaz ◽  
M. Cakmak ◽  
B. Ceydilek ◽  
C. Demir ◽  
A. Aktas
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Critical Role ◽  
Thyroid Stimulating Hormone ◽  
Hashimoto's Thyroiditis ◽  
Interleukin 12 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thyroid Peroxidase ◽  
Newly Diagnosed ◽  
Group 2 ◽  
Group 1

AbstractObjective. Interleukin-35 (IL-35), an interleukin-12 (IL-12) cytokine family member, is shown to be a potent immunosuppressive and anti-inflammatory cytokine. Inducible regulatory T cells (Tregs) produce IL-35 that mediates the immune inhibitory function of Tregs. Growing evidence revealed that upregulation of IL-35 expression may play a critical role in the prevention of autoimmune diseases in various experimental autoimmunity models and vice versa. Hashimoto’s thyroiditis (HT) is considered to be a Treg cell-related autoimmune disease with loss of self-tolerance. Methods. One hundred-twenty eight subjects, newly diagnosed hypothyroid HT patients [56 overt (Group 1), 72 subclinical hypothyroid (Group 2)] and 38 healthy controls (Group 3) were enrolled in the study. The levels of serum IL-35 were determined by enzyme-linked immunosorbent assay (ELISA). Results. Serum IL-35 levels were lower in the HT group when compared with subclinical HT group [304.5 (834.6) pg/ml vs. 636.1 (1542.0) pg/ml, p=0.004] and control cases [304.5 (834.6) pg/ml vs. 1064.7 (2526.8) pg/ml, p<0.001]. Serum IL-35 levels were inversely associated with thyroid stimulating hormone (TSH; rs=-0.396, p<0.001) and anti-thyroid peroxidase antibodies (TPOAb; rs=-0.571, p<0.001) in whole group. Serum IL-35 were negatively associated with TSH (rs=-0.264, p=0.003) and TPOAb (rs=-0.735, p<0.001) in patients with Hashimoto’s thyroiditis (Group 1 + Group 2). Conclusion. The results suggest that IL-35 may play a role in the pathogenesis of HT.

Thyroglobulin and Thyroid Peroxidase Share Common Epitopes Recognized by Autoantibodies in Patients with Chronic Autoimmune Thyroiditis

1988 ◽  
Vol 67 (5) ◽  
pp. 899-907 ◽  
Author(s):  
YOICHI KOHNO ◽  
NAOKAZU NAITO ◽  
YOSHIO HIYAMA ◽  
NAOKI YOSHIO ◽  
NORIAKI SUZUKI ◽  
...  
Keyword(s):  
Autoimmune Thyroiditis ◽  
Thyroid Peroxidase ◽  
Chronic Autoimmune Thyroiditis

scholarly journals Increase of Circulating CXCL9 and CXCL11 Associated with Euthyroid or Subclinically Hypothyroid Autoimmune Thyroiditis

2011 ◽  
Vol 96 (6) ◽  
pp. 1859-1863 ◽  
Author(s):  
Alessandro Antonelli ◽  
Silvia Martina Ferrari ◽  
Silvia Frascerra ◽  
Andrea Di Domenicantonio ◽  
Andrea Nicolini ◽  
...  
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Multiple Linear Regression ◽  
Autoimmune Thyroiditis ◽  
Linear Regression Model ◽  
Thyroid Autoimmunity ◽  
Thyroid Volume ◽  
Multiple Linear Regression Model ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid

Context: Recently, CXCL9 and CXCL11 have been shown to be involved in autoimmune thyroid disorders; however, no data are present about CXCL9 and CXCL11 circulating levels in thyroid autoimmunity. Objective: Our objective was to evaluate circulating CXCL9 and CXCL11 in autoimmune thyroiditis (AIT). Design and Patients or Other Participants: Serum CXCL9 and CXCL11 have been measured in 141 consecutive patients with newly diagnosed AIT (AIT-p), 70 euthyroid controls, and 35 patients with nontoxic multinodular thyroid. The three groups were similar in gender distribution and age; among the AIT-p, 26% had subclinical hypothyroidism. Results: Serum CXCL9 and CXCL11 levels were significantly (P &lt; 0.0001 for both) higher in AIT-p (143 ± 164 and 121 ± 63 pg/ml, respectively) than in controls (68 ± 37 and 65 ± 19 pg/ml, respectively) or patients with multinodular thyroid (87 ± 43 and 71 ± 20 pg/ml, respectively). Among AIT-p, CXCL9 and CXCL11 levels were significantly higher in patients older than 50 yr or those with a hypoechoic ultrasonographic pattern or with hypothyroidism. In a multiple linear regression model including age, thyroid volume, hypoechogenicity, hypervascularity, TSH, anti-thyroglobulin, and anti-thyroid peroxidase, only age and TSH were significantly (P &lt; 0.05) related to serum CXCL9 or CXCL11 levels. In a multiple linear regression model of CXCL9 vs. age, TSH, and CXCL11, TSH (P = 0.032) and CXCL11 (P = 0.001) were significantly and independently related to CXCL9. Conclusions: We first show that circulating CXCL9 and CXCL11 are increased in patients with thyroiditis and hypothyroidism and are related to each other. These results underline the importance of a Th1 immune attack in the initiation of AIT.

scholarly journals Thyroid Functions in Bamboo-Shoots Consuming Children of Tripura, North-east India

2021 ◽  
Author(s):  
Indrajit Ray ◽  
A. K. Chandra ◽  
Saru Kumar Debbarma ◽  
Sekhar Kumar Mookerjee ◽  
Ajoy Datta ◽  
...  
Keyword(s):  
Urinary Iodine ◽  
Thyroid Volume ◽  
Thyroid Stimulating Hormone ◽  
Consumption Pattern ◽  
Thyroid Peroxidase ◽  
Free Triiodothyronine ◽  
Cross Sectional ◽  
North East ◽  
Bamboo Shoots ◽  
The Village

Abstract PurposeInformation on thyroid functions in populations consuming potent antithyroidal bamboo-shoots (BS) was found scanty. Therefore, to assess thyroid function in BS consuming children was found relevant.MethodsThis cross-sectional study included 127 children from 3 villages. Thyroid volume (TV), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), thyroglobulin antibody (Tg-Ab), thyroid peroxidase antibody (TPO-Ab), urinary iodine (UI), urinary thiocyanate (USCN), salt iodine (SI), water iodine (WI), and BS consumption pattern were assessed. ResultsVariable-wise overall mean±SDs/medians/interquartile ranges (IQR) were - age: 8.69±1.69/8.77/7.22-9.74 y, TVol: 0.82±0.27/0.82/0.67-0.96 ml, FT4: 19.5+5.6/20.1/16.9-22.0 pmol/L, FT3: 4.27+1.24/4.22/3.35-4.96 pmol/L, TSH: 2.44+1.39/2.33/1.60-3.15 mIU/L, Tg-Ab: 15.2+10.0/12.5/11.1-14.5 IU/ml, TPO-Ab: 5.58+12.25/3.89/2.90-5.11 IU/ml, UI: 117.4±58.5/108/73-160.5 µg/L, USCN: 0.99+0.67/0.8/0.5-1.2 mg/dl, WI: 4 .69±4.56/3.0/1.35–7µg/L, and BS consumption: 153.8±01.4/119/71.4–214.3 g/person/day respectively. Only 80.3% salt samples had ≥15 ppm iodine. Thyroid dysfunction prevalence was 6.3%. There were positive correlations between TV and FT4 (r=0.2466, p=0.005), UI and TSH (r=0.2633, p=0.003), TSH and FT4 (r=0.2135, p=0.016), TSH and FT3 (r=0.1898, p=0.033), USCN and FT4 (r=0.2477, p=0.005), Tg-Ab and TPO-Ab (r=0.3768, p=<0.001), and negative correlations between Tg-Ab and TSH (r=-0.2024, p=0.023), Tg-Ab and FT4 (r=-0.1869, p=0.035). In boys, USCN had a positive correlation with TPO-Ab (r=0.3069, p=0.018). The village having highest levels of BS consumption (p=0.037) and median UI showed higher TSH levels (p=0.037) and higher FT3 level (p=0.001) compared to the village of lowest BS consumption.ConclusionsThe BS consuming children appear at risk of developing hypothyroidism by Tg-Ab, which may partly be diminished by reducing BS consumption.

scholarly journals Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study

2020 ◽  
Vol 183 (3) ◽  
pp. 317-323
Author(s):  
Mario Rotondi ◽  
Gloria Groppelli ◽  
Laura Croce ◽  
Francesco Latrofa ◽  
Giuseppe Ancona ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Autoimmune Thyroiditis ◽  
Thyroid Nodules ◽  
Thyroid Volume ◽  
Needle Aspiration ◽  
Chronic Autoimmune Thyroiditis ◽  
Needle Aspiration Cytology ◽  
Design And Methods

Objective: The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. Design and methods: A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD−; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up. Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD− group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. Conclusions: In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.

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