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Abstract: Ponce, T, Mainenti, MRM, de Barros, T, Cahuê, FLC, Fernanda, C, Piazera, BKL, Salerno, VP, and Vaisman, M. Biochemical and hormone markers in firefighters: effects of "search, rescue, and survival training" and its recovery. J Strength Cond Res 38(4): e189-e201, 2024-This study aimed to evaluate the hormonal and biochemical responses in military firefighter cadets to a search, rescue, and survival training (SRST) course. Forty-three male volunteers participated in the SRST over 15 days consisting of intense physical effort, sleep deprivation, and a survival period with food deprivation. At 3 timepoints (baseline, SRST, and 1 week rec), subjects submitted to blood collections, body composition examinations, physical performance evaluations, and cognitive function tests. After the SRST, lower values were registered for testosterone (764.0; 565.1-895.0 to 180.6; 133.6-253.5 ng·dl -1 ) and insulin-like growth factor-1 (IGF-1) (217; 180-238 to 116; 102-143 ng·ml -1 ). Increases were observed for cortisol (9.7; 8.2-11.7 to 18.3; 16.5-21,2 μg·dl -1 ), growth hormone (GH) (0.11; 0.06-0.20 to 2.17; 1.4-3.4 ng·ml -1 ), CP, GSSG, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase as well as the antioxidant response of superoxide dismutase and glutathione peroxidase. The values of gamma-glutamyl transferase were reduced. After 1 week of recovery, levels of GH, creatine kinase, GSH, and GSSG returned to baseline values ( p < 0.05). Vertical jump performance presented a regular positive correlation with testosterone (rho = 0.56 and p < 0.0001) and a strong negative correlation with cortisol (rho = -0.61 and p < 0.0001). Body fat showed a regular and positive correlation with both testosterone and IGF-1. We conclude that participation in the SRST caused significant hormonal and biochemical changes in individuals that correlated with a loss in physical performance. Importantly, the results suggest the need for longer recovery times before a return to normal military duties., (Copyright © 2024 National Strength and Conditioning Association.)

Objective:  We compared thyroid volume (TV) and presence of nodular goiter (NG) in pregnant vs. non-pregnant women in an iodine-sufficient area. We also evaluated the relationship between gestational age, parity, and TV in the pregnant women group, and determined the 2.5 th and 97.5 th percentiles of normal TV in pregnancy., Methods:  This cross-sectional study included 299 healthy women (216 pregnant) without previous thyroid diseases. Thyroid ultrasounds were performed and compared between pregnant and non-pregnant women. The range of normal distribution of TV (2.5 th and 97.5 th percentiles) in pregnancy was determined after excluding individuals with positive thyroid antibodies, NG, and/or abnormal serum thyrotropin (TSH) or free thyroxine (FT4)., Results:  Thyroid volume was larger among pregnant compared to non-pregnant women (8.6 vs 6.1 cm 3 ; p  < 0.001) and was positively correlated with gestational age (rs = 0.221; p  = 0.001), body mass index (BMI, rs 0.165; p  = 0.002), and FT4 levels (rs 0.118 p  = 0.021). Nodular goiter frequency did not differ between the two groups. There was a negative correlation between TV and TSH (rs -0.13; p  = 0.014). Thyroid volume was lower among primiparous compared to multiparous patients (7.8 vs 8.9; p  < 0.001) and was positively correlated with parity (rs 0.161; p  = 0.016). The 2.5 th and 97.5 th percentiles of TV were 4.23 and 16.47 cm 3 , respectively., Conclusion:  Thyroid volume was higher in pregnant compared to non-pregnant women and was positively related to parity, BMI, and gestational age in a normal iodine status population. Pregnancy did not interfere with the development of NG., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

High caloric intake and physical inactivity are known precursors to the development of several chronic metabolic diseases. For obesity and sedentarism, High Intensity Intermittent Exercise (HIIE) and Intermittent Fasting (IF) have emerged as individual strategies to attenuate their negative effects by improving metabolism. To study their combined effects, Wistar male rats (n = 74, 60 days old) were divided into four groups: Sedentary Control (C), swimming-based HIIE only (HIIE), Intermittent Fasting only (IF), and swimming-based HIIE associated with Intermittent Fasting (HIIE/IF). Over an eight-week period swimming performance, body composition, weight and feeding behavior were analyzed. The final morphology of white adipose tissue showed a significant reduction in adipocyte size consistent with a higher number of cells per area in exercised animals (vs C and IF, p < 0.05), which also displayed characteristics of browning through UCP-1 levels and CD31 staining. These results suggest that the increased performance in the HIIE/IF group is, in part, by modifications of WAT metabolism through the browning process., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Menopause and post-menopause are characterized by low levels of estrogen that can be associated with the emergence of metabolic diseases. While hormone replacement therapy can alleviate many symptoms, it can also exacerbate other diseases such as breast cancer. In the search for natural alternatives, Ilex paraguariensis (Yerba Mate) has been identified as a potential therapy for the onset of obesity. Here, the effect of MATE consumption on white adipose tissue (WAT) was studied in ovariectomized rats, an animal model for post-menopause hormone loss., Methods: Four groups of animals were used: ovariectomy with MATE (OVX MATE) and without MATE (OVX), as well as sham surgery with MATE (Sham MATE) and without MATE (Sham). MATE was provided by gavage at 1 g/kg of body weight for eight weeks before measuring biochemical parameters in plasma and characterizing WAT morphology., Results: The consumption of Yerba MATE significantly decreased weight gain in ovariectomized rats and presented near control levels of triglycerides, total cholesterol, and LDL. A morphometric analysis of WAT showed a significant decrease in the area occupied by adipocytes in the group that consumed MATE. Finally, MATE consumption increased the UCP1 content in the WAT of the ovariectomized group. Yerba MATE treatment was also associated with higher levels of SIRT1 protein., Conclusion: MATE consumption has a preventive effect on the weight gain observed in ovariectomized rats and potential benefits in naturally avoiding the onset of obesity post menopause., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plant viruses cause systemic diseases that severely impair plant growth and development. While the accumulation of viruses in the root system has long been established, little is known as to how viruses affect root architecture. Here, we examined how the emerging tobamovirus, tomato brown rugose fruit virus (ToBRFV), alters root development in tomato. We found that ToBRFV and tobacco mosaic virus both invaded root systems during the first week of infection. ToBRFV infection of tomato plants resulted in a significant decrease in root biomass and elongation and root-to-shoot ratio and a marked suppression of root branching. Mutation in RNA-dependent RNA polymerase 6 increased the susceptibility of tomato plants to ToBRFV, resulting in severe reduction of various root growth parameters including root branching. Viral root symptoms were associated with the accumulation of auxin response factor 10a (SlARF10a) transcript, a homolog of Arabidopsis ARF10, a known suppressor of lateral root development. Interestingly, loss-of-function mutation in SlARF10a moderated the effect of ToBRFV on root branching. In contrast, downregulation of sly-miR160a, which targets SlARF10a, was associated with constitutive suppression root branching independent of viral infection. In addition, overexpression of a microRNA-insensitive mutant of SlARF10a mimicked the effect of ToBRFV on root development, suggesting a specific role for SlARF10a in ToBRFV-mediated suppression of root branching. Taken together, our results provide new insights into the impact of tobamoviruses on root development and the role of ARF10a in the suppression of root branching in tomato., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

Background: The diagnosis of cancer in Bethesda III/IV thyroid nodules is challenging as fine-needle aspiration (FNA) has limitations, and these cases usually require diagnostic surgery. As approximately 77% of these nodules are not malignant, a diagnostic test accurately identifying benign thyroid nodules can reduce "potentially unnecessary" surgery rates. We have previously reported the development and validation of a microRNA-based thyroid classifier (mir-THYpe) with high sensitivity and specificity, which could be performed directly from FNA smear slides. We sought to evaluate the performance of this test in real-world clinical routine to support clinical decisions and to reduce surgery rates., Methods: We designed a real-world, prospective, multicentre study. Molecular tests were performed with FNA samples prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (patients with no indication for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports., Findings: A total of 435 patients (440 nodules) classified as Bethesda III/IV were followed-up. The rate of avoided surgeries was 52·5% for all surgeries and 74·6% for "potentially unnecessary" surgeries. The test achieved 89·3% sensitivity, 81·65% specificity, 66·2% positive predictive value, and 95% negative predictive value. The test supported 92·3% of clinical decisions., Interpretation: The reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgeries with robust performance and support clinical decision-making., Funding: The São Paulo Research-Foundation (FAPESP) and Onkos., Competing Interests: Declaration of interests MTS holds equity at Onkos Molecular Diagnostics. BMR, SS, AFO and MO are formal employees at Onkos Molecular Diagnostics. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The fundamental objective of military field training exercises (FTX) is to prepare military personnel for real-life operations through simulated scenarios. These training sessions often require extreme physical efforts with prolonged, high-intensity exercises that can be combined with food restrictions and partial, or total, sleep deprivation. Such conditions can compromise an individual's physical performance and cause tissue damage, thus affecting their health. This study aimed to perform a systematic review of the literature to identify studies that measured the changes in hormone levels and biomarkers of cellular injury and oxidative stress resulting from FTX with high levels of energy expenditure combined with food and sleep restrictions. PubMed and the Scopus database were searched for articles that combined physical effort/food restriction/sleep deprivation with military training. The initial database search identified 158 articles that were reduced to 18 after confirmation. Significant reductions were reported in thyroid hormones, T3, T4, and anabolic hormones such as testosterone, insulin and androstenedione. An exception for GH was found, which increased throughout FTX. Less distinct responses to FTX were observed with cortisol, TSH and LH. The presence of biomarkers for cellular damage (myoglobin, TNF, and CRP) and increased immune response activities were also described. The scarcity of information on oxidative stress, analyses of cellular injury and biomarkers of inflammatory responses warrants the future study of these topics, which could be helpful in facilitating the safe and effective physical preparations of the members of the armed forces.

Objective: A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors., Design and Methods: Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff., Results: Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status., Conclusion: Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

Purpose: To assess the associations between TSH and free thyroxine (FT4) levels and decline in functional status in euthyroid older patients at risk of frailty., Design: Longitudinal prospective study., Methods: Participants from the geriatric outpatient clinic of a university hospital, who fulfilled the criteria for frailty or were at risk of frailty, were recruited. Only those euthyroid, defined by age-specific reference range of TSH, were included. Serum was collected during enrollment and at the third and sixth years of follow-up to assess the mean value of all follow-up levels of serum TSH and FT4. Functional status assessing activities of daily living (ADL) and instrumental ADL were evaluated using the Katz Index and the Health Assessment Questionnaire, respectively. Functional decline was defined by a positive variation in any of the applied scales in the absence of disagreement between the scales or if the patient was institutionalized., Results: Of the 273 participants (72.5% females) enrolled (mean age 80 years old), 48 died and 102 presented functional decline at the end of follow-up (mean 3.6 ± 1.7 years). Each 0.1 ng/dL increase in baseline and mean follow-up serum FT4 levels increased the risk of functional decline by 14.1% and 7.7%, respectively. The risk of functional decline was 9 times greater with baseline FT4 levels in the fourth and fifth quintiles (p = 0.049) and 50% lower with baseline FT4 levels in the first quintile (p = 0.046). No association between TSH and the outcome was found., Conclusions: Higher and lower FT4 levels were, respectively, a risk and a protective factor for the decline in functional status in a cohort of euthyroid older adults at risk of frailty., (© 2021. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients. Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease. Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW. Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve). Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Higuchi, Fernanda, Jurnior, Andrade, Corbo, Vaisman, Vaisman and Bulzico.)

Thyroid cancer is the most frequent cancer of the endocrine system. Most patients are treated with thyroidectomy followed by radioiodine therapy. However, in part of the patients, a reduction of the sodium-iodide symporter (NIS) occurs, rendering radioiodine therapy ineffective. Moreover, epithelial-mesenchymal transition (EMT) may occur, leading to more aggressive and invasive features. Herein, we evaluated the effect of the flavonoid quercetin on EMT and NIS expression in BCPAP, a papillary thyroid carcinoma cell line. BCPAP was treated with 100 μM quercetin for 24 h and cell viability, apoptosis, EMT markers and NIS were evaluated. Quercetin decreased cell viability by enhancing apoptosis. The flavonoid also reduced matrix metalloproteinase 9 and increased E-cadherin mRNA levels, inhibiting BCPAP adhesion and migration. Additionally, quercetin increased NIS expression and function. Thus, our results suggest that quercetin could be useful as adjuvant in thyroid cancer therapy, inducing apoptosis, reducing invasion and increasing the efficacy of radioiodine therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The risk of malignancy (RoM) of indeterminate thyroid nodules (ITNs) shows a high variability in interinstitutional cohorts. The RoM is partially associated with the cytological degree of atypia and the ultrasound (US) pattern. This study evaluated the cancer risk of ITNs by jointly considering the cytological subcategory and the American Thyroid Association (ATA)-based US risk classification. Methods: This study features a retrospective cohort from two Brazilian centers comprising 238 ITNs with confirmed outcomes. US classification, according to ATA-based guidelines, and cytological subcategorization were determined. The cytological subgroups were as follows: (1) nuclear atypia (NA) related to papillary thyroid carcinoma (PTC) but insufficient to categorize the cytology as suspicious for malignancy; (2) architectural atypia without NA (AA); (3) both architectural and nuclear atypia (ANA); (4) oncocytic pattern (OP) without NA; and (5) NA not related to PTC (NANP). NA was divided into three subgroups: nuclear size and shape, nuclear membrane appearance, and/or chromatin aspects. Results: The overall frequency of malignancy was 39.5%. Among the cytological subcategories, the highest RoM was related to the NA (43.9%) and to the ANA (43.5%), followed by AA (29.4%), and OP (9.4%). NA was positively and independently associated with cancer (odds ratio [OR]: 4.5; confidence interval [CI: 1.2-16.6]) as was the occurrence of ANA (OR 6.6 [CI 1.5-29.5]). AA and OP were not independently associated with cancer. Both ATA-based high- and intermediate-risk categories showed an independent association with cancer (OR 6.8 [CI 2.9-15.5] and OR: 2.6 [CI 1.1-5.8], respectively). ITNs with cytological findings of NA or ANA when combined with intermediate US patterns had RoM values of 47.5% and 56.7%, respectively. Both cytological subcategories, when combined with the ATA high-suspicion class reached an RoM >70%. The type of NA with the highest odds for cancer was related to the nuclear membrane (OR 11.5). Conclusions: The RoM of ITNs can reach almost 80% when both NA and ATA-based high-risk US features are present. The presence of such cytological features also increased the RoM in the ATA-based intermediate-risk US category. In addition, AA and OP were not independently related to higher cancer risk. These results strengthen the recommendations for combing cytological subcategorization and US risk classification in the workup for ITNs before the decision of a molecular testing, clinical observation, or diagnostic surgery.

Background: Insufficient or excessive iodine intake during gestation may compromise adaptive mechanisms in maternal thyroid function and lead to adverse pregnancy outcomes. In this context, we aimed to study the effects of maternal iodine status in the first and third trimesters of gestation on obstetric and neonatal outcomes in an iodine-sufficient population in Rio de Janeiro, Brazil. Methods: A total of 214 pregnant women in the first trimester of gestation were enrolled and prospectively followed until delivery between 2014 and 2017. All participants were ≥18 and ≤35 years, had a spontaneous single pregnancy, and had no history of thyroid or other chronic diseases, nor were they taking iodine-containing supplements at enrollment. In the first trimester, we obtained clinical information and determined thyroid function and the urinary iodine concentration (UIC) of the participants. Thyroid function and UIC were reassessed in the third trimester. Iodine status was determined by the median of UIC obtained from six urine spot samples by the inductively coupled plasma mass spectrometry method. Pregnancy and neonatal outcomes and delivery information were obtained from medical records. Results: The median UIC in the whole population was 219.7 μg/L. The prevalence of UIC <150 μg/L was 17.2%, and 38.7% had UIC ≥250 μg/L. Gestational diabetes (GDM) was higher in the group with UIC 250-499 μg/L ( n  = 77) compared with the group with UIC 150-249 μg/L ( n  = 94) (20.3% vs. 9.7%, p  < 0.05). Ultimately, UIC ≥250 μg/L was an independent risk factors for GDM (relative risk [RR] = 2.9 [confidence interval, CI = 1.1-7.46], p  = 0.027) and hypertensive disorders of pregnancy (HDP) (RR = 4.6 [CI = 1.1-18.0], p  = 0.029). Among 196 live-born newborns, lower birth length was observed in infants whose mothers had UIC <150μg/L ( n  = 37) in the first trimester compared with those with UIC 150-249 μg/L ( n  = 86) (median interquartile range: 48.0 [2.2] vs. 49.0 [4.0] cm, p  = 0.01). Maternal UIC <150 μg/L was negatively associated with birth length of newborns (Exp (B) = 0.33 [CI = 0.1-0.9], p  = 0.03). Conclusions: In a population whose median iodine intake is sufficient, extensive individual variation occurs. Such abnormalities are associated with increased GDM and HDP when UIC is ≥250 μg/L, and lower infant birth length when UIC is <150 μg/L.

Objective Maternal hypothyroidism during pregnancy may lead to adverse outcomes. Recently published guidelines by the American Thyroid Association (ATA) do not advocate for universal screening but recommend a case-finding approach in high-risk pregnant women. The present study aims to evaluate the accuracy of this approach in identifying women with thyroid dysfunction during early pregnancy. Subjects and methods This is a multiple-center, cross-sectional study. Three hundred and one pregnant women were enrolled. Anamnesis and a physical examination were performed to detect which women fulfilled the criteria to undergo laboratory screening of thyroid dysfunction, according to the ATA's 2017 guidelines. The Zulewski's validated clinical score was applied to assess signs and symptoms of hypothyroidism. Serum levels of thyrotropin (TSH), free thyroxine (FT4), anti-thyroperoxidase (TPO-Ab), and anti-thyroglobulin (Tg-Ab) antibodies were determined. Results Two hundred and thirty one women (78%) were classified as high risk, and 65 (22%) were classified as low risk for thyroid dysfunction. Regarding the clinical score, 75 patients (31.2%) presented mild symptoms that were compatible with SCH, of which 22 (7.4%) had symptoms as the only risk factor for thyroid disease. 17 patients (5.7%) had SCH, of which 10 (58.8%) belonged to the high-risk group, and 7 (41.2%) belonged to the low-risk group. OH was found in 4 patients (1.4%): 3 (75%) in the high-risk group and 1 (25%) in the low-risk group. Conclusions The ATA's proposed screening criteria were not accurate in the diagnosis of thyroid dysfunction in pregnancy. Testing only the high-risk pregnant women would miss approximately 40% of all hypothyroid patients.

The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (-0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05-1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (-0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (-0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02-0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.

Objective: To assess iodine status and its effects on maternal thyroid function throughout pregnancy., Design: In the present prospective cohort study, three urinary samples were requested for urinary iodine concentration (UIC) determinations in both the first and third gestational trimesters. Serum thyrotropin (TSH) and free thyroxine (FT4) were analysed in both trimesters and thyroid antibodies were assessed once., Setting: Rio de Janeiro, Brazil.ParticipantsFirst-trimester pregnant women (n 243), of whom 100 were re-evaluated during the third trimester., Results: Iodine sufficiency was found in the studied population (median UIC=216·7 µg/l). The first- and third-trimester median UIC was 221·0 and 208·0 µg/l, respectively. TSH levels (mean (sd)) were higher in the third trimester (1·08 (0·67) v. 1·67 (0·86) mIU/l; P&lt;0·001), while FT4 levels decreased significantly (1·18 (0·16) v. 0·88 (0·12) ng/dl; P&lt;0·001), regardless the presence of iodine deficiency (UIC&lt;150 µg/l) or circulating thyroid antibodies. UIC correlated (β; 95% CI) independently and negatively with age (-0·43; -0·71, -0·17) and positively with multiparity (0·15; 0·02, 0·28) and BMI (0·25; 0·00, 0·50). Furthermore, median UIC per pregnant woman tended to correlate positively with TSH (0·07; -0·01, 0·14). Women with median UIC≥250 µg/l and at least one sample ≥500 µg/l throughout pregnancy had a higher risk of subclinical hypothyroidism (OR=6·6; 95% CI 1·2, 37·4)., Conclusions: In this cohort with adequate iodine status during pregnancy, excessive UIC was associated with an increased risk of subclinical hypothyroidism.

It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVG ROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVG ROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVG ROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders., (© 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: The aim of this study was to compare oxidative stress biomarkers, antioxidant capacity, muscle damage and hormone response between vision impaired and non-vision impaired athletes after a single maximal exercise test., Methods: Eight vision impaired and fifteen non-vision impaired athletes performed a maximal aerobic test with blood collected before and after., Results: Non-vision impaired athletes displayed greater aerobic capacity than blind individuals (P<0.05). Lactate increased by four-fold, while creatine kinase and gamma-glutamyltransferase as well as the oxidative stress biomarkers and antioxidants were unchanged. Cortisol increased, but testosterone and their ratio were not altered. Differences were observed for alanine transaminase and aspartate transaminase, which were increased only in non-blind athletes., Conclusions: Our data suggest that blind soccer players, in comparison to those with vision, experienced less cellular damage.

Objective: Bone metastases bring greater morbi-mortality to patients with differentiated thyroid carcinoma (DTC). Treatment was limited to radioactive iodine (RAI) and local approaches. Currently, bisphosphonates are included in the therapeutic arsenal. The aim of this study is to evaluate the impact of bone metastases and their treatment with zoledronic acid (ZA) and RAI therapy., Methods: We retrospectively review 50 DTC patients with structurally evident bone metastases followed in a tertiary cancer center from 1994 to 2018. Clinical-pathologic characteristics, skeletal related events (SRE), and therapeutic approaches were recorded., Results: Among the 50 patients analyzed, 22 underwent ZA adjuvant therapy and 28 did not. Mortality rate was 44%. Those patients presented SREs more frequently (90.9 vs. 67.9% the survival group, p = 0.05) and also had a greater number of bone lesions (40.9 vs. 10.7% had more than 6 metastatic sites, p = 0.03). The same group of patients was analyzed before and after therapy with ZA and the incidence of SRE decreased from 1.81 (0-8) before therapy to 0.29 (0-7) after therapy ( p = 0.006). Comparing similar groups of 22 patients treated with ZA with 28 patients not treated, there was a trend of better overall survival (OS) in the group that received this drug (147 vs. 119 months, p = 0.06) and significantly improvement when bone metastases were RAI avid 155 (125-185) versus 120 (85-157) months, p < 0.01. Conclusion : ZA can successfully diminish the chance of having new SRE and possibly affect OS in DTC patients with bone metastases. The positive impact of RAI adjuvant treatment on OS is directly associated with RAI uptake.

Objective: The aim was to evaluate the quality of life (HRQoL) in women with subclinical hypothyroidism (sHT) after 16 weeks of endurance training., Subjects and Methods: In the first phase, a cross-sectional study was conducted in which 22 women with sHT (median age: 41.5 (interquartile range: 175) years, body mass index: 26.2 (8.7) kg/m2, thyroid stimulating hormone > 4.94 mIU/L and free thyroxine between 0.8 and 1.3 ng/dL were compared to a group of 33 euthyroid women concerned to HRQoL. In the second phase, a randomized clinical trial was conducted where only women with sHT were randomly divided into two groups: sHT-Tr (n = 10) - participants that performed an exercise program - and sHT-Sed (n = 10) - controls. Exercise training consisted of 60 minutes of aerobic activities (bike and treadmill), three times a week, for 16 weeks. The HRQoL was assessed by the SF-36 questionnaire in the early and at the end of four months., Results: Women with sHT had lower scores on functional capacity domain in relation to the euthyroid ones (770 ± 23.0 vs. 88.8 ± 14.6; p = 0.020). The sHT-Tr group improved functional capacity, general health, emotional aspects, mental and physical component of HRQoL after training period, while the sHT-Sed group showed no significant changes., Conclusion: After 16 weeks of aerobic exercise training, there were remarkable improvements in HRQoL in women with sHT.

Objective: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL)., Subjects and Methods: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase)., Results: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group., Conclusion: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.

Objective: To evaluate iodine status among pregnant women from a coastal state after Brazilian governmental resolution reducing iodine concentrations in table salt. Secondarily, we correlated urinary iodine concentration (UIC) with thyroid volume and hormones., Methods: Inductively coupled plasma mass spectrometry was used to assess UIC from 629 samples of 244 first trimester pregnant women. Thyroid ultrasound, serum thyroglobulin, thyrotropin, free thyroxine, and antithyroid antibodies were measured as iodine concentrations on samples of table salt from patient's home., Results: Median UIC was adequate (221.0 µg/L); however, 48.7% of women had insufficient (<150 µg/L), and 4.5% excessive UIC (≥500 µg/L) in at least one sample. UIC was independently and negatively correlated with age (β: -0.58; 95% confidence interval [CI], -0.89 to -0.27) and positively with multiparity (β: 0.20; 95% CI, 0.04-0.34). In those without thyroiditis, UIC tended to be positively correlated with body mass index (P = 0.098) and thyrotropin (P = 0.072). Independent variables associated with iodine insufficiency were age >30 y (odds ratio [OR] = 2.0; 95% CI, 1.2-3.2) and obesity (OR = 0.2; 95% CI, 0.2-0.7). Excessive UIC was associated negatively with age (OR = 0.2; 95% CI, 0.04-0.8) and positively with multiparity (OR = 2.5; 95% CI, 1.0-6.0) and subclinical hypothyroidism (OR = 5.6; 95% CI, 1.0-30.2)., Conclusion: This population has iodine sufficiency, and supplementation should not be generally considered, based on the risk association between excessive UIC and subclinical hypothyroidism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined., Methods: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes., Results: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression., Conclusions: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State., Subjects and Methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L., Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively., Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Objective: Life expectancy is increasing worldwide and studies have been demonstrating that elevated serum thyroid stimulating hormone (TSH) concentration in elderly is associated with some better health outcomes. This elevation is somewhat physiological as aging. The aim of this study was to investigate the heart rate (HR) response during a graded exercise test and its recovery in healthy elderly, comparing subjects within serum TSH in the lower limit of reference range to those within the TSH in the upper limit., Subjects and Methods: A cross-sectional study was conducted with 86 healthy elderly aged 71.5 ± 5.1 years, with serum TSH between 0.4 - 4.0 mUl/mL. The participants were divided into two groups according to TSH level: < 1.0 mUl/mL (n = 13) and ≥ 1.0 µUI/mL (n = 73). All participants performed an ergometric test on a treadmill. The HR was recorded and analyzed at rest, during exercise and during the three minutes immediately after exercise., Results: No differences were observed in relation to HR at peak of exercise (TSH < 1.0 µUI/mL: 133.9 ± 22.5 bpm vs. TSH ≥ 1.0 µUI/mL: 132.4 ± 21.3 bpm; p = 0.70) and during the first minute of recovery phase (TSH < 1.0 µUI/mL: 122.3 ± 23.1 bpm vs. TSH ≥ 1.0 µUI/mL: 115.7 ± 18.4 bpm p = 0.33). The groups also presented similar chronotropic index (TSH < 1.0 µUI/mL: 78.1 ± 30.6 vs. TSH ≥ 1.0 µUI/mL: 79.5 ± 26.4; p = 0.74)., Conclusion: In this sample studied, there were no difference between lower and upper TSH level concerning HR response during rest, peak of exercise and exercise recovery.