ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction. Objective TSH T FT , (FT3) (FT4) FT3FT4 FTFT (FT3:FT4 methods ELSABrasil ELSA Brasil FT3:FT defined 14090 140 90 140/9 mmHg 82 8 2 8. followup. followup follow up. up follow-up 1unit unit 1 variance RR (RR 95 CIs (CIs Results 5915 5 915 5,91 58 hypothyroidism 3 hyperthyroidism 28 (95 CI 27%29.3%. 27293 27% 29.3% . 27 29 27%-29.3%) 0.181.06 018106 0.18 1.06 0 18 06 (0.18-1.0 ng/dL ngdL ng dL 103 03 1.03 1.011.06 101106 1.01 01 1.01-1.06 104 04 1.04 1.011.07. 101107 1.07 07 1.01-1.07) However Conclusion (FT3 (FT4 FT3FT (FT3:FT 1409 14 9 140/ 591 91 5,9 (9 27%29.3% 2729 293 29.3 27%-29.3% 181 0.181.0 01810 018 0.1 106 1.0 (0.18-1. 10 011 1.011.0 10110 101 1.01-1.0 1.011.07 107 1.01-1.07 (FT 59 5, ( 27%29.3 272 29. 27%-29.3 0.181. 0181 0. 1. (0.18-1 1.011. 1011 1.01-1. 27%29. 27%-29. 0.181 (0.18- 1.011 1.01-1 27%29 27%-29 (0.18 1.01- 27%2 27%-2 (0.1 27%- (0. (0

ABSTRACT Noroviruses are highly infectious, genetically diverse viruses. Global outbreaks occur frequently, making molecular surveillance important for infection monitoring. This cross-sectional descriptive study aimed to monitor cases of norovirus gastroenteritis in the Brazilian Amazon. Fecal samples were tested by immunoenzymatic assay, RT-PCR and genetic sequencing for the ORF1/ORF2 and protease regions. Bayesian inference with a molecular clock was employed to construct the phylogeny. The norovirus prevalence was 25.8%, with a higher positivity rate among children aged 0-24 months. Genogroup GII accounted for 98.1% of the sequenced samples, while GI accounted for 1.9% of them. The GII.P16/GII.4 genotype was the most prevalent, with an evolution rate of 2.87x10−3 and TMRCA estimated in 2012. This study demonstrates that norovirus is a primary causative agent of gastroenteritis and provides data on viral genetic diversity that may facilitate infection surveillance and vaccine development. infectious viruses frequently monitoring crosssectional cross sectional Amazon assay RTPCR RT PCR ORF1ORF2 ORFORF ORF1 ORF2 ORF ORF1/ORF regions phylogeny 258 25 8 25.8% 024 0 24 0-2 months 981 98 1 98.1 19 9 1.9 them GIIP16GII4 GIIPGII P16 4 P GII.P16/GII. prevalent 287x103 x 2 87x10 3 2.87x10− 2012 development ORF1ORF 25.8 02 0- 98. 1. GIIP GIIP16GII P1 GII.P16/GII 287x10 87x1 2.87x10 201 25. 287x1 87x 2.87x1 20 287x 2.87x

Resumo Objetivo Avaliar associações entre a média da tireotropina (TSH) e tiroxina livre (T4L) mantida durante follow-up, e mortalidade em pacientes idosos eutireoidianos definidos de acordo com a faixa de referência específica para a idade (FR-e) do TSH. Método Coorte retrospectiva tipo análise de sobrevivência incluindo pacientes idosos eutireoidianos acompanhados no ambulatório de hospital universitário entre 2010 e 2013. Todos os participantes haviam sido avaliados quanto ao risco de incapacidade funcional como critério para admissão nesse ambulatório. As médias dos valores de TSH e T4L foram calculadas através das dosagens obtidas no período de acompanhamento. Cada FR-e de TSH foi dividida em quatro partes iguais, considerando níveis mais baixos como variável de exposição (≤1,75 mUI/L para <80 e ≤2,0 mUI/L para ≥80 anos). Os níveis de T4L foram dicotomizados em duas categorias (< e ≥1,37 ng/dL). O desfecho foi o tempo até a morte. A regressão de risco proporcional de Cox foi empregada para estimar a hazard ratio (HR) e o intervalo de confiança (IC) de 95% Resultados 285 participantes (73% mulheres, idade média =80,4 anos) seguidos pela mediana de 5,7 anos (IQR =3,7–6,4; máximo =7), sendo que 114 faleceram. Após o modelo final ajustado, a mortalidade esteve associada ao TSH no limite inferior (HR=1,7; IC=1,1–2,7; p=0,016) e ao T4L mais elevado. (HR=2,0; IC=1,0–3,8; p=0,052). Conclusão Níveis médios de T4L mais altos e de TSH mais baixos foram associados ao risco de morte em coorte de idosos eutireoidianos usando FR-e de TSH. (TSH TL T L (T4L followup, followup follow up, up follow-up FRe FR (FR-e 201 2013 acompanhamento iguais ≤1,75 175 1 75 (≤1,7 mUIL mUI 80 <8 20 2 0 ≤2, ≥8 anos. . < ( 137 37 ≥1,3 ng/dL. ngdL ng/dL ng dL ng/dL) HR (HR IC (IC 95 28 73% 73 (73 mulheres 804 4 =80, 57 5 7 5, IQR =3,7–6,4 3764 3 6 =7, =7 , =7) 11 faleceram ajustado HR=1,7 HR17 (HR=1,7 IC=1,1–2,7 IC1127 p=0,016 p0016 p 016 elevado HR=2,0 HR20 (HR=2,0 IC=1,0–3,8 IC1038 8 p=0,052. p0052 p=0,052 052 p=0,052) ≤1,7 17 (≤1, ≤2 ≥ 13 ≥1, 9 (7 =80 =3,7–6, 376 = HR=1, HR1 (HR=1, IC=1,1–2, IC112 p=0,01 p001 01 HR=2, HR2 (HR=2, IC=1,0–3, IC103 p005 p=0,05 05 ≤1, (≤1 ≤ ≥1 =8 =3,7–6 HR=1 (HR=1 IC=1,1–2 IC11 p=0,0 p00 HR=2 (HR=2 IC=1,0–3 IC10 ≤1 (≤ =3,7– HR= (HR= IC=1,1– IC1 p=0, p0 IC=1,0– =3,7 IC=1,1 p=0 IC=1,0 =3, IC=1, p= =3 IC=1 IC=

Abstract Objective To assess the associations between the mean thyrotropin (TSH) and mean free thyroxine (FT4), detected during follow-up, and mortality in a group of older euthyroid patients according to age-specific reference range (as-RR) for TSH. Method Retrospective survival analysis cohort including euthyroid elderly patients who were being monitored at the outpatient clinic of a university hospital from 2010 to 2013. All participants had been assessed for the risk of functional disability as a criterion for admission to this outpatient clinic. Mean TSH and FT4 values were calculated using hormone dosages obtained during the follow-up period. Each as-RR for TSH was divided into four equal parts, considering the lower levels as the main exposure variable (≤1.75 mlU/L for <80, and ≤2.0 mlU/L for ≥80 years). FT4 levels were explored according to two categories (< e ≥1.37 ng/dL). The outcome was time to death. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results 285 participants (73% females, mean age =80.4 years) followed by a median of 5.7 years (IQR =3.7–6.4; maximum =7), of which 114 died. After the adjusted final model, mortality was associated with the lowest mean TSH (HR=1.7; CI=1.1–2.7; p=0.016) and with the upper mean of FT4 (HR=2.0; CI=1.0–3.8; p=0.052). Conclusions Higher FT4 and lower TSH mean levels were associated with risk of death in a cohort of euthyroid older adults using an as-RR of TSH. (TSH FT4, FT , (FT4) followup, followup follow up, up agespecific specific asRR RR (as-RR 201 2013 period parts ≤1.75 175 1 75 (≤1.7 mlUL mlU L 80 <80 20 2 0 ≤2. ≥8 years. . < ( 137 37 ≥1.3 ng/dL. ngdL ng/dL ng dL ng/dL) HR (HR 95 CI. CI (CI) 28 73% 73 (73 females 804 4 =80. 57 5 7 5. IQR =3.7–6.4 3764 3 6 =7, =7 =7) 11 died model HR=1.7 HR17 (HR=1.7 CI=1.1–2.7 CI1127 p=0.016 p0016 p 016 HR=2.0 HR20 (HR=2.0 CI=1.0–3.8 CI1038 8 p=0.052. p0052 p=0.052 052 p=0.052) (FT4 ≤1.7 17 (≤1. <8 ≤2 ≥ 13 ≥1. 9 (CI (7 =80 =3.7–6. 376 = HR=1. HR1 (HR=1. CI=1.1–2. CI112 p=0.01 p001 01 HR=2. HR2 (HR=2. CI=1.0–3. CI103 p005 p=0.05 05 (FT ≤1. (≤1 ≤ ≥1 =8 =3.7–6 HR=1 (HR=1 CI=1.1–2 CI11 p=0.0 p00 HR=2 (HR=2 CI=1.0–3 CI10 ≤1 (≤ =3.7– HR= (HR= CI=1.1– CI1 p=0. p0 CI=1.0– =3.7 CI=1.1 p=0 CI=1.0 =3. CI=1. p= =3 CI=1 CI=

ABSTRACT Objective: To evaluate the association between subclinical hypothyroidism and hepatic steatosis and fibrosis using the noninvasive diagnostic methods transient hepatic elastography (TE) and controlled attenuation parameter (CAP) in patients with subclinical hypothyroidism. Subjects and methods: This was a cross-sectional study including women with confirmed spontaneous subclinical hypothyroidism and an age- and body mass index (BMI)-matched control group without thyroid disease or circulating antithyroperoxidase (anti-TPO) antibodies. Exclusion criteria were age > 65 years, thyroid-stimulating hormone (TSH) > 10.0 mIUI/L, BMI ≥ 35 kg/m2, diabetes, or other chronic liver diseases. Liver stiffness was classified according to TE values (in kPa) and ranged from absence of fibrosis (F0) to advanced fibrosis (F3). Hepatic steatosis was classified according to CAP values (in dB/m) and ranged from low-grade (S1) to advanced (S3) steatosis. Results: Of 68 women enrolled, 27 were included in the subclinical hypothyroidism group and 41 in the control group. Advanced steatosis (S3) was more frequent in the subclinical hypothyroidism group (25.9% versus 7.3%, respectively, p = 0.034). Circulating anti-TPO was an independent factor associated with advanced steatosis (odds ratio 9.5, 95% confidence interval 1.3–68.3). In multiple linear regression analysis, TE values (which evaluated fibrosis) correlated negatively with free thyroxine levels. Conclusion: The results of this study strengthen the hypothesis that hepatic steatosis is associated with autoimmune (positive anti-TPO) subclinical hypothyroidism, independently from BMI. However, subclinical hypothyroidism alone does not appear to be associated with a significantly increased risk of hepatic fibrosis. Objective (TE (CAP crosssectional cross sectional BMImatched matched antiTPO anti TPO (anti-TPO antibodies 6 years thyroidstimulating stimulating TSH (TSH 100 10 0 10. mIUIL mIUI L mIUI/L 3 kgm2 kgm kg m2 m kg/m2 diabetes diseases kPa F0 F (F0 F3. F3 . (F3) dB/m dBm dB lowgrade low grade S1 S (S1 S3 (S3 Results enrolled 2 4 25.9% 259 25 9 (25.9 73 7 7.3% respectively 0.034. 0034 0.034 034 0.034) odds 95 5 9.5 1.3–68.3. 13683 1.3–68.3 1 1.3–68.3) analysis which levels Conclusion positive However kg/m (F (F3 (S 25.9 (25. 7.3 003 0.03 03 9. 1368 1.3–68. 25. (25 7. 00 0.0 136 1.3–68 (2 0. 13 1.3–6 ( 1.3– 1.3 1.

Resumo Objetivo Comparamos o volume tireoidiano (VT) e a presença de bócio nodular (BN) em mulheres grávidas e não grávidas em uma área suficiente em iodo. Também avaliamos a relação entre idade gestacional, paridade e VT no grupo de gestantes e determinamos os percentis 2,5 e 97,5 de VT normal na gestação. Métodos Este estudo transversal incluiu 299 mulheres saudáveis (216 grávidas) sem doenças tireoidianas prévias. Ultrassonografias de tireoide foram realizadas e comparadas entre mulheres grávidas e não grávidas. A faixa de distribuição normal de VT (percentis 2,5 e 97,5) na gestação foi determinada após a exclusão de indivíduos com anticorpos tireoidianos positivos, BN e/ou tireotropina sérica (TSH) ou tiroxina livre (T4L) anormais. Resultados O VT foi maior entre as gestantes em comparação com as mulheres não grávidas (8,6 vs 6,1 cm3; p< 0,001) e foi positivamente correlacionado com a idade gestacional (rs = 0,221; p= 0,001), índice de massa corporal (IMC, rs 0,165; p= 0,002) e níveis de T4L (rs 0,118 p= 0,021). A frequência de BN não diferiu entre os dois grupos. Houve correlação negativa entre VT e TSH (rs -0,13; p= 0,014). O VT foi menor entre as primíparas em comparação com as multíparas (7,8 vs 8,9; p< 0,001) e foi positivamente correlacionado com a paridade (rs 0,161; p= 0,016). Os percentis 2,5 e 97,5 de VT foram 4,23 e 16,47 cm3, respectivamente. Conclusão O VT foi maior em gestantes em comparação com mulheres não grávidas e foi positivamente relacionado à paridade, IMC e idade gestacional em uma população com status iódico normal. A gravidez não interferiu no desenvolvimento de BN. (VT (BN iodo 25 2 5 2, 975 97 97, 29 216 (21 prévias positivos eou (TSH TL T L (T4L anormais 8,6 86 8 6 (8, 61 1 6, cm3 cm p 0,001 0001 0 001 0,221 0221 221 0,001, , IMC, (IMC 0,165 0165 165 0,002 0002 002 0118 118 0,11 0,021. 0021 0,021 . 021 0,021) grupos 0,13 013 13 -0,13 0,014. 0014 0,014 014 0,014) 7,8 78 7 (7, 8,9 89 9 0,161 0161 161 0,016. 0016 0,016 016 0,016) 423 4 23 4,2 1647 16 47 16,4 respectivamente 21 (2 8, (8 0,00 000 00 0,22 022 22 0,16 011 11 0,1 0,02 02 01 -0,1 0,01 7, (7 42 4, 164 16, ( 0,0 0,2 0, -0, -0 -

Abstract 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 2.5th and 97.5th 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 (2.5th and 97.5th 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 cm3; 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 2.5th and 97.5th percentiles of TV were 4.23 and 16.47 cm3, 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. (TV NG (NG nonpregnant non iodinesufficient sufficient area group 25th th 2 5th 975th 97 crosssectional cross sectional 29 216 (21 diseases antibodies andor (TSH FT4. FT . (FT4) 8.6 86 8 6 (8. 61 1 6. cm3 cm p 0.001 0001 0 001 0.221 0221 221 0.001, , BMI (BMI 0.165 0165 165 0.002, 0002 0.002 002 0.002) 0118 118 0.11 0.021. 0021 0.021 021 0.021) groups 0.13 013 13 -0.13 0.014. 0014 0.014 014 0.014) 7.8 78 7 (7. 8.9 89 9 0.161 0161 161 0.016. 0016 0.016 016 0.016) 423 4 23 4.2 1647 16 47 16.4 respectively population 21 (2 (FT4 8. (8 0.00 000 00 0.22 022 22 0.16 011 11 0.1 0.02 02 01 -0.1 0.01 7. (7 42 4. 164 16. ( (FT 0.0 0.2 0. -0. -0 -

ABSTRACT Objective: The aim of this study was to determine whether classifying hypoechogenicity in three degrees (mild, moderate, and marked) could improve the distinction between benign and malignant nodules and whether such an approach could influence Category 4 of the Thyroid Imaging Reporting and Data System (TI-RADS). Materials and methods: In total, 2,574 nodules submitted to fine needle aspiration, classified by the Bethesda System, were retrospectively assessed. Further, a subanalysis considering solid nodules without any additional suspicious findings (n = 565) was performed with the purpose of evaluating mainly TI-RADS 4 nodules. Results: Mild hypoechogenicity was significantly less related to malignancy (odds ratio [OR]: 1.409; CI: 1.086-1.829; p = 0.01), compared to moderate (OR: 4.775; CI: 3.700-6.163; p < 0.001) and marked hypoechogenicity (OR: 8.540; CI: 6.355-11.445; p < 0.001). In addition, mild hypoechogenicity (20.7%) and iso-hyperechogenicity (20.5%) presented a similar rate in the malignant sample. Regarding the subanalysis, no significant association was found between mildly hypoechoic solid nodules and cancer. Conclusion: Stratifying hypoechogenicity into three degrees influences the confidence in the assessment of the rate of malignancy, indicating that mild hypoechogenicity has a unique low-risk biological behavior that resembles iso-hyperechogenicity, but with minor malignant potential when compared to moderate and marked hypoechogenicity, with special influence on the TI-RADS 4 category. Objective mild, (mild TIRADS. TIRADS TI RADS . (TI-RADS) methods total 2574 2 574 2,57 aspiration assessed Further n 565 Results odds OR [OR] 1.409 1409 1 409 CI 1.0861.829 10861829 1.086 1.829 086 829 1.086-1.829 0.01, 001 0.01 , 0 01 0.01) (OR 4.775 4775 775 3.7006.163 37006163 3.700 6.163 3 700 6 163 3.700-6.163 0.001 0001 8.540 8540 8 540 6.35511.445 635511445 6.355 11.445 355 11 445 6.355-11.445 0.001. addition 20.7% 207 20 7 (20.7% isohyperechogenicity iso hyperechogenicity 20.5% 205 5 (20.5% sample cancer Conclusion lowrisk low risk isohyperechogenicity, hyperechogenicity, category (TI-RADS 257 57 2,5 56 [OR 1.40 140 40 0861 1.0861.82 1086182 1086 1.08 1829 1.82 08 82 1.086-1.82 00 0.0 4.77 477 77 7006 3.7006.16 3700616 3700 3.70 6163 6.16 70 16 3.700-6.16 0.00 000 8.54 854 54 35511 6.35511.44 63551144 6355 6.35 11445 11.44 35 44 6.355-11.44 20.7 (20.7 20.5 (20.5 25 2, 1.4 14 1.0861.8 108618 108 1.0 182 1.8 1.086-1.8 0. 4.7 47 3.7006.1 370061 370 3.7 616 6.1 3.700-6.1 8.5 85 3551 6.35511.4 6355114 635 6.3 1144 11.4 6.355-11.4 20. (20. 1. 1.0861. 10861 10 18 1.086-1. 4. 3.7006. 37006 37 3. 61 6. 3.700-6. 8. 6.35511. 635511 63 114 11. 6.355-11. (20 1.0861 1.086-1 3.7006 3.700-6 6.35511 63551 6.355-11 (2 1.086- 3.700- 6.3551 6.355-1 ( 6.355-

Key points Pregnancy places a metabolic overload on the maternal thyroid, especially in the first trimester, mainly because of the demand imposed by the conceptus. The fetal thyroid becomes functionally mature only around pregnancy week 20. Until then, the fetus depends on the transfer of maternal thyroid hormones (THs). Thyroid hormones are essential for the adequate fetal neurofunctional and cognitive development. Hypothyroidism brings higher risks of obstetric and fetal complications, namely, first-trimester miscarriage, preeclampsia and gestational hypertension, placental abruption, prematurity, low birth weight, and higher perinatal morbidity and mortality. Primary hypothyroidism (involvement of the gland with difficulty in producing and/or releasing TH) is the most common form of disease presentation, with the main etiology of Hashimoto's thyroiditis of autoimmune origin. In about 85%-90% of cases of Hashimoto's thyroiditis, antithyroid antibodies are present; the antithyroperoxidase (ATPO) is the most frequent. Positivity for ATPO is determined when circulating values exceed the upper limit of the laboratory reference. It implies greater risks of adverse maternal-fetal outcomes. Such a correlation occurs even in ranges of maternal euthyroidism. The critical point for the diagnosis of hypothyroidism during pregnancy is an elevation of thyroid-stimulating hormone (TSH). The measurement of free thyroxine (FT4) differentiates between subclinical and overt hypothyroidism. In subclinical hypothyroidism, FT4 is within the normal range, whereas in overt hypothyroidism, FT4 values are below the lower limit of the laboratory reference. Treatment of hypothyroidism is performed with levothyroxine (LT4) replacement with the aim of achieving adequate TSH levels for pregnancy. Some women have a previous diagnosis of hypothyroidism, and may or may not be compensated at the beginning of pregnancy. Even in compensated cases, the increase in LT4 dose is necessary as soon as possible. In the postpartum period, adjustment of the LT4 dose depends on the condition of previous disease, on the positivity for ATPO, and also on the value of LT4 in use at the end of pregnancy. Recommendations In places with full technical and financial conditions, TSH testing should be performed for all pregnant women (universal screening) as early as possible, ideally at the beginning of the first trimester or even in preconception planning. In places with less access to laboratory tests, screening is reserved for cases with greater risk factors for decompensation, namely: previous thyroidectomy or radioiodine therapy, type 1 diabetes mellitus or other autoimmune diseases, presence of goiter, previous history of hypo or hyperthyroidism or previous ATPO positivity. The TSH dosage should be repeated throughout pregnancy only in these cases. The diagnosis of hypothyroidism is made from the TSH value > 4.0 mIU/L. Pregnant women with previous hypothyroidism, overt hypothyroidism diagnosed during pregnancy or those with the above-mentioned higher risk factors for decompensation should be referred for risk antenatal care, preferably in conjunction with the endocrinologist. Overt hypothyroidism in pregnancy is identified when TSH > 10 mIU/L, and treatment with LT4 is readily recommended at an initial dose of 2 mcg/kg/day. TSH values > 4.0 mUI/L and ≤ 10.0 mUI/L require FT4 measurement with two diagnostic possibilities: overt hypothyroidism when FT4 levels are below the lower limit of the laboratory reference, or subclinical hypothyroidism when FT4 levels are normal. The treatment for subclinical hypothyroidism is LT4 at an initial dose of 1 mcg/kg/day, and the dose should be doubled upon diagnosis of overt hypothyroidism. In cases of TSH > 2.5 and ≤ 4.0 mIU/L, if there are complete conditions, ATPO should be measured. If positive (above the upper limit of normal), treatment with LT4 at a dose of 50 mcg/day is indicated. If conditions are not complete, the repetition of the TSH dosage should be done only for cases at higher risk. In these cases, treatment with LT4 will be established when TSH > 4.0 mIU/L at a dose of 1 mcg/kg/day; if needed, the dose can be adjusted after FT4 evaluation. Women with previous hypothyroidism should have their LT4 dose adjusted to achieve TSH < 2.5 mIU/L at preconception. As soon as they become pregnant, they need a 30% increase in LT4 as early as possible. In practice, they should double the usual dose on two days a week. Levothyroxine should be given 30-60 minutes before breakfast or three hours or more after the last meal. Concomitant intake with ferrous sulfate, calcium carbonate, aluminum hydroxide and sucralfate should be avoided. The target of LT4 therapy during pregnancy is to achieve a TSH value < 2.5 mIU/L. Once the therapy is started, monthly control must be performed until the mentioned goal is reached. In the postpartum period, women with previous disease should resume the preconception dose. Cases diagnosed during pregnancy in use of LT4 ≤ 50 mcg/day may have the medication suspended. The others should reduce the current dose by 25% to 50% and repeat the TSH measurement in six weeks. Cases of ATPO positivity are at higher risk of developing postpartum thyroiditis and de-escalation of LT4 should be performed as explained. conceptus 20 then THs. THs . (THs) development complications namely firsttrimester miscarriage hypertension abruption prematurity weight mortality involvement andor TH presentation Hashimotos Hashimoto s origin 85%90% 8590 85% 90% 85 90 85%-90 present (ATPO frequent reference maternalfetal outcomes euthyroidism thyroidstimulating stimulating TSH. (TSH) FT (FT4 range LT (LT4 possible period universal planning tests diseases goiter 40 4 0 4. mIUL mIU L abovementioned above care endocrinologist mcgkgday mcg kg day mcg/kg/day mUIL mUI 100 10. possibilities 25 5 2. measured normal, , normal) mcgday indicated needed evaluation 30 practice 3060 60 30-6 meal sulfate carbonate avoided started reached suspended weeks deescalation de escalation explained (THs 85%90 859 8 9 85%-9 (TSH (FT (LT 3 306 6 30- 85%9 85%-

ABSTRACT Objective: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. Materials and methods: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. Results: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. Conclusion: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology. This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT Objective The aim of this study was to describe the ultrasound features of benign and malignant thyroid nodules and evaluate the likelihood of malignancy associated with each feature according to the Bethesda System for Reporting Thyroid Cytopathology and histopathology. With this analysis, we propose a new TI-RADS classification system. Materials and methods The likelihood of malignancy from ultrasound features were assessed in 1413 thyroid nodules according to the Bethesda System for Reporting Thyroid Cytopathology and histopathological findings. A score was established by attributing different weights to each ultrasound feature evaluated. Results Features positively associated with malignancy in bivariate analysis received a score weight of +1. We attributed a weight of +2 to features which were independently associated with malignancy in a multivariate analysis and +3 for those associated with the highest odds ratio for malignancy (> 10.0). Hence, hypoechogenicity (graded as mild, moderate or marked, according to a comparison with the overlying strap muscle), microcalcification and irregular/microlobulated margin received the highest weights in our scoring system. Features that were negatively associated with malignancy received weights of -2 or -1. In the proposed system a cutoff score of 2 (sensitivity 97.4% and specificity 51.6%) was adopted as a transition between probably benign (TI-RADS 3) and TI-RADS 4a nodules. Overall, the frequency of malignancy in thyroid nodules according to the categories was 1.0% for TI-RADS 3, 7.8% for TI-RADS 4a, 35.3% for TI-RADS 4b, and 84.7% for TI-RADS 5. Conclusion A newly proposed TI-RADS classification adequately assessed the likelihood of malignancy in thyroid nodules.

Resumo Objetivo Investigar a relação entre tireotrofina sérica (TSH), resistência à insulina (RI) e fatores de risco cardiovascular (FRC) em uma amostra de adolescentes brasileiros acima do peso e obesos. Métodos Foi realizada uma análise longitudinal retrospectiva de 190 adolescentes púberes acima do peso e obesos. Foram analisados os níveis de TSH e T4 livre (T4l), as medidas antropométricas e os resultados de exames laboratoriais desses pacientes. Resultados 27 indivíduos (13,56%) apresentaram níveis de TSH acima do normal (hipotireoidismo subclínico (HSC)). Eles apresentaram circunferência da cintura (CC) significativamente maior que os indivíduos eutireoideos. A TSH sérica foi positivamente correlacionada ao índice do modelo de avaliação da homeostase de resistência à insulina (HOMA-IR), triglicerídeos (TG) e lipoproteína de alta densidade-colesterol (HDL-C). Usando TSH e IMC como variáveis independentes, os níveis de TSH estavam relacionados ao HOMA-IR (p = 0.001) e a TG (p = 0.007) de forma independente. Entre os pacientes eutireoideos, indivíduos com valores de TSH < 2.5 mIU/mL apresentaram reduções estatisticamente significativas na razão cintura/quadril, nos níveis de HDL-C e nos escores de HOMA-IR e tendência a menores valores de CC. Conclusão O HSC em adolescentes acima do peso e obesos parece estar associado ao excesso de peso, principalmente de peso visceral. Em adolescentes eutireoideos, parece haver uma relação direta entre TSH e alguns FRC. Concluindo, em nossa amostra de adolescentes acima do peso e obesos, os níveis de TSH parecem estar associados a RI e FRC.

Abstract Objective: To investigate the relationship between serum thyrotropin (TSH), insulin resistance (IR), and cardiovascular risk factors (CRF) in a sample of overweight and obese Brazilian adolescents. Methods: A retrospective, longitudinal analysis of 199 overweight and obese pubescent adolescents was performed. The TSH and free T4 (fT4) levels, anthropometric measurements, and laboratory test results of these patients were analyzed. Results: 27 individuals (13.56%) presented with TSH levels above the normal level (subclinical hypothyroidism [SCH]). Their waist circumference (WC) was significantly higher than those of euthyroid individuals. Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Using TSH and BMI as independent variables, TSH levels were shown to be independently related to HOMA-IR (p = 0.001) and TG (p = 0.007). Among euthyroid subjects, individuals with TSH values <2.5 mIU/mL exhibited statistically significant decreases in waist-to-hip ratio, HDL-C levels, and HOMA-IR scores and a tendency toward lower WC values. Conclusion: SCH in overweight and obese adolescents appears to be associated with excess weight, especially visceral weight. In euthyroid adolescents, there appears to be a direct relationship between TSH and some CRF. In conclusion, in the present sample of overweight and obese adolescents, TSH levels appear to be associated with IR and CRF.

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.