Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area.

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.

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.

Yerba mate consumption by ovariectomized rats alters white adipose tissue.

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.

Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area / O volume tireoidiano em gestantes está associado à paridade, idade gestacional e índice de massa corporal em uma área suficiente em iodo

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.

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.

Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT 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.

Clinical decision support analysis of a microRNA-based thyroid molecular classifier: A real-world, prospective and multicentre validation study.

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.

A systematic review of hormone levels, biomarkers of cellular injury and oxidative stress in multi-stressor military field training exercises

ABSTRACT 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.

Puberty and sex in pediatric thyroid cancer: could expression of estrogen and progesterone receptors affect prognosis?

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.

The flavonoid quercetin reduces cell migration and increases NIS and E-cadherin mRNA in the human thyroid cancer cell line BCPAP.

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.

Combining the American Thyroid Association's Ultrasound Classification with Cytological Subcategorization Improves the Assessment of Malignancy Risk in Indeterminate Thyroid Nodules.

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.

Selective case finding versus universal screening for detecting hypothyroidism in the first trimester of pregnancy: a comparative evaluation of a group of pregnant women from Rio de Janeiro.

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.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion

ABSTRACT 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.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion.

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.

Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency.

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.

The Impact of Zoledronic Acid and Radioactive Iodine Therapy on Morbi-Mortality of Patients with Bone Metastases of Thyroid Cancer Derived from Follicular Cells.

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.

Technetium-99m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy.

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 (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (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.

Heart rate response to graded exercise test of elderly subjects in different ranges of TSH levels

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.

Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression.

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.

Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression

ABSTRACT 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.

Exercise training improves quality of life in women with subclinical hypothyroidism: a randomized clinical trial

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.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro

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.