Biochemical and Hormone Markers in Firefighters: Effects of "Search, Rescue, and Survival Training" and Its Recovery.

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.

Variation of iodine status during pregnancy and its associations with thyroid function in women from Rio de Janeiro, Brazil.

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<0·001), while FT4 levels decreased significantly (1·18 (0·16) v. 0·88 (0·12) ng/dl; P<0·001), regardless the presence of iodine deficiency (UIC<150 µg/l) or circulating thyroid antibodies. UIC correlated (ß; 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.

High Serum Thyrotropin Concentrations within the Reference Range: A Predictor of Malignancy in Nodular Thyroid Disease.

OBJECTIVE: This study assessed whether or not a simple biochemical parameter, serum thyrotropin (TSH), within the reference range can predict the likelihood of thyroid malignancy in subjects undergoing fine-needle aspiration biopsy (FNAB) for thyroid nodules. SUBJECTS AND METHODS: This cross-sectional study evaluated 236 patients without overt thyroid dysfunction who were not on levothyroxine therapy. They underwent FNAB of the thyroid nodules at the Clementino Fraga Filho University Hospital between 2011 and 2012. The reference range and serum TSH quartiles were determined according to age-specific values for serum TSH and then compared between the cases with benign thyroid nodular disease and differentiated thyroid carcinoma (DTC) based on surgical pathology reports. RESULTS: Of the 236 patients, 201 (85.1%) underwent a surgical procedure (thyroidectomy) and 89/236 (44.3%) had DTC. The mean TSH concentrations were 2.09 ± 1.15 mU/L in benign patients versus 2.73 ± 1.33 mU/L in cases of DTC (p < 0.01). As TSH increased from quartiles 1 to 4, the frequency of a malignant diagnosis also increased progressively from 22% in quartile 1 to 65% in the last quartile (p ≤ 0.001). CONCLUSION: Thyrotropin levels were positively associated with the diagnosis of DTC in thyroid nodules.

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes.

Thyroid cancer derived from follicular cells (TCDFC) comprises well-differentiated (papillary and follicular) carcinoma, poorly differentiated carcinoma, and anaplastic carcinoma. Papillary thyroid carcinoma is the most common endocrine cancer, and its incidence is steadily increasing. Lethality and aggressiveness of TCDFC is inversely correlated with differentiation degree. In this review, an emphasis has been put on molecular markers involved in tumorigenesis of thyroid carcinoma with a focus on aggressive histotypes and the role of such biomarkers in predicting thyroid cancer outcome. Genetic rearrangements in TCDFC (RET/PTC, PAX8/PPARG) and mutations in RAS, BRAF, TERT promoter (TERTp), TP53, PIK3CA, and AKT1 are discussed. The majority of the studies to date indicate that TERTp mutations can serve as a marker of more aggressive disease in all the subtypes of thyroid carcinoma, being the best current marker of poor prognosis, due to its independent association with distant metastases and increased disease-specific mortality. Some studies suggested that a more accurate prediction of thyroid cancer outcome may be possible through a more extensive genetic analysis. The same is true concerning the identification of other mutations that are only relatively frequent in advanced tumors (e.g., TP53, PIK3CA, or AKT1). A better understanding of the prognostic role of TERTp mutation (together with additional ones like BRAF, RAS, PIK3CA, AKT1, or TP53) and the clarification of their putative role in fine-needle aspiration biopsies are likely to allow, in the future, an early refinement of the stratification risk in patients with well-differentiated carcinomas. It is worth noting that, as with any categorical staging system, the risk evaluation within each category (low, intermediate, and high) varies depending on the specific clinicopathologic features of individual patients and the specific biological behavior of the tumor. Finally, besides the diagnostic and/or prognostic significance of the above-mentioned mutations, it is crucial to understand that the molecular pathways and epigenetic alterations will likely turn into interesting targets for new therapies.

Does low-normal serum TSH level adversely impact cognition in elderly adults and might methimazole therapy improve outcomes?

Serum thyroid stimulating hormone (TSH) levels increase with age. This elevation has been associated with better outcomes in very elderly subjects; however, little is known about the relationship between TSH below the lower limit of the reference range and health-related outcomes. Here, we investigated the association between cognitive impairment or depressive symptoms and low-normal serum TSH (<1.0 µIU/mL, in the reference range) in elderly subjects and whether the use of methimazole in subjects without dementia but with low-normal TSH could affect cognition or depressive symptoms. From 293 healthy adults ≥65 years old with normal TSH included in the sectional phase, only subjects without dementia were prospectively analyzed: 1) TSH ≥1.0 µIU/mL (observation; untreated); 2) TSH <1.0 µIU/mL (observation; untreated); and 3) TSH <1.0 µIU/mL (methimazole therapy). Cognition was assessed, using the Mini Mental State Examination (MMSE) and depressive symptoms (at MMSE ≥ 13) by the Geriatric Depression Scale (GDS). Age >80 years was the sole independent factor associated with dementia (OR=2.89; confidence interval [CI] 1.72-4.86; p<0.01). Prospectively, 93 completed follow-up, with 7.5% (7) receiving methimazole intervention. Untreated subjects with lower TSH showed the greatest declines in MMSE scores during follow-up that was not observed in those with serum TSH ≥1.0 µIU/mL. Lower MMSE score reductions were associated with elderly subjects receiving methimazole. There were no significant changes in depressive symptoms and GDS scores among those with serum TSH <1.0 µIU/mL. In this study, low-normal TSH was not associated with higher prevalence of dementia. However, in elderly subjects without dementia, low TSH was associated with worsening cognition.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

Combined effects of intermittent fasting with swimming-based high intensity intermittent exercise training in Wistar rats.

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.

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.

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.

Atrial fibrillation and hyperthyroidism: relation between transoesophageal markers of a thrombogenic milieu and clinical risk factors for thromboembolism.

UNLABELLED: Hyperthyroidism is a questionable risk factor for thromboembolism among patients with atrial fibrillation. OBJECTIVE: To correlate clinical risk factors for thromboembolism from a group of patients with atrial fibrillation related to hyperthyroidism with transoesophageal echocardiography (TOE) markers of a thrombogenic milieu. DESIGN: Clinical risk factors for thromboembolism, thyroid hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a thrombogenic milieu were assessed in consecutive patients with atrial fibrillation related to hyperthyroidism. The following TOE parameters were assessed to define the presence of thrombogenic milieu: dense spontaneous echo contrast, thrombi or left atrial appendage blood flow velocities <0·20 m/s. Clinical risk factors for thromboembolism were based on CHADS(2) (Cardiac failure, Hypertension, Age, Diabetes and Stroke) classification. PATIENTS: This study included 31 consecutive patients aged between 18 and 65 years with atrial fibrillation related to hyperthyroidism scheduled for TOE. RESULTS: Thrombogenic milieu was present in 14 of 31 (45·2%) patients. The thyroid status could not predict the presence of a thrombogenic milieu. Despite low CHADS(2) score of 0/1, 6 of 13 (46·1%) patients had a thrombogenic milieu, whereas 10 of 18 (55·6%) patients with score ≥2 had none. The probability of having a thrombogenic milieu did not correlate with the number of clinical risk factors. CONCLUSION: Among patients younger than 65 years of age with atrial fibrillation related to hyperthyroidism, there is no association between clinical risk factors with TOE markers of a thrombogenic milieu. TOE adds useful information that may affect antithrombotic therapy guided by clinical risk classification.

Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy.

OBJECTIVE: To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re-stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States. DESIGN: Retrospective chart review. PATIENTS: Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil. MEASUREMENTS: Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete). RESULTS: The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low-risk patients, 36% in intermediate risk patients, and 68% in high-risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow-up, 34% of the biochemical incomplete response patients had been re-classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re-classified as NED. CONCLUSIONS: These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.

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

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.

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).

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.

Free thyroxine but not TSH levels are associated with decline in functional status in a cohort of geriatric outpatients.

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.

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.

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.

Clinical Outcomes After Radioiodine Therapy, According to the Method of Preparation by Recombinant TSH vs. Endogenous Hypothyroidism, in Thyroid Cancer Patients at Intermediate-High Risk of Recurrence.

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.

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.

Consequences of Iodine Deficiency and Excess in Pregnancy and Neonatal Outcomes: A Prospective Cohort Study in Rio de Janeiro, Brazil.

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.