DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.

Conserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isoform's Key Role in Mammalian Physiology.

p53 is the most commonly mutated gene in human cancers. Two fundamental reasons for this are its long protein isoforms protect from cancer, while its shorter C-terminal isoforms can support cancer and metastasis. Previously, we have shown that the Δ160p53 protein isoform enhances survival and the invasive character of cancer cells. Here, we identified a translation initiation site nine codons downstream of codon 160-the known initiation codon for the translation of Δ160p53-that is recognized by the translation machinery. When translation failed to initiate from AUG160 due to mutation, it initiated from AUG169 instead, producing similar levels of a similar protein, Δ169p53, which promoted cell survival as efficiently as Δ160p53 following DNA damage. Interestingly, almost all mammalian species with an orthologue to human AUG160 also possess one for AUG169, while none of the non-mammalian species lacking AUG160 have AUG169, even if that region of the p53 gene is well conserved. In view of our findings, we do not believe that Δ169p53 acts as a different p53 protein isoform; instead, we propose that the double translation initiation site strengthens the translation of these products with a critical role in cell homeostasis. Future studies will help verify if this is a more general mechanism for the expression of essential proteins in mammals.

Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition.

The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for mTOR gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions.

Alternative Mechanisms of mRNA Translation Initiation in Cellular Stress Response and Cancer.

Throughout evolution, eukaryotic cells have devised different mechanisms to cope with stressful environments. When eukaryotic cells are exposed to stress stimuli, they activate adaptive pathways that allow them to restore cellular homeostasis. Most types of stress stimuli have been reported to induce a decrease in overall protein synthesis accompanied by induction of alternative mechanisms of mRNA translation initiation. Here, we present well-studied and recent examples of such stress responses and the alternative translation initiation mechanisms they induce, and discuss the consequences of such regulation for cell homeostasis and oncogenic transformation.

eIF3: a factor for human health and disease.

The eukaryotic initiation factor 3 (eIF3) is one of the most complex translation initiation factors in mammalian cells, consisting of several subunits (eIF3a to eIF3m). It is crucial in translation initiation and termination, and in ribosomal recycling. Accordingly, deregulated eIF3 expression is associated with different pathological conditions, including cancer. In this manuscript, we discuss the interactome and function of each subunit of the human eIF3 complex. Furthermore, we review how altered levels of eIF3 subunits correlate with neurodegenerative disorders and cancer onset and development; in addition, we evaluate how such misregulation may also trigger infection cascades. A deep understanding of the molecular mechanisms underlying eIF3 role in human disease is essential to develop new eIF3-targeted therapeutic approaches and thus, overcome such conditions.

More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer.

The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment. In most cap-independent translation initiation events there is a direct recruitment of the 40S ribosome into a position upstream, or directly at, the initiation codon via a specific internal ribosome entry site (IRES) element in the 5'UTR. Yet, in some cellular mRNAs, a different translation initiation mechanism that is neither cap- nor IRES-dependent seems to occur through a special RNA structure called cap-independent translational enhancer (CITE). Recent evidence uncovered a distinct mechanism through which mRNAs containing N 6-methyladenosine (m6A) residues in their 5'UTR directly bind eukaryotic initiation factor 3 (eIF3) and the 40S ribosomal subunit in order to initiate translation in the absence of the cap-binding proteins. This review focuses on the important role of cap-independent translation mechanisms in human cells and how these alternative mechanisms can either act individually or cooperate with other cis-acting RNA regulons to orchestrate specific translational responses triggered upon several cellular stress states, and diseases such as cancer. Elucidation of these non-canonical mechanisms reveals the complexity of translational control and points out their potential as prospective novel therapeutic targets.

Internal Ribosome Entry Site (IRES)-Mediated Translation and Its Potential for Novel mRNA-Based Therapy Development.

Many conditions can benefit from RNA-based therapies, namely, those targeting internal ribosome entry sites (IRESs) and their regulatory proteins, the IRES trans-acting factors (ITAFs). IRES-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is impaired. During a stress response, it contributes to cell reprogramming and adaptation to the new environment. The relationship between IRESs and ITAFs with tumorigenesis and resistance to therapy has been studied in recent years, proposing new therapeutic targets and treatments. In addition, IRES-dependent translation initiation dysregulation is also related to neurological and cardiovascular diseases, muscular atrophies, or other syndromes. The participation of these structures in the development of such pathologies has been studied, yet to a far lesser extent than in cancer. Strategies involving the disruption of IRES-ITAF interactions or the modification of ITAF expression levels may be used with great impact in the development of new therapeutics. In this review, we aim to comprehend the current data on groups of human pathologies associated with IRES and/or ITAF dysregulation and their application in the designing of new therapeutic approaches using them as targets or tools. Thus, we wish to summarise the evidence in the field hoping to open new promising lines of investigation toward personalised treatments.

Genetics of personalized medicine: cancer and rare diseases.

The 21st annual meeting of the Portuguese Society of Human Genetics (SPGH), organized by Luísa Romão, Ana Sousa and Rosário Pinto Leite, was held in Caparica, Portugal, from the 16th to the 18th of November 2017. Having entered an era in which personalized medicine is emerging as a paradigm for disease diagnosis, treatment and prevention, the program of this meeting intended to include lectures by leading national and international scientists presenting exceptional findings on the genetics of personalized medicine. Various topics were discussed, including cancer genetics, transcriptome dynamics and novel therapeutics for cancers and rare disorders that are designed to specifically target molecular alterations in individual patients. Several panel discussions were held to emphasize (ethical) issues associated with personalized medicine, including genetic cancer counseling.

[Impairment of muscle vasodilation during mental stress in women with subclinical hypothyroidism]. / Prejuízo da vasodilatação muscular durante estresse mental em mulheres com hipotireoidismo subclínico.

OBJECTIVE: To test the hypothesis that women with subclinical hypothyroidism (SH) have forearm vascular conductance (FVC) impaired during mental stress. SUBJECTS AND METHODS: We evaluated 20 women with SH and 21 euthyroid (Control group), matched for age (p = 0.699) and body mass index (p = 0.462). Muscle blood flow (MBF) was assessed by venous occlusion plethysmography and blood pressure by Dixtal2023. Both variables were recorded simultaneously for 3 minutes of baseline followed by 3 minutes of mental stress. The FVC was calculated by dividing MBF by mean arterial pressure. Significant differences were assumed at p < 0.05. RESULTS: The SH group had higher concentrations of thyroid stimulating hormone (7.57 ± 3.17 vs. 2.10 ± 0,88 mU/L, p < 0.001). At baseline, the SH and control groups were similar for MBF (2.50 ± 0.79 vs. 2.55 ± 0,71 mL/ min/100 mL, p = 0.905, respectively) and FVC (2.80 ± 0.90 vs. 2.92 ± 0.88 units, p = 0.952, respectively). Throughout the mental stress test the SH and Control groups increased the MBF (time effect, p < 0.001) and FVC (time effect, p < 0.001) compared to baseline protocol. However, these variables were lower in SH group during the first (MBF: 3.66 ± 0.96 vs. 4.66 ± 1,61 mL/min/100 mL, p = 0.018, FVC: 3.95 ± 1.08 vs. 5.19 ± 1,96 units, p = 0.010) and second (MBF: 3.55 ± 1.01 vs. 4.62 ± 2,27 mL/min/100 ml, p = 0.018; FVC: 3.75 ± 1.07 vs. 4.92 ± 2,37 units, p = 0.020) minutes of mental stress test. CONCLUSION: Women with SH have reduced muscle vasodilatatory response during mental stress.

Recombinant human TSH for thyroid remnant ablation with (131)I in children and adolescents with papillary carcinoma.

BACKGROUND: The objective of this study was to report the results of a series of 12 patients with papillary carcinoma aged 16 years or younger, who were prepared with recombinant human TSH (rhTSH) for remnant ablation with (131)I. The TSH levels achieved and the safety of 24 cycles of rhTSH administration (ablation and control assessment) are reported. METHODS: All patients were prepared using the same protocol as recommended for adults. Eight to 12 months after initial therapy, the patients were submitted to neck ultrasound, measurement of stimulated Tg and anti-Tg antibodies (TgAb), and diagnostic whole-body scanning (DxWBS). RESULTS: TSH levels >50 mIU/l were achieved in all patients. An adverse reaction (mild nausea and headache) was observed in 1/24 cycles (4.1%). Eight (88.8%) of 9 patients with uptake in the thyroid bed in post-therapy whole-body scanning (RxWBS) achieved complete remission. One patient presented TgAb in the absence of apparent disease. In addition, imaging methods showed no apparent disease in the 2 patients with lymph node metastases in RxWBS. Elevated Tg persisted in 1 patient with pulmonary micrometastases. CONCLUSION: The present results demonstrate the efficacy and safety of rhTSH in children and adolescents.

Value of diagnostic radioiodine whole-body scanning after initial therapy in patients with differentiated thyroid cancer at intermediate and high risk for recurrence.

BACKGROUND: Diagnostic radioiodine whole-body scanning (DxWBS) in combination with stimulated thyroglobulin (Tg) (i.e., measurement after levothyroxine [L-T4] withdrawal or recombinant human TSH administration) continues to be recommended for patients with differentiated thyroid carcinoma (DTC) at high or intermediate risk for recurrence with negative basal Tg and ultrasonography (US) after ablation. However, the value of DxWBS has been questioned, even in these cases. The objective of this prospective study was to evaluate the value of DxWBS in these patients. METHODS: The study consisted of 318 patients who had total thyroidectomy with apparent complete tumor resection for DTC. Further, per inclusion criteria, they had the following characteristics (i) a post-therapy radioiodine whole-body scan (RxWBS) showing no metastases and uptake in the thyroid bed of ≤2%, (ii) classification as high or intermediate risk for recurrence based on the large tumor size, tumor extension beyond the thyroid capsule, and lymph node metastases, (iii) Tg during L-T4 therapy (TgT4) of <1 ng/mL, (iv) negative anti-Tg antibodies (TgAb), and (v) normal US performed 8-12 months after ablation. Tg stimulation combined with DxWBS was performed in all patients. Patients without apparent disease in the initial assessment were followed up for 24 to 96 months. RESULTS: In the initial assessment, stimulated Tg continued to be <1 ng/mL in 253 (79.5%) patients and converted to levels >1 ng/mL in 65 (20.4%). None of the patients had metastases on DxWBS, and 46 (14.4%) had discrete uptake (<0.5%) only in the thyroid bed. (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography (FDG-PET/CT) revealed metastases in three patients with elevated stimulated Tg. Fourteen (4.4%) patients without initially apparent disease relapsed during follow-up, including five (2%) with initial stimulated Tg < 1 ng/mL. There was no disease-related death. Thyroid bed uptake on DxWBS had no prognostic value for recurrence, irrespective of stimulated Tg levels. CONCLUSIONS: DxWBS can be avoided in patients with large tumors or extensions beyond the thyroid capsule or lymph node metastases, but who show no apparent disease upon initial RxWBS and US and whose serum TgT4 of <1 ng/mL and negative TgAb after thyroidectomy and ablation.

Ultrasonographic screening for thyroid cancer in siblings of patients with apparently sporadic papillary carcinoma.

BACKGROUND: Epidemiological studies have shown a higher risk of thyroid cancer among individuals who have a relative with papillary thyroid cancer (PTC) compared to those without a family history. This study evaluated the prevalence of thyroid cancer among subjects with only one first-degree relative (sibling) with PTC who had no palpable nodules, factors predictive of this malignancy, and the characteristics of tumors discovered during ultrasonographic screening. METHODS: A total of 757 siblings of 447 patients with apparently sporadic PTC were examined. Nodules were palpable in 34 subjects (excluded). The 723 individuals without palpable abnormalities were submitted to thyroid ultrasonography and comprised the study group. The control group, consisting of 241 volunteers without a family history of thyroid cancer matched for gender and age to the study group, was also submitted to thyroid ultrasonography. All nodules ≥ 5 mm were examined by fine-needle aspiration cytology. Subjects with benign cytology were not submitted to surgery, whereas the subjects having malignant, suspicious for a malignancy, indeterminate, or inadequate cytology were referred for thyroidectomy. RESULTS: Ultrasonography detected nodules in 303 (41.9%) study subjects. PTC was observed in 5.94% of the 723 subjects studied (8% women and 3.75% men, p=0.017) and in 14.2% of the 303 subjects with nonpalpable nodular disease. In the control group, 80 (33.2%) of the volunteers had nodules. PTC was observed in 1.2% of them and in 3.8% of those with nodular disease. In addition, 7.17% of the 447 patients had siblings with PTC detected only by ultrasonography. Multicentricity of the tumor was the main predictor of the presence of malignancy in siblings of patients with PTC. Twenty-two subjects (3% of those screened) had tumors that were not intrathyroid microcarcinomas (whereas all three tumors detected in controls were intrathyroid microcarcinomas). Screening permitted an earlier diagnosis of the disease when compared to siblings with a spontaneous diagnosis. CONCLUSIONS: The present results favor ultrasonographic screening of first-degree relatives of patients with apparently sporadic multicentric PTC, especially among women.

Ensino de lutas: relatos de uma experiência na rede pública / Fights of education: an experience report in public school

Entende-se que a dificuldade para a inserção do conteúdo das lutas na escola está atrelada a múltiplos fatores e que os alunos têm interesse neste conteúdo. Objetivo: este estudo de caso tem a intenção de verificar como o conteúdo de lutas é trabalhado na experiência de um professor de Educação Física da rede pública Municipal da cidade de Juiz de Fora. Métodos: para este estudo adotamos o procedimento metodológico da abordagem qualitativa, através de entrevista semiestruturada, devidamente validada. A entrevista foi gravada e transcrita para posterior análise. As perguntas foram divididas em três (3) blocos: Formação acadêmica e motivação, Experiência com o ensino das lutas e Reflexão sobre o ensino de lutas. Analisamos também o plano de ensino fornecido pela professora, com as atividades propostas em cada aula. Resultados e Discussão: os resultados do estudo nos mostram que com um planejamento estruturado, estudo contínuo e dedicação, os professores podem ministrar aulas sobre o conteúdo lutas e possibilitar essa vivência para os alunos, driblando as aparentes dificuldades e barreiras colocadas pelas pesquisas revisadas. Conclusão: conclui-se sobre a relevância de trabalhos que se utilizem da metodologia proposta nesta investigação, para revelar formas alternativas e possibilidades de se trabalhar o conteúdo das lutas dentro do ambiente escolar, tendo em vista a grande aceitação dos alunos. Mesmo que muitos professores não tenham experiência pessoal e formação nas lutas, é preciso buscar outras formas de trabalhar o conteúdo da cultura corporal...

It seems clear that the difficulty of inserting the content of the fights in school is linked to multiple factors and that students are interested in this content. Objective: this case study is intended to determine how the fights of content are worked on the experience of a teacher of Physical Education of in city public schools of the town of Juiz de Fora. Methods: for this study we adopt the methodological procedure of qualitative approach, through semistructured interview, duly executed. The interview was recorded and transcribed for further analysis. The questions were divided into three groups: Education and motivation, Experience with the fights education and Reflections on the teaching of fights. We also analyzed the syllabus provided by the teacher, with the activities proposed in each class. Results and discussion: the study results show that with a structured planning, continuous study and dedication, teachers can teach classes on the contents fights and enable this experience for students while dodging the apparent difficulties and barriers posed by revised research. Conclusion: it is concluded on the relevance of works that use of the proposed methodology in this investigation to reveal alternative ways and possibilities of working content of the fights within the school environment, in view of the wide acceptance of students. Even though many teachers do not have personal experience and training in the fights, we must find other ways to work the contents of corporal culture...

Prejuízo da vasodilatação muscular durante estresse mental em mulheres com hipotireoidismo subclínico / Impairment of muscle vasodilation during mental stress in women with subclinical hypothyroidism

Objetivo Testar a hipótese de que mulheres com hipotireoidismo subclínico (HSC) possuem condutância vascular do antebraço (CVA) prejudicados durante estresse mental. Sujeitos e métodos Foram avaliadas 20 mulheres com HSC e 21 eutireoidianas (Grupo Controle), pareadas por idade (p = 0,699) e índice de massa corporal (p = 0,462). O fluxo sanguíneo muscular (FSM), avaliado pela pletismografia de oclusão venosa, e a pressão arterial, medida pelo Dixtal2023, foram registrados simultaneamente durante 3 minutos de basal, seguidos de 3 minutos de estresse mental. A CVA foi calculada pela divisão do FSM pela pressão arterial média. Foi adotada significância de p < 0,05. Resultados O grupo HSC apresentou maior concentração do hormônio tireoestimulante (7,57 ± 3,17 vs. 2,10 ± 0,88 mU/L, p < 0,001). No basal, os grupos HSC e Controle foram semelhantes respectivamente para FSM (2,50 ± 0,79 vs. 2,55 ± 0,71 mL/min/100 mL, p = 0,905) e CVA (2,80 ± 0,90 vs. 2,92 ± 0,88 unidades, p = 0,952). Durante todo o estresse mental, os grupos HSC e Controle aumentaram significativamente o FSM (efeito tempo, p < 0,001) e CVA (efeito tempo, p < 0,001) em relação ao basal. Porém, essas variáveis foram significativamente menores no grupo HSC durante o primeiro (FSM: 3,66 ± 0,96 vs. 4,66 ± 1,61 mL/ min/100 mL, p = 0,018; CVA: 3,95 ± 1,08 vs. 5,19 ± 1,96 unidades, p = 0,010) e segundo (FSM: 3,55 ± 1,01 vs. 4,62 ± 2,27 mL/min/100 mL, p = 0,018; CVA: 3,75 ± 1,07 vs. 4,92 ± 2,37 unidades, p = 0,020) minutos do teste de estresse mental. Conclusão Mulheres com HSC possuem comportamento vasodilatador prejudicado durante o estresse mental. .

Objective To test the hypothesis that women with subclinical hypothyroidism (SH) have forearm vascular conductance (FVC) impaired during mental stress. Subjects and methods We evaluated 20 women with SH and 21 euthyroid (Control group), matched for age (p = 0.699) and body mass index (p = 0.462). Muscle blood flow (MBF) was assessed by venous occlusion plethysmography and blood pressure by Dixtal2023. Both variables were recorded simultaneously for 3 minutes of baseline followed by 3 minutes of mental stress. The FVC was calculated by dividing MBF by mean arterial pressure. Significant differences were assumed at p < 0.05. Results The SH group had higher concentrations of thyroid stimulating hormone (7.57 ± 3.17 vs. 2.10 ± 0,88 mU/L, p < 0.001). At baseline, the SH and control groups were similar for MBF (2.50 ± 0.79 vs. 2.55 ± 0,71 mL/ min/100 mL, p = 0.905, respectively) and FVC (2.80 ± 0.90 vs. 2.92 ± 0.88 units, p = 0.952, respectively). Throughout the mental stress test the SH and Control groups increased the MBF (time effect, p < 0.001) and FVC (time effect, p < 0.001) compared to baseline protocol. However, these variables were lower in SH group during the first (MBF: 3.66 ± 0.96 vs. 4.66 ± 1,61 mL/min/100 mL, p = 0.018, FVC: 3.95 ± 1.08 vs. 5.19 ± 1,96 units, p = 0.010) and second (MBF: 3.55 ± 1.01 vs. 4.62 ± 2,27 mL/min/100 ml, p = 0.018; FVC: 3.75 ± 1.07 vs. 4.92 ± 2,37 units, p = 0.020) minutes of mental stress test. Conclusion Women with SH have reduced muscle vasodilatatory response during mental stress. .

Exercício físico e qualidade de vida de mulheres com hipotireoidismo tratadas com levotiroxina / Physical exercise and quality of life in l-thyroxine treated hypothyroid women

Introdução: Pouco se sabe sobre os benefícios do exercício em pacientes com hipotireoidismo. Objetivo: Testar a hipótese de que a prática regular de exercícios físicos melhora a qualidade de vida de mulheres com hipotireoidismo tratadas com levotiroxina (L-T4). Material e métodos: Participaram deste estudo transversal 53 pacientes (mulheres de 20 a 65 anos) tratadas com L-T4 (25 a 200 mg), apresentando níveis normais de TSH (2,83±1,76 ?UI/ml) e T4 livre (1,11±0,42 ng/dl). As pacientes foram classificadas quanto à prática regular de atividades físicas em dois grupos: sedentárias e fisicamente ativas. A qualidade de vida foi mensurada pelo questionário SF-36 e o perfil dos estados de humor pelo POMS. O teste U de Mann-Whitney foi usado para comparar os grupos nas variáveis contínuas; e o coeficiente de correlação de Spearman, para testar a relação entre as variáveis de interesse. Resultados: As pacientes fisicamente ativas apresentaram maior capacidade funcional (79±17 vs. 60±28; p=0,01), maior percepção de saúde geral (76±16 vs. 60±21; p=0,01) e maior escore físico de qualidade de vida (72±20 vs. 59±22; p=0,04), quando comparadas às sedentárias. Não houve diferença significativa entre os grupos no perfil de humor (p>0,05). A presença do sintoma fraqueza muscular foi menor nas pacientes ativas (10,7% vs. 36%; p=0,03). Não foi observada correlação entre os níveis de TSH e as variáveis do SF-36 ou do POMS (p>0,05). Conclusões: Os resultados demonstram que mulheres com hipotireoidismo tratadas com L-T4 que praticam atividade física regularmente possuem melhor qualidade de vida, especialmente em relação aos aspectos de saúde física.