ABSTRACT
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.
ABSTRACT
Triiodothyronine (T3) and estrogen (E2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa ß (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E2 in human cells. AIMS: This study evaluated the effects of the physiological concentration of E2 (10?nM), alone or in association with physiological (1nM) and supraphysiological (10nM) concentrations of T3, on RANKL and OPG gene expression in human osteoblasts. MAIN METHODS: Alkaline phosphatase and osteocalcin assays were performed to verify the presence of mature osteoblasts. After mimicking the experimental hyperthyroidism in osteoblasts untreated or treated with E2, RANKL and OPG gene expression was analyzed by real-time PCR and protein expression by western Blot and ELISA. Alizarin Red staining analyzed the amount of bone matrix after hormonal treatments. KEY FINDINGS: E2 enhanced the gene expression of OPG when associated with 1nM and 10nMT3. E2 was able to restore the bone matrix after an initial decrease using 1nM and 10nMT3. The protective effect of E2 on the RANKL and OPG signaling pathway was demonstrated. E2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE: The data highlight the importance of E2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T3 is in excess.
ABSTRACT
Triiodothyronine (T3) and estrogen (E2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa ß (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E2 in human cells. AIMS: This study evaluated the effects of the physiological concentration of E2 (10?nM), alone or in association with physiological (1nM) and supraphysiological (10nM) concentrations of T3, on RANKL and OPG gene expression in human osteoblasts. MAIN METHODS: Alkaline phosphatase and osteocalcin assays were performed to verify the presence of mature osteoblasts. After mimicking the experimental hyperthyroidism in osteoblasts untreated or treated with E2, RANKL and OPG gene expression was analyzed by real-time PCR and protein expression by western Blot and ELISA. Alizarin Red staining analyzed the amount of bone matrix after hormonal treatments. KEY FINDINGS: E2 enhanced the gene expression of OPG when associated with 1nM and 10nMT3. E2 was able to restore the bone matrix after an initial decrease using 1nM and 10nMT3. The protective effect of E2 on the RANKL and OPG signaling pathway was demonstrated. E2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE: The data highlight the importance of E2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T3 is in excess.
ABSTRACT
ABSTRACT Objective: Graves' ophthalmopathy (GO) is an autoimmune disease that leads to ocular proptosis caused by fat accumulation and inflammation, and the main treatment is corticosteroid therapy. Retinoid acid receptor-alpha (RARα) seems to be associated with inflammation and adipocyte differentiation. This study aimed to assess the effect of glucocorticoid treatment on orbital fibroblasts of GO patient treated or not with different glucocorticoid doses. Materials and methods: Orbital fibroblasts collected during orbital decompression of a female patient with moderately severe/severe GO were cultivated and treated with 10 nM and 100 nM dexamethasone (Dex). rRARα gene expression in the treated and untreated cells was then compared. Results: Fibroblast RARα expression was not affected by 100 nM Dex. On the other hand, RARα expression was 24% lower in cells treated with 10 nM Dex (p < 0.05). Conclusions: Orbital fibroblasts from a GO patient expressed the RARα gene, which was unaffected by higher, but decreased with lower doses of glucocorticoid.
Subject(s)
Humans , Orbit/drug effects , Dexamethasone/administration & dosage , Gene Expression/drug effects , Graves Ophthalmopathy/drug therapy , Fibroblasts/chemistry , Glucocorticoids/administration & dosage , Orbit/pathology , Severity of Illness Index , Graves Ophthalmopathy/pathology , Fibroblasts/drug effects , Retinoic Acid Receptor alpha/drug effects , Retinoic Acid Receptor alpha/geneticsABSTRACT
Hyperprolactinemia is a frequent condition in clinical practice, responsible for 20-25% of secondary amenorrhea cases. We performed an electronic survey among members of the Brazilian Society of Metabolism and Endocrinology (SBEM) and the Brazilian Federation of Association of Gynecology and Obstetrics (FEBRASGO) to assess diagnostic and therapeutic preferences for management of hyperprolactinemia. Electronic addresses of SBEM and FEBRASGO members were obtained from the directories of these societies, and these members were invited, through electronic messages (e-mail), to answer an online questionnaire that included 10 questions about the treatment of micro and macropro-lactinomas, maximum dose of dopamine agonist, how to exclude primary hypothyroidism and macroprolactinemia, hyperprolactinemia and pregnancy. We received responses to the questionnaire by e-mail from 521 SBEM members and 233 FEBRASGO members. The results of this survey demonstrate that there are many area of agreement between SBEM and FEBRASGO members and most of their responses follow the latest Endocrine Society Guideline. Relative to a survey performed several years ago, our findings show that SBEM members have incorporated some of latest recommendations in this field. The principal issues of concern for both groups are duration of dopamine agonist treatment for patients with microprolactinoma and dopamine agonist withdrawal during pregnancy.
La hiperprolactinemia es una alteración frecuente, siendo responsable del 20 al 25% de los casos de amenorrea secundaria. Se realizó una investigación electrónica entre los miembros de la Sociedad Brasileña de Endocrinología y Metabología (SBEM) y de la Federación Brasileña de Ginecología y Obstetricia (FEBRASGO) para evaluar sus preferencias en el diagnóstico y el tratamiento de la hiperprolactinemia. Las direcciones electrónicas de miembros SBEM y de FEBRASGO se obtuvieron a partir de los directorios de esas sociedades. Se invitó a estos miembros a responder un cuestionario que incluía 10 cuestiones sobre el tratamiento de los micro y macroprolactinomas, dosis máxima del agonista dopaminérgico, hiperprolactinemia e hipotiroidismo primario, macroprolactinemia, prolactinoma y embarazo. Hemos recibido respuestas de 521 miembros de la SBEM y de 233 miembros FEBRASGO. Los resultados demuestran que hay bastantes áreas de concordancia entre los miembros de la SBEM y de la FEBRASGO y que la mayoría de las respuestas están de acuerdo con el último consenso de la Endocrine Society. En cuanto a una encuesta similar realizada hace años, nuestros resultados muestran que los socios de SBEM incorporaron algunas de las últimas recomendaciones propuestas en esa área. Los principales aspectos de interés en ambos grupos son la duración del tratamiento con el agonista dopaminérgico y la retirada del mismo durante el embarazo.
Subject(s)
Humans , Female , Hyperprolactinemia/diagnosis , Hyperprolactinemia/therapy , Brazil , Prolactinoma/therapy , Dopamine Agonists/administration & dosage , Research ReportABSTRACT
Graves’ ophthalmopathy (GO) is one of the most severe clinical manifestations of Graves’ disease (GD), and its treatment might involve high-dose glucocorticoid therapy. The higher incidence of GO among females, and the reported association between polymorphisms of estrogen receptor (ER) and GD susceptibility have led us to question the role of estrogen and its receptor in GO pathogenesis. We, thus, assessed estrogen receptor-alpha (ERA) gene expression in cultures of orbital fibroblasts from a patient with GO before (controls) and after treatment with 10 nM and 100 nM dexamethasone (DEX). Orbital fibroblasts showed ERA gene expression. In the cells treated with 10 nM and 100 nM DEX, ERA gene expression was, respectively, 85% higher and 74% lower, than in the control group. We concluded that ERA gene expression is found in the orbital fibroblasts of patient with GO, which may be affected by glucocorticoids in a dose-related manner. Arch Endocrinol Metab. 2015;59(3):273-6.
Subject(s)
Humans , Adenocarcinoma/pathology , Barrett Esophagus/pathology , Carcinoma in Situ/pathology , Esophageal Neoplasms/pathology , Esophagogastric Junction/pathology , Mucous Membrane/pathologyABSTRACT
Objective To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. Methods 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey’s test or Student’s t test, were used to analyze data, and significance level was set at 5%. Results Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. Conclusion These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases. .
Objetivo Examinar o efeito de diferentes doses de triiodotironina sobre a expressão gênica das adipocinas leptina e adiponectina, em diferentes períodos de tempo, além de avaliar a diferença de expressão entre as duas adipocinas em cada grupo. Métodos Adipócitos 3T3-L1 foram incubados com triiodotironina nas doses fisiológica (10nM) e suprafisiológicas (100nM ou 1.000nM), ou na ausência de triiodotironina (controle, C) durante 0,5, 6 ou 24 horas. O mRNA das adipocinas foi analisado em tempo real, utilizando a reação em cadeia de polimerase. Para as análises dos dados, foi utilizada a análise de variância, complementada com o teste de Tukey, ou o teste t de Student com 5% de significância. Resultados Os níveis de leptina diminuíram no grupo com dose de 1.000nM em 0,5 hora. A adiponectina também diminuiu no grupo com dose de 10nM, porém se elevou com a dose de 100nM. Após 6 horas, ambos os genes foram suprimidos em todas concentrações de hormônio. Em 24 horas, os níveis de leptina foram elevados em 10, 100 e 1.000nM, em relação ao grupo controle. No que concerne à adiponectina, observou-se aumento apenas no grupo cuja dose foi de 100nM, em comparação ao controle. Conclusão Foram demonstradas ações rápidas da triiodotironina sobre a expressão da leptina e da adiponectina, iniciando em 0,5 hora na dose de 1.000nM, para a primeira, e na dose de 100nM, para a segunda. A triiodotironina estimulou ou inibiu a expressão de adipocinas em adipócitos em diferentes tempos e doses, o que pode auxiliar no tratamento da obesidade, levando em consideração que, nesta, a leptina está aumentada e adiponectina, diminuída. .
Subject(s)
Animals , Mice , /drug effects , Adipocytes/drug effects , Adiponectin/genetics , Gene Expression/drug effects , Leptin/genetics , Triiodothyronine/pharmacology , Analysis of Variance , Adiponectin/analysis , Cells, Cultured , Cell Differentiation/drug effects , Leptin/analysis , Obesity/genetics , Real-Time Polymerase Chain Reaction , Reference Values , RNA, Messenger/analysis , RNA, Messenger/drug effects , Time Factors , Triiodothyronine/administration & dosageABSTRACT
Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes. .
Objetivo O objetivo do presente estudo foi analisar os efeitos do hormônio tireoidiano (HT), triiodotironina (T3), na modulação da expressão de mRNA do receptor alfa (TRα) de HT e o envolvimento da via de sinalização da via fosfatidilinositol 3-quinase (PI3K) em adipócitos, 3T3-L1. Materiais e métodos: Foi examinado o envolvimento da via PI3K nos efeitos do T3 nos tratamentos de adipócitos, 3T3-L1, nas doses fisiológica (P=10nM) ou suprafisiológica (SI =100 nM) durante uma hora (tempo curto), na ausência ou na presença do inibidor da PI3K (LY294002). A ausência de qualquer tratamento foi considerada o grupo controle (C). RT-qPCR foi utilizado para analisar a expressão do mRNA. Para as análises dos dados, utilizou-se ANOVA complementada com o teste de Tukey a 5% de significância. Resultados O T3 aumentou a expressão de mRNA de TRα em P (1,91±0,13, p<0,001) e SI (2,14±0,44, p<0,001) em comparação com o grupo C (1±0,08). Esse aumento foi completamente abolido por LY294002 em P (0,53±0,03, p<0,001) e SI (0,31±0,03, p<0,001). Para examinar se a expressão de TRα foi diretamente induzida pelo T3, utilizou-se o inibidor de tradução, ciclohexamida (CHX). A presença de CHX reduziu os níveis de mRNA de TRα em P (1,15±0,05, p>0,001) e SI (0,99±0,15, p>0,001), induzidos pelo T3. Conclusão Esses resultados demonstram que a ativação da via de sinalização de PI3K tem um papel importante na expressão do gene TRα mediada indiretamente pelo T3, em adipócitos 3T3-L1. .
Subject(s)
Animals , Mice , Adipocytes/drug effects , /metabolism , RNA, Messenger/metabolism , Thyroid Hormone Receptors alpha/metabolism , Triiodothyronine/pharmacology , Adipocytes/metabolism , Cell Differentiation , Chromones/pharmacology , Gene Expression/genetics , Genes, erbA/drug effects , Morpholines/pharmacology , Time Factors , Thyroid Hormone Receptors alpha/geneticsABSTRACT
OBJECTIVE: To examine the effect of different doses of triiodothyronine (T3) on mRNA levels of thyroid hormone receptors, TRα and TRβ, at different times. MATERIALS AND METHODS: 3T3-L1 adipocytes were incubated with T3 (physiological dose: F; supraphysiological doses: SI or SII), or without T3 (control, C) for 0.5, 1, 6, or 24h. TRα and TRβ mRNA was detected using real-time polymerase chain reaction. RESULTS: F increased TRβ mRNA levels at 0.5h. After 1h, TRα levels increased with F and SI and TRβ levels decreased with SII compared with C, F, and SI. After 6h, both genes were suppressed at all concentrations. In 24h, TRα and TRβ levels were similar to those of C group. CONCLUSIONS: T3 action with F began at 1h for TRα and at 0.5h for TRβ. These results suggest the importance of knowing the times and doses that activate T3 receptors in adipocytes.
OBJETIVO: Examinar o efeito de diferentes doses de triiodotironina (T3) sobre a expressão gênica dos receptores TRα e TRβ em diferentes tempos. MATERIAIS E MÉTODOS: Adipócitos, 3T3-L1, foram incubados com T3 nas doses fisiológica (F, 10nM) e suprafisiológicas (SI, 100nM ou SII, 1000nM) ou veículo (controle, C) durante 0,5, 1, 6 ou 24h. mRNA dos TRs foram detectados utilizando PCR em tempo real. RESULTADOS: Níveis de TRβ aumentaram em F em 0,5h. Após 1h, níveis de TRα aumentaram em F e SI comparado ao C, enquanto TRβ diminuiu no SII comparado com C, F, e SI. Após 6h, ambos os genes foram suprimidos em todas concentrações. Em 24h, níveis de TRα e TRβ retornaram aos do C. CONCLUSÕES: Ação do T3 em F iniciou-se em 1h para TRα e 0,5h para TRβ. Esses resultados são importantes para determinar tempo inicial e dose de T3 em que os receptores de HT são ativados em adipócitos.
Subject(s)
Animals , Adipocytes/drug effects , Antigenic Modulation/immunology , Thyroid Hormone Receptors alpha/metabolism , Thyroid Hormone Receptors beta/metabolism , Triiodothyronine/administration & dosage , Adipocytes/metabolism , Cell Line , Drug Administration Schedule , RNA, Messenger/analysis , Thyroid Hormone Receptors alpha/genetics , Thyroid Hormone Receptors beta/genetics , Triiodothyronine/pharmacologyABSTRACT
O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar as complicações da falta do hormônio. A maioria dos casos de hipotireoidismo congênito é decorrente de disgenesias tireoidianas (85%), entre elas a ectopia, hipoplasia ou agenesia tireoidianas, e os demais resultam de defeitos de síntese hormonal. As crianças afetadas (> 95%) geralmente não apresentam sintomas sugestivos da doença ao nascimento. Os sintomas e sinais mais comuns são: icterícia neonatal prolongada, choro rouco, letargia, movimentos lentos, constipação, macroglossia, hérnia umbilical, fontanelas amplas, hipotonia e pele seca. Várias estratégias são utilizadas para a triagem do HC. No Brasil, esta é obrigatória por lei e geralmente é feita com a dosagem de TSH em sangue seco coletado do calcanhar. A idade recomendada para sua realização é após as 48 horas de vida até o quarto dia. A confirmação diagnóstica é obrigatória com as dosagens de TSH e T4 livre ou T4 total.
Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with an incidence of 1:2,000 to 1:4,000 live births and it is a leading preventable mental retardation. Neonatal Screening Programs allow early identification of the disease and the adequate treatment of affected children can avoid the complications related to deprivation of the hormone. Most cases of primary congenital hypothyroidism (85%) are due to thyroid dysgenesis (ectopia, hypoplasia or agenesis) while the remaining result from defects in hormone synthesis. Affected children (> 95%) usually have no symptoms suggesting the disease at birth. The most frequent symptoms and signs are prolonged neonatal jaundice, hoarse cry, lethargy, slow movements, constipation, macroglossia, umbilical hernia, large fontanelle, hypotonia and dry skin. Around the world, various strategies are used for the screening of the CH. In Brazil, screening for CH is mandatory by law and usually done by serum TSH in dried blood collected from the heel. The recommended age for performing this test is after 48 hours of life until the 4th day. Diagnostic confirmation is required dosing TSH and free T4 or total T4 in serum.
Subject(s)
Child , Humans , Infant, Newborn , Congenital Hypothyroidism , Evidence-Based Medicine/standards , Thyrotropin/blood , Thyroxine/blood , Brazil , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/drug therapy , Congenital Hypothyroidism/etiology , Neonatal Screening , Quality Assurance, Health Care , Reference Values , Thyroid Function Tests , Thyroid Dysgenesis/complications , Thyroxine/therapeutic useABSTRACT
FUNDAMENTO: Vários autores mostraram que a deterioração da função cardíaca associa-se com o grau e a duração da obesidade. Os padrões de expressão gênica após longos períodos de obesidade precisam ser estabelecidos. OBJETIVO: Este estudo testou a hipótese de que a exposição prolongada à obesidade leva à redução nos níveis de RNAm de proteínas envolvidas na homeostase do Ca2+ miocárdico. Além disso, este estudo avaliou se uma diminuição no hormônio tireoidiano causava redução na expressão de RNAm. MÉTODOS: Ratos Wistar machos de 30 dias de idade foram distribuídos em dois grupos: controle (C) e obeso (Ob). O grupo C recebeu uma dieta padrão e o grupo Ob recebeu dietas hiperlipídicas por 15, 30 e 45 semanas. A obesidade foi definida pelo índice de adiposidade. A expressão gênica foi avaliada por PCR em tempo real quantitativa. RESULTADOS: O índice de adiposidade foi maior no grupo Ob do que no C em todas as etapas. Enquanto a obesidade nas semanas 15 e 45 determinou uma redução no RNAm de Ca2+-ATPase do retículo sarcoplasmático (SERCA2a), trocador Na+/Ca2+ (NCX) e calsequestrina (CSQ), observou-se aumento da expressão do RNAm de canal de Ca2+ do tipo L, receptor de rianodina, SERCA2a, fosfolamban (PLB), NCX e CSQ após a semana 30, em comparação ao grupo C. Não houve associação significativa entre os níveis de T3 e a expressão de RNAm. CONCLUSÕES: Nossos dados indicam que a obesidade por curtos ou longos períodos de tempo pode promover alteração na expressão gênica de proteínas reguladoras da homeostase do Ca2+ sem influência do hormônio tireoidiano.
BACKGROUND: Several authors have shown that deterioration of cardiac function is associated with the degree and duration of obesity. It is necessary to establish the gene expression patterns after prolonged periods of obesity. OBJECTIVE: This study tested the hypothesis that increased duration of exposure to obesity leads to a reduction in the mRNA levels of proteins involved in regulation of myocardial Ca2+ homeostasis. In addition, this study verified whether the decrease in mRNA expression was caused by a reduction in thyroid hormone. METHODS: Thirty-day-old male Wistar rats were distributed in two groups: control (C) and obese (Ob). The C group was fed a standard diet and the Ob was fed with high-fat diets for 15, 30 and 45 weeks. Obesity was defined by adiposity index. The gene expression was assessed by quantitative real-time PCR. RESULTS: The adiposity index was higher in the Ob compared to the C after all periods. While obesity at 15 and 45 weeks resulted in a reduction in mRNA of sarcoplasmic reticulum Ca2+- ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and calsequestrin (CSQ), L-type Ca2+ channels, ryanodine receptor, SERCA2a, phospholamban (PLB), NCX, and CSQ expression were increased compared to the C after 30 weeks. There was no significant association between T3 levels and mRNA expression. CONCLUSIONS: Our data indicate that obesity over the short and long periods of time may promote alteration in gene expression of Ca2+ homeostasis regulatory proteins without influence by thyroid hormone.
Subject(s)
Animals , Male , Rats , Calcium-Binding Proteins/genetics , Calcium/metabolism , Gene Expression/genetics , Homeostasis/genetics , Myocardium/metabolism , Obesity/complications , Thyroid Hormones/metabolism , Analysis of Variance , Disease Models, Animal , Obesity/chemically induced , Obesity/metabolism , Random Allocation , Rats, Wistar , RNA, Messenger/genetics , Time FactorsABSTRACT
OBJETIVO: Verificar o perfil dos hormônios tireóideos (HTs) em pacientes pós-menopausa portadoras de carcinoma de mama (CaM). SUJEITOS E MÉTODOS: Participaram 12 pacientes com CaM em estádio I ou II sem intervenções que pudessem interferir na progressão tumoral e um grupo controle com 18 pacientes em pós-menopausa sem CaM. Foram dosados os níveis séricos de anticorpo antitiroperoxidase (TPOAB), hormônio estimulante da tireoide (TSH), tiroxina livre (T4L), estradiol (E2), hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) antes e após a cirurgia, e realizada a imunoistoquímica dos receptores de estrógeno (ER) e progesterona (PR). RESULTADOS: Quatro pacientes com CaM apresentaram alterações do perfil hormonal tireoidiano: dois hipertireoidismo, um hipotireoidismo e positividade TPO-AB, todas com ER e PR positivos. Os níveis de TSH dessas pacientes não foram diferentes dos níveis encontrados no grupo controle (1,89 ± 1,56 vs. 2,86 ± 3,12 mUI/mL), porém os níveis de T4L nas pacientes com CaM foram estatisticamente maiores que o controle (1,83 ± 0,57 vs. 1,10 ± 0,20 ng/dL). CONCLUSÃO: Esses resultados reforçam a necessidade de avaliação do status tireoidiano em pacientes com CaM, uma vez que, na ausência de E2, mudanças clínicas nos HTs podem atuar em vias controladas pelo E2.
OBJECTIVE: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). SUBJECTS AND METHODS: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. RESULTS: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL). CONCLUSION: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes.
Subject(s)
Aged , Female , Humans , Middle Aged , Breast Neoplasms/blood , Carcinoma/blood , Postmenopause/blood , Thyroid Hormones/blood , Breast Neoplasms/pathology , Carcinoma/pathology , Immunohistochemistry , Luminescence , Statistics, Nonparametric , Thyroid Diseases/blood , Biomarkers, Tumor/bloodABSTRACT
CONTEXT AND OBJECTIVE: An association between chronic idiopathic urticaria (CIU) and autoimmune thyroid disease (ATD) has been reported. However, there have not been any reports on whether ATD raises the risk of angioedema, which is a more severe clinical presentation of CIU. Thus, the aim of the present study was to evaluate whether the risk of angioedema is increased in patients with CIU and ATD. DESIGN AND SETTING: Case-control study including 115 patients with CIU at a tertiary public institution. METHODS: The patients were evaluated with regard to occurrence of angioedema and presence of ATD, hypothyroidism or hyperthyroidism. RESULTS: Angioedema was detected in 70 patients (60.9%). There were 22 cases (19.1%) of ATD, 19 (16.5%) of hypothyroidism and nine (7.8%) of hyperthyroidism. The risk among patients with ATD was 16.2 times greater than among those without this thyroid abnormality (confidence interval, CI = 2.07-126.86). The odds ratio for hypothyroidism was 4.6 (CI = 1.00-21.54) and, for hyperthyroidism, 3.3 (CI = 0.38-28.36). CONCLUSIONS: Patients with CIU and ATD presented greater risk of angioedema, which reinforces the idea that a relationship exists between this allergic condition and thyroid autoimmunity. This finding could imply that such patients require specifically directed therapy.
CONTEXTO E OBJETIVO: A associação de urticária crônica idiopática (UCI) com doença autoimune da tireoide (DAT) é relatada. Porém, não foram encontrados relatos se a DAT eleva o risco de angioedema, uma apresentação clínica mais grave da UCI. Assim, o objetivo do presente estudo foi avaliar se o risco de angioedema está aumentado em pacientes com UCI e DAT. TIPO DE ESTUDO E LOCAL: Estudo caso-controle, incluindo 115 pacientes com UCI em uma instituição pública terciária. MÉTODOS: Os pacientes foram avaliados quanto à ocorrência de angioedema e à presença de DAT, hiper ou hipotireoidismo. RESULTADOS: Angioedema ocorreu em 70 pacientes (60,9%). Foram observados 22 (19,1%) casos de DAT, 19 (16,5%) de hipotireoidismo e 9 (7,8%) de hipertireoidismo. Os pacientes com DAT apresentaram risco 16,2 vezes maior de angioedema do que os sem a alteração tireoidiana (intervalo de confiança, IC = 2.07-126.86). O odds ratio, para hipotireoidismo, foi de 4,6 (IC = 1.00-21.54) e para hipertireoidismo foi de 3,3 (IC = 0.38-28.36). CONCLUSÕES: Pacientes com UCI e DAT apresentaram maior risco de angioedema, reforçando a ideia de existência de relação entre o quadro alérgico e autoimunidade tireoidiana. Este achado poderia implicar em um direcionamento terapêutico específico para tais pacientes.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Angioedema/immunology , Hyperthyroidism/complications , Hypothyroidism/complications , Thyroiditis, Autoimmune/complications , Age Distribution , Autoimmunity , Case-Control Studies , Chi-Square Distribution , Chronic Disease , Risk Factors , Urticaria/immunologyABSTRACT
JUSTIFICATIVA E OBJETIVOS: Tem sido estimado que a síndrome metabólica (SM) afeta uma substancial porcentagem da população idosa e de média idade, conferindo um aumento de risco para o desenvolvimento de doenças cardiovasculares e diabetes mellitus do tipo 2 (DM2), riscos esses que irão conduzir a uma situação economicamente insustentável nos próximos anos. O objetivo deste estudo foi apresentar critérios diagnósticos atualizados, detalhar o papel do estresse oxidativo em cada um dos diversos sinais, sumarizar os principais estudos clínicos e experimentais,e abordar o tratamento com antioxidantes. CONTEÚDO: SM corresponde a um conjunto de anormalidades,incluindo entre outros sinais, aumento da pressão arterial,alteração da glicemia, hipertrigliceridemia, baixos níveis de lipoproteína-colesterol de baixa densidade e obesidade abdominal. Estresse oxidativo é um importante mecanismo no desenvolvimentodos sinais da SM. CONCLUSÃO: Embora o estresse oxidativo parecesse ser mecanismo determinante na SM, a prescrição de suplementação com antioxidantes não é recomendada de rotina.
BACKGROUND AND OBJECTIVES: Metabolic syndrome (MS) affects a substantial percentage of the middle-aged and elderly populations and confers increased risk for type 2 diabetes and cardiovascular disease that ultimately will lead to economically-unsustainable costs of health care in the next years. This review shows updated diagnostic criteria, detailing the role of oxidative stress in each sign, summarizing the main clinical andexperimental studies and approaching the antioxidant treatment. CONTENTS: MS correspond to a cluster of abnormalities, includin gamong other signs, raised blood pressure, dysglycemia, and elevated triglyceride levels, low high-density lipoprotein cholesterol levels, and abdominal obesity. Oxidative stress is importan tmechanism involved in the MS sign development. CONCLUSION: Although oxidative stress seems to play an importantrole in its pathophysiological mechanism, routine use of antioxidant supplements is not recommended.
Subject(s)
Humans , Oxidative Stress , Metabolic Syndrome/diagnosis , Metabolic Syndrome/etiology , Metabolic Syndrome/therapy , Cardiovascular Diseases , Diabetes MellitusABSTRACT
OBJECTIVE: To better understand the estrogen (E2) agonist action of triiodothyronine (T3) the effects of these hormones on ER negative MDA-MB-231 breast cancer cells were compared with those on S30, a clone of MDA-MB-231 stably transfected with ERα cDNA, in terms of proliferation and modulation of hormone receptors. RESULTS: Growth experiments showed that MDA-MB-231 was not modulated by any hormone or tamoxifen (TAM). Treatment with E2, 10-8M or 10-9M had little effect on S30 proliferation. T3 at 10-8M significantly inhibited proliferation. This effect was not reverted by TAM. Treatments with 10-8M concentration of E2 or T3 reduced ERα gene expression in S30, an effect partially blocked by association with TAM, with no effect on TR expression. These results suggest that, in S30, 10-8M T3 has a similar action to E2 relative to ERα gene modulation. CONCLUSIONS: Such results emphasize the need of determining T3 levels, before the introduction of antiestrogenic forms of treatment in breast cancer patients.
OBJETIVO: Para compreender melhor a ação da triiodotironina (T3) agonista de estrógeno (E2), foram comparados os efeitos destes hormônios em células de câncer de mama MDA-MB-231 ER negativas com um clone de MDA-MB-231, transfectado estavelmente com o cDNA de ERα (S30), em termos de proliferação e modulação dos receptores hormonais. RESULTADOS: Experimentos de crescimento mostraram que MDA-MB-231 não foi modulada por qualquer hormônio ou pelo tamoxifeno (TAM). O crescimento de S30 foi essencialmente inalterado por tratamento com E2 10-9M ou 10-8M, mas T3 10-8M inibiu significativamente a proliferação quando comparada a ambas concentrações de E2. Esse efeito não foi revertido pelo TAM, sugerindo um resultado não genômico, independente de ERE. Tratamentos com 10-8M de E2 ou de T3 reduziram a expressão do gene ERα em S30, efeito parcialmente impedido pela associação com TAM, sem efeito na expressão de TR. Os resultados sugerem que, em S30, T3 10-8M tem ação semelhante ao E2 com relação à modulação do gene ERα. CONCLUSÕES: Esses resultados enfatizam a necessidade de dosagem de T3 circulante antes da introdução do tratamento antiestrogênico no câncer de mama.
Subject(s)
Female , Humans , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Estradiol/pharmacology , Receptors, Estrogen/metabolism , Receptors, Thyroid Hormone/metabolism , Triiodothyronine/pharmacology , Analysis of Variance , Breast Neoplasms/metabolism , Cell Line, Tumor , Clone Cells , Estrogen Antagonists/pharmacology , Receptors, Estrogen/genetics , Receptors, Thyroid Hormone/genetics , Tamoxifen/pharmacologyABSTRACT
OBJECTIVES: To estimate oculometric parameters of Graves' ophthalmopathy in comparison to healthy eyes using digital photography and digital image analysis. INTRODUCTION: Graves' ophthalmopathy is the main cause of eye proptosis. Because these protrusions cause clinically perceived distortions in orbital architecture, digital photographs can be used to detect and quantify these changes. METHODS: We carried out a cross-sectional study comprising 12 healthy volunteers and 15 Graves' ophthalmopathy patients with the purpose of evaluating the use of simple, non-invasive digital photography to estimate oculometric parameters of Graves' ophthalmopathy and compare them with the parameters of unaffected eyes. Facial photographs of cases and controls were taken in a standardized manner. Oculometric parameters were compared between the groups and then correlated to proptometer measures. RESULTS: All estimated oculometric variables showed significant differences between the groups, in particular with regard to mediopupilar aperture, lateral height, distance from the iris edge to the lateral boundary of the palpebral fissure, and distance from the higher point of the iris to the lateral limit of the palpebral fissure. The product of medial aperture and horizontal palpebral fissure also revealed greater discrepancy between the groups. Proptometer measures showed significant linear correlation between the distance from the iris edge to the lateral boundary of the palpebral fissure and between the distance from the higher point of the iris to the lateral limit of palpebral fissure (p<0.05). CONCLUSIONS: Comparative analysis of oculometric parameters in Graves' ophthalmopathy suggests that eye proptosis is related to an asymmetric increase in lateral oculometric measures. Standardized digital photographs can be used in clinical practice to objectively estimate oculometric parameters of Graves' ophthalmopathy patients.
Subject(s)
Adult , Female , Humans , Male , Eye/pathology , Graves Ophthalmopathy/pathology , Photography/methods , Case-Control Studies , Cross-Sectional Studies , Eye/anatomy & histology , Graves Ophthalmopathy/complications , Image Processing, Computer-AssistedABSTRACT
Osteoclastogenesis may be regulated via activation of the RANK/RANKL (receptor activator of nuclear factor-kappa B/ receptor activator of nuclear factor-kappa B ligand) system, which is mediated by osteoblasts. However, the bone loss mechanism induced by T3 (triiodothyronine) is still controversial. In this study, osteoblastic lineage rat cells (ROS 17/2.8) were treated with T3 (10-8 M, 10-9 M, and 10-10 M), and RANKL mRNA (messenger RNA) expression was measured by semiquantitative RT-PCR. Our results show that T3 concentrations used did not significantly enhance RANKL expression compared to controls without hormone treatment. This data suggests that other mechanisms, unrelated to the RANK/RANKL system, might be to activate osteoclast differentiation in these cells.
A osteoclastogênese pode ser regulada via ativação do sistema RANK/RANKL (receptor ativador do fator nuclear kapa B/ ligante do receptor do fator nuclear kapa B), que é mediado pelos osteoblastos. Entretanto, o mecanismo de perda óssea induzido pelo T3 (triiodotironina) ainda é controverso. Neste estudo, a linhagem osteoblástica de células de rato ROS 17/2.8 foi tratada com T3 (10-8 M, 10-9 M e 10-10 M), e a expressão do mRNA do RANKL foi medida por RT-PCR semiquantitativo. Nossos resultados mostraram que as concentrações de T3 utilizadas não induziram significativamente a expressão do RANKL, comparado ao controle (sem tratamento hormonal). Estes dados sugerem que outros mecanismos, não relacionados ao sistema RANK/RANKL, são usados para ativar a diferenciação osteoclástica nestas células.
Subject(s)
Animals , Rats , Bone Resorption/drug therapy , Osteoblasts/drug effects , RANK Ligand/metabolism , RNA, Messenger/metabolism , Receptors, Thyroid Hormone/metabolism , Triiodothyronine/pharmacology , Bone Resorption/metabolism , Cell Differentiation/drug effects , Electrophoresis, Agar Gel , Osteoblasts/cytology , Osteoclasts/metabolism , RANK Ligand/genetics , Reverse Transcriptase Polymerase Chain Reaction , Receptors, Thyroid Hormone/geneticsABSTRACT
Introdução: O avanço terapêutico e tecnológico em cardiologia tem possibilitado a sobrevivência de pessoas acometidas pela doença arterial coronária. Técnicas de cirurgia de revascularização miocárdica (RM) sem o uso de circulação extracorpórea (CEC) possibilitaram resultados operatórios com menor dano sistêmico, menor ocorrência de complicações clínicas, menor permanência na sala de terapia intensiva e também no tempo de internação, gerando expectativas de melhor qualidade de vida (QV) dos pacientes. Objetivo: Avaliar e comparar a qualidade de vida em pacientes portadores de doença arterial coronária em múltiplos vasos, com angina estável e função ventricular preservada encaminhados para revascularização miocárdica com e sem circulação extracorpórea no período de 12 meses. Métodos: Utilizou-se o questionário genérico de avaliação de qualidade de vida Medical Outcomes Study 36-ItemShort-Form Health Survey (SF-36) e o questionário perfil demográfico em 202 pacientes randomizados para uma das duas técnicas cirúrgicas nos períodos préoperatório, 6 e 12 meses após o procedimento. Resultados: Entre janeiro de 2002 e dezembro de 2006, 105 pacientes foram encaminhados para cirurgia sem circulação extracorpórea e 97 deles foram submetidos à cirurgia com circulação extracorpórea. As características demográficas, clínicas, laboratoriais e angiográficas foram semelhantes nos dois grupos. A avaliação da qualidade de vida mostrou similaridade nos dois grupos em relação ao componente físico e mental, demonstrando melhora de todos os domínios analisados no decorrer do seguimento. Não foi também observada interferência da técnica cirúrgica em relação ao gênero. Entretanto, analisando a freqüência da melhora em cada dimensão ao final de 12 meses, conforme o tipo de cirurgia, foi observado que a cirurgia sem CEC foi um marcador independente de melhora no domínio estado geral de saúde, e os pacientes submetidos à cirurgia sem CEC apresentaram uma chance duas vezes maior...
Introduction: The therapeutic and technological advances in cardiology have enabled the survival of people affected by coronary artery disease. Techniques for coronary artery bypass grafting (CABG) without the use of cardiopulmonary bypass (CPB) has enabled surgical results, with less systemic damage, lower incidence of clinical complications, a shorter stay in the intensive care room and also in length of stay, generating expectations of better quality of life (QoL) of patients. Objective: To evaluate and compare the self-perceived quality of life in patients with multivessel coronary artery disease with stable angina and preserved ventricular function randomized for CABG with or without cardiopulmonary bypass during the twelve months period. Methods: The generic questionnaire of QoL Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and demographic profile questionnaire were applied on 202 patients randomized for one of the two surgical techniques options at baseline, 6 and 12 months follow-up. Results: Between January 2002 and December 2006, 105 and 97 patients were submitted to surgery without cardiopulmonary bypass or with cardiopulmonary bypass, respectively. The demographic, clinical, laboratory and angiographic characteristics were similar in both groups. The assessment of quality of life showed similarity in both groups regarding to physical and mental components, showing improvement in all 8 subscales domain of the SF-36 across the follow-up. Additionally, analyzing the frequency of improvement in each dimension at 12 months, stratified by the type of technical surgery, we found the off-pump surgery was an independent marker of improvement in overall health status. Patients underwent surgery without CPB had two-fold increase risk of improvement in health status. In addition, no interaction was found between surgical technique and gender. Regarding to return to work after surgery, higher number of patients on offpump group was observed...
Subject(s)
Humans , Female , Adult , Middle Aged , Coronary Disease , Extracorporeal Circulation , Myocardial Revascularization , Quality of LifeABSTRACT
FUNDAMENTO: Ainda que os benefícios clínicos das intervenções coronarianas parecem confirmados, seus efeitos na qualidade de vida (QV) permanecem pouco estudados. OBJETIVO: Avaliar a qualidade de vida (QV) na doença multiarterial coronariana em pacientes submetidos randomicamente a cirurgia, angioplastia ou tratamento clínico. MÉTODOS: Foi utilizando Short-Form Health Survey (SF36) questionnaire em 483 pacientes. Desses, 161 foram revascularizados; 166 receberam angioplastia e 153 tiveram tratamento clínico. RESULTADOS: Na internação, 86 por cento referiam angina; 34 por cento, infarto; e 32 por cento fumavam. Tratamento clínico: 12 pacientes (7,7 por cento) tiveram infarto agudo do miocárdio (IAM); 24 (15,3 por cento) receberam cirurgia; e 19 (12,1 por cento) morreram. Além disso, cinco (3,2 por cento) sofreram AVC e 40 (25,6 por cento) tinham angina. No componente mental, 64,1 por cento melhoram e 30,8 por cento pioram a condição. No componente físico, 70,5 por cento melhoram e 27,6 por cento pioram a condição. Cirurgia: 13 pacientes (8,1 por cento) tiveram IAM, dois (1,2 por cento) receberam cirurgia; 12 (7,4 por cento) morreram. Em adição, nove (5,6 por cento) sofreram AVC e 30 (18,6 por cento) sofriam angina. No componente mental, 72,7 por cento melhoram e 25,5 por cento pioram a condição. No componente físico, 82,6 por cento melhoram e 16,1 por cento pioram a condição. Angioplastia: 18 pacientes (10,9 por cento) tiveram IAM, 51 (30,7 por cento) receberam intervenções e 18 (19,9 por cento) morreram. Além disso, seis (3,6 por cento) sofreram AVC e 35 (21 por cento) relatavam angina. No componente mental, 66,9 por cento melhoram e 26,5 por cento pioram a condição No componente físico, 77,1 por cento melhoram e 20,5 por cento pioram a condição. CONCLUSÃO: Observou-se melhora em todos os domínios e nas três opções terapêuticas. Comparativamente, a cirurgia ofereceu melhor qualidade de vida após quatro anos de seguimento.
BACKGROUND: Although the clinical benefits of coronary interventions seem to be confirmed, their effects on quality of life (QoL) are still scarcely studied. OBJECTIVE: To assess the QoL in multivessel coronary disease in patients randomly undergoing surgery, angioplasty or medical treatment. METHODS: The Short-Form Health Survey (SF-36) questionnaire was answered by 483 patients. Of these, 161 underwent surgical revascularization, 166 underwent angioplasty, and 153 were medically treated. RESULTS: At baseline, 86 percent of the patients referred angina, 34 percent referred infarction, and 32 percent were smokers. Medical Treatment: 12 patients (7.7 percent) had AMI, 24 (15.3 percent) underwent surgery, and 19 (12.1 percent) died. In addition, 5 (3.2 percent) had stroke, and 40 (25.6 percent) had angina. As regards the mental component, 64.1 percent and 30.8 percent had their condition improved and worsened, respectively. As regards the physical component, 70.5 percent and 27.6 percent had their condition improved and worsened, respectively. Surgery: 13 patients (8.1 percent) had AMI, 2 (1.2 percent) underwent surgery, and 12(7.4 percent) died. Also, 9 (5.6 percent) had stroke and 30 (18.6 percent) had angina. As regards the mental component, 72.7 percent and 25.5 percent had their condition improved and worsened, respectively. As regards the physical component, 82.6 percent and 16.1 percent had their condition improved and worsened, respectively. Angioplasty: 18 patients (10.9 percent) had AMI, 51 (30.7 percent) underwent interventions, and 18 (19.9 percent) died. Additionally, six (3.6 percent) presented stroke and 35 (21 percent) reported angina. As regards the mental component, 66.9 percent and 26.5 percent had their condition improved and worsened, respectively. As regards the physical component, 77.1 percent and 20.5 percent had their condition improved and worsened, respectively. CONCLUSION: Improvement was observed in all domains...