Research progress on the relationship between liver cirrhosis and thyroid hormones / 中华肝脏病杂志

There exists a complex relationship between liver and thyroid hormones. Liver plays an important role in the activation, inactivation, transportation, and metabolism of thyroid hormones. At the same time, thyroid hormones also affect hepatocytes activity and liver metabolism, such as lipid and bilirubin metabolism. Importantly, thyroid hormone levels often change abnormally in patients with liver cirrhosis. Therefore, studying the change of thyroid hormone levels in patients with liver cirrhosis has a certain clinical value for assessing the severity, prognosis, diagnosis and treatment. This paper reviews the research progress on the relationship between liver cirrhosis and thyroid hormone.

Hypothyroid offspring replacement with euthyroid wet nurses during lactation improves thyroid programming without modifying metabolic programming

ABSTRACT Objective Determine the milk quality effect during lactation on the metabolic and thyroid programming of hypothyroid offspring. Materials and methods Ten-week-old female Wistar rats were divided into two groups: euthyroid and thyroidectomy-caused hypothyroidism. The rats were matted and, one day after birth, the pups were divided into three groups: euthyroid offspring (EO), hypothyroid offspring (HO) and hypothyroid with a euthyroid replacement wet nurse (HRO). During lactation, the milk quality and offspring body length were evaluated. The body weight and energy intake were determined on a weekly basis, as well as the metabolic profile at the prepubertal (P35-36) and postpubertal (P55-56) ages. At P56, the animals were sacrificed, the adipose tissues were weighed and the thyroid glands were dissected for histological processing. Results The milk of the hypothyroid wet nurse decreases proteins (16-26%), lipids (22-29%) and lactate (22-37%) with respect to euthyroid. The HO has a lower body weight gain (23-33%), length (11-13%) and energy intake (15-21%). In addition, HO presents impaired fasting glucose and dyslipidemia, as well as a reduction in seric thyroid hormone (18-34%), adipose reserves (26-68%) and thyroid gland weight (25-34%). The HO present thyroid gland cytoarchitecture alteration. The HRO develop the same metabolic alterations as the HO. However, the thyroid gland dysfunction was partially prevented because the HRO improved under about 10% of the serum thyroid hormone concentration, the thyroid gland weight although histological glandular changes presented. Conclusions The replacement of hypothyroid offspring with a euthyroid wet nurse during lactation can improve the thyroid programming without modifying metabolic programming.

Síndrome nefrótico asociado a hipotiroidismo severo / Nephrotic syndrome associated to severe hypothyroidism

Las hormonas tiroideas tienen acciones renales directas en conjunto con efectos dinámicos y cardiovasculares que influyen en la función renal. Cuadros de hipotiroidismo con enfermedad renal son una combinación peculiar y poco descrita, es por ello que el propósito de este trabajo es exponer el caso de dos pacientes con síndrome nefrótico asociado a hipotiroidismo severo, los cuales presentaron disminución de la proteinuria y casi normalización de función renal luego de iniciar tratamiento de reemplazo con levotiroxina.

Thyroid hormones have direct renal actions in conjunction with dynamic and cardiovascular effects that influence renal function. Cases of primary hypothyroidism with renal disease are a peculiar and poorly described combination, is for it that the objective of this work is to expose the cases of two patients with nephrotic syndrome associated with severe hypothyroidism, whom presented decreased proteinuria and almost normalized renal function after starting replacement therapy with levothyroxine.

Enfermedad no tiroidea / Non-thyroidal illness

La enfermedad no tiroidea es una entidad que se presenta frecuentemente en los pacientes que se encuentran cursando algún tipo de enfermedad, ya sea crítica o no; y puede manifestarse aun en ausencia de enfermedad tiroidea subyacente, condicionando cambios en el eje tiroideo. Es importante poder reconocer la enfermedad no tiroidea para hacer diagnóstico diferencial con la patología tiroidea verdadera y evaluar si merece ser tratada. Aún no existe consenso acerca de si la enfermedad no tiroidea representa una respuesta fisiológica a una enfermedad sistémica para que disminuyan los requerimientos de energía o si se trata de una condición adaptativa que induce un estado hipotiroideo que finalmente resulta perjudicial a nivel tisular.

Non-thyroidal illness is a disorder that occurs frequently in patients that are experiencing some kind of illness, whether critical or not. It can manifest even in the absence of thyroid dysfunction, leading to changes in the thyroid axis. It is important to detect Non-Thyroidal Illness in order to establish a differential diagnosis with the true thyroid disease and to determine whether treatment is required. Currently, there is still no consensus on whether Non-Thyroidal Illness is a physiological response to a systemic disease to reduce energy requirements or whether it is an adaptive condition that induces a hypothyroid state that ultimately is harmful at the tissue level.

Disfunción tiroidea y corazón / Thyroid dysfunction and heart

Los trastornos de la función tiroidea afectan profundamente al sistema cardiovascular. En esta revisión se presentan algunos aspectos fisiológicos de la interrelación entre tiroides y corazón, como también las consecuencias de la tirotoxicosis e hipotiroidismo sobre el aparato cardiovascular. Se analiza la influencia del hipertiroidismo en la gèc)nesis de la fibrilación auricular y del hipotiroidismo en el metabolismo de las lipoproteínas. Adicionalmente, el artículo se referirá a los potenciales efectos adversos del antiarrítmico amiodarona sobre la función tiroidea y cómo se investigan y tratan. Finalmente, se expone un caso clínico real para ilustrar con mayor claridad la enorme importancia que pueden alcanzar las relaciones fisiopatológicas entre el corazón y las afecciones de esta glándula endocrina.

Disorders of thyroid function profoundly affect the cardiovascular system. Inthisreviewsomephysiologicalaspectsoftherelationship between thyroid and the heart as well as the consequences of thyrotoxicosis and hypothyroidism on the cardiovascular system are presented. The influence of hyperthyroidism is analyzed in the genesis of atrial fibrillation and of hypothyroidism on lipoprotein metabolism. Furthermore, we refer to the potential adverse effects of the antiarrhythmic amiodarone on thyroid function and how they are investigated and treated. Finally, a real clinical case is exposed to more clearly illustrate the enormous importance that can reach the pathophysiological relationships between the heart and the diseases of the thyroid gland.

Marcadores de risco cardiovascular em indivíduos com infarto do miocárdio precoce e em seus familiares de primeiro grau / Cardiovascular risk factors in patients with premature myocardial infarction and in their first-degree relatives

INTRODUÇÃO: O Infarto agudo do miocárdio (IAM) é infrequente em indivíduos jovens (<45 anos) e está associado à história familiar precoce de doença cardiovascular.OBJETIVO: O presente estudo descreveu o perfil sócio-demográfico e os fatores de risco cardiovascular de indivíduos com diagnóstico de IAM < 45 anos de idade e seus familiares de primeiro grau. Avaliou-se também a relação de parâmetros clínico-laboratoriais de acordo com a extensão angiográfica da doença arterial coronária (DAC) dos casos índices (doença uniarterial vs. multiarterial) e dos seus respectivos familiares.MÉTODOS: Estudo transversal realizado de novembro de 2010 a janeiro de 2015 em hospital terciário em Fortaleza, Ceará. Foram incluídos 103 casos índices e 166 familiares de primeiro grau que não apresentavam suspeita de hipercolesterolemia familiar. Estes foram comparados com 111 indivíduos assintomáticos e sem história familiar de DAC pareados para sexo e idade. Foram avaliados os parâmetros clínicos e laboratoriais dos 3 grupos. Os dados foram estudados por análises uni e multivariadas. RESULTADOS:O grupo casos apresentou maior prevalência de tabagismo (57,3 vs. 28,6%, p < 0,001), diabete melito tipo 2 - DM2 (43,4 vs. 19,5%, p < 0,001) e hipertensão arterial sistêmica - HAS (42,7 vs. 19%, p < 0,001) quando comparado aos familiares pareados para sexo e idade. Da mesma forma, os casos, quando comparados ao grupo controle, apresentaram, além destes fatores, concentrações mais elevadas de triglicerídeos (192 ± 75 vs. 140±74mg/dL, p < 0,001), menores concentrações de HDL-c (36 ± 12 vs. 48 ± 14mg/dL, p < 0,001) e uma maior prevalência de síndrome metabólica -SM (82,2 vs. 36%, p<0,001). Observou-se que 50,5% dos casos tinham acometimento multiarterial. Após análise multivariada, a HAS (p=0,030) e o DM2 (p=0,028) associaram-se de forma independente à DAC multiarterial. Quando comparados ao grupo controle, os familiares apresentaram maior prevalência de tabagismo...

BACKGROUND: The acute myocardial infarction (AMI) is uncommon in young individuals ( < 45 years), and is associated with premature family history of cardiovascular disease. OBJECTIVE: This study described the socio-demographic and cardiovascular risk factors of both subjects with AMI < 45 years of age and their first-degree relatives. The association of clinical and laboratory parameters with the angiographic extension of coronary artery disease (CAD) of index cases (single-vessel vs. multivessel disease) and in their respective relatives was also evaluated. METHODS: Cross-sectional study conducted from November 2010 to January 2015 in a tertiary hospital in Fortaleza, Ceara. One hundred and three index cases and 166 first-degree relatives without suspicion of familial hypercholesterolemia were included. These were compared with 111 asymptomatic individuals without family history of CAD matched for sex and age. Clinical and laboratory parameters of the 3 groups were evaluated. Associations were tested by univariate and multivariate analysis. RESULTS: AMI cases presented a higher prevalence of smoking (57.3% vs. 28.6%, p < 0.001), type 2 diabetes mellitus -DM2 (43.4 vs. 19.5%, p < 0.001), and hypertension (42.7 vs. 19%, p < 0.001) when compared to relatives matched for sex and age. Likewise cases, when compared to controls showed in addition higher triglycerides (192 ± 75mg/dL vs. 140 ± 74mg/dL, p < 0.001), lower HDL-C (36 ± 12mg/dL vs. 48±14mg/dL, p < 0.001), and a greater prevalence of the metabolic syndrome-MS (82.2% vs. 36%, p < 0.001). Multivessel disease was found in 50.5% of cases. After multivariate analysis, hypertension (p=0.030), and DM2 (p=0.028) were independently associated with multivessel disease. First-degree relatives showed a greater prevalence of smoking (29.5% vs. 6.3%, p < 0.001), DM2 (19.9% vs. 1.8%, p < 0.001), pre-diabetes (40.4 % vs. 27%, p < 0.024) and MS (64.7% vs. 36%, p < 0.001), when compared to controls. Lower HDL...

Diabetes mellitus tipo 1 e disfunções tireoidianas / Diabetes Mellitus type 1 and thyroid dysfunction

Os pacientes com diabetes mellitus (DM) apresentam maior prevalência de doenças tireoidianas que a população geral. A autoimunidade certamente é um fator-chave na relação entre essas disfunções endócrinas. Entretanto, outros mecanismos, como redução da captação de iodeto, da atividade tireoperoxidase e aumento do estresse oxidativo na glândula tireoide, também parecem contribuir para este fato. O presente trabalho visa rever aspectos importantes na relação entre DM e doenças tireoidianas, com especial ênfase nos mecanismos envolvidos no aumento do estresse oxidativo na glândula tireoide decorrente do DM...

Diabetes mellitus (DM) patients show a greater prevalence of thyroid disorders than general population. Autoimmunity is a key factor in the relation between these endocrine diseases. However, additional mechanisms, such as reduction of iodide uptake and thyroperoxidase activity, besides increased oxidative stress in the thyroid gland seem to contribute for this fact. The present work aims to review important aspects in the relation between DM and thyroid disease, with special emphasis in the mechanisms involved in the increased oxidative stress in the thyroid gland due to DM...

Saint John's wort, an herbal inducer of the cytochrome P4503A4 isoform, may alleviate symptoms of Willis-Ekbom's disease

OBJECTIVE: Certain drug classes alleviate the symptoms of Willis-Ekbom's disease, whereas others aggravate them. The pharmacological profiles of these drugs suggest that drugs that alleviate Willis-Ekbom's disease inhibit thyroid hormone activity, whereas drugs that aggravate Willis-Ekbom's disease increase thyroid hormone activity. These different effects may be secondary to the opposing actions that drugs have on the CYP4503A4 enzyme isoform. Drugs that worsen the symptoms of the Willis-Ekbom's disease inhibit the CYP4503A4 isoform, and drugs that ameliorate the symptoms induce CYP4503A4. The aim of this study is to determine whether Saint John's wort, as an inducer of the CYP4503A4 isoform, diminishes the severity of Willis-Ekbom's disease symptoms by increasing the metabolism of thyroid hormone in treated patients. METHODS: In an open-label pilot trial, we treated 21 Willis-Ekbom's disease patients with a concentrated extract of Saint John's wort at a daily dose of 300 mg over the course of three months. RESULTS: Saint John's wort reduced the severity of Willis-Ekbom's disease symptoms in 17 of the 21 patients. CONCLUSION: Results of this trial suggest that Saint John's wort may benefit some Willis-Ekbom's disease patients. However, as this trial was not placebo-controlled, the extent to which Saint John's wort is effective as a Willis-Ekbom's disease treatment will depend on future, blinded placebo-controlled studies. .

Influência de prolongados períodos de obesidade sobre a expressão gênica miocárdica / Influence of long-term obesity on myocardial gene expression

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.

The Genetically Modified Polysialylated Form of Neural Cell Adhesion Molecule-Positive Cells for Potential Treatment of X-Linked Adrenoleukodystrophy

PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.

Hipertireoidismo: abordagem das principais causas e conduta diagnóstica / Hyperthyroidism: approach the main causes and conduct diagnostic

A tireotoxicose é um estado hipermetabólico decorrente dos efeitos de níveis teciduais elevados de hormônios tireoideanos (HTs). O hipertireoidismo é a causa mais comum, e decorre do excesso de hormônios produzidos pela tireoide. Outras causas de tireotoxicose ocorrem por produção extratireoideana ou administração exógena de hormônios tireoideanos. A principal causa de tireotoxicose, o bócio difuso tóxico (BDT) de causa autoimune, responsável por até 80% dos casos, é aqui abordado, assim como as demais causas. O tratamento é realizado com drogas antitireoideanas, iodo radioativo ou cirurgia e exige acompanhamento de longo prazo, tanto pela possibilidade de recidivas como do desenvolvimento de hipotireoidismo.

Thyrotoxicosis is a hypermetabolic state due to the effects of high tissue levels of thyroid hormones (TH). Hyperthyroidism is the most common cause and results from excess hormones produced by the thyroid. Other causes of thyrotoxicosis occur extra thyroid production or exogenous administration of thyroid hormones. The main cause of thyrotoxicosis, the diffuse toxic goiter (DTG) of autoimmune cause, accounting for up to 80% of cases, is discussed here, as well as other causes. The treatment is performed with antithyroid drugs, radioactive iodine or surgery and requires long-term follow-up, due to both the possibility of recurrence and the development of hypothyroidism.

Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH) are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i) osteoprotegerin (OPG) and osteopontine (OPN) mRNA expression in the maxilla and ii) myoglobin (Mb) mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g) were divided into thyroidectomized (Tx) and sham-operated (SO) groups (N = 24/group) treated with T3 or saline (0.9 percent) for 15 days. Thyroidectomy increased OPG (~40 percent) and OPN (~75 percent) mRNA expression, while T3 treatment reduced OPG (~40 percent) and OPN (~75 percent) in Tx, and both (~50 percent) in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.

Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity.

Background & objectives: Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India. Methods: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T3, T4, TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium. Results: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P= 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 µg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 µg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group (P <0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 µg/l) as compared to controls (11, 6.4%; P<0.001). Serum ferritin level negatively correlated with the presence of goitre (r = - 0.22, P =0.008) and had an OR of 2.8 (CI 1.20 - 6.37, P =0.017). Interpretation & conclusions: There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.

[Survey the changes of thyroid functional tests in patients with liver cirrhosis due to hepatitis B and C and correlation of thyroid hormone levels with severity of liver dysfunction]

The liver played an important role in the metabolism of thyroid hormones and was involved in their conjugation, excretion and peripheral deiodination in synthesizing Thyroid Binding Globulin [TBG]. Thus liver dysfunction can be influenced thyroid function. Determine the changes of thyroid functional tests in patients with liver cirrhosis due to hepatitis B and C and correlation of thyroid hormone levels with severity of liver dysfunction. Sixty Four Cirrhotic patients due to hepatitis B and C referring to Razi hospital were studied during 2007-2009 years. Data were collected by prepared questionnaire. Thyroid hormone levels were measured in a unit laboratory. Liver dysfunction was scored by MELD and child pugh scoring systems. Mann-Whitney U, chi square and kruskal wallis test were used for measuring severity of liver dysfunction. Among 64 patients, [42 patients were male and 22 patients were female]. Mean age of patients was 55.03 +/- 12.05. Level of TT3 TT4 and FT3 had decreased in the majority of patients, TT3, TT4 and FT3 levels. There was a correlation between level of TT3 and severity of liver dysfunction base on Child score [p=0.0001] and MELD [p=0.02].There was a reciprocal correlation between TT3 level and probability of the history of digestive systems bleedings, Ascites and encephalopathy [P=0.01, P=0.011, P=0.009] .It means that when TT3 level was low probability of this complication was high. This study showed that liver disease is accompanied by changes in thyroid hormone levels specially decrease the level of TT3, TT4, FT3 and it is indicated that TT3 level can be used as liver function index in cirrhotic patients due to hepatitis B and C

El tejido graso como modulador endocrino: Cambios hormonales asociados a la obesidad / Adipose tissue as an endocrine modulator: Hormonal changes associated with obesity

Adipose tissue not only stores fat, but secretes factors and hormones, which modify the regulation, metabolism and secretion of several other hormones. The objective of this review is to describe the hormonal disorders associated with increased adipose tissue, which acts as a modulator or disruptor of the endocrine physiology, with special reference to cortisol, androgens, growth hormone and thyroid axis, and discuss the implications for the management and treatment of these patients.

[ Effects of cabergoline on pituitary- thyroid hormones in adult male rats]

Cabergoline is a strong dopaminergic agonist that is derived from Ergot fungus. Although, this drug can be so important in treating many disorders such as hyperprolactinemia, but its side effects are considerable on the endocrinal axis. The purpose of this study was to determine effects of cabergoline on serum levels of TSH, T[4] and T[3] hormones in adult male rats. In this experimental study, 40 adult male wistar rats were used in five groups of eight. The drug was subcutaneously injected for a period of 14 days. The experimental groups received 0.1, 0.5 and 1 mg/kg, respectively. The control group received no drug. The sham group received only distilled water. At the end of 14[th] day, blood samples were taken and the concentration of TSH, T[4] and T[3] were measured by RIA. The results were analyzed by ANOVA and TUKEY test between the control and experimental group. Serum levels of TSH and T4 hormones in the experimental groups with doses of 0.1, 0.5 and 1 mg/kg showed statistically significant decrease compared with control group [p<0.05]. Concentration of T[3] hormone showed significant increase in the experimental group with 0.1 mg/kg in comparison with control group [p<0.05]. Cabergoline probably decreases the release of TSH and T[4] by stimulating the D[2]-dopaminergic receptor existing in thyrotrophic cells. According to the increase of T[3] concentration with low dose of drug, cabergoline may have different physiological effects in different amounts, and alter the function of pituitary -thyroid axis

Splicing variants impact in thyroid normal physiology and pathological conditions / Variantes de splicing e seu impacto em condições fisiológicas e patológicas da tireoide

RNA splicing is an essential, precisely regulated process that occurs after gene transcription and before mRNA translation, in which introns may be removed and exons, retained. Variability in splicing patterns is a major source of protein diversity from the genome and function to generate a tremendously diverse proteome from a relatively small number of genes. Changes in splice site choice can determine different effects on the encoded protein. Small changes in peptide sequence can alter ligand binding, enzymatic activity, allosteric regulation, or protein localization. Errors in splicing regulation have been implicated in a number of different disease states. This study reviewed the mechanisms of splicing and their repercussion in endocrinology, emphasizing its importance in some thyroid physiological and pathological conditions.

Após a transcrição genética e antes da tradução do mRNA, ocorre o splicing do RNA, que consiste em um processo essencial, precisamente regulado, por meio do qual podem ocorrer excisões de íntrons e retenções de éxons. A variabilidade dos padrões de splicing é a principal fonte de diversidade de proteínas geradas por um pequeno número de genes. Alterações na escolha do sítio de splicing podem determinar efeitos diferentes nas proteínas codificadas. Pequenas alterações na sequência peptídica podem alterar o seu sítio de ligação de substratos, sua atividade enzimática, a regulação alostérica ou a localização proteica. Erros na regulação do splicing têm sido implicados em grande número de doenças. Nessa revisão, foram descritos os mecanismos de splicing enfatizando sua importância em algumas condições fisiológicas e patológicas envolvendo a tireoide.

influence of thyroid hormones on hemoglobin A2 and F expression

To evaluate the effect of thyroid hormones on the production of hemoglobin A2 and F [Hb A2 and F]. Sixty three patients were enrolled in this study including new cases of hyperthyroidism, hypothyroidism and thalassemia minor; 28 healthy subjects were used as control group. Assessment of Hb A2, Hb F levels as well as measurement of thyroid hormones were performed for each of them. Hb A2 was significantly higher in hyperthyroid patients than in control group [P=0.002], while Hb F was significantly higher in hypothyroid group in comparison with the control [P=0.012]. Hemoglobin A2 levels are increased in hyperthyroidism and decreased in hypothyroidism, unlike hemoglobin F. This may clarify the effect of thyroid hormones on globin chain synthesis

E449X mutation in the thyroid hormone receptor β associated with autoimmune thyroid disease and severe neuropsychomotor involvement / Mutação E449X no receptor β do hormônio tireoidiano associada com doença tireoidiana auto-imune e retardo neuropscicomotor grave

OBJECTIVE: To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation. METHODS: We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH. RESULTS: A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 µg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH. CONCLUSION: This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than β receptor of thyroid hormone (TRβ) might modulate the phenotype of RTH.

OBJETIVOS: Descrever aspectos clínicos e moleculares de um paciente com resistência ao hormônio tireoidiano (RHT) portador da mutação E449X associada a doença tireoideana auto-imune e retardo neuropscicomotor grave. MÉTODOS: Relatamos um caso incluindo achados clínicos, laboratoriais e análise molecular de um paciente brasileiro com RHT. RESULTADOS: Paciente masculino, 23 anos de idade, apresentou-se com distúrbio de hiperatividade, déficit de atenção, retardo no desenvolvimento neuropsicomotor e bócio. Desde 1 ano e 8 meses de idade, sua mãe procurou assistência médica para investigação do retardo do desenvolvimento neuropsicomotor associado com irritabilidade, agressividade, cefaléia recorrente, sudorese profusa, diarréia intermitente, polifagia, bócio e perda de peso. Avaliação laboratorial evidenciou TSH normal e aumento do T3, T4 e anticorpos antimicrossomal e antitireoglobulina. Doses crescentes de levotiroxina foram prescritas, máximo de 200 µg/dia, sem significativas alterações em seu quadro clínico-laboratorial. Doses crescentes de tiratricol foram introduzidas com melhora clínica evidente da agressividade, da hiperatividade, do tremor de extremidades e maior ganho de peso. O estudo molecular revelou uma mutação nonsense no éxon 10, no qual a substituição da guanina pela tirosina no nucleotídeo 1345 (códon 449) gerou um stop códon TAA, confirmando o diagnóstico da RHT. CONCLUSÃO: Este paciente tem um grave retardo neuropiscomotor não observado em um relato único anterior com a mesma mutação. Isto pode refletir a falta de relação genotipo-fenótipo nos casos afetados com esta síndrome sugerindo que a variabilidade genética de outros fatores, além do receptor do hormônio tireoidiano (HT), possa modular o fenótipo da RHT.

Tireóide e gravidez / Thyroid and pregnancy

A gravidez está associada com a necessidade aumentada de secreção hormonal pela tireóide desde as primeiras semanas após a concepção. Para que esta maior demanda ocorra, a gestação induz uma série de alterações fisiológicas que afetam a função tireoidiana e, portanto, os testes de avaliação da função glandular. Para as mulheres grávidas normais que vivem em áreas suficientes em iodo, este desafio em ajustar a liberação de hormônios tireoidianos para o novo estado de equilíbrio e manter até o término da gestação, geralmente, ocorre sem dificuldades. Entretanto, em mulheres com a capacidade funcional da tireóide prejudicada por alguma doença tireoidiana ou naquelas que residem em áreas de insuficiência iódica, isso não ocorre. O manejo de disfunções tireoidianas durante a gestação requer considerações especiais, pois tanto o hipotireoidismo quanto o hipertireoidismo podem levar a complicações maternas e fetais. Além disso, nódulos tireoidianos são detectados, com certa freqüência, em gestantes, o que pode gerar a necessidade do diagnóstico diferencial entre benignos e malignos ainda durante a gestação.

Pregnancy is associated with an increased requirement of hormone secretion by the thyroid, within the first weeks after conception. To this greater demand to occurs, pregnancy induces a series of physiological changes that affect thyroid function and, consequently, the tests of glandular function. For normal pregnant women living in areas with a sufficient supply of iodine, this challenge regarding the adjustment of thyroid hormone releases to this new state of equilibrium and its maintenance until the end of pregnancy it meets no difficulties. However, among women with impaired thyroid function due to some thyroid disease or among women residing in areas with an insufficient iodine supply, this does not occur. The management of thyroid dysfunction during gestation requires special considerations, since both hypothyroidism and hyperthyroidism can lead to maternal and fetal complications. In addition, thyroid nodules are detected at reasonable frequency among pregnant women, a fact that requires a differential diagnosis between benign and malignant growths during the pregnancy itself.