Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.

Reconhecimento da paralisia periódica hipocalêmica tireotóxica na emergência: relato de caso e revisão da literatura / Recognizing thyrotoxic hypokalemic periodic paralysis on emergency settings: a case report and literature revie

A paralisia periódica hipocalêmica tireotóxica é uma complicação inusitada do hipertireoidismo, porém é considerada urgência endocrinológica e ainda frequentemente subdiagnosticada. Sua apresentação clínica consiste na tríade de défice de potássio, tireotoxicose e fraqueza muscular ­ sendo esse último sintoma comum em diversas patologias. Realizamos uma revisão bibliográfica e destacamos, por meio do relato de caso, a importância do diagnóstico precoce dessa doença, possibilitando uma evolução favorável ao paciente, independente de sua etnia, sexo ou região geográfica. Atentamos ainda ao tratamento da doença, que, apesar de sua simplicidade, acarreta muitos equívocos.

The thyrotoxic hypokalemic periodic paralysis is a rare complication of hyperthyroidism, but is considered an endocrinological urgency, and yet frequently underdiagnosed. Its clinical presentation consists of potassium deficit, thyrotoxicosis, and muscular weakness, with the latter symptom being very common in several pathologies. We performed a bibliographic review and highlight, through a case report, the importance of the early diagnosis of this disease to allow favorable progression to the patient, regardless of ethnicity, sex, or geographical region. We also reinforce the importance of the disease treatment which, despite its simplicity, leads to many mistakes.

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats / Timoquinona protegeu contra deficiências de aprendizagem e memória e danos nos tecidos cerebrais em ratos hipotireoidais juvenis

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

Drug-induced hypothyroidism

The thyroid axis is particularly prone to interactions with a wide variety of drugs, whose list increases year by year. Hypothyroidism is the most frequent consequence of drug-induced thyroid dysfunction. The main mechanisms involved in the development of primary hypothyroidism are: inhibition of the synthesis and/or release of thyroid hormones, immune mechanisms related to the use of interferon and other cytokines, and the induction of thyroiditis associated with the use of tyrosine kinase inhibitors and drugs blocking the receptors for vascular endothelial growth factor. Central hypothyroidism may be induced by inhibition of thyroid-stimulating hormone (bexarotene or corticosteroids) or by immunological mechanisms (anti-CTLA4 or anti-PD-1 antibody drugs). It is also important to recognize those drugs that generate hypothyroidism by interaction in its treatment, either by reducing the absorption or by altering the transport and metabolism of levothyroxine. Thus, it is strongly recommended to evaluate thyroid function prior to the prescription of medications such as amiodarone, lithium, or interferon, and the new biological therapies that show important interaction with thyroid and endocrine function in general.

El eje tiroideo es particularmente proclive a sufrir interacciones con una amplia variedad de drogas, cuya lista se acrecienta año a año. El hipotiroidismo es la consecuencia más frecuente de disfunción tiroidea inducida por fármacos. Los principales mecanismos involucrados en el desarrollo de hipotiroidismo primario son: la inhibición de la síntesis y/o liberación de las hormonas tiroideas, mecanismos inmunes relacionados con el uso de interferón y otras citoquinas, y la inducción de tiroiditis asociada al uso de los inhibidores tirosina-kinasa y a drogas bloqueantes del receptor del factor de crecimiento del endotelio vascular. El hipotiroidismo central puede ser inducido por la inhibición de la tirotrofina (bexaroteno o corticoides) o por mecanismos inmunológicos (drogas anti-CTLA4 o anti PD-1). Es importante reconocer aquellas drogas que generan hipotiroidismo por interacción en su tratamiento, ya sea disminuyendo la absorción o alterando el transporte y metabolismo de la levotiroxina. Sería recomendable evaluar la función tiroidea previa a la prescripción de medicamentos como amiodarona, litio o interferón, y a las nuevas terapias biológicas que muestran importante interacción sobre la función tiroidea y endocrina en general.

Co-administration of Apelin and T4 Protects Inotropic and Chronotropic Changes Occurring in Hypothyroid Rats / Coadministração de Apelina e T4 tem Efeito Protetor nas Alterações Inotrópicas e Cronotrópicas que Ocorrem em Ratos Hipotireoideos

AbstractBackground:One of the most important thyroid hormone targets is the cardiovascular system. Hemodynamic changes, such as decreased resting heart rate (HR), myocardial contractility, and cardiac output, and increased diastolic pressure and systemic vascular resistance, have been observed in hypothyroid patients. Moreover, in these patients, ECG changes include sinus bradycardia and low voltage complexes (P waves or QRS complexes).Objective:This study aimed at evaluating the prophylactic effect of apelin on HR changes and QRS voltage that occur in propylthiouracil (PTU)-induced hypothyroid rats.Method:In this study, 48 adult male Wistar rats weighing 170-235g were randomly divided into 6 groups: Control group (normal saline ip injection + tap water gavage); P group (PTU 0.05%, in drinking water); A group (apelin 200 µg.kg-1.day-1, ip); PA group [co-administration of PTU and apelin]; PT group [co-administration of PTU + T4 (0.2 mg/g per day, gavage)]; and PAT group (co-administration of PTU, apelin and T4). All experiments were performed for 28 consecutive days, and then the animals were anesthetized with an ip injection of ketamine (80 mg/kg) and xylazine (12 mg/kg). Lead II electrocardiogram was recorded to calculate HR and QRS voltage.Results:Heart rate and QRS voltage increased more significantly in the hypothyroid group that consumed both apelin and T4 (201 ± 4 beat/min, 0.71 ± 0.02 mv vs. hypothyroid 145 ± 9 beat/min, 0.563 ± 0.015 mv; respectively).Conclusion:The co-administration of apelin and T4 showed a protective effect on QRS voltage and HR in PTU‑induced hypothyroid rats.

ResumoFundamento:O sistema cardiovascular é um dos alvos mais importantes dos hormônios tireoidianos. As seguintes alterações hemodinâmicas foram observadas em pacientes com hipotireoidismo: redução da frequência cardíaca (FC) de repouso, da contratilidade miocárdica e do débito cardíaco; e aumento da pressão diastólica e da resistência vascular sistêmica. Além disso, tais pacientes apresentam alterações eletrocardiográficas, como bradicardia sinusal e baixa voltagem dos complexos (ondas P e complexos QRS).Objetivo:Avaliar o efeito profilático da apelina nas alterações de FC e voltagem de QRS que ocorrem em ratos com hipotireoidismo induzido por propiltiouracil (PTU).Método:Este estudo dividiu de maneira aleatória 48 ratos Wistar machos adultos, pesando 170-235g, em seis grupos: grupo controle (CO), injeção intraperitoneal (ip) de solução salina + água potável gavagem; grupo hipotireoideo (P), PTU 0,05% em água potável; grupo A, apelina ip (200 µg.kg-1.dia-1); grupo PA, coadministração de PTU e apelina; grupo PT, coadministração de PTU e T4, 0.2 mg/g por dia por gavagem; e grupo PAT, coadministração de PTU, apelina e T4. Todos os experimentos foram realizados durante 28 dias consecutivos, sendo então os animais anestesiados com injeção ip de cetamina (80 mg/kg) e xilazina (12 mg/kg). Utilizou-se o registro do ECG na derivação DII para calcular a FC e a voltagem do QRS.Resultados:Houve aumento mais significativo da FC e da voltagem do QRS no grupo hipotireoideo que recebeu apelina e T4 (201±4 bpm, 0,71±0,02mV) do que no hipotireoideo (145±9 bpm, 0,563±0,015 mV), respectivamente.Conclusão:A coadministração de apelina e T4 mostrou efeito protetor na voltagem do QRS e FC em ratos com hipotireoidismo induzido por PTU.

The thyroid hormone receptor β-selective agonist GC-1 does not affect tolerance to exercise in hypothyroid rats

Objective Investigate the effect of GC-1 on tolerance to exercise in rats with experimental hypothyroidism. Materials and methods Hypothyroidism was induced with methimazole sodium and perchlorate treatment. Six groups with eight animals were studied: control group (C), hypothyroid group without treatment (HYPO); hypothyroidism treated with physiological doses of tetraiodothyronine (T4) or 10 times higher (10×T4); hypothyroidism treated with equal molar doses of GC-1 (GC-1) or 10 times higher (10×GC-1). After eight weeks, each animal underwent an exercise tolerance test by measuring the time (seconds), in which the rats were swimming with a load attached to their tails without being submerging for more than 10 sec. After the test, the animals were killed, and blood samples were collected for biochemical analysis, and the heart and soleus muscle were removed for weighing and morphometric analysis of the cardiomyocyte. Results Hypothyroidism significantly reduced tolerance to exercise and, treatment with GC-1 1× or T4 in physiological doses recover tolerance test to normal parameters. However, high doses of T4 also decreased tolerance to physical exercise. Conversely, ten times higher doses of GC-1 did not impair tolerance to exercise. Interestingly, hypothyroidism, treated or not with T4 in a physiological range, GC-1 or even high doses of GC-1 (10X) did not change cardiomyocyte diameters and relative weight of the soleus muscle. In contrast, higher doses of T4 significantly increased cardiomyocyte diameter and induced atrophy of the soleus muscle. Conclusion Unlike T4, GC-1 in high doses did not modify tolerance to physical exercise in the rats with hypothyroidism. .

Association between antiretrovirals and thyroid diseases: a cross-sectional study

Objective This study aims to estimate the prevalence of thyroid diseases and anti-TPO status. We searched for an association among presence of immune reconstitution and use of stavudine, didanosine and protease inhibitors with thyroid diseases. Materials and methods A cross-sectional study was performed to analyze the records of 117 HIV-infected patients who had their CD4+ cell count, viral load, anti-TPO, TSH and free T4 levels collected on the same day. Immune reconstitution was considered in those whose T CD4+ count was below 200 cells/mm3, but these values increased above 200 cells/mm3 after the use of antiretrovirals. The odds ratio obtained by a 2x2 contingency table and a chi-square test were used to measure the association between categorical variables. Results The prevalence of thyroid disease was 34.18%; of these, 4.34% were positive for anti-TPO. There was an association of risk between stavudine use and subclinical hypothyroidism (OR = 4.19, 95% CI: 1.29 to 13.59, X2 = 6.37, p = 0.01). Immune reconstitution achieved protection associated with thyroid disease that was near statistical significance OR = 0.45, 95% CI: 0.19 to 1.04, X2 = 3.55, p = 0.059. Conclusion The prevalence of thyroid disease in the sample studied was higher than what had been found in the literature, with a low positive anti-TPO frequency. The historical use of stavudine has an association of risk for the presence of subclinical hypothyroidism, and immune reconstitution has trends towards protection for the presence of thyroid diseases. .

Fármacos de amplo uso na prática clínica que interagem com os hormônios tireoidianos / Widely used drugs in clinical practice that interact with thyroid hormones

Vários fármacos de amplo uso na prática clínica interagem com os hormônios tireoidianos, alterando a função da tireoide. Boa parte dos pacientes submetidos à avaliação da tireoide faz uso de diversos fármacos, sendo importante saber quais são as interações. O objetivo deste estudo foi rever, na literatura, os principais medicamentos amplamente utilizados na prática clínica que interagem com os hormônios tireoidianos. A produção desses hormônios ocorre por meio de diversos mecanismos, que podem interagir com várias drogas, resultando em disfunção tireoidiana. Alguns fármacos podem causar tanto tireotoxicose, como hipotireoidismo; é o caso do iodo, da amiodarona e da interleucina-2. A radiação ionizante pode produzir tireoidite aguda, crônica e câncer de tireoide. O carbonato de lítio inibe a secreção dos hormônios tireoidianos, estimulando o hormôniotireo estimulante e levando à formação de bócio. A quimioterapia citotóxica pode causar alterações no hipotálamo, na hipófise e na tireoide. Os glicocorticoides apresentam efeitos variáveis e múltiplos. Alguns fármacos afetam as proteínas transportadoras de hormônios tireoidianos, como os salicilatos, a heparina e o estrogênio. Anticonvulsivantes atuam sobre os hormônios tireoidianos, interferindo na ligação com proteínas transportadoras e acelerando o metabolismo hepático. A dopamina inibe diretamente a secreção do TSH. O propranolol tem efeito discreto, relacionado a doses >160mg/dia.O conhecimento sobre as interações permite identificar uma droga como causa de disfunção da tireóide, a execução de testes de triagem em indivíduos expostos a elas e evitar seu uso em pacientes com risco de desenvolver doenças da tireóide...

Many drugs of wide use in clinical practice interact with thyroid hormones, changing thyroid function. Much of the patients that have their thyroid studied make use of multiple medications, being important to know which the interactionsare. The aim of this study was to review in the literature the main drugs widely used in clinical practice that interacts with thyroid hormones. The production of these hormones occurs through several mechanisms which may interact with various drugs, causing thyroid dysfunction. Some medicines cancause both thyrotoxicosis and hypothyroidism, such as iodine, amiodarone and interleukin-2. Ionizing radiation may produce acute thyroiditis, chronic thyroiditis and thyroid cancer. Lithium carbonate inhibits the secretion of thyroid hormones, stimulating TSH, leading to the formation of goiter. Cytotoxic chemotherapy can cause changes in the hypothalamus, pituitary and thyroid. Glucocorticoids have multiple and variables effects. Some drugs affect thyroid hormones transporter proteins, such assalicylates, heparin and estrogen. Anticonvulsants have effect on thyroid hormones, interfering with protein binding carriers and accelerating hepatic metabolism. Dopamine inhibits directly the secretion of TSH. Propranolol has slight effect, related to doses>160mg/day. The knowledge about the interactions allows to identify a drug as a cause of thyroid dysfunction, the execution of screening tests in individuals exposed to them and avoid its use in patients with risk of developing thyroid disease...

Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon and ribavirin treatment for chronic hepatitis C: case report and literature review

Pegylated interferon alpha (Peg IFN-α) in combination with ribavirin is the backbone of treatment in chronic hepatitis C (CHC). Cardiotoxicity due to interferon therapy is rare. The most frequent cardiovascular complications are arrhythmias and ischemic manifestations. Cardiomyopathy is extremely rare but can be life threatening. We present the case of a 41-year-old female patient with CHC in whom Peg IFN-α induced dilated cardiomyopathy and hypothyroidism. Chest radiography showed an enlarged and globular cardiac silhouette and pulmonary congestion. Echocardiography showed decreased left ventricular systolic function with an ejection fraction of 32% and fractional shortening of 15%. Cardiomyopathy had a complete remission after cessation of antiviral therapy with short-term heart failure medications and supportive care. Then we review the current literature about interferon induced cardiomyopathy in patients with HCV infection, as well as share our clinical experience in diagnosing and managing this rare complication.

Avaliação histológica do reparo de defeitos ósseos de tamanhos críticos tratados com enxerto xenógeno em ratos induzidos ao hipotireoidismo / Histological evaluation of critical size bone repair treated with xenogen graft in rats induced to hypothyroidism

O objetivo do presente trabalho foi avaliar o reparo de defeitos de tamanho crítico comparando animais saudáveis, com hipotireoidismo e com ou sem enxerto ósseo (Bio-Oss Geistlich Pharma AG, Wolhusen, Suíça), e em dois tempos de morte (30 e 60 dias). Foram utilizados 42 animais da linhagem Wistar, distribuídos em dois grupos: Grupo 1 Eutireoideo, sem enxerto 30 dias (G1E30); Eutireoideo, sem enxerto 60 dias (G1E60); Hipotireoidiano, sem enxerto 30 dias (G1H30); e Hipotireoidiano, sem enxerto 60 dias (G1H60); e Grupo 2 Eutireoideo, com enxerto 30 dias (G2E30); Eutireoideo, com enxerto 60 dias (G2E60); Hipotireoidiano, com enxerto 30 dias (G2H30) e Hipotireoidiano, com enxerto 60 dias (G2H60). Os animais com hipotireoidismo foram induzidos por meio da diluição do propiltiouracil (PTU) na água de beber dos ratos. Foram confeccionados defeitos de tamanho crítico por meio de brocas trefinas na calvária desses animais, e posterior tratamento para confecção de lâminas, avaliação histológica e testes estatísticos. Um intervalo de confiança de 95% (p < 0,05) foi empregado. Os resultados encontrados revelaram que não houve diferença estatisticamente significativa no reparo cortical entre os animais hipotireoidianos e eutireoidianos nos dois tempos propostos, entretanto, foram encontradas diferenças estatisticamente significativas nos cruzamentos de 30 x 60 dias (G1E60 > G1E30; p = 0,01, G1H60 > G1H30; e p = 0,01, G2h60 > G2H30). A formação ao redor da partícula do enxerto não foi estatisticamente diferente na avaliação dentro do mesmo tempo de morte, contudo os animais com hipotireoidismo apresentaram uma formação associada à partícula estatisticamente maior ao final de 60 dias de reparo (G2H60 > G2H30 p=0,03). Diante dos achados, pode-se concluir que a condição sistêmica de hipotireoidismo pareceu não influir de forma significativa no reparo ósseo, e o enxerto pareceu contribuir de uma forma mais positiva para a formação óssea

The objective of this study was to evaluate the repair of critical-size defects by comparing normal animals, with hypothyroidism, with or without bone graft (Bio-Oss R GeistlichPharma AG, Wolhusen, Switzerland) and two times of death (30 and 60 days). It was used 42 Wistar animals, divided into two major groups namely: Group 1 Euthyroid without graft 30 days (G1E30) Euthyroid without graft 60 days (G1E60), hypothyroid, without graft 30 days (G1H30) and hypothyroid, 60 days without graft (G1H60) and Group 2 Euthyroid, graft 30 days (G2E30) Euthyroid, graft 60 days (G2E60), hypothyroid, graft 30 days (G2H30) and hypothyroid, graft 60 days (G2H60) . The animals were induced with hypothyroidism by dilution of propylthiouracil (OCT) in the drinking water of mice. Were prepared by critical-size defects in calvaria of drills you train these animals and subsequent treatment for the manufacture of blades, histological and statistical tests. A confidence interval of 95% (ñ <0.05) was employed. The results showed that there was no statistically significant difference in cortical repair between euthyroid and hypothyroid animals in the proposed two-stroke, however statistically significant differences were found at intersections 30x60 days (G1E60> G1E30, p = 0.01 G1H60> G1H30 and p = 0.01 G2h60> G2H30). The formation around the graft particles was not statistically different in the evaluation within the same time of death, but the animals with hypothyroidism had a particle formation associated with statistically higher at 60 days of repair (G2H60> G2H30 p = 0.03) Given the findings we can conclude that thesystemic condition did not appear to significantly affect bone healing, but the graft seemed to contribute to a more positive for bone formation in animals induced with the disorder

Disfunção tiróidea e amiodarona / Thyroid dysfunction and amiodarone

Apesar de a maioria dos doentes tratados com amiodarona permanecer em eutiroidia, alguns desenvolvem hipertiroidismo (HPEIA) ou hipotiroidismo (HPOIA) induzidos pela amiodarona. Os autores apresentam uma análise retrospectiva dos processos de dez doentes com disfunção tiróidea induzida pela amiodarona. Verificou-se que seis doentes eram mulheres e que o tempo médio de toma da amiodarona foi de 17,7 meses. O HPOIA foi o mais frequente (seis doentes). Dos doentes com HPEIA, dois tinham HPEIA tipo 2, um tipo 1 e um tipo 3. Sintomas sugestivos de disfunção tiróidea ocorreram em cinco doentes, a maioria com HPOIA. No HPEIA, a clínica mais comum foi exacerbação da arritmia de base (três doentes). A interrupção da amiodarona e administração de levotiroxina foi a terapêutica escolhida em 83,3% dos casos de HPOIA, enquanto a tionamida associada a corticoide com suspensão da amiodarona foi opção em 75% dos casos de HPEIA. Registraram-se três óbitos, todos com HPEIA. O HPEIA constituiu uma complicação potencialmente fatal. A clínica pode ser vaga, pelo que a monitorização da função tiróidea é obrigatória.

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

A Case of Simultaneously Occurred Amiodarone-induced Hepatitis and Hypothyroidism / 대한소화기학회지

Amiodarone is a di-iodated benzofuran derivative that is commonly used to treat patients with various cardiac arrhythmias. It is associated with side effects that involve the liver, thyroid, and other organs. Approximately 1-3% of patients treated with amiodarone suffer from symptomatic liver disease. Thyroid dysfunction occurs in 10% of patients treated with amiodarone. A 65-year-old woman with coronary heart disease and atrial fibrillation was administered with amiodarone. She developed nausea, vomiting, dyspepsia, and sweating within 9 months of amiodarone administration (200 mg orally once a day). Results of the laboratory finding showed increased hepatic enzymes, and low thyroid hormone levels. A liver biopsy showed irregular arrangement of hepatocytes and diffuse micro- and macrovesicular fatty changes. Electron microscopy findings showed pleomorphic mitochondria with crystalloid inclusions and membrane-bound lysosomal structures. The liver and thyroid functions returned to normal, after the amiodarone was stopped. We describe an unusual case in which amiodarone induced hepatitis and hypothyroidism simultaneously. Physicians should take a close look to the adverse event when using amiodarone which can cause adverse effects in multiple organs.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32 percent) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C

OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82 percent (n = 20); 6.14 percent hypothyroidism; 0.68 percent hyperthyroidism. TPOAb was present in 5.46 percent of euthyroid patients. Out of 273 euthyroid patients at baseline, 19 percent developed TD: 17.2 percent hypothyroidism; 1.8 percent hyperthyroidism; 5.1 percent destructive thyroiditis (DT). 90 percent of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5 percent of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2 percent of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95 percent CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95 percent CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34 percent of TD was transient.

Evaluación de la función tiroídea en pacientes pediátricos durante el uso de fármacos antiepilépticos / Assessment of thyroid in pediatric patients during the use of antiepileptic drugs

El objetivo principal de este trabajo es evaluar las alteraciones en la función tiroídea de pacientes pediátricos con epilepsia en tratamiento con fármacos antiepilépticos (FAEs). Un segundo objetivo es evaluar la severidad y manifestaciones clínicas de estas alteraciones y los FAEs asociados a ellas. Se revisó las historias clínicas de pacientes de 0-18 años, en control por epilepsia, pertenecientes a la unidad de Neuropsiquiatría Infantil del Hospital Dr. Lautaro Navarro Avaria de Punta Arenas, durante el periodo comprendido entre julio del 2008 y junio del 2009. Criterios de inclusión: estar en tratamiento con FAEs y tener registro de evaluación de función tiroídea en su ficha clínica. De los 59 pacientes que cumplieron con los criterios de inclusión, 21 tenían niveles de hormona tiro-estimulante (TSH) elevados, seis de ellos presentaron manifestaciones clínicas de hipotiroidismo. La mayoría presentó hipotiroidismo subclínico y recibía tratamiento con ácido valproico (VPA) como monoterapia. Es por esto y considerando que el desarrollo cerebral de los niños es altamente sensible a los niveles de tiroxina, parece fundamental el monitoreo de la función tiroídea en niños y adolescentes en tratamiento con FAES.

Our aim was to evaluate severity and clinical manifestations of thyroid function abnormalities in pediatric epileptic patients in therapy with antiepileptic drugs (AED). Medical histories of patients attending to the Pediatric Neuropsychiatric Unit of Dr. Lautaro Navarro Avaria Hospital, Punta Arenas were reviewed. Fifty nine epileptic patients aged between 0-18 years, on AED therapy between July 2008 and June 2009, with evaluation of thyroid function were included. Thyroid-stimulating hormone (TSH) serum levels were high in 21 of the 59 patients, six of them showed clinical signs of hypothyroidism. Most of them exhibited TSH values in the subclinical hypothyroidism range and were on valproic acid (VPA) monotherapy. Considering that children’s brain development is highly sensitive to thyroxine levels, we emphasize the relevance of monitoring thyroid function in children and adolescents receiving antiepileptic treatment.

Disfunción tiroidea inducida por amiodarona en la práctica clínica: [revisión] / Thyroid dysfunction induced by amiodarone in clinical practice: [review]

La amiodarona (AMD) es una droga antiarrítmica potente (clase III) usada en la práctica clínica para la profilaxis y el tratamiento de muchos disturbios del ritmo cardiaco, desde la fibrilación auricular paroxística hasta las taquiarritmias ventriculares que amenazan la vida. Frecuentemente causa cambios en las pruebas de función tiroidea principalmente relacionados a la inhibición de la actividad de la 5'-deiodinasa, resultando en una disminución de la generación de T3 desde T4 y el consecuente incremento en la producción de T3 reversa y una disminución de su aclaramiento. En 14 a 18 por ciento de pacientes tratados con AMD hay una disfunción tiroidea manifiesta, ya sea tirotoxicosis inducida por amiodarona (TIA) o hipotiroidismo inducido por amiodarona (HIA). Tanto TIA como HIA pueden desarrollarse en glándulas aparentemente normales o en glándulas con anormalidades preexistentes clínicamente silentes. La TIA está primariamente relacionada a la síntesis de hormonas tiroideas inducida por el exceso de yodo en una glándula tiroidea anormal (TIA tipo 1) o a una tiroiditis destructiva relacionada a la amiodarona (TIA tipo 2), aunque frecuentemente ocurren formas mixtas. La tiroiditis de Hashimoto preexistente es un factor de riesgo definido para la ocurrencia de HIA. La patogenia del HIA es la falla para escapar del efecto agudo de Wolff-Chaikoff inducido por el yodo, debido a los defectos en la hormonogénesis tiroidea y, en pacientes con pruebas de autoanticuerpos tiroideos positivos, para tiroiditis de Hashimoto concomitante. La TIA es más común en zonas deficientes de yodo mientras que el HIA es usualmente visto en zonas suficientes en yodo. En contraste al HIA, la TIA es una condición difícil de diagnosticar y tratar, y usualmente se recomienda la descontinuación de la amiodarona. En esta revisión se analiza, de acuerdo a los datos actuales, las alteraciones en las pruebas de función tiroidea vistas en pacientes eutirodeos bajo tratamiento con AMD así como la epidemiología y opciones de tratamiento disponibles para ambos tipo de disfunción tiroidea inducida por amiodarona, TIA e HIA.

Amiodarone is a potent class III anti-arrhythmic drug used in clinical practice for the prophylaxis and treatment of many cardiac rhythm disturbances, ranging from paroxismal atrial fibrillation to life threatening ventricular tachyarrhythmias. Amiodarone often causes changes in thyroid function tests mainly related to inhibition of 5'-deiodinase activity resulting in decrease in the generation of T3 from T4 with consequent increase in rT3 production and decrease in its clearance. In 14-18 per cent of amiodarone-treated patients, there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting clinically silent abnormalities. AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT). AIH pathogenesis is related to escape failure from the acute Wolff-Chaikoff effect due to defects in thyroid hormonogenesis or, in patients with positive thyroid autoantibody test, to concomitant Hashimoto's thyroiditis. AIT is more common in iodine-deficient regions of the world, whereas AIH is usually seen in iodine-sufficient areas. In contrast to AIH, AIT is a condition difficult to diagnose and treat, and discontinuation of amiodarone is usually recommended. In this review discusses, according to data from current literature, alterations in thyroid laboratory tests seen in euthyroid patients under treatment with amiodarone and the epidemiology and treatment options available of amiodarone-induced thyroid dysfunctions (AIT and AIH).

Detección de hipotiroidismo en un programa de atención de VIH/SIDA en un hospital de Bogotá, Colombia / Mass screening for hypothyroidism in a cohort of HIV infected patients in a Bogotá hospital, Colombia

Objetivos: Evaluar la frecuencia de alteración tiroidea y los factores asociados en los pacientes con VIH/SIDA de un hospital universitario en Colombia. Pacientes y Métodos: Estudio tipo corte transversal de pacientes con VIH/SIDA durante el periodo de 2007 a 2008. Se registró niveles hormonales, inmunológicos, carga viral y tratamiento anti-retroviral. Resultados: En 636 pacientes la prevalencia de hipotiroidismo (TSH > 4,6 μUI/mL) fue de 15,5 por ciento (100/636). El análisis independiente demostró relación significativa para el uso de nevirapina (RR 1,6; IC 95 por ciento 1,1 - 2,3) y estavudina (RR 1,5; IC 95 por cientoo 1 - 2,3). Conclusiones: La prevalencia de hipotiroidismo fue alta y se relacionó con el uso de nevirapina.

Introduction: The objective of this study was to evaluate the frequency of thyroid function alterations and its associated factors in a group of patients from a university hospital in Colombia. Methods: From June 2007 through June 2008, 636 HIV patients were followed in order to assess the relation of thyroid function with the use of HAART. Results: The overall prevalence of hypothyroidism (TSH > 4.6 μUI/mL) was 15.5 percent (100/636). The association of hypothyroidism in the independent analysis showed significant relation only for the use of nevirapine (RR 1.6; CI 95 percent 1.1- 2.34) and stavudine (RR 1.5; CI 95 percent, 1 - 2.3). Conclusions: The prevalence of hypothyroidism was surprisingly high among the studied population.

Propylthiouracil-induced hypothyroidism delays apoptosis during the first wave of spermatogenesis

Mammalian germ cell apoptosis plays a key role in controlling the correct number of germ cells supported by Sertoli cells during the first wave of spermatogenesis in mammalian puberty. However, little is known about hormonal factors that could influence the rate of germ cell apoptosis during puberty or adulthood. In this work we evaluate germ cell apoptosis under hypothyroidism induced by goitrogen propylthiouracil (PTU) during the first wave of spermatogenesis. Neonatally administered PTU promoted a delay in the differentiation of Sertoli cells as evaluated by the expression of clusterin using immunohistochemistry and RT-PCR. Clusterin had different expression levels in control and PTU-treated animals, but under both conditions the highest levels were found in 35-day-old rats. In addition, clusterin displayed a cytoplasmic localization in control testes, but appeared located in the nucleus in PTU-treated animals. The wave of apoptosis (determined by caspase activity and quantification of apoptotic cells) characteristic of the first round of spermatogenesis was delayed by at least 10 days in these animals. The expression levels of proapoptotic genes like BAX or BAD were different between control and PTU-treated rats; although in both groups the highest level was found at the same age (days). Thus our results indicate that the characteristic pubertal apoptotic wave during rat spermatogenesis is delayed in neonatal hypothyroid rats.

[Effect of long-term continuous methimazole treatment of thyrotoxicosis: comparison with radioiodine]

The major complication of radioiodine therapy for thyrotoxicosis is hypothyroidism, the long-term management of which is often problematic. In this study, the long-term effects of continuous methimazole [MMI] therapy are investigated. One hundred and thirty-two patients, aged between 36-66 years, with Graves recurrence, were semi randomly randomized in 2 groups for continuous antithyroid and radioiodine treatment. The number of thyroid dysfunctions in each patient were recorded and serum TSH, FT4, Anti TPO, TRAb, FBS, HOMA IR, and lipid profiles were measured. Bone mineral density and echocardiography were performed. There was no significant differences in age, duration of symptoms and thyroid function between the 2 groups. No serious complications occurred in the MMI group and no difference in any of parameters was seen between groups 1 and 2. Goiter rate and anti TPO concentration were higher in group 1 than in group 2. Serum triglycerides and cholesterol were increased in group 2 as compared to group 1. Bone mineral density was more reduced in group 2, especially in the spine. Echocardiography showed diastolic dysfunction in group 2 as compared to group 1. Some parameters in neuro-pschyciatric evaluation were significantly better in the MMI group, as compared to the radioiodine one. Considering it is a safe treatment and has fewer complications, methimazole is another option for patients with recurrent Graves', who do not wish to use radioiodine