Medical treatment in pregnant women with subclinical hypothyroidism: systematic review and meta-analysis / Tratamiento médico en gestantes con hipotiroidismo subclínico: revisión sistemática y meta-análisis

Abstract Objectives: to determine the effectiveness of medical therapy in reducing complications associated with subclinical hypothyroidism during pregnancy. Methods: in 2021, a systematic review of available cohort studies was carried out in three databases, with no publication date limit. Study selection and data extraction were performed in duplicate. Random-effects meta-analysis was performed, and odds ratios were calculated, with the corresponding 95% confidence intervals. Cohort risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The certainty of the evidence was assessed using the GRADE methodology. Results: five studies were included for qualitative and quantitative synthesis. A statistically significant relationship was found between medical treatment in pregnant women with subclinical hypothyroidism with respect to spontaneous abortion (p=0.03; OR=0.77; CI95%=0.61-0.97), and no statistically significant relationship was found for delivery preterm (p=0.46; OR=1.11; CI95%=0.85-1.44), nor for abrupt placentae (p=0.56; OR=1.60; CI95%=0.33-7.66). Three studies were at moderate risk of bias, and two were at low risk of bias. In all the results the certainty was very low. Conclusions: medical treatment of subclinical hypothyroidism during pregnancy can have a beneficial effect in reducing cases of spontaneous abortion.

Resumo Objetivos: determinar la efectividad de la terapia médica para disminuir las complicaciones asociadas al hipotiroidismo subclínico durante la gestación. Métodos: en el 2021 se realizó una revisión sistemática de estudios de cohortes disponibles en tres bases de datos, sin límite de fecha de publicación. La selección de estudios y extracción de datos se realizaron por duplicado. Se realizó metaanálisis de efectos aleatorios y se calcularon los Odds ratio, con los correspondientes intervalos de confanza al 95%. El riesgo de sesgo de las cohortes se evaluó mediante la escala de Newcastle-Ottawa (NOS). La certeza de la evidencia se evaluó con la metodología GRADE. Resultados: cinco estudios fueron incluidos para síntesis cualitativa y cuantitativa. Se encontró una relación estadísticamente significativa del tratamiento médico en gestantes con hipotiroidismo subclínico con respecto al aborto espontáneo (p=0,03; OR=0,77; IC95%=0,61-0.97), no se encontró relación estadísticamente significativa para parto pre término (p=0.46; OR=1,11; IC95%=0.85-1.44), ni para abrupto placentae (p=0.56; OR=1,60; IC95%=0.33-7.66). Tres estudios tenían riesgo moderado de sesgo, y dos tenían riesgo de sesgo bajo. En todos los resultados la certeza fue muy baja. Conclusiones: el tratamiento médico del hipotiroidismo subclínico durante la gestación puede tener un efecto beneficioso para reducir los casos de aborto espontaneo.

Urgencias endocrinológicas: coma mixedematoso / Endocrine emergencies: myxedema coma

Introducción: en el presente reporte de caso se presenta una urgencia endocrinológica, el coma mixedematoso. Se considera una descompensación del hipotiroidismo y su mortalidad es alta alcanzando hasta 52% en algunas series de casos. Puede desencadenarse por múltiples factores y su presentación clínica es muy variada ya que comprende la afección de diversos sistemas. Presentación del caso: se presenta el caso de una paciente femenina de 42 años de edad que consultó al servicio de urgencias del Hospital de San José de Bogotá con sospecha inicial de una de falla cardiaca descompensada, sin embargo, cursó con pobre mejoría ante el manejo instaurado, por lo cual se realizaron estudios de extensión en donde se encontró una función tiroidea deprimida. Discusión y conclusiones: en este momento se consideró que la paciente padecía un coma mixedematoso, se instauró manejo con dosis altas de levotiroxina oral con lo cual evolucionó de manera favorable y se logró dar de alta a los pocos días.

Introduction: herein we present an endocrine emergency, myxedema coma, which is a form of decompensated hypothyroidism, whose mortality may be as high as 52% as evidenced in some case series. It may be triggered by multiplefactors and has varied clinical presentations for it affects diverse organ systems. Case presentation:we present the case of a 42-year-old female who presented to the emergency department of Hospital de San José in Bogotá with clinical suspicion of decompensated heart failure upon admission, however, her response was poor to the treatment she received. Extension studies were performed which showed low thyroid function. Discussion and conclusions: at this point the patient was diagnosed with myxedema coma, and was started on high doses of oral levothyroxine, with which she evolved favorably and was discharged a few days later.

A suggested screening method for hypothyroidism in very preterm and/or very low birth weight neonates / Método de triagem para hipotireoidismo sugerido em recém-nascidos muito prematuros ou de muito baixo peso

ABSTRACT Objective: To assess thyroid function in very preterm or very low birth weight (VLBW) neonates by measuring combination levels of thyroid-stimulating hormone TSH and free T4 (FT4) Methods: Inclusion criteria were defined as all very preterm (gestational age <32 weeks) or VLBW (birth weight ≤1500g) neonates with initial Thyroid Function Test (TFT) who were admitted to the Neonatal Intense Care Unit (NICU) of Taleghani Hospital, Tabriz, Iran, from March 2015 to March 2016. Exclusion criteria were the absence of initial TFT with any major congenital anomaly. The primary value of TSH was evaluated at 3-5 days, and mean levels of TSH with FT4 were measured at 2, 4, and 8-weeks. Results: Ninety-five neonates with a mean gestational age of 29.5 weeks were included, and the mean levels of thyrotropin and FT4 at postnatal week two were 4.4mIU/L and 1.4ng/dL, respectively. Two of the patients had serum TSH concentration >25mIU/L that was considered as permanent primary hypothyroidism. Among nine hypothyroxinemia cases, two had elevated TSH levels (10.8±0.4mIU/L at the end of 8 weeks) and normal FT4 concentration, and were considered transient hypothyroidism. Seven cases had normal TSH levels (1.6±1.0mIU/L at 2 weeks, 3.5±2.8mIU/L at 8 weeks) and low FT4 concentrations. Conclusions: Combined venous TSH and FT4 concentration at the end of the first postnatal month can be an efficient approach for detecting neonatal hypothyroidism.

RESUMO Objetivo: Avaliar a função da tireoide em recém-nascidos muito prematuros ou de muito baixo peso por meio dos níveis de combinação de TSH e T4 livre (FT4). Métodos: Os critérios de inclusão foram: todos os recém-nascidos muito prematuros (idade gestacional <32 semanas) ou de muito baixo peso (peso ao nascer ≤500g) com teste de função tireoidiana inicial e que foram admitidos na Unidade de Terapia Intensiva Neonatal do Hospital de Taleghani, Tabriz, Irã, de março de 2015 a março de 2016. Os critérios de exclusão foram: ausência de TFT inicial com qualquer anomalia congênita importante. Resultados: 95 neonatos com idade gestacional média de 29.5 semanas foram incluídos, e os níveis médios de tireotropina e FT4 na 2ª semana pós-natal foram 4.4mIU/L e 1.4ng/dL, respectivamente. Dois dos pacientes apresentavam concentração sérica de TSH >25mIU/L, considerada hipotireoidismo primário permanente. Entre nove casos de hipotiroxinemia, dois tinham níveis elevados de TSH (10.8±0.4mIU/L ao final de 8 semanas) e concentração normal de FT4 e foram considerados hipotireoidismo transitório. Sete casos tinham níveis normais de TSH (1,6±1,0mIU/L em 2 semanas, 3,5±2,8mIU/L em 8 semanas) e baixas concentrações de FT4. Conclusões: A concentração combinada de TSH e FT4 venoso no final do primeiro mês pós-natal pode ser uma abordagem eficiente para detectar hipotireoidismo neonatal.

Doença de Graves e sua recidiva: relato de caso / Grave's disease and its relapse: case repor

A doença de Graves (DG) é uma patologia autoimune que acomete a glândula tireoide e é a causa mais comum de hipertireoidismo. O principal grupo acometido por DG são as mulheres. Sendo assim, relatamos caso de paciente com 52 anos, do sexo feminino, com diagnóstico de Doença de Graves, que caracteriza quadro de hipertireoidismo. A paciente iniciou tratamento com tapazol (tiamazol) durante um ano e realizou pausa, recomendada pelo médico. No entanto, a paciente não retratou melhora e iniciou sintomatologia semelhante a dengue, como mal estar geral e fadiga muscular. Assim, realizou procura médica, e, inicialmente, foi diagnosticada com quadro de dengue, mas não houve melhora dos sintomas e procurou, portanto, endocrinologista. Realizou novos exames e foi confirmado quadro recidivo de Doença de Graves. Dessa maneira, iniciou novo tratamento. O estudo tem como objetivo relatar e discutir quadro de Doença de Graves associada a hipertireoidismo

Grave's disease (DG) is an autoimmune pathology that affects the thyroid gland and it's the most commom cause of hipertireoidism. The main group affected by DG are woman. That way we related a case of patient with 52 years, female with the diagnose of Grave's disease, that shows a patient conditioning of hipertireoidism. The patient began the treatment with tapazol during a year and made a pause recommended by the doctor. Therefore the patient didn't indicate progress and started a symptomatology similar to dengue fever, as general malaise and muscle fatigue. There by the patient searched for a doctor and initially was diagnosed with a patient conditioning of dengue fever, but she didn't manifested a improving of symptoms, and then searched for an endocrinologist. Realized then new exams and a recurrence case of grave´s disease was confirmed. This way the patient started a new treatment. Thus, the present study aims to report and discuss Graves' disease associated with hyperthyroidism.

Hiperplasia de hipófise secundária a hipotireoidismo primário - relato de caso / Pituitary hyperplasia secondary to primary hypothyroidism - case report

A hiperplasia hipofisária é definida como um aumento não neoplásico no número de um dos tipos de células presentes na hipófise. Ela pode ocorrer por um processo fisiológico ou patológico. O hipotireoidismo primário prolongado é uma das causas patológicas desta condição, e ocorre devido a perda do feedback negativo. O objetivo desse relato foi demonstrar a presença de hiperplasia hipofisária em um paciente masculino com características corporais sugestivas de acromegalia. A investigação laboratorial confirmou a presença de hipotireoidismo primário e descartou a acromegalia. Foi instituído tratamento com levotiroxina, levando a regressão da hiperplasia hipofisária. Esse caso ilustra a importância de uma investigação apropriada em pacientes com hiperplasia hipofisária, bem como discute a fisiopatologia e o tratamento dessa doença.

Pituitary hyperplasia is defined as a non-neoplastic increase in the number of one of the cell types present in the pituitary gland. It can occur by a physiological or pathological process. Prolonged primary hypothyroidism is one of the pathological causes of this condition and occurs due to the lack of negative feedback. The objective of this report was to demonstrate the presence of pituitary hyperplasia in a male patient with body characteristics suggestive of acromegaly. Laboratory investigation confirmed the presence of primary hypothyroidism and ruled out acromegaly. Treatment with levothyroxine was instituted, leading to regression of pituitary hyperplasia. This case illustrates the importance of an appropriate investigation in patients with pituitary hyperplasia, as well as discussing the pathophysiology and treatment of this disease.

¿El tratamiento del hipotiroidismo subclínico tiene efecto sobre la morbimortalidad cardiovascular? / Does treatment of subclinical hypothyroidism have an effect on cardiovascular morbidity and mortality?

Un estudio mostró que el aumento de valores de la hormona estimulante de la tiroides se asoció a un aumento de mortalidad por todas las causas, estimando que las enfermedades cardiovasculares mediaban dicha asociación en aproximada-mente el 14 % de los casos. Asimismo se observó que el reemplazo con levotiroxina disminuiría los niveles de colesterol, lo cual podría tener un efecto en la reducción de enfermedades cardiovasculares. Partiendo de una viñeta clínica la autora intenta, a través de una búsqueda bibliográfica y análisis de la evidencia, determinar si el tratamiento del hipotiroidismo subclínico en adultos mayores reduciría la morbimortalidad por eventos cardiovasculares. (AU)

A study showed that increased thyroid-stimulating hormone levels were associated with increased all-cause mortality, with cardiovascular disease estimated to mediate this association in approximately 14 % of cases. Additionally, levothyroxine replacement was found to lower cholesterol levels, which could have an effect in reducing cardiovascular diseases. Basedon a clinical vignette, the author attempts, through a literature search and an analysis of the evidence, to determine whether treatment of subclinical hypothyroidism in older adults would reduce morbidity and mortality from cardiovascular events. (AU)

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Serum concentration of thyroxine and triiodothyronine in newborn calves from cows supplemented with barium selenate / Concentración sérica de tiroxina y triiodotironina en terneros recién nacidos de madres suplementadas con selenato de bario / Concentração de tiroxina e triiodotironina sérica em bezerros recém-nascidos de mães suplementadas com selenato de bário

Abstract Background: Barium selenate is an inorganic source of selenium (Se) used in prolonged-release preparations to treat selenium deficiency in bovines. Objective: To evaluate serum concentrations of triiodothyronine (T3) and thyroxine (T4) hormones in newborn calves from mothers supplemented with barium selenate during prepartum. Methods: Six black Frisian pregnant cows were supplemented with barium selenate subcutaneously during the last two months of gestation, until calving. Six cows were used as controls. All cows were subjected to a low Se diet, consisting of hay from natural pasture and commercial concentrate lacking Se. The Se balance was measured through the activity of erythrocyte glutathione peroxidase (GPx). Serum concentration of T3 and T4 in calves was determined by electrochemiluminescence. Results: Se supplementation during prepartum increased GPx activity in cows from day 45 post-supplementation (p<0.05). Calves from supplemented mothers showed higher average serum Se concentration than calves from non-supplemented mothers. The average concentration of T3 in the calves from supplemented mothers was lower in the first hour of life (p<0.05) compared with calves from mothers of the non-supplemented group. A decrease (p<0.05) in T4 serum concentrations was observed in both groups at seven days of age. Conclusions: Administration of barium selenate to cows during prepartum generates a reduction in serum concentration of T3 in the first hour of life of calves.

Resumen Antecedentes: El selenato de bario es una fuente inorgánica de selenio (Se) utilizada en preparaciones de liberación prolongada para corregir el estado de carencia de Se en bovinos. Objetivo: Evaluar las concentraciones séricas de triyodotironina (T3) y tiroxina (T4) en terneros recién nacidos de madres suplementadas durante el preparto con selenato de bario. Métodos: Seis vacas frisón negro con 7 meses de gestación fueron suplementadas vía subcutánea con selenato de bario dos meses previos a la fecha de parto. Otras seis vacas permanecieron como controles. Todas las vacas se mantuvieron con una dieta cuyo aporte de Se fue inferior a los requerimientos y consistió en heno de pradera natural y concentrado comercial sin Se. El balance de Se se midió usando la actividad eritrocitaria de glutatión peroxidasa (GPx) y las concentraciones de T3 y T4 en terneros mediante electroquimioluminiscencia. Resultados: La suplementación con Se aumentó la actividad de GPx en vacas desde el día 45 post suplementación (p<0,05). Los terneros de madres suplementadas mostraron una concentración sérica promedio de Se mayor que los terneros de madres no suplementadas. La concentración promedio de T3 de terneros de madres suplementadas fue menor en la primera hora de vida (p<0,05) que en terneros de madres no suplementadas. A los 7 días de edad hubo una disminución (p<0,05) en las concentraciones séricas de T4 en ambos grupos. Conclusión: La administración de selenato de bario en vacas preparto genera una disminución en la concentración sérica de T3 en la primera hora de vida del ternero.

Resumo Antecedentes: O selenato de bário é uma fonte inorgânica de selênio (Se) usada em preparações de liberação prolongada para corrigir o status de deficiência de Se em bovinos. Objetivo: Avaliar as concentrações séricas de triiodotironina (T3) e tiroxina (T4) em bezerros recém-nascidos de mães suplementadas durante o pré-parto com selenato de bário. Métodos: Seis vacas friesianas negras aos 7 meses de gestação foram suplementadas com selenato de bário por via subcutânea dois meses antes do parto. Seis outras vacas permaneceram como controle. Todas as vacas foram mantidas em uma dieta cuja contribuição de Se foi inferior aos requeridos e consistiram em feno natural da pradaria e concentrado comercial sem Se. O balanço de Se foi medido usando a atividade eritrocitária das concentrações de glutationa peroxidase (GPx) e T3 e T4 em bezerros por eletroquimiluminescência. Resultados: A suplementação com atividade de GPx aumentou em vacas a partir do dia 45 após a suplementação (p<0,05). Os bezerros de mães suplementadas apresentaram uma concentração sérica média de Se maior que os bezerros de mães não suplementadas. A concentração média de T3 dos bezerros das mães suplementadas foi menor na primeira hora de vida (p<0,05) do que nos bezerros das mães não suplementadas. Aos 7 dias de idade houve uma diminuição (p<0,05) nas concentrações séricas de T4 nos dois grupos. Conclusão: A administração de selenato de bário em vacas de parto gera uma diminuição na concentração sérica de T3 na primeira hora de vida do bezerro.

Caracterización de pacientes con hipotiroidismo congénito en el Hospital Universitario San Ignacio entre 2001 y 2017 / Characterization of patients diagnosed with congenital hypothyroidism at the Hospital Universitario San Ignacio between 2001 and 2017

Introducción. El hipotiroidismo congénito es una causa prevenible de discapacidad cognitiva. Dada la ausencia de signos y síntomas al nacer, es necesario hacer pruebas de tamización para detectarlo. Su incidencia oscila entre uno de cada 2.500 y uno de cada 6.000 nacidos vivos. Objetivo. Describir las características antropométricas y demográficas de los participantes, así como medir la concentración de tirotropina (TSH) en sangre de cordón umbilical y de TSH y tiroxina libre (T4 libre) en el suero de los recién nacidos positivos en la prueba de tamización y de aquellos con hipotiroidismo congénito confirmado. Materiales y métodos. Se hizo un estudio observacional retrospectivo de un periodo de 17 años mediante la revisión de los registros de laboratorio clínico y las historias para establecer las características demográficas y antropométricas en el momento del nacimiento. Resultados. Se analizaron 41.494 recién nacidos. Se encontraron 217 (0,52 %) recién nacidos con prueba positiva de tamización, 19 (8,76 %) de ellos con diagnóstico confirmado mediante pruebas séricas (TSH y T4 libre), para una incidencia de uno por cada 2.183 nacidos vivos. El 78,95 % de los casos de hipotiroidismo congénito correspondió a nacidos a término, el promedio de la edad gestacional fue de 37,3 semanas, similar al de quienes no lo presentaban. No hubo diferencia en el promedio de peso ni en la talla al nacer entre los afectados y los no afectados. La concentración de TSH en sangre de cordón umbilical fue significativamente mayor en los casos de hipotiroidismo congénito que en los recién nacidos sanos. Conclusiones. La incidencia de hipotiroidismo congénito fue similar a la encontrada en los estudios consultados. No hubo diferencias clínicas relevantes entre los casos confirmados y los descartados, lo que resalta la pertinencia de la tamización neonatal para el diagnóstico temprano y el tratamiento oportuno.

Introduction: Congenital hypothyroidism is a preventable cause of cognitive disability. Due to the absence of symptoms and signs in the newborn, it is necessary to perform screening tests. Its incidence ranges between 1:2,500 and 1:6,000. Objective: To describe the anthropometric and demographic characteristics, as well as the cord TSH levels, serum TSH, and serum T4L levels of the positive patients during screening and patients with confirmed congenital hypothyroidism. Materials and methods: We conducted a retrospective observational study for 17 years based on the review of clinical laboratory and medical records to describe the demographic and anthropometric characteristics of the patients at the time of diagnosis. Results: We analyzed 41,494 newborns in the 17 years of follow-up; 217 (0.52%) were positive in the screening test and the diagnosis was confirmed by serum tests (TSH and free T4) in 19 cases (8.76%) for an incidence of one for every 2,183 live births; 78.95% of the children with congenital hypothyroidism were born full-term and the average gestational age was 37.3 weeks, similar to that of those with no congenital hypothyroidism. There was no difference in the average weight and height at birth between the children with the condition and those who did not have it. TSH in the cord in the cases of congenital hypothyroidism was significantly higher than in the discarded cases. Conclusions: The incidence of congenital hypothyroidism was similar to that found in the literature. There were no relevant clinical differences between confirmed and ruled out cases reflecting the relevance of neonatal screening.

Adherence to levothyroxine prescription in patients with hypothyroidism / Adherencia al uso de levotiroxina en pacientes con hipotiroidismo

ABSTRACT Background: Hypothyroidism occurs in 1-2% of the general population, is associated with significant morbidity and requires continuous treatment with levothyroxine. Aim: To determine the effectiveness, adherence and safety of levothyroxine therapy in patients with hypothyroidism. Material and Methods: The Morisky-Green adherence test was applied, and effectiveness was determined by measuring thyroid-stimulating hormone (TSH) in 330 patients with with hypothyroidism; the mean age was 64+-15 years and 76% was women. Results: Median TSH was 2.09 mIU/L (interquartile range: 1.16-3.61 mIU/L). Two hundred thirty-five (71%) patients had TSH levels in the euthyroid range, 64 (19%) in the hypothyroid range and 31 (9%) in the hyperthyroid range. Complete, moderate and lack of adherence with levothyroxine was reported in 283 (86%), 29 (9%) and 18 (5%) of patients, respectively. The presence of anemia (odds ratio (OR): 0.37, 95% confidence intervals (CI): 0.15-0.98) or the need of doses over 100 µg/day (OR: 0.47, 95%CI: 0.28-0.80) increased the probability of having an abnormal TSH level. Conclusions: In a large proportion of these patients, TSH levels were controlled, and most patients were adherent to levothyroxine therapy.

Antecedentes: El hipotiroidismo se presenta entre el 1-2% de la población general, genera importante morbilidad y requiere tratamiento con levotiroxina de manera continua. Objetivo: Determinar la efectividad, adherencia y seguridad de la terapia con levotiroxina en pacientes con hipotiroidismo. Material y Métodos: Se aplicó test de adherencia de Morisky-Green y se determinó efectividad mediante medición de TSH en 330 pacientes con edad promedio 63 ± 15 años (76% mujeres). Resultados: La mediana de TSH fue 2,09 mUI/l, (rango intercuartílico: 1,16mUI/l-3,61mUI/l). Un total de 235 (71,2%) tenían cifras de TSH en rango de estado eutiroideo, 64 (19,4%) se catalogaron hipotiroideos y 31 (9,4%) hipertiroideos. El 86% (n = 283) manifestó tener adherencia completa al medicamento, 29 (9%) moderada y 18 (5%) se clasificaron poco adherentes. Tener diagnóstico de anemia (razón de riesgo (RR): 0,37; intervalos de confianza (IC) 95%: 0,15-0,98) o necesitar dosis mayores de 100 µg/día (RR: 0,47; IC95%: 0,28-0,80) elevaron la probabilidad de no controlar el hipotiroidismo. Conclusiones. Una alta proporción de pacientes se encuentran controlados y con mucha frecuencia son adherentes a la terapia con levotiroxina.

Disfunción tiroidea y trastornos del ánimo: revisión del estado del arte / Thyroid dysfunction and mood disorders: review of the state of the art

La relación entre función tiroidea y trastornos del ánimo se ha observado desde hace más de 50 años. Las hormonas tiroideas, actúan en el cerebro modulando génicamente proteínas asociadas a la fisiopatología de los trastornos del ánimo y potenciando los sistemas de neurotransmisión serotoninérgica y noradrenérgica. En el tratamiento de un episodio depresivo, la normalización de hormonas tiroideas es fundamental, y debe realizarse en todo paciente con sintomatología anímica, especialmente en aquellos con respuestas insuficientes a tratamiento, que requieren niveles de hormonas más estrictos que lo recomendado para población general. En pacientes eutiroideos, la potenciación con triyodotironina ha sido probada, pero también se ha utilizado T4 en altas dosis en casos resistentes, en que se postula que pudiese existir un estado de resistencia a hormonas tiroideas, no reflejado en los niveles hormonales periféricos evaluados rutinariamente. Las enzimas deiodasas, el receptor de hormona tiroidea, y el transportador de hormona tiroidea en la barrera hematoencefálica son blancos a investigar. Los objetivos de la presente revisión son ofrecer orientaciones respecto del uso de hormonas tiroideas en pacientes con trastornos del ánimo, una puesta al día sobre la relación entre hormonas tiroídeas y sistema nervioso central, y las interacciones entre psicofármacos y función tiroidea.

The relationship between thyroid function and mood disorders has been observed for more than 50 years. Thyroid hormones act in the brain genetically modulating proteins associated with the pathophysiology of mood disorders and potentiating the serotonergic and noradrenergic neurotransmission systems. In the treatment of a depressive episode, the normalization of thyroid hormones is essential, and should be performed in all patients with mood symptoms, especially in those with insufficient responses to treatment, which require more stringent hormone levels than recommended for the general population. In euthyroid patients, potentiation with triiodothyronine has been proven, but T4 has also been used in high doses in resistant cases, in which it is postulated that there might be a state of resistance to thyroid hormones, not reflected in the peripheral hormonal levels evaluated routinely. The enzymes deiodasas, the thyroid hormone receptor, and the thyroid hormone transporter in the blood brain barrier are white to investigate. The objectives of this review are to provide guidance regarding the use of thyroid hormones in patients with mood disorders, an update on the relationship between thyroid hormones and central nervous system, and the interactions between psychoactive drugs and thyroid function.

Interpretación de las pruebas de función tiroidea / Interpretation of thyroid function tests

Los desórdenes de la glándula tiroides son comunes y pueden afectar hasta el 10% de la población en general. En muchas ocasiones los síntomas pueden ser inespecíficos, por lo que el médico en busca de un trastorno tiroideo debe llegar a un diagnóstico funcional y anatómico. Las mediciones séricas de las hormonas tiroideas confirman si hay un exceso, un déficit o si las concentraciones son normales. Para ello, se requiere un rango de referencia de la población local, y específicamente por grupos de edad, para una correcta interpretación de las pruebas de función tiroidea. Las hormonas tiroideas juegan un papel fundamental en el sistema endocrino, controlan el metabolismo general del cuerpo, el desarrollo neural, el crecimiento normal y la maduración de los huesos, así como funciones cardiovasculares y renales, entre otras. En esta revisión se pretende dar una aproximación a las pruebas tiroideas más relevantes, partiendo de la biosíntesis y secreción de las hormonas tiroideas, hasta llegar al abordaje para un diagnóstico inicial del paciente con trastorno tiroideo, mencionando los aspectos más importantes de los diferentes patrones tiroideos. El tratamiento detallado de cada uno de ellos, supera las expectativas de esta revisión

Thyroid gland disorders are common and can affect up to 10% of the general population. In many cases the symptoms can be nonspecific, so the physician in search for a thyroid disorder should reach a functional and anatomical diagnosis. Serum measurements of thyroid hormones confirm if there is an excess, a deficit, or if concentrations are normal. For this, reference ranges of the local population, and specifically by age groups, are required for a correct interpretation of thyroid function tests. Thyroid hormones play a fundamental role in the endocrine system, control of the general metabolism of the body, neural development, normal growth and maturation of bones, as well as in cardiovascular and renal functions, among others. In this review, the most relevant thyroid tests will be described, starting with the biosynthesis and secretion of thyroid hormones, and continuing with an approach to reach an initial diagnosis. Finally, the most important aspects of the different thyroid patterns will be mentioned. It is beyond the scope of this review, to describe the treatment for thyroid disorders.

Alteraciones cardiovasculares causadas por hipotiroidismo clínico y subclínico / Cardiovascular disorders caused by clinical and subclinical hypothyroidism

El hipotiroidismo es un trastorno endocrino en el cual la glándula tiroides tiene su función disminuida; teniendo como consecuencia paralela la perdida de homeostasia del cuerpo alterando así su adecuado funcionamiento. Para diagnosticar la enfermedad, sumado a la clínica, se recurre a medir los niveles sanguíneos de hormonas tiroideas. Como el sistema cardiovascular y la glándula tiroides están relacionados fisiológicamente, los trastornos de la glándula tiroides afectan de gran manera al sistema cardiovascular. Se detallan los mecanismos intracelulares y extracelulares de las hormonas tiroideas; y, utilizando esta información, se explican todos los cambios morfológicos y fisiológicos que esta patología causa en el corazón y en las células de músculo liso. Además, se dan a conocer las implicaciones que la enfermedad tiene a nivel del miocardio, sobre la hemodinámica, su relación con la insuficiencia cardíaca congestiva, la hipertensión y los efectos en general sobre los vasos sanguíneos, con el objetivo de describir la relación entre hipofunción tiroidea clínica y subclínica como factor de riesgo determinante para el desarrollo de alteraciones cardiovasculares.

Hypothyroidism is an endocrine disorder in which the thyroid gland has a diminished function; having as a consequence the loss of homeostasis of the body, therefore, altering its proper functioning. To diagnose this disease, physical examination, blood tests and thyroid stimulating hormone tests are utilized. Since the cardiovascular system and the thyroid gland are physiological related, the general disorders of the thyroid gland greatly affect the cardiovascular system. The intracellular and extracellular mechanisms of thyroid hormones are detailed; and, using this information, all the morphological and physiological changes that this pathology causes in the heart and on smooth muscle cells are explained. In addition, the implications of the disease on the myocardium, on hemodynamics, its relation to congestive heart failure, hypertension and general effects on blood vessels are revealed, with the objective of describing the relationship between clinical and subclinical thyroid hypofunction as a determining risk factor for the development of cardiovascular disorders.

Coexistence of thyroid disease and oral lichen planus in a Colombian population / Coexistencia de enfermedad de la tiroides y liquen plano oral en una población colombiana

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease of unknown etiology. OLP has recently been linked to thyroid disease, mainly hypothyroidism. The aim of this study was to determine the prevalence of thyroid disease in Colombian patients with OLP. A total of860 clinical records of patients attending the clinics of oral medicine and oral and maxillofacial surgery at IPS CES Sabaneta, Colombia, between 2010 and 2016 were reviewed. Fourteen patients (1.6%) had a diagnosis of OLP. The prevalence of hypothyroidism in patients with OLP was 35.7%, compared to 3.95% in the entire study population (OR 15.92, 95% CI: 5.63-50.09, P = 0.0001). Patients with concomitant hypothyroidism and OLP presented with less severe oral lesions compared to those without thyroid disease. This study supports the notion that patients with OLP should be screened for thyroid disease.

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria crónica de etiología desconocida. El LPO ha sido asociado recientemente con la enfermedad de la tiroides, especialmente con hipotiroidismo. El objetivo con este estudio fue determinar la prevalencia de la enfermedad de la tiroides en pacientes colombianos con LPO. Un total de 860 historias clínicas de pacientes que asistieron entre 2010 y 2016 a las clínicas de medicina oral y de cirugía oral y maxilofacial de la IPS CES Sabaneta, Colombia, fueron revisadas. Catorce pacientes (1.6%) habían sido diagnosticados con LPO. La prevalencia de hipotiroidismo en pacientes con LPO fue 35.7%, comparada con 3.95% en toda la población de estudio (RM 15.92, 95% IC: 5.63-50.09, P = 0.0001). Pacientes con hipotiroidismo y LPO concomitante presentaron lesiones orales menos severas comparado con aquellos sin enfermedad de la tiroides. Este estudio respalda la idea de que se debe investigar la presencia de enfermedad de la tiroides en pacientes con LPO.

Prevalence of thyroid autoimmunity in a population of pregnant women in Santa Marta, Magdalena (Colombia) / Prevalencia de autoinmunidad tiroidea en una población de gestantes de Santa Marta, Magdalena (Colombia)

ABSTRACT Objective: To describe the prevalence of thyroid autoimmunity in a hospital-based population of pregnant women, and to explore its frequency in euthyroid and hypothyroid women, as well as the association between autoimmunity and the presence of obstetric complications. Materials and methods: Descriptive cross-sectional study. Accesible population: pregnant women seen at Centros Hospitalarios del Caribe (CEHOCA) in the city of Santa Marta, Magdalena (Colombia), between August 1 and October 31, 2017. Convenience sampling. Sample size: 120 subjects. Thyroid stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), thyroglobulin (TG) and thyroid peroxidase (TPO) antibodies were determined. Descriptive statistics were used. Prevalence was calculated as the number of women with positive TG or TPO antibodies/number of women surveyed. Categorization by type of positive antibody and thyroid function (normal or hypothyroidism) was also done. Results: In women with uncomplicated pregnancies, the frequency of thyroid autoimmunity was 14.29%. Five patients (4.5%) had positive TPO antibodies, 14 patients (12.61%) had positive TG antibodies, while 3 of the women were positive for the two types of antibodies. Antithyroglobulin antibodies were the most frequent. Autoimmunity was found in 13.5% of euthyroid women, and in 18.2% of the women with subclinical hypothyroidism. No association was found between the presence of antibodies and miscarriage, pregnancy-associated hypertension or preterm delivery. Conclusions: The presence of antithyroid antibodies was found in 1 out of every 7 pregnant women as a sign of autoimmunity. Further observations are required in order to determine frequencies and normality ranges in the local population, as well as the clinical significance of this thyroid autoimmunity.

RESUMEN Objetivo: describir la prevalencia de autoinmunidad tiroidea en una población de gestantes de base hospitalaria, y hacer una exploración a la frecuencia en pacientes eutiroideas o hipotiroideas, y de la asociación entre autoinmunidad y la presencia de complicaciones obstétricas. Materiales y métodos: estudio de corte transversal, descriptivo. Población accesible: gestantes atendidas en Centros Hospitalarios del Caribe (CEHOCA), de la ciudad de Santa Marta, Magdalena (Colombia), entre el 1 de agosto y el 31 de octubre de 2017. Muestreo por conveniencia. Tamaño muestral: 120 sujetos. Se determinó hormona tiroestimulante (TSH), T4 libre, T3 libre, anticuerpos antitiroglobulina (ATG) y antiperoxidasa (ATPO). Se utilizó estadística descriptiva. La prevalencia se calculó como número de mujeres con anticuerpos ATG o ATPO positivos/número de mujeres encuestadas, además se categorizó por tipo de anticuerpo positivo y función tiroidea (normal o hipotiroidismo). Resultados: en las gestantes con embarazo sin mención de complicación la frecuencia de autoinmunidad tiroidea fue del 14,29 %. Cinco pacientes (4,5 %) presentaron anticuerpos ATPO positivos, 14 pacientes (12,61 %) anticuerpos ATG positivos, en tanto que 3 embarazadas mostraron positividad para ambos tipos de anticuerpos. Los anticuerpos antitiroglobulina fueron los más frecuentes. Se halló autoinmunidad en el 13,5 % de las gestantes eutiroideas, y en el 18,2 % de las pacientes con hipotiroidismo subclínico. No se encontró asociación entre la presencia de anticuerpos y la presencia de aborto, hipertensión asociada al embarazo o parto pretérmino. Conclusiones: una de cada 7 gestantes mostró presencia de anticuerpos antitiroideos como signo de autoinmunidad. Son necesarias más observaciones a fin de poder establecer frecuencias y rangos de normalidad en la población local y el significado clínico de esta autoinmunidad tiroidea.

Evaluation of serum concentrations of cortisol and thyroxine in bitches with early-stage mammary carcinoma / Concentrações séricas de cortisol e tiroxina em cadelas com carcinoma mamário em estádio inicial

In view of the fact that cancer is considered a chronic disease that can interfere with hormonal homeostasis by means of cytokines, we hypothesized that, even at early stages, mammary carcinoma is able to alter the balance of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. To test this hypothesis, the serum concentrations of basal cortisol, thyroxine (T4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated in 20 unspayed bitches that had a histopathological diagnosis of grade 1 mammary carcinoma at clinical stage I according to the World Health Organization (WHO) classification (T1N0M0). The control animals comprised 10 unspayed bitches in perfect health conditions that were matched with those with mammary carcinoma by age. No significant differences regarding the concentrations of basal cortisol, TSH, t4, and fT4 were found between the bitches carrying early stage mammary carcinoma when compared to the control group. This suggests that, even if malignant, early-stage mammary carcinomas do not exhibit the ability to alter the concentrations of hormones produced by the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-thyroid axes.(AU)

Em vista do fato de neoplasias serem consideradas doenças crônicas que por meio de citocinas podem interferir na homeostase hormonal, hipotetizou-se que o carcinoma mamário, mesmo nos seus estádios iniciais, fosse capaz de alterar o equilíbrio dos eixos hipotalâmico-hipofisário-tireóideo e hipotalâmico-hipofisário-adrenal. Para tal, foram avaliadas as concentrações séricas de cortisol basal, tiroxina (T4), tiroxina livre (fT4) e tireotrofina (TSH) de 20 fêmeas caninas, inteiras, com diagnóstico histopatológico de carcinoma mamário grau 1 e estadiamento clínico I segundo a classificação da Organização Mundial da Saúde - OMS (T1N0M0). Os animais controle constituíram-se por 10 fêmeas caninas inteiras, em perfeitas condições de higidez, as quais foram pareadas, por idade, com aquelas portadoras de carcinoma mamário. Não foram encontradas diferenças significativas nas concentrações de cortisol basal, TSH, T4 e fT4 das cadelas portadoras de carcinoma mamário em estádio inicial quando comparadas às controles sugerindo que, mesmo considerados malignos, ainda não apresentam a capacidade de alterar as concentrações dos hormônios produzidos pelos eixos hipotalâmico-hipofisário-adrenal e tireóideo.(AU)

Niveles de hormonas tiroideas en recién nacidos muy prematuros y prematuros extremos / Thyroid hormone Levels in very preterm neonates and extremely preterm

INTRODUCCIÓN: La función tiroidea del prematuro se ve alterada por la relativa inmadurez del eje hipotálamo-hipófisis-tiroides, junto a otros factores como la incidencia de enfermedades o el uso de algunos fármacos. Actualmente existe controversia sobre los niveles normales de tiroxina libre (T4L) en recién nacidos prematuros. Nuestro objetivo fue determinar la distribución de los valores de hormonas T4L y TSH, en recién nacidos menores de 32 semanas o 1.500g de peso al nacer, a los 15 días de edad cronológica, en el servicio de neonatología Hospital Dr. Hernán Henríquez Aravena, Temuco. Pacientes y MÉTODO: Estudio de corte trasversal, se analizaron los resultados de T4L y TSH desde una base de datos a 308 recién nacidos, los que fueron categorizados en tres rangos de edad gestacional: 31 a 34, 28 a 30 y 23 a 27 semanas. Se utilizó Chi-cuadrado de Pearson para asociaciones entre variables categóricas, y T-Test o ANOVA para comparaciones entre variables continuas. RESULTADOS: Observamos diferencias significativas entre los valores promedio de T4L por rangos de edad gestacional (p = 0,000), estos fueron 1,13 ng/dl para el rango de 31 a 34 semanas, 1,03 ng/dl para el rango de 28 a 30 semanas y 0,92 ng/dl para el rango de 23 a 27 semanas; no observamos diferencias significativas en los niveles de TSH por categorías de edad gestacional (p = 0,663). CONCLUSIONES: Establecimos la distribución de los niveles de T4L y TSH en nuestra población de recién nacidos muy prematuros y prematuros extremos, encontrando diferencias con reportes anteriores.

INTRODUCTION: The thyroid function of the pretern infant is altered by the relative immaturity of the hypothalamus-pituitary thyroid gland axis, along with other factors such as the incidence of diseases or the use of some drugs. Currently, there is controversy over normal levels of free thyroxine (FT4) in preterm infants. Our objective was to determine the distribution of FT4 and TSH values in newborn younger than 32 weeks or 1500 g of birth weight at 15 days of chronological age, in the neonatology service at Dr. Hernán Henríquez Aravena Hospital, Temuco. PATIENTS AND METHOD: Cross-sectional study; the results of FT4 and TSH from a database of 308 newborns, were analyzed, which were categorized into three gestational age ranges, 31-34, 28-30 and 23-27 weeks. It was used Pearson Chi-square for comparisons between categorical variables, and T-Test or ANOVA for categorical-variable ratios. RESULTS: Significant differences were observed between the average values of FT4 by gestatio nal age ranges (p = 0.000), these were 1.13 ng/dl for the range of 31 to 34 weeks, 1.03 ng/dl for the range of 28 to 30 weeks and 0.92 ng/dl for the range of 23 to 27 weeks; we did not observe significant differences in TSH levels by gestational age categories (p = 0.663). CONCLUSIONS: We established the distribution of FT4 and TSH levels in our population of very preterm and extremely preterm infants, finding differences with previous papers.

Hipotiroidismo subclínico y embarazo / Sub-clinical hypothyroidism and pregnancy

El hipotiroidismo subclínico se define como una concentración sérica elevada de tirotropina (TSH), con T4 libre normal. En el embarazo, se ha descrito efectos deletéreos tales como riesgo aumentado de aborto espontáneo y déficit cognitivo del niño en mujeres con esta condición; además, se debe considerar la posible progresión a hipotiroidismo clínico. Se ha planteado el rol de la autoinmunidad mediante la presencia de anticuerpos anti-tiroperoxidasa (AntiTPO), describiéndose este como factor de riesgo para desenlaces adversos. No se ha comprobado la utilidad del tamizaje universal con TSH, siendo el enfoque actualmente el estudio de pacientes de riesgo. El tratamiento se inicia según los resultados de la cuantificación deTSH y AntiTPO, siendo el fármaco de elección la levotiroxina.El seguimiento es conmediciones deTSH.

Sub-clinical hypothyroidism is defined to be raised plasma thyrotropin (TSH) with normal levels of free T4. Detrimental effects such as increased abortion risk and newborns with cognitive deficit have been reported in pregnancies with this condition. Possible progression to clinical hypothyroidism must be considered. A possible auto-immune mechanism mediated by anti-thyroperoxidase (AntiPO) has been postulated where AntiPO should be considered a risk factor for adverse outcomes. Universal screening using TSH has not been found to be of use and at present only high risk women are screened. Women are treated with levothyroxine, the dose depending on the TSH andAntiPO levels, and follow up is done bymonitoringTSHlevels.

Thyroid hormones affect decidualization and angiogenesis in the decidua and metrial gland of rats / Hormônios tireoidianos afetam a decidualização e a angiogênese na decídua e glândula metrial de ratas

This study aimed to evaluate the effects of thyroid hormone on the decidua and metrial gland of rats and to examine the expression of angiogenic factors. 72 adult, female rats were divided into hypothyroid, T4-treated2, and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of the expression of VEGF, Flk-1 and Tie-2. Hypothyroidism reduced the area of the decidua at 10 and 19 DG. Furthermore, VEGF was increased at 10 and 14 DG, and Flk-1 only at 14 DG, but both was reduced at 19 DG in the metrial gland without significantly changing the area occupied by blood vessels. Rats treated with T4 showed an increase in the decidua blood vessels at 10 and 19 DG. However, at 10 DG, excess T4 resulted in increased of Flk-1 in the decidua and metrial gland. Hypothyroidism increased the Tie-2 at 10 and 19 DG in the decidua and metrial gland. In conclusion, hypothyroidism reduces the area of the decidua and increases the expression of VEGF, Tie-2 and Flk-1. The excess of T4 promotes tissue angiogenesis by increasing the number of vessels in the decidua because of the increased expression of Flk-1.(AU)

Este estudo teve como objetivo avaliar os efeitos dos hormônios tireoidianos sobre a decídua e a glândula metrial pela análise da expressão de fatores angiogênicos em ratas. 72 ratas adultas, fêmeas foram distribuídas nos grupos hipotiroideo, tratado com T4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão de VEGF, Flk-1 e Tie-2. O hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, mas ambos foram reduzidos aos 19 DG na glândula metrial sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T4 apresentaram aumento do número de vasos sanguíneos na decídua aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 em 10 e 19 DG na decídua e na glândula metrial. Desta forma, pode-se concluir que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua devido ao aumento da expressão de Flk-1.(AU)

Excesso de tiroxina materna associado ao hipertireoidismo pós-natal reduz o crescimento ósseo e o perfil proliferativo e angiogênico das cartilagens de crescimento de ratos / Excess maternal thyroxine associated with postnatal hyperthyroidism reduces bone growth and proliferative and angiogenic profile of rats growth cartilage

Foram estudados os efeitos do excesso da tiroxina materna associado ao hipertireoidismo pós-natal sobre o crescimento ósseo e o perfil proliferativo e angiogênico das cartilagens. Dezesseis ratas Wistar adultas foram distribuídas nos grupos tratados com L-tiroxina e controle. A prole do grupo tratado recebeu L-tiroxina do desmame até 40 dias de idade. Ao desmame, foi realizada dosagem plasmática de T4 livre nas mães. Na prole, foram realizados: dosagem plasmática de T3 total e T4 livre, morfometria das tireoides, mensuração do comprimento e largura do fêmur. Nas cartilagens, foi avaliada a expressão imuno-histoquímica e gênica de CDC-47, VEGF, Flk-1, Ang1, Ang2 e Tie2. As médias entre grupos foram comparadas pelo teste T de Student. As concentrações de T4 livre das mães tratadas e de T3 total e T4 livre da prole foram significativamente mais elevadas. A largura do fêmur foi menor nos animais tratados. Houve também redução da imunoexpressão de CDC-47 e de VEGF e dos transcritos gênicos para VEGF e Ang1 nas cartilagens. Conclui-se que o excesso de tiroxina materna associado ao hipertireoidismo pós-natal reduz a largura da diáfise femoral, a proliferação celular e a expressão de VEGF e de Ang1 nas cartilagens de crescimento de ratos.(AU)

The effects of excess of maternal thyroxine associated with postnatal hyperthyroidism at bone growth and proliferative and angiogenic profile of cartilage were studied. Sixteen adult Wistar rats were divided into treated and control groups. The offspring of the treated group received L-thyroxine from weaning to 40 days-old. At weaning, plasma assay of free T4 was measurement on female rats. In the offspring, the following assessments were performed: measurement of total T3 and free T4, histomorphometry analysis of the thyroid, measurement of body weight and length and width of the femur. In femoral growth cartilage, immunostaining of CDC-47, gene or protein expression of VEGF, Flk-1, Ang1, Ang2 and Tie2 were evaluated. Data were analyzed using Student's t-test. Free T4 was significantly higher in treated rats and total T3 and free T4 were significantly higher in offspring. The width of the femur was significantly lower in treated animals. There was lower immunoreactivity of CDC-47, VEGF and lower expression of gene transcripts for VEGF and Ang1. We concluded that the excess maternal thyroxine associated with postnatal hyperthyroidism reduces the width of the femoral shaft, the cell proliferation and gene and protein expression of VEGF and gene expression of Ang1 on the growth cartilage in rats.(AU)