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.

Approach to Subclinical Hypothyroidism in Adults / Abordaje del Hipotiroidismo subclínico en el Adulto

Thyroid pathology is the morphofunctional evolution of the thyroid glands that leads to different types of clinical pictures. Within it is subclinical hypothyroidism, which is a biochemical alteration due to the elevation of thyroid-stimulating hormone (TSH) between 4.5 to 10 mUI that can occur with or without symptoms of multifactorial origin. The worldwide prevalence is 4-10% and Latin America 15-25%. 90% of patients with this pathology do not require treatment, but in turn there is an overmedicalization and underdiagnosis of it. This bibliographic review analyzes from its morphofunctional changes towards clinical criteria for a comprehensive approach to subclinical hypothyroidism, where we have an individualization by its comorbidities, age group, diagnostic algorithm, follow-up and differentiated treatment according to recent studies within this pathology. Therefore, an adequate diagnosis, follow-up and treatment provides a better lifestyle for patients.

La patología tiroidea es la alteración morfofuncional de la glándula tiroides que lleva a diferentes tipos de cuadros clínicos. Dentro de ella se encuentra el Hipotiroidismo subclínico que es una alteración bioquímica por la elevación de la Hormona Estimulante de la tiroides (TSH) entre 4,5 a 10 mUI que puede presentarse con o sin sintomatología y tiene etiología multifactorial. La prevalencia mundial es del 4-10 % y latinoamericana del 15-25%. El 90% de pacientes con esta patología no requieren tratamiento, pero a su vez existe una sobremedicalización y una subdiagnóstico del mismo. La presente revisión bibliografía analiza a partir de su alteración morfofuncional hacia criterios clínicos para un abordaje integral del Hipotiroidismo subclínico, donde tenemos una individualización por sus comorbilidades, grupo etario, algoritmo diagnóstico, seguimiento y tratamiento diferenciado según últimos estudios dentro de esta patología. Por lo que un adecuado diagnóstico, seguimiento y tratamiento brinda un mejor estilo de vida a los pacientes.

Elementos básicos para el diagnóstico y manejo terapéutico del coma mixedematoso en el paciente adulto / Basic elements for the diagnosis and therapeutic management of myxedematous coma in adult patients

Introducción: A pesar de su baja incidencia, la gravedad del cuadro clínico y la alta mortalidad hacen del coma mixedematoso una complicación a tener en cuenta. Objetivo: Describir los elementos básicos para el diagnóstico y manejo terapéutico del coma mixedematoso en el paciente adulto. Métodos: Se realizó una búsqueda de literatura relevante sobre el tema. Se utilizaron buscadores de información científica como Pubmed y Google Académico. La estrategia de búsqueda incluyó los siguientes términos como palabras clave: hipotiroidismo primario, hipotiroidismo subclínico, diagnóstico y tratamiento. Fueron evaluados artículos de revisión, de investigación y páginas web que tuvieran menos de 10 años de publicados. Se consideraron los textos en idioma español e inglés y que hicieran referencia específicamente al tema de estudio a través del título. Fueron excluidos los artículos que no cumplieron con estas condiciones. Esto permitió el estudio de 64 artículos, de los cuales 40 fueron referenciados. Conclusiones: Para el diagnóstico del coma mixedematoso en el paciente adulto lo más importante es sospecharlo en aquellas personas que presenten factores precipitantes, acompañados de síntomas y signos de hipotiroidismo severo con diferentes grados de insuficiencia del sistema nervioso central, hipotermia, hipoventilación, insuficiencia circulatoria e hiponatremia. A esto se sumaría el escenario humoral característico y los posibles hallazgos dependientes de la enfermedad causante del hipotiroidismo. Se debe tratar con un reemplazo agresivo de levotiroxina sódica (vía endovenosa u oral, según posibilidades), unido a otras medidas de apoyo en el entorno hospitalario(AU)

Introduction: Despite its low incidence, the severity of the clinical picture and the high mortality make myxedematous coma a complication to be taken into account. Objective: Describe the basic elements for the diagnosis and therapeutic management of myxedematous coma in adult patients. Methods: A search of relevant literature on the subject was carried out. Pubmed and Google Scholar were used as search engines for scientific information. The search strategy included the following keyword terms: primary hypothyroidism, subclinical hypothyroidism, diagnosis and treatment. Review articles, research articles and Web pages that, in general, had less than 10 years of publication, in Spanish and English that specifically referred to the subject of study through the title were evaluated. Articles that did not meet these conditions were excluded. This allowed the study of 64 articles, of which 40 were referenced. Conclusions: For the diagnosis of myxedematous coma in the adult patient, the most important thing is to suspect it in those people who present precipitating factors, accompanied by symptoms and signs of severe hypothyroidism with different degrees of central nervous system insufficiency, hypothermia, hypoventilation, circulatory insufficiency and hyponatremia. To this would be added the characteristic humoral scenario and the possible findings dependent on the disease causing hypothyroidism. It should be treated with an aggressive replacement of levothyroxine sodium (intravenous or oral way, accodring to the possibilities), together with other supportive measures in the hospital setting(AU)

¿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)

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.

Hipotiroidismo subclínico en el embarazo / Subclinical hypothyroidism in pregnancy

Las alteraciones de la función tiroidea incluida el hipotiroidismo subclínico son unas de las patologías más frecuentes durante el embarazo, y se asocian a importantes complicaciones maternas, fetales y neonatales. Se han desarrollado múltiples guías de práctica clínica por sociedades internacionales en busca de unificar el enfoque diagnóstico y terapéutico de las patologías tiroideas durante la gestación, sin embargo hay evidencia insuficiente sobre la realización de tamizaje y aún más sobre las intervenciones terapéuticas en caso del hipotiroidismo subclínico, se presenta la siguiente revisión de la literatura para vislumbrar a la luz de información actualizada como realizar el abordaje integral de las pacientes gestantes con hipotiroidismo subclínico (AU)

Alterations in thyroid function, including subclinical hypothyroidism, are one of the most frequent pathologies during pregnancy, and are associated with important maternal, fetal, and neonatal complications. Multiple clinical practice guidelines have been developed by international societies in search of unifying the diagnostic and therapeutic approach of thyroid pathologies during pregnancy, however there is insufficient evidence on screening and even more on therapeutic interventions in case of subclinical hypothyroidism , the following review of the literature is presented to envision in the light of updated information how to carry out a comprehensive approach to pregnant patients with subclinical hypothyroidism (AU)

A practical contemporary approach to decision-making on subclinical hypothyroidism

ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

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.

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.

Efectos adversos inmunomediados por inhibidores de PD-1 / PD-1 inhibitors immune-mediated side effects

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)

Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)

Síndrome de Van Wyk-Grumbach / Van Wyk-Grumbach syndrome

RESUMEN El síndrome de Van Wyk-Grumbach se caracteriza por hipotiroidismo primario de larga duración asociado a pubertad precoz. Se presenta una paciente de 7 años, mestiza, que acude por sangrado vaginal, acompañado de hiperpigmentación de las areolas sin galactorrea, abdomen globuloso, mixedema, hirsutismo, baja talla, astenia y retraso escolar. La química sanguínea mostró anemia, hipercolesterolemia y hipertransaminasemia; los estudios de imágenes constataron derrame pericárdico, retraso marcado de la edad ósea, incremento de las dimensiones de la silla turca y gran quiste del ovario con aparente criterio quirúrgico. Los estudios hormonales confirmaron la sospecha de hipotiroidismo primario asociado a hiperprolactinemia. El tratamiento sustitutivo con levotiroxina sódica revirtió los signos y síntomas de pubertad precoz, lo que evitó la cirugía del quiste de ovario; la recuperación en el ambiente escolar y social fue indiscutible. Reconocer esta entidad evita tratamientos absolutamente contraindicados, como la extirpación de los quistes o el tratamiento quirúrgico de la hiperplasia hipofisaria(AU)

ABSTRACT Van Wyk-Grumbach syndrome is characterized by long-lasting primary hypothyroidism associated with precocious puberty. A case of a 7-year-old female mestizo patient is reported. She came to consultation for vaginal bleeding, accompanied by hyperpigmentation of the areolas without galactorrhea, globular abdomen, myxedema, hirsutism, short stature, asthenia and school delay. Blood chemistry showed anemia, hypercholesterolemia and hypertransaminasemia. Imaging studies showed pericardial effusion, marked delay in bone age, increased dimensions of Turkish chair and large ovarian cyst with apparent surgical criteria. Hormonal studies confirmed the suspicion of primary hypothyroidism associated with hyperprolactinemia. Substitute treatment with levothyroxine sodium reversed the signs and symptoms of precocious puberty, which prevented ovarian cyst surgery; the recovery in the school and social environment was certain. Recognizing this entity avoids absolutely contraindicated treatments, such as the removal of cysts or the surgical treatment of pituitary hyperplasia(AU)

Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism

ABSTRACT Objective: In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT). Subjects and methods: The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid. Results: Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041). Conclusions: Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.

Hipotiroidismo subclínico en mujeres en edad reproductiva y embarazadas / Subclinical hypothyroidism in women of reproductive age and in pregnancy

El hipotiroidismo subclínico suele ser identificado como un cuadro que disminuye la capacidad reproductiva de las mujeresy está asociado a un riesgo aumentado de complicaciones perinatales. A partir de un caso clínico real, revisamos laevidencia disponible y encontramos que existen pruebas que contradicen este conocimiento tradicional sobre el pronósticoy la necesidad de tratamiento de este cuadro. (AU)

Subclinical hypothyroidism is usually identified as a condition that decreases the reproductive capacity of women and isassociated with a higher risk of perinatal complications. From a real clinical case, we review the available evidence andfound that there is evidence that contradicts this traditional knowledge about the prognosis and the need for treatment ofthis condition. (AU)

Selective screening for thyroid dysfunction in pregnant women: How often do low-risk women cease to be treated following the new guidelines of the American Thyroid Association?

ABSTRACT Objective: Universal screening for thyroid dysfunction in pregnant women is not recommended by the American Thyroid Association (ATA) or the American Association of Clinical Endocrinologists (AACE). This study evaluated the frequency of pregnant women that would have an indication for levothyroxine (L-T4) according to the new ATA/AACE guidelines among low-risk women without an indication for screening with TSH. Subjects and methods: The sample consisted of 412 pregnant women ranging in age from 18 to 30 years. These women were considered to be at low risk for thyroid dysfunction according to ATA/AACE and would not be candidates for screening with TSH. Anti-thyroid peroxidase antibodies (TPOAb) and TSH were measured. Women who had TSH > 2.5 mIU/L or TPOAb in the first trimester were submitted to subsequent evaluations in the second and third trimester. Results: In the first trimester, none of the pregnant women would have L-T4 therapy "recommended" and treatment would be "considered" in only two. In the second trimester, pregnant women with positive TPOAb or TSH > 2.5 mIU/L in the first trimester (n = 30) were reevaluated. L-T4 treatment would be "recommended" in only one woman and would be "considered" in two others. The 28 women that were not treated in the second trimester were reevaluated in the third trimester, but none of them would have L-T4 "recommended". Conclusion: The findings of the study suggest that selective screening, recommended by ATA/AACE does not result in a significant loss of pregnant women with an indication for L-T4 treatment.

Endotelina-1, proteína C reactiva ultrasensible y actividad antioxidante en pacientes con hipotiroidismo subclínico y en eutiroideos con autoinmunidad tiroidea. Efectos del tratamiento con levotiroxina / Endothelin-1, high sensitivity C reactive protein and antioxidant activity in subclinical hypothyroid patients. Effects of levothyroxine treatment

RESUMEN La Endotelina-1 (ET1) y Proteína C Reactiva ultrasensible (PCRus) como marcadores de disfunción endotelial (DE) e inflamación vascular en hipotiroidismo subclínico (HS) han mostrado resultados controvertidos. El rol del estrés oxidativo y defensa antioxidante (TRAP) es motivo de discusión. Objetivos Establecer si el HS y la autoinmunidad tiroidea (AIT), excluyendo otros factores de riesgo cardiovascular, pueden causar DE e inflamación vascular, evaluadas a través de ET1 y PCRus, respectivamente. Establecer si TRAP juega algún rol. Evaluar cambios en ET1 y PCRus luego del tratamiento con levotiroxina (LT4). Material y métodos Se evaluaron prospectivamente 70 pacientes divididos en 3 grupos: HS: 41 pacientes (T4 normal,TSH >4,2 y <10 mUI/L), AIT: 10 pacientes eutiroideos (TSH <4,2 mUI/L) con aTPO y/o aTg (+) y Control: 19 pacientes eutiroideos sin AIT. Se excluyeron otros factores de riesgo cardiovascular. Se midió basalmente ET1, PCRus y TRAP plasmáticos, y en HS bajo LT4 (n = 24): ET1 y PCRus. Resultados No hubo diferencias significativas en edad, IMC, perfil lipídico y TRAP. ET1 y PCRus fueron significativamente mayores en pacientes con HS (media ± DS 1,77 ± 0,85 pg/ml y 1,5 ± 0,6 mg/l vs. controles (0,8 ± 0,3 pg/ml y 0,5 ± 0,2 mg/l) p <0,0001 y <0,008 respectivamente. Del mismo modo en AIT (1,4 ± 0.4 pg/ml y 2,3 ± 1,3 mg/l) vs controles p <0,0001 y <0,034, respectivamente. La TSH fue mayor en el grupo AIT vs. Control 2,57 ± 0,88 vs. 1,64 ± 0,5 mUI/L; p = 0,002. En HS bajo LT4 (8,7 ± 3,8 meses) se observó descenso de ET1 (p <0,001). ET1 correlacionó con TSH (r = 0,5 p <0,0001). El punto de corte de ET1 mediante curva ROC fue 1,32 pg/ml (Sensibilidad 81,6%-Especificidad 75%). Conclusiones ET1 y PCRus resultaron marcadores útiles para evaluar DE e inflamación vascular asociadas a HS. La defensa antioxidante no ejercería un rol en estos mecanismos. El tratamiento con LT4 produjo una significativa caída de ET1, pudiendo necesitarse un período más largo de eutiroidismo para normalizarla. En AIT, niveles de TSH >2,5 mUI/L podrían sugerir un mínimo grado de hipotiroidismo justificando la elevación en ET1 y PCR, sin descartar el rol de la AIT "per se".

ABSTRACT The measurement of endothelin-1 (ET1) and high sensitivity C-reactive protein (hsCRP) as markers of endothelial dysfunction (ED) and vascular inflammation in subclinical hypothyroidism (SH) has shown controversial results. The role of oxidative stress and antioxidant defense (TRAP) is a matter of discussion. Objectives To establish if SH and thyroid autoimmunity (TAI), excluding other cardiovascular risk factors, may cause ED and vascular inflammation, evaluated through the measurement of ET1 and hsCRP respectively. To determine if TRAP could have some role. Additionally, changes in these parameters after treatment with levothyroxine (LT4) will be evaluated. Material and methods: 70 patients were prospectively evaluated. They were classified into: SH Group: 41 patients (normal T4, TSH> 4.2 and <10 mIU/L), TAI Group: 10 euthyroid patients (TSH <4.2 mUI/L) with positive aTPO and/or aTg and Control Group: 19 euthyroid patients without TAI. Other cardiovascular risk factors were excluded in patients and controls. Plasma ET1, hsCRP and TRAP were measured basally, and ET1 and hsCRP under LT4 therapy in the HS Group. Results There were no significant differences between the 3 groups in age, BMI, lipids and TRAP. ET1 and hsCRP were significantly higher in patients with SH (mean ± SD 1.77 ± 0.85 pg/ml and 1.5 ± 0.6 mg/l) vs. controls (0.8 ± 0.3 pg/ml y 0.5 ± 0.2 mg/l) p <0.0001 y <0.008 respectively. Similarly, in TAI patients (1.4 ± 0.4 pg/ml y 2.3 ± 1.3 mg/l) vs controls, p <0.0001 and <0.034, respectively. TSH was higher in the TAI patients versus control group (2.5 ± 0.88 versus 1.64 ± 0.5 mIU/L, p = 0.002). Twenty-four patients with SH showed a significant decrease in ET1 (p <0.001) under treatment with LT4 (8.7 ± 3.8 months). ET1 had a highly significant correlation (p <0.0001) with TSH (r = 0.5). The cut-off level of ET1 established by ROC curve was 1.32 pg/ml (Sensitivity 81.6%-Specificity 75%). Conclusions ET1 and hsCRP were useful markers to evaluate ED and vascular inflammation associated with SH. There were no differences in TRAP levels between patients and controls, so it does not appear that oxidative stress would have played any role. Treatment with LT4 produced a significant drop in ET1. Probably, a longer period of euthyroidism might be necessary to normalize ET1 levels. In TAI Group, TSH levels >2.5 mUI/L could suggest a "minimal degree" of hypothyroidism justifying the elevation in ET1 and hs CRP. The role of the TAI "per se" couldn't be completely ruled out.

The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism

ABSTRACT Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (762 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs. −20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 762 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs. −19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r = −0.15, p < 0.05), E/A (r = −0.14, p < 0.05), GLS (r = −0.26, p < 0.001), and S/TDI (r = −0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

TeleCondutas: nódulo de tireoide / TeleGuides: thyroid nodule

É uma condição comum, encontrada em 5% das mulheres e 1% dos homens. Se avaliada por ecografia, a prevalência aumenta para 19% a 68%. A principal preocupação com nódulos de tireoide é a possibilidade de neoplasia maligna de tireoide. Apesar disso, a frequência de câncer de tireoide é baixa (7% a 15 % do total de nódulos) e a maioria dos pacientes com esse diagnóstico costuma ter um bom prognóstico (mais de 90% das neoplasias são papilares ou foliculares). Esta guia apresenta informação que orienta a conduta para casos de nódulo de tireoide no contexto da Atenção Primária à Saúde, incluindo: Manifestação Clínica, Diagnóstico, Avaliação Inicial, Indicação de PAAF, Acompanhamento ecográfico de nódulo não puncionado, Conduta após PAAF, Tireoide com múltiplos nódulos, Tratamento, Encaminhamento para serviço especializado.

Neonatal screening: 9% of children with filter paper thyroid-stimulating hormone levels between 5 and 10 µIU/mL have congenital hypothyroidism / Triagem neonatal: 9% das crianças com TSH em papel filtro entre 5 e 10 µUI/mL têm hipotireoidismo congênito

Abstract Objectives: To determine the prevalence of congenital hypothyroidism in children with filter-paper blood-spot TSH (b-TSH) between 5 and 10 µIU/mL in the neonatal screening. Methods: This was a retrospective study including children screened from 2003 to 2010, with b-TSH levels between 5 and 10 µIU/mL, who were followed-up during the first two years of life when there was no serum TSH normalization. The diagnosis of congenital hypothyroidism was defined as serum TSH ≥10 µIU/mL and start of levothyroxine treatment up to 2 years of age. Results: Of the 380,741 live births, 3713 (1.04%) had filter paper TSH levels between 5 and 10 µIU/mL and, of these, 339 (9.13%) had congenital hypothyroidism. Of these, 76.11% of the cases were diagnosed in the first three months of life and 7.96% between 1 and 2 years of age. Conclusion: The study showed that 9.13% of the children with b-TSH levels between 5 and 10 µIU/mL developed hypothyroidism and that in approximately one-quarter of them, the diagnosis was confirmed only after the third month of life. Based on these findings, the authors suggest the use of a 5 µIU/mL cutoff for b-TSH levels and long-term follow-up of infants whose serum TSH has not normalized to rule out congenital hypothyroidism.

Resumo Objetivos: Determinar a prevalência de hipotireoidismo congênito em crianças com TSH em papel filtro (TSH-f) entre 5 e 10 µUI/mL na triagem neonatal. Métodos: Estudo retrospectivo que incluiu crianças triadas de 2003 a 2010, com TSH-f entre 5 e 10 µUI/mL, acompanhadas nos dois primeiros anos de vida quando não houve normalização do TSH sérico. O diagnóstico de hipotireoidismo congênito foi definido como TSH sérico igual ou superior a 10 µUI/mL e início de tratamento com levotiroxina até os dois anos. Resultados: Dos 380.741 nascidos vivos triados, 3.713 (1,04%) apresentaram TSH-f entre 5 e 10 µUI/mL e, desses, 339 (9,13%) tinham hipotireoidismo congênito. Desses, 76,11% dos casos foram diagnosticados nos primeiros três meses de vida e 7,96% entre um e dois anos. Conclusão: O estudo mostra que 9,13% das crianças com TSH-f entre 5 e 10 µUI/mL desenvolveram hipotireoidismo e que em cerca de um quarto delas o diagnóstico só se confirmou após o terceiro mês de vida. Com base nesses achados, sugere-se, para descartar o hipotireoidismo congênito, o uso do ponto de corte de TSH-f de 5 µUI/mL e o acompanhamento em longo prazo dos lactentes cujo TSH sérico não tenha se normalizado.