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.

Multidisciplinary Treatment for Severe Secondary Raynaud's Phenomenon: A Case Report / 中国医学科学杂志(英文版)

Raynaud's phenomenon is a symptom complex manifested as intermittent fingertip ischemia caused by cold or other sympathetic drivers. Secondary Raynaud's phenomenon is often more severe and could even lead to finger ulceration, making it particularly complicated to treat. We describe a case of severe Raynaud's phenomenon secondary to subclinical hypothyroidism lasting for more than 6 hours in a 65-year-old woman. The patient was also diagnosed with hypothyroidism, epilepsy, and secondary soft tissue infection of the right middle and ring fingers. After careful multidisciplinary consultation and discussion, the patient received vasodilation, anticoagulation, thyroxine supplementation, stellate ganglion block, hyperbaric oxygen therapy and debridement. The patient responded well to the medication, avoiding amputation or obviously dysfunction. Multidisciplinary team gathering the doctors from different departments proposes appropriate strategies for patients with severe Raynaud's phenomenon and could improve the prognosis and satisfaction of patient effectively.

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.

Incremento de la proteína C reactiva ultrasensible en pacientes con hipotiroidismo subclínico y su posible relación con el desarrollo de daño cardiovascular / Increase in high sensitivity C-reactive protein in patients with subclinical hypothyroidism and its possible relationship to the development of cardiovascular damages

INTRODUCCIÓN: El hipotiroidismo subclínico (HSC) se define bioquímicamente por una elevación en la concentración sérica de la hormona estimulante de la tiroides (TSH), con niveles normales de tiroxina libre (T4L). La asociación entre el HSC y el daño cardiovascular ha sido un tema controversial. OBJETIVO: determinar la asociación entre el HSC y el desarrollo de la enfermedad cardiovascular mediante la cuantificación de la proteína C reactiva ultrasensible PCR-us y la determinación de lípidos circulantes asociados a la enfermedad cardiovascular y la ateroesclerosis. MÉTODOS: Estudio descriptivo, correlacional de corte transversal realizado en el Hospital IESS de Riobamba, Ecuador en el periodo comprendido desde enero a diciembre de 2019. Se estudiaron 70 individuos (40 pacientes con HSC y 30 controles) con edades entre 18 y 75 años. Se realizaron las historias clínicas y el examen físico a cada paciente y la toma de las muestras sanguíneas para determinar la concentración sérica de los siguientes parámetros bioquímicos y hormonales: colesterol total, triglicéridos, HDL colesterol y LDL colesterol, TSH, T4L y PCR-us. RESULTADOS: Se encontró un incremento significativo en la concentración de colesterol total (p<0.0001), LDL colesterol (p<0.01) y PCR-us (p<0.0001) en los pacientes con HSC vs los controles. Se observó una correlación positiva (p<0.0001; r=0.9148) entre la TSH y la PCR-us en los pacientes con HSC. CONCLUSIÓN: los pacientes con HSC experimentan una elevación en los niveles séricos de PCR-us la cual está correlacionada con un incremento en la concentración sérica de TSH. Estos parámetros asociados a un aumento del colesterol total y de la LDL colesterol sugieren un estado inflamatorio de bajo grado que podría estar asociado con el desarrollo de aterosclerosis y daño cardiovascular.

INTRODUCTION: Subclinical hypothyroidism (SH) is defined biochemically by an elevation in serum thyroid stimulating hormone (TSH) concentration, with normal levels of free thyroxine (T4L). The association between SH and cardiovascular damage has been a controversial issue. OBJECTIVE: to determine the association between SH and the development of cardiovascular disease through the quantification of the high sensitivity C-reactive protein (hs-PCR) and the determination of circulating lipids associated to cardiovascular disease and atherosclerosis. METHODS: Observational, correlational cross-sectional study with patients captured in the internal medicine office as well as those attending screening activities at the IESS Hospital in Riobamba- Ecuador, in the period from January to December 2019. Seventy individuals (40 patients with SH and 30 controls) between the ages of 18 and 75 years were studied. Each patient's medical history and physical examination were performed, and blood samples were taken to determine the serum concentration of the following biochemical and hormonal parameters: total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, TSH, T4L and hs-PCR. RESULTS: A significant increase in the concentration of total cholesterol (p<0.0001), LDL cholesterol (p<0.01) and hs-PCR (p<0.0001) was found in patients with SH vs. controls. A positive correlation (p<0.0001; r=0.9148) was observed between TSH and hs-PCR in patients with SH. CONCLUSION: patients with SH experience an elevation in serum hs-PCR levels which is correlated with an increase in serum TSH concentration. These parameters associated with an increase in total cholesterol and LDL cholesterol suggest a low-grade inflammatory state that may be associated with the development of atherosclerosis and cardiovascular damage.

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

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

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Efectos del entrenamiento físico en pacientes con hipotiroidismo subclínico: una revisión sistemática / Effects of physical training in patients with subclinical hypothyroidism: a systematic review

OBJETIVO: revisar la bibliografía disponible sobre los efectos del entrenamiento en pacientes con hipotiroidismo subclínico. MATERIAL Y MÉTODOS: se realizó una revisión de las bases de datos PubMed, Scopus y Springer incluyendo artículos originales publicados desde el 01 enero del 2009 hasta 11 de junio de 2019 en los que se intervino de forma aguda o prolongada con entrenamiento en pacientes con hipotiroidismo subclínico. Los conectores utilizados fueron AND y OR junto con las palabras claves hypothyroidism, exercise, effect, thyroid hormone, training, subclinical hypothyroidism, underactive thyroid, aerobic training, anaerobic training, resistance training, strength training. Las palabras claves debían encontrarse en los títulos y resumen. Se evaluó en dos fases la elegibilidad de los artículos según: título, idioma, año de publicación y el análisis de texto completo. RESULTADOS: 8 de las 17 publicaciones encontradas en la búsqueda cumplieron con los criterios de inclusión. En estos se reportó una mejora en la calidad de vida y capacidad física posterior a la aplicación de un programa de entrenamiento mientras que ante un ejercicio físico agudo se observó una cinética cardiorrespiratoria más lenta en pacientes con HSC. CONCLUSIONES: el entrenamiento físico produce mejoras en la calidad de vida y capacidad aeróbica. Se requiere de más investigación en el área.

OBJECTIVE: the aim of this article was to perform a systematic review investigating the effects of training in patients with subclinical hypothyroidism (HSC). MATERIAL AND METHODS: PubMed, Scopus and Springer databases were searched. Original articles published between January 01, 2009 -June 11, 2019 in which acute exercise or prolonged training programs applied to patients with HSC were included. The search was made using AND & OR boolean operators and the following key words: hypothyroidism, exercise, effect, thyroid hormone, training, subclinical hypothyroidism, underactive thyroid, aerobic training, anaerobic training, resistance training, strength training, were required to be found in titles or abstract for the first eligibility phase, while the second phase consisted in article analysis. RESULTS: eight studies met the inclusion criteria. Improves in quality of life, and physical fitness were found as effect of a training program while kinematic cardiorespiratory acute response to exercise was found to be slower in patients with HSC. CONCLUSIONS: physical training improves quality of life and aerobic capacity in patients with subclinical hypothyroidism. More investigation in this area is needed.

Resección transoral endoscópica de tiroides lingual / Endoscopic transoral resection of lingual thyroid

La presencia de tejido tiroideo ectópico en la base de la lengua es muy infrecuente, y la mayoría de los pacientes tienen hipotiroidismo. La indicación de tratamiento depende de la presencia o no de síntomas; la cirugía es la primera elección. Diversas técnicas quirúrgicas han sido descriptas, pero para nosotros el abordaje transoral con endoscopios constituye la mejor opción, por la buena exposición y la mínima morbilidad que produce. Se describe el caso clínico de una mujer que consultó por odinofagia, con diagnóstico de tiroides lingual y que fue tratada con éxito mediante un abordaje transoral con asistencia de endoscopios. (AU)

The presence of ectopic thyroid tissue at the base of the tongue is very rare, and most patients have hypothyroidism. The indication of treatment depends on the presence or not of symptoms, surgery being the first choice. Various surgical techniques have been described, being for us the transoral approach with endoscopes the best option, due to the good exposure, and minimum morbidity that it produces. The clinical case of a woman who consulted for odynophagia, with a diagnosis of lingual thyroid and who was successfully treated by a transoral approach with endoscopic assistance is described. (AU)

Relación entre hipotiroidismo y artritis reumatoide / Relationship between hypothyroidism and rheumatoid arthritis

Introducción: el hipotiroidismo es una enfermedad sistémica, crónica caracterizada por la disminución de la producción de hormonas tiroideas, en muchas ocasiones el trastorno inmunológico forma parte del mecanismo etiopatogénico de la enfermedad. Se asocian con otras enfermedades autoinmunes como es el caso de la artritis reumatoide, generando de esta forma un complejo cortejo sintomático en el que ambas afecciones pueden coexistir provocando importantes grados de discapacidad funcional y de disminución de la percepción de calidad de vida relacionada con la salud. Objetivo: describir la relación existente entre las enfermedades tiroideas y la artritis reumatoide. Método: estudio descriptivo en 265 pacientes con artritis reumatoide según los criterios del Colegio Americano de Reumatología para describir la relación entre esta enfermedad y los trastornos de la glándula tiroides. Se utilizó coeficiente de correlación de Pearson para determinar la relación existente entre ambas afecciones. Resultados: promedio de edad general de 58,39 años y de pacientes con hipotiroidismo de 66,32 años. Predominio de pacientes femeninas (76,98 por ciento ) y con tiempo de evolución entre 3 y 5 años. El 29,81 por ciento de los casos presentó diagnóstico de hipotiroidismo confirmado, con predominio en pacientes femeninas (86,08 por ciento ), edad mayor de 65 años (49,37 por ciento ) y tiempo de evolución de la artritis reumatoide mayor de cinco años (53,16 por ciento ). Conclusiones: existe un elevado por ciento de pacientes con hipotiroidismo y artritis reumatoide; aunque ambas afecciones comparten mecanismos inmunológicos comunes, no se encuentra una relación directa entre ambas, no pudiéndose establecer una relación causa efecto entre ambas afecciones(AU)

Introduction: hypothyroidism is a systemic, chronic disease characterized by decreased production of thyroid hormones, in many cases the immune disorder is part of the etiopathogenic mechanism of the disease. They are associated with other autoimmune diseases such as rheumatoid arthritis, thus generating a complex symptomatic courtship in which both conditions can coexist leading to significant degrees of functional disability and decreased perception of quality of life related to health. Objective: to describe the relationship between thyroid diseases and rheumatoid arthritis. Method: descriptive study in 265 patients with rheumatoid arthritis according to the criteria of the American College of Rheumatology to describe the relationship between this disease and disorders of the thyroid gland. Pearson's correlation coefficient was used to determine the relationship between both conditions. Results: average age of 58.39 years and of patients with hypothyroidism of 66.32 years. Predominance of female patients (76.98 percent) and with evolution time between 3 and 5 years. The 29.81 percent of the cases presented a diagnosis of confirmed hypothyroidism, with predominance in female patients (86.08 percent), age over 65 years (49.37 percent) and time of evolution of rheumatoid arthritis greater than five years (53.16 percent). Conclusions: there is a high percentage of patients with hypothyroidism and rheumatoid arthritis; although both conditions share common immunological mechanisms, there is no direct relationship between the two, and a causal relationship can´t be established between the two conditions(AU)

Hipotiroidismo primario, insulinorresistencia y la aterosclerosis carotídea subclínica / Primary hypothyroidism, insulin resistance, and subclinical carotid atherosclerosis

Introducción: El hipotiroidismo es considerado un factor de riesgo de enfermedad cardiovascular por su relación con la dislipidemia, la hipertensión arterial y la cardiopatía isquémica. En Cuba, después de la diabetes, ocupa el segundo lugar en la prevalencia de las enfermedades endocrinas. Objetivo: Identificar si existe relación entre la presencia de hipotiroidismo primario e insulinorresistencia y la aterosclerosis carotídea subclínica. Métodos: Se realizó un estudio analítico, multicéntrico, de corte transversal, en 150 pacientes divididos en dos grupos de comparación: 1) hipotiroidismo primario (n=75) y 2) insulinorresistencia sin hipotiroidismo (n=75) a los cuales se les realizaron procederes de laboratorio y ecográficos. Los pacientes fueron atendidos en las consultas de endocrinología de Hospital Clínico Quirúrgico 10 de Octubre, Hospital Miguel Enríquez y del Instituto Nacional de Endocrinología. Resultados: En el grupo con hipotiroidismo, los valores medios de índice de masa corporal, colesterol total, hormona estimulante de la tiroides y grosor íntima-media carotideo fueron significativamente mayores respecto a los insulinorresistentes. El HOMA-IR fue significativamente mayor en el grupo con insulinorresistencia. El valor de TSH 8805; 4,20 µmol/L mostró sensibilidad de 95,5 por ciento y especificidad de 73,3 por ciento en la predicción de aumento del GIMC. El HOMA-IR 8805;3,10 tuvo sensibilidad de 95,5 por ciento y especificidad de 73,1 por ciento. Conclusiones: El hipotiroidismo y la insulinorresistencia son predictores independientes de aterosclerosis carotídea subclínica(AU)

Introduction: Hypothyroidism is considered a risk factor for cardiovascular disease due to its relationship with dyslipidemia, high blood pressure and ischemic heart disease. In Cuba, after diabetes, it ranks second in the prevalence of endocrine diseases. Objective: To identify if there is a relationship between the presence of primary hypothyroidism and insulin resistance and subclinical carotid atherosclerosis. Methods: An analytical, multicenter, cross-sectional study was carried out in 150 patients separated into two comparison groups: 1) primary hypothyroidism (n = 75) and 2) insulin resistance with no hypothyroidism (n = 75). They underwent laboratory and ultrasound procedures. The patients were treated at the endocrinology consultations from 10 de Octubre Clinical Surgical Hospital, Miguel Enríquez Hospital and the National Institute of Endocrinology. Results: The hypothyroidism group showed mean values of body mass index, total cholesterol, thyroid-stimulating hormone and carotid intima-media thickness significantly higher compared to insulin-resistant drugs. HOMA-IR was significantly higher in the insulin resistance group. TSH value #8805; 4.20 µmol / L showed 95.5 and 73.3 percent specificity in predicting GIMC increase. HOMA-IR #8805; 3.10 had 95.5 percent sensitivity and 73.1 percent specificity. Conclusions: Hypothyroidism and insulin resistance are independent predictors of subclinical carotid atherosclerosis(AU)

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

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

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

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 refractario idiopático: un caso clínico / Idiopathic refractory hypothyroidism: case report

Introducción: El hipotiroidismo constituye una patología frecuente, y su tratamiento habitual es el suplemento de levotiroxina (LT4) oral (VO). Sin embargo, existen casos inhabituales donde no es posible corregir esta condición a pesar de la utilización de LT4 en dosis alta. El hipotiroidismo refractario se define como la persistencia del hipotiroidismo a pesar del uso de LT4 > 1,9 ug/kg/día. La prevalencia del hipotiroidismo refractario no ha sido suficientemente documentada hasta ahora. Descripción del caso: Mujer de 53 años con antecedentes de hipotiroidismo, obesidad, dislipidemia, hipertensión arterial e insulinorresistencia. Fue derivada desde APS a nivel terciario por hipotiroidismo persistente a pesar del uso de LT4 800 ug/día y liotironina 80 ug/día. En forma ambulatoria se descartaron distintas causas, como mala adhesión al tratamiento, pseudo-malabsorción, síndromes de malabsorción; interacciones farmacológicas o interacciones alimentarias. Ante esto, y manteniéndose en su condición, se decide hospitalizar. Durante la hospitalización se prueban distintas fórmulas de administración. Finalmente, se logra respuesta adecuada con LT4 por vía rectal 100 ug/día asociado a 100 ug c/12 horas VO. Discusión: A pesar de no contar con herramientas óptimas para enfrentar este caso, se logró aplicar una estrategia sistemática especializada, que permitió un buen manejo de la paciente. Luego de probar distintas formulaciones de hormonas tiroideas, se logró respuesta mediante la administración por vía rectal, lo cual sugiere que esta paciente presentaba algún trastorno celular/bioquímico intestinal alto, que impedía la absorción óptima de LT4 VO. Conclusiones: La principal fortaleza de este trabajo consiste en la demostración de la utilidad práctica, en un contexto de recursos limitados, de una estrategia de estudio y tratamiento sistemático del hipotiroidismo refractario, lo cual ha sido escasamente publicado en la literatura internacional. Además, se recalca la importancia de una intervención especializada oportuna para evitar los riesgos sistémicos asociados a dosis altas de hormonas tiroideas.

Introduction: Hypothyroidism is a common condition, and its usual treatment is the supplement of oral levothyroxine (po). However, there are unusual cases where it is not possible to correct this condition despite the use of high-dose levothyroxine. Refractory hypothyroidism is defined as the persistence of hypothyroidism despite the use of levothyroxine > 1.9 ug/kg/ day. The prevalence of refractory hypothyroidism has not been sufficiently documented so far. Case description: 53 year old woman with a history of hypothyroidism, obesity, dyslipidemia, hypertension and insulin resistance. She was sent from primary care to tertiary level due to persistent hypothyroidism despite the use of 800 ug/day levothyroxine and liothyronine 80 ug/ day. On an outpatient basis, different causes were excluded as poor adherence to treatment, pseudo-malabsorption, malabsorption syndromes; drug interactions or food interactions. Given this, and staying on her condition, it was decided to hospitalize. Different forms of administration were tested during hospitalization. Finally, got adequate response with levothyroxine rectally 100 ug/day associated with 100 ug po bid. Discussion: Despite not having optimum tools to deal with this case, it was succeeded thanks to the implementation of a specialized systematic strategy. After testing different formulations of thyroid hormones, a positive response by rectal administration was achieved, which suggests that this patient presented any high intestinal cell/biochemist disorder that prevented the optimal absorption of levothyroxine po. Conclusions: The main strength of this work consists in demonstrating the practical utility, in a context of limited resources, of a study and systematic treatment strategy of refractory hypothyroidism, which has barely been published in the international literature. It is also highlighted the importance of an early specialized intervention to prevent the systemic risks associated with high doses of thyroid hormones.

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.

Miocardiopatía dilatada secundaria a hipotiroidismo primario. Reporte de un caso / Dilated cardiomyopathy secondary to primary hypothyroidism. A case report

Resumen El vínculo entre el hipotiroidismo y varias enfermedades cardiovasculares va más allá de la asociación con los factores de riesgo vascular clásicos. Sin embargo, la miocardiopatía dilatada es una forma rara de presentación del hipotiroidismo. Se reporta el caso de una paciente femenina de 52 años que acude a urgencias por presentar tos húmeda, edema en miembros inferiores y disnea de esfuerzo, así como otros síntomas y signos típicos de hipotiroidismo. La radiografía de tórax revela cardiomegalia y el ecocardiograma informa ventrículo izquierdo dilatado, fracción de eyección disminuida y derrame pericárdico. La TSH estaba aumentada y T4 libre disminuida. Luego de comenzar tratamiento hormonal con levotiroxina se alcanzó la resolución de los síntomas y de las alteraciones radiológicas y ecocardiográficas. El presente caso resalta la importancia de realizar un interrogatorio exhaustivo y examen físico completo que aporten las pistas diagnósticas para sospechar el hipotiroidismo en pacientes con miocardiopatía dilatada.

ABSTRACT The link between hypothyroidism and several cardiovascular diseases goes beyond the association with classical vascular risk factors. However, dilated cardiomyopathy is a rare form of presentation of hypothyroidism. We report the case of a 52-year-old female patient who comes to the emergency room for having wet cough, lower limb edema and dyspnea on exertion, as well as other typical symptoms and signs of hypothyroidism. Chest x-ray reveals cardiomegaly and the echocardiogram reports dilated left ventricle, decreased ejection fraction and pericardial effusion. TSH was increased and free T4 was decreased. After starting hormonal treatment with levothyroxine, resolution of symptoms and radiological and echocardiographic alterations was achieved. The present case highlights the importance of a thorough interrogatory and complete physical examination that provide the diagnostic clues to suspect hypothyroidism in patients with dilated cardiomyopathy.

Is There Any Relationship between TSH Levels and Prognosis in Acute Coronary Syndrome? / Existe Alguma Relação entre Níveis de TSH e Prognóstico em Síndrome Coronariana Aguda?

Abstract Background: Some small studies have related higher levels of thyrotropin (TSH) to potentially worse prognosis in acute coronary syndromes. However, this relationship remains uncertain. Objective: To analyze the outcomes of patients with acute coronary syndromes in relation to the value of TSH at admission. Methods: Observational and retrospective study with 505 patients (446 in group I [TSH ≤ 4 mIU/L] and 59 in group II [TSH > 4 mIU/L]) with acute coronary syndromes between May 2010 and May 2014. We obtained data about comorbidities and the medications used at the hospital. The primary endpoint was in-hospital all-cause death. The secondary endpoint included combined events (death, non-fatal unstable angina or myocardial infarction, cardiogenic shock, bleeding and stroke). Comparisons between groups were made by one-way ANOVA and chi-square test. Multivariate analysis was determined by logistic regression. Analyses were considered significant when p < 0.05. Results: Significant differences between groups I and II were observed regarding the use of enoxaparin (75.2% vs. 57.63%, p = 0.02) and statins (84.08% vs. 71.19%, p < 0.0001), previous stroke (5.83% vs. 15.25%, p = 0.007), combined events (14.80% vs. 27.12%, OR = 3.05, p = 0.004), cardiogenic shock (4.77% vs. 6.05%, OR = 4.77, p = 0.02) and bleeding (12.09% vs. 15.25%, OR = 3.36, p = 0.012). Conclusions: In patients with acute coronary syndromes and TSH > 4 mIU/L at admission, worse prognosis was observed, with higher incidences of in-hospital combined events, cardiogenic shock and bleeding.

Resumo Fundamento: Estudos pequenos têm relacionado níveis mais elevados de hormônio tireoestimulante (TSH) a pior prognóstico em pacientes com síndrome coronariana aguda (SCA). Tal relação, no entanto, permanece incerta. Objetivo: Analisar os desfechos de pacientes com SCA, relacionando-os aos níveis de TSH medidos no setor de emergência. Métodos: Estudo retrospectivo observacional incluindo 505 pacientes com SCA (446 no grupo I: TSH ± 4 mUI/L; 59 no grupo II: TSH > 4 mUI/L) entre maio de 2010 e maio de 2014. Dados sobre comorbidades e medicamentos usados foram obtidos. O desfecho primário foi mortalidade intra-hospitalar por todas as causas. O desfecho secundário incluiu eventos combinados (morte, angina instável não fatal ou infarto do miocárdio, choque cardiogênico, sangramento e acidente vascular encefálico). A comparação entre grupos foi realizada através de ANOVA de uma via e teste do qui-quadrado. A análise multivariada foi realizada por regressão logística, adotando-se o nível de significância de p < 0,05. Resultados: Diferenças significativas foram observadas entre os grupos I e II relacionadas ao uso de enoxaparina (75,2% vs. 57,63%; p = 0,02) e estatinas (84,08% vs. 71,19%; p < 0,0001), acidente vascular encefálico prévio (5,83% vs. 15,25%; p = 0,007), eventos combinados (14,80% vs. 27,12%, OR = 3,05; p = 0,004), choque cardiogênico (4,77% vs. 6,05%, OR = 4,77; p = 0,02) e sangramento (12,09% vs. 15,25%, OR = 3,36; p = 0,012). Conclusão: Em pacientes com SCA e TSH > 4 mUI/L à admissão hospitalar, observou-se pior prognóstico associado à maior incidência de eventos combinados intra-hospitalares, choque cardiogênico e sangramentos.

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

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

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

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (β: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (β: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.