Momento de administración de la levotiroxina en pacientes con hipotiroidismo / Timing of levothyroxine administration in patients with hypothyroidism

El hipotiroidismo primario, caracterizado por una disminución en la síntesis de hormonas tiroideas, es el trastorno endocrinológico más frecuente, y la levotiroxina, el tratamiento de elección. Usualmente se recomienda su administración por la mañana, una hora antes del desayuno. A partir de la consulta de una paciente con dificultades para la adherencia ala toma de la medicación en ayunas, la autora de este artículo lleva a cabo una búsqueda bibliográfica para revisar la evidencia que avala la administración de levotiroxina antes de acostarse. (AU)

Primary hypothyroidism, characterized by a decrease in the synthesis of thyroid hormones, is the most common endocrine disorder, and levothyroxine being the treatment of choice. Its administration is usually recommended in the morning, one hour before breakfast. Based on the consultation of a patient with difficulties in sticking to taking medication on an empty stomach, the author of this article carried out a bibliographic search to review the evidence that supports the administrationof levothyroxine before bedtime. (AU)

Atipicidad en el hipotiroidismo congénito: síndrome de Kocher-Debré-Semelaigne. Reporte de caso / Atypicality in congenital hypothyroidism: Kocher-Debré-Semelaigne. Case report

El síndrome de Kocher Debré Semelaigne (SKDS) se describe dentro de las formas clínicas atípicas asociadas al hipotiroidismo congénito (HC) severo, no tratado y de larga evolución, con manifestaciones de pseudohipertrofia muscular difusa y debilidad muscular predominantemente proximal, reversible al reemplazo con tiroxina. Es raro en países con programas de pesquisa neonatal. Objetivo: reportar el caso de un niño con diagnóstico de HC por disembriogenesis (atireosis), que se mantuvo con mal control de la enfermedad durante el primer año de vida y manifestaciones miopáticas desde la etapa neonatal. Resultados: se confirma el diagnóstico a través de estudios específicos, con evidencias de patrones miopáticos característicos. Se logra regresión clínica parcial a los nueve meses de mantener estabilidad de la TSH y las hormonas tiroideas (HT), coincidiendo con la normalización de la enzima de músculo creatinfosfoquinasa (CPK). A los 12 años de seguimiento, mantenía ligera hipertrofia de la musculatura de las extremidades superiores, dorsales y glúteos, a pesar de mantenerse eutiroideo. Conclusiones: la presencia de hipertrofia muscular debe considerarse un dato clínico de sospecha de hipotiroidismo, aun con la implementación de los programas de pesquisa neonatal. Es posible la regresión parcial de la pseudohipertrofia muscular con el restablecimiento de la función tiroidea. Se debe tomar en cuenta en el diagnóstico diferencial de otras miopatías primarias

Kocher-Debré-Semelaigne Syndrome (SKDS) is described within the atypical clinical forms associated with severe, untreated and long-standing congenital hypothyroidism with manifestations of diffuse muscle pseudohypertrophy and predominantly proximal muscle weakness, reversible to replacement with levothyroxine. objective: To report the case of a child with congenital hypothyroidism due to disembriogenesis (atyreosis), who remained with poor control of the disease during the 1st year of life and myopathic manifestations from de neonatal stage. Results: The diagnosis is confirmed through specific studies, with evidence of characteristic myopathic patterns. Partial clinical regression is achieved 9 months after maintaining stability of TSH and thyroid hormones, coinciding with the normalization of the muscle enzyme creatine phosphokinase (CPK). At 12 years of follow-up, he maintained slight hypertrophy of the muscle of the upper extremities, dorsal and buttocks, despite remaining euthyroid. Conclusions: The presence of muscular hypertrophy should be considered a clinical finding of suspected hypothyroidism, even with the implementation of neonatal screening programs. Partial regression of muscle pseudohypertrophy is possible with restoration of thyroid function, and should be taken into account in the differential diagnosis of other primary myopathies

Endocrinopatías por inmunoterapia oncológica / Endocrinopathies by oncological immunotherapy

La relación entre inmunidad y cáncer es compleja. Las células tumorales desarrollan mecanismos de evasión a las respuestas del sistema inmunitario. Esta capacidad permite su supervivencia y crecimiento. La inmunoterapia ha transformado el tratamiento oncológico mejorando la respuesta inmunitaria contra la célula tumoral. Esta se basa en el bloqueo de los puntos de control inmunitario mediante anticuerpos monoclonales contra la molécula inhibidora CTLA-4 (antígeno 4 del linfocito T citotóxico [CTLA-4]) y la proteína 1 de muerte celular programada y su ligando (PD-1/PD-L1). Aunque los inhibidores de los puntos de control inmunitario (ICIs) son fármacos bien tolerados, tienen un perfil de efectos adversos conocido como eventos adversos inmunorrelacionados (EAI). Estos afectan varios sistemas, incluyendo las glándulas endocrinas. Los eventos adversos endocrinos más frecuentes son la disfunción tiroidea, la insuficiencia hipofisaria, la diabetes mellitus autoinmune y la insuficiencia suprarrenal primaria. El creciente conocimiento de estos efectos adversos endocrinos ha llevado a estrategias de tratamiento efectivo con el reemplazo hormonal correspondiente. El objetivo de esta revisión es reconocer la incidencia de estas nuevas endocrinopatías, la fisiopatología, su valoración clínica y el manejo terapéutico. (AU)

The relationship between immunity and cancer is complex. Tumor cells develop evasion mechanisms to the immune system responses. This ability allows their survival and progression. Immunotherapy has transformed cancer treatment by improving the immune response against tumor cells. This is achieved by blocking immune checkpoints with monoclonal antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 and its ligand (PD-1 / PD-L1). Although the immune checkpoint inhibitors (ICIs) are well tolerated drugs, they have a profile of adverse effects known as immune-related adverse events (irAES). These involve diverse systems, including the endocrine glands. The most frequent endocrine immune-related adverse events are thyroid and pituitary dysfunction, autoimmune diabetes mellitus and primary adrenal insufficiency. The increasing knowledge of these irAES has led to effective treatment strategies with the corresponding hormonal replacement. The objective of this review is to recognize the incidence of these new endocrinopathies, the physiopathology, their clinical evaluation, and therapeutic management. (AU)

Macro TSH como causa de hipotiroidismo refractario: a propósito de dos casos clínicos / Macro TSH as a cause of refractory hypothyroidism: based on two clinical cases

Se presenta el caso de dos mujeres con hipotiroidismo, con TSH persistentemente elevada, lo que hacía aumentar la dosis de levotiroxina y llegar a un hipertiroidismo clínico con TSH anormalmente alto. Se realizó un seguimiento de los niveles de TSH y T4 libre, durante un período de 20 y 10 meses respectivamente. En ambas situaciones no hubo una respuesta esperable a las dosis de levotiroxina ascendentes. Después de descartar causas posibles que explicaran esta situación, se sospechó y confirmó la presencia de Macro TSH, que es un complejo biológicamente inactivo de TSH e Inmunoglobulina G. Se obtiene como resultado la estabilidad de ambas pacientes siendo su seguimiento prioritariamente clínico y con mediciones de T4L, comprendiendo por qué la TSH persiste elevada. Nos pareció interesante la comunicación de estos casos, que permite recordar causas atípicas de refractariedad al tratamiento con levotiroxina, como es la macro TSH, indispensable pesquisar para el manejo adecuado de estos pacientes.

An inadequate response to levothyroxine treatment in a patient with hypothyroidism suggests lack of intake, lack of absorption, nephrotic syndrome, thyroid hormone resistance among other reasons. We present the case of two women with hypothyroidism and a persistently elevated level of TSH, which required increasing the dose of levothyroxine, resulting in a clinical hyperthyroidism with an abnormally high TSH. A TSH and free T4 follow up was performed during a period of 20 and 10 months respectively, in both situations there was not an adequate response to rising levothyroxine treatment. After ruling out other possible causes that could explain this situation, it was suspected and then confirmed the presence of Macro TSH, which is a biologically inactive complex of TSH and Immunoglobulin G. Therefore, both patients achieved disease stability once controlled by clinical state and free T4 measurements, understanding why THS persited high. We present these interesting cases, because this allows us to remember atypical causes of refractory treatment with levothyroxine, such as the Macro TSH, indispensable to search for the proper management of these patients.

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)

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.

Conversion to Graves disease from Hashimoto thyroiditis: a study of 24 patients

ABSTRACT Objective: The conversion of Hashimoto's thyroiditis (HT) to hyperthyroidism due to thyrotropin receptor antibodies is intriguing and considered rare. The contribution of TSH receptor blocking antibodies (TRAb), which may be stimulators (TSAb) or blockers (TBAb), is suspected. We describe clinical and biological variables in a series of patients switching from Hashimoto's thyroiditis to Grave's disease. Subjects and methods: Retrospective case study of 24 patients with Hashimoto's thyroiditis followed during 48 ± 36 months that developed later Graves' disease (GD). These variables were analysed in the hypo and hyperthyroid phase: age, sex, initial TSH, free triiodothyronine (fT3), free thyroxine (fT4), anti-TPO, TBII antibodies, parietal cell autoantibodies, time between hypo and hyperthyroidism, thyroid volume and levothyroxine doses (LT). Results: In HT, mean TSH was 9.4 ± 26.1 UI/L and levothyroxine treatment was 66.2 ± 30.8 µg/day. The switch to GD was observed 38 ± 45 months after HT diagnosis. As expected, we found significant differences on TSH, FT3, FT4 and TBAb levels. Three out of 14 patients had parietal cell autoantibodies. In two of these three cases there was an Helicobacter pylori infection. There were no significant differences between HT and GD groups with respect to thyroid volume. Conclusions: To our knowledge, large series documenting the conversion of HT to GD are scarce. Although rare, this phenomenon should not be misdiagnosed. Suspicion should be raised whenever thyroxine posology must be tapered down during the follow-up of HT patients. Further immunological and genetic studies are needed to explain this unusual autoimmune change.

Tratamiento con radioyodo endovenoso y estimulación con TSH recombinante humana en paciente con cáncer de tiroides extenso: caso clínico / Intravenous radioiodine and recombinant human TSH in a patient with extensive thyroid cáncer: report of one case

Abstract: We report a 72-years-old male patient with extensive differentiated thyroid cancer (DTC), who required a tracheostomy and gastrostomy. Considering his clinical condition, risk of aspiration and management of the ostomies, radioiodine (131I) was administered intravenously, using recombinant human thyrotropin (rhTSH) and levothyroxine. The procedure was successful, both clinically and in terms of radioprotection.

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.

Terapia combinada de levotiroxina y liotironina para hipotiroidismo / Combined therapy with levothyroxine and liothyronine for hypothyroidism

INTRODUCCIÓN La suplementación habitual del hipotiroidismo se basa en la monoterapia con levotiroxina, sin embargo, algunos pacientes persisten con síntomas atribuibles al déficit de hormona tiroidea. Debido a esto se ha planteado que el uso de un tratamiento combinado con liotironina y levotiroxina otorgaría un mayor beneficio. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos tres revisiones sistemáticas que en conjunto incluyeron 12 estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que la adición de liotironina al tratamiento del hipotiroidismo tiene un efecto mínimo o nulo sobre fatiga y calidad de vida. Probablemente tampoco mejora estado de ánimo, dolor ni función cognitiva, y no reduciría el peso corporal.

INTRODUCTION The usual supplementation for hypothyroidism is based on monotherapy with levothyroxine. However, some patients persist with symptoms attributable to the deficit of thyroid hormone. It has been suggested that the a combined treatment with liothyronine and levothyroxine would provide a greater benefit. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified three systematic reviews including twelve primary studies overall, all of which were randomized trials. We concluded that the addition of liothyronine to the treatment of hypothyroidism has minimal or no effect on fatigue and quality of life. It probably does not improve mood, pain or function cognitive, and it would not reduce body weight.

Thyroxine increases Serca2 and Ryr2 gene expression in heart failure rats with euthyroid sick syndrome

ABSTRACT Objective The current study was aimed at analyzing sarcoplasmic reticulum Ca2+ ATPase (Serca2) and ryanodine receptor type 2 (Ryr2) gene expression in rats subjected to surgery that induced HF and were subsequently treated with T4 using physiological doses. Materials and methods HF was induced in 18 male Wistar rats by clipping the ascending thoracic aorta to generate aortic stenosis (HFS group), while the control group (9-sham) underwent thoracotomy. After 21 weeks, the HFS group was subdivided into two subgroups. One group (9 Wistar rats) with HF received 1.0 µg of T4/100 g of body weight for five consecutive days (HFS/T4); the other group (9 Wistar rats) received isotonic saline solution (HFS/S). The animals were sacrificed after this treatment and examined for signs of HF. Samples from the left ventricles of these animals were analyzed by RT-qPCR for the expression of Serca2 and Ryr2 genes. Results Rats with HF developed euthyroid sick syndrome (ESS) and treatment with T4 restored the T3 values to the Sham level and increased Serca2 and Ryr2 gene expression, thereby demonstrating a possible benefit of T4 treatment for heart function in ESS associated with HF. Conclusion The T4 treatment can potentially normalize the levels of T3 as well elevated Serca2 and Ryr2 gene expression in the myocardium in heart failure rats with euthyroid sick syndrome.

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

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

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

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

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

Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole? / É necessário aumentar a dose de levotiroxina em pacientes com hipotireoidismo que usam omeprazol?

Objective It is believed that gastric pH interferes in levothyroxine absorption. Omeprazole, which acts by blocking the secretion of gastric acid, might interfere in hypothyroidism control in patients using levothyroxine and this effect could be dose dependent. The present study aimed to investigate this possibility. Subjects and methods Twenty-one patients with primary hypothyroidism who had been using a stabilized levothyroxine dosage for at least one year were selected and randomly assigned to take omeprazole at the dosage of 40 mg or 20 mg per day. The mean levels of thyroid-stimulating hormone (TSH) before and 3 months after omeprazole usage were compared in the entire sample and in each group. Results Ten patients concluded the entire treatment protocol in the 20 mg group and nine patients in the 40 mg group. There was no significant difference in TSH levels before and 3 months after omeprazole treatment in the entire patient sample (median levels: 2.28 vs. 2.30 mU/L, respectively: p = 0.56). Analysis of each subgroup (20 and 40 mg) showed no significant variation in TSH levels before and 3 months after omeprazole treatment (median levels: 2.24 vs. 2.42 mU/L, p = 0.62, and 2.28 vs. 2.30 mU/L, p = 0.82, respectively). No significant difference in the absolute (p = 0.93) or relative (p = 0.87) delta were observed between the two subgroups. Conclusion Omeprazole in the dosage of 20 or 40 mg/day does not interfere in a clinically relevant manner in the treatment of patients with hypothyroidism that was previously under control. .

Objetivo Acredita-se que o pH gástrico possa interferir na absorção de levotiroxina. O omeprazol, ao inibir a secreção de ácido gástrico, poderia interferir no controle do hipotireoidismo em pacientes em uso de levotiroxina de forma dose-dependente. O presente estudo tem como objetivo investigar essa hipótese. Sujeitos e métodos Vinte e um pacientes em uso de dose estável de levotiroxina por no mínimo um ano foram incluídos e aleatoriamente selecionados para iniciar o uso de omeprazol na dose de 40 mg ou 20 mg por dia. Foram comparados os níveis médios de hormônio tireoestimulante (TSH) antes e 3 meses após o uso de omeprazol, na amostra total e em cada grupo. Resultados Dez pacientes concluíram o protocolo de tratamento no grupo de 20 mg e nove, no grupo de 40 mg. Não houve diferença significativa nos níveis de TSH antes e 3 meses após terapia com omeprazol na amostra total de pacientes (média: 2,28 vs. 2,30 mU/L, respectivamente: p = 0,56). A análise de cada subgrupo (20 e 40 mg) não demonstrou variação significativa nos níveis de TSH antes e 3 meses após terapia com omeprazol (média: 2,24 vs. 2,42 mU/L, p = 0,62 e 2,28 vs. 2,30 um/L, p = 0,82, respectivamente). Não houve diferença significativa no delta absoluto (p = 0,93) ou relativo (p = 0,87) entre os dois subgrupos. Conclusão Omeprazol na dose de 20 ou 40 mg/dia não interfere de forma clinicamente relevante no tratamento de pacientes com hipotireoidismo previamente bem controlados. .

Tratamento do hipotireoidismo no idoso / Treatment of hypothyroidism in the elderly

A população mundial está envelhecendo, e o interesse pelo estudo da associação entre disfunções tireoidianas e o processo de envelhecimento também. Existem evidências de que os níveis de TSH são mais elevados na população idosa, com uma relação positiva entre os aumentos da faixa etária e do TSH. A elevação do TSH pode chegar a mais de 20%, sendo que a grande maioria apresenta hipotireoidismo subclínico (HSC). Essa elevação ocorre também na população idosa sem doença autoimune tireoidiana, sugerindo que faça parte do processo fisiológico relacionado ao envelhecimento...

The world population is aging and the interest in the study of association between thyroid dysfunctions and aging process is also increasing. There are evidences that serum TSH levels are higher in the elderly population, with a positive relationship between age and TSH. The prevalence of TSH elevations can reach over 20%, and the vast majority has subclinical hypothyroidism (SCH). This elevation of TSH occurs also in the elderly population without autoimmune thyroid disease, suggesting that it could be part of a physiological process related to aging...

Study of Hypothyroid Related Atrioventricular Block in Elderly Hypothyroid Patients and Assessment of Any Reversal After L-Thyroxin Therapy.

We intend to study the pattern of atrioventricular conduction blockage in hypothyroidism in elderly population and assessment of any reversal after Lthyroxin therapy. Aims : 1) To detect hypothyroid related AV block in elderly hypothyroid patients. 2) To supplement L-thyroxin for 6 weeksand check whether the AV conduction is restored or not. Settings and design : The proposed study is a hospital based case control study followed by interventional one. Hypothyroid elderly subjects attending OPD over a period of one year were considered for the purposes of observation. Age and gender matched controls were selected simultaneously. Methods and materials : 42 elderly (>60 years) hypothyroid patients were selected as case and 45euthyroid sage and gender matched subjects as control. ECG was done to asses the degree of AV block. Any degree of AV conduction block noted, was supplemented with L-thyroxin for 6 weeks and later resting ECG was done to assess whether the normal AV conduction was restored or not. Statistical analysis : Chi square test done between the case and control group and paired T test done before and after L-thyroxin supplementation. Results : Chi square test revealed that out of 42 cases, a significant proportion of 62% had increased P-R interval (P<.001), whereas 76% out of 45 control had normal P-R interval.After L-thyroxin supplementation in 69% of the cases, normal P-R interval was restored (P< .001, paired T test value 13.484). Conclusion : In hypothyroid patients AV block detected in resting ECG should be a matter of concern, because if the conduction block is reversed to normal sinus rhythm by thyroxin supplementation, unnecessary pacemaker implantation can be avoided.

Resposta Hipertrofica da Associacao de Hormonio Tireoidiano e de Exercicio Fisico no Coracao de Ratos / Hypertrophic response of the Association of Thyroid Hormone and Exercise in the Heart of Rats

Fundamento: A hipertrofia cardíaca constitui um dos componentes do remodelamento cardíaco e ocorre em resposta a aumento da atividade ou da sobrecarga funcional do coração. Objetivo: Avaliar a resposta hipertrófica da associação do hormônio tireoidiano e do exercício físico no coração de ratos. Método: Foram utilizados 37 ratos da linhagem Wistar, machos, adultos, distribuídos aleatoriamente em quatro grupos: controle, hormônio (HT), exercício (E), hormônio tireoidiano e exercício (H + E). O grupo hormônio recebeu diariamente levotiroxina sódica por gavagem, na dose de 20 μg de hormônio tireoidiano/100 g de peso corporal; o grupo exercício realizou natação cinco vezes por semana, com peso adicional correspondente a 20% do peso corporal, durante seis semanas; no grupo H + E foram aplicados simultaneamente os tratamentos dos grupos HT e E. A estatísica utilizada foi a análise de variância complementada, quando necessário, pelo teste de Tukey e o teste de correlação de Pearson. Resultados: O T4 foi mais elevado nos grupos HT e H + E. O peso total do coração foi maior nos grupos que receberam hormônio tireoidiano, e o peso ventricular esquerdo foi maior no grupo HT. O diâmetro transversal dos cardiomiócitos aumentou nos grupos HT, E e H + E. A porcentagem de colágeno foi maior nos grupos E e H + E. A análise da correlação entre as variáveis apresentou distintas respostas. Conclusão: A associação do hormônio tireoidiano com exercício físico de elevada intensidade produziu hipertrofia cardíaca e gerou um padrão hipertrófico não correlacionado diretamente ao grau de fibrose. .

Background: Cardiac hypertrophy is a component of cardiac remodeling occurring in response to an increase of the activity or functional overload of the heart. Objective: Assess hypertrophic response of the association of thyroid hormone and exercise in the rat heart. Methods: We used 37 Wistar rats, male, adults were randomly divided into four groups: control, hormone (TH), exercise (E), thyroid hormone and exercise (H + E); the group received daily hormone levothyroxine sodium by gavage at a dose of 20 μg thyroid hormone/100g body weight, the exercise group took swimming five times a week, with additional weight corresponding to 20% of body weight for six weeks; in group H + E were applied simultaneously TH treatment groups and E. The statistics used was analysis of variance, where appropriate, by Tukey test and Pearson correlation test. Results: The T4 was greater in groups TH and H + E. The total weight of the heart was greater in patients who received thyroid hormone and left ventricular weight was greater in the TH group. The transverse diameter of cardiomyocytes increased in groups TH, E and H + E. The percentage of collagen was greater in groups E and H + E Correlation analysis between variables showed distinct responses. Conclusion: The association of thyroid hormone with high-intensity exercise produced cardiac hypertrophy, and generated a standard hypertrophy not directly correlated to the degree of fibrosis. .

Avaliação terapêutica e posológica da levotiroxina sódica em cães com hipotiroidismo primário adquirido / L-levothyroxine therapeutic dosage evaluation in dogs with primary hypothyroidism

O hipotireoidismo primário adquirido é uma endocrinopatia frequentemente diagnosticada na espécie canina. A terapia consiste na suplementação oral com levotiroxina sódica (L-tiroxina), no entanto vários protocolos terapêuticos têm sido propostos pela literatura, com doses variando 11 a 44µg/kg uma a duas vezes ao dia, visto à grande variabilidade de absorção e meia-vida plasmática do fármaco. Foram estudados 30 cães com hipotiroidismo primário adquirido (13 machos e 17 fêmeas, idade média de 7,9±1,9 anos e peso médio de 19,1±12,6 kg) atendidos no Hospital Veterinário da Universidade Guarulhos (UnG) e no Serviço de Endocrinologia de duas clínicas particulares da cidade de São Paulo (2009-2011), com o objetivo de avaliar a posologia e a frequência de administração da L-tiroxina, mais frequentemente utilizada, capaz de garantir um controle terapêutico satisfatório, avaliado através dos sinais clínicos e do teste pós-tiroxina, além de correlacionar a dose de tiroxina empregada com o peso dos animais. A dose média de tiroxina utilizada em nossa casuística foi de 16,9±3,1µg/kg, sendo a frequência de administração a cada 12 horas em 50% dos casos. Para se investigar uma possível correlação entre o peso e a dosagem de tiroxina utilizada, uma vez que cães de pequeno porte apresentam maior taxa metabólica que cães de grande porte, os animais foram agrupados em grupo A, cães com peso <10 Kg (n=12/30; 7,7±2,1 kg) e grupo B, cães com peso >10 kg (n=18/30, 26,8±10,7 kg). A dose média de tiroxina empregada nos grupos A e B não apresentaram diferença estatística e foram, respectivamente, 16±3µg/kg e 17±3µg/kg. A frequência de administração foi 50% a cada 24 horas e 50% a cada 12 horas para ambos os grupos. Dessa forma, a dose de tiroxina não parece se correlacionar com o peso do animal, sendo imprevisível quem deverá receber dose e frequência máxima da medicação. O protocolo deve ser individualizado e o paciente devidamente monitorado.

The acquired primary hypothyroidism is a frequently diagnosed endocrinopathy in dogs. The therapy constitutes in oral supplementation with sodium levothyroxine (L-thyroxine), however various therapeutic protocols have been proposed in the literature, with doses ranging from11 to 44mg/kg once or twice a day, since L-thyroxine has a great variability of absorption and plasma half life. We studied 30 dogs with primary hypothyroidism (13 males and 17 females, mean age 7.9±1.9 years and mean weight of 19.1±12.6 kg), in order to evaluate the dose and frequency of administration of L-thyroxine used more often able to secure a satisfactory therapeutic control as measured by clinical signs and test post-pill, and to correlate the amount of thyroxine employed with the animals' weight. The mean dose of thyroxine used in our study was 16.9±3.1mg/kg, and the frequency of administration every 12 hours in 50% of cases. To investigate a possible correlation between weight and dose of thyroxine used, since small dogs have a higher metabolic rate than large dogs, the animals were grouped in Group A, dogs weighing <10 kg (n=12/30, 7.7±2.1 kg) and group B, dogs weighing> 10 kg (n=18/30, 26.8±10.7 kg). The mean dose of thyroxine used in groups A and B did not differ significantly and were respectively 16±3mg/kg and 17±3mg/kg. The frequency of administration was 50% every 24 hours and 50% every 12 hours for both groups. Thus, the dose of thyroxine does not seem to correlate with the weight of the animal being unpredictable who should receive the highest dose and frequency of the medication. The protocol should be individualized and the patient adequately monitored.

Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study / Tratamento de hipotiroidismo primário com doses semanais de levotiroxina: um estudo randomizado, unicego, crossover

OBJECTIVE: Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative. SUBJECTS AND METHODS: This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4. After six weeks, they switched regimens. Thyroid parameters were measured at baseline, and after 42 and 84 days. Echocardiogram and hyperthyroidism symptoms were evaluated before and four hours after LT4 intake. RESULTS: In the weekly dose treatment, fT4 levels were higher after taking LT4, and lower seven days after the last dose; by the 6th week there was a small decrease in T3 levels. TSH remained unchanged and there were no hyperthyroidism symptoms or echocardiographic manifestations. CONCLUSION: Weekly dose leads to transient increases in fT4, without hyperthyroidism or cardiac symptoms. That approach seems to be a safe alternative for the treatment of hypothyroidism.

OBJETIVO: Aderência ao tratamento do hipotiroidismo é comprometido pelo uso diário de levotiroxina, e doses semanais poderiam ser uma alternativa. SUJEITOS E MÉTODOS: Este é um estudo randomizado, crossover. Quatorze mulheres foram selecionadas para receber LT4 diariamente ou semanalmente. Após seis semanas, houve inversão do regime de tratamento. Avaliações tireoideanas foram realizadas antes, após 42 e 84 dias. Avaliação de sintomas de hipertireoidismo e ecocardiograma foi realizada antes e após quatro horas de LT4. RESULTADOS: Com dose semanal, os níveis de fT4 foram mais elevados logo após a dose de LT4, e menores após sete dias; após seis semanas, houve diminuição de T3. TSH permaneceu inalterado e não houve manifestações ecocardiográficas ou de hipertireodismo. CONCLUSÃO: Dose semanal de LT4 leva à elevação de fT4, sem manifestações de hipertireoidismo, e parece ser uma alternativa segura para o tratamento do hipotireoidismo.

Resistencia a hormonas tiroideas no asociada a mutación de la isoforma beta del receptor de hormonas tiroideas: caso clínico / Thyroid hormone resistance not associated to mutation on the beta isoform of the thyroid hormone receptor: report of one case

Thyroid hormone resistance (RTH) is inherited as an autosomal dominant trait, with variable clinical presentations. The hallmark of the syndrome is a variable degree of resistance to thyroid hormones, with high levels of circulating thyroid hormones, inappropriately normal or elevated TSH values and a clinical pattern of mixed hypothyroidism and hyperthyroidism. RTH is related in more than 85 percent of cases to thyroid hormone beta receptor mutations. We report a 11 years female with a history of treatment with propylthiouracil (PTU) for hyperthyroidism, presenting with a progressive goiter. Thyroidectomy was performed, removing 233 grams of thyroid tissue showing follicular hyperplasia. After surgery, a fast growth of the remnant thyroid gland was observed along with tachycardia. Laboratory showed a TSH of 38 mU/mL a triiodothyronine level of 300 ng/dL a thyroxin level of 14.8 ug/dL and a free thyroxin of 3.19 ng/dL, suggesting the diagnosis of RTH. The molecular study was negative for mutation of the beta isoform of thyroid hormone receptor. The possible theories that can explain these findings are discussed.