Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8 / Treatment with TRIAC in pediatric patients with MCT8

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Nutritional and quality changes in piglet concentrate affected by the mix / [Mudanças nutricionais e de qualidade no concentrado de leitão afetadas pela mistura]

The aim of this study was to evaluate the reasons of quality deviation of a concentrate from a predefined standard. Five treatments were established: T1 - Control, standard concentrate formulation (SCF); T2 - PXMore5, SCF with more 5% vitamin-mineral premix (VMP); T3 - PXLess5, SCF with less 5% VMP. All three treatments used a 400kg batches in an INTECNIAL mixer; T4 - FeedMixer, SCF using a 4,000kg batch in an IMOTO mixer; T5 - PremixMixer, SCF using a 1,200kg batch in an MUYANG mixer. For each treatment, bags of 20 kg were stored in three storage places for four months. Water activity of concentrate was affected by temperature and air relative humidity in different storage places. Regarding the kind of mixer, the greatest variation in concentration of crude protein, mineral residue, copper, zinc, and selenium was observed in the PremixMixer. Adjustments are imperative in the handling and use procedures of this kind of mixer to meet the quality requirements required in the concentrate production. Analyzing the effect of the mineral-vitamin premix level, no difference could be defined with the evaluated parameters.(AU)

O objetivo deste estudo foi avaliar as razões do desvio de qualidade de um concentrado de um padrão predefinido. Foram estabelecidos cinco tratamentos: T1 - controle, concentrado com formulação padrão (CFP); T2 - PXMais5, CFP com 5% a mais de vitaminas e minerais da pré-mistura (PVM); T3 - PXMenos5, CFP com 5% a menos de PVM. Todos esses três tratamentos utilizaram lotes de 400kg em um misturador INTECNIAL; T4 - FeedMixer, CFP usando um lote de 4.000kg em um misturador IMOTO; T5 - PremixMixer, CFP usando um lote de 1.200kg em um misturador MUYANG. Para cada tratamento, sacos de 20kg foram armazenados em três ambientes distintos por quatro meses. A atividade de água do concentrado foi afetada pela temperatura e umidade relativa do ar em diferentes locais de armazenamento. Em relação ao tipo de misturador, a maior variação na concentração de proteína bruta, resíduo mineral, cobre, zinco e selênio foi devido ao PremixMixer. Ajustes são imperativos nos procedimentos de manuseio e uso desse tipo de misturador para atender aos requisitos de qualidade exigidos na produção de concentrado. Ao se analisar o efeito do nível da pré-mistura de vitaminas e minerais, nenhuma diferença pôde ser definida com os parâmetros avaliados.(AU)

Perinatal effects of maternal FT3/FT4 ratio on gestational transient thyrotoxicosis

ABSTRACT Objective: The effects of maternal thyroid hormone levels on the course of pregnancy and birth weight have attracted interest. The aim of the present study was to consider FT3 and FT3/FT4 ratio in the evaluation of the effects of maternal thyroid functions in gestational transient thyrotoxicosis (GTT). Materials and methods: This case-control study included 45 patients with GTT and 45 healthy pregnant women. Maternal history before pregnancy, thyroid function tests, thyroid autoantibodies, and thyroid ultrasonography results in 6th to 10th weeks of pregnancy were used in the differential diagnosis of GTT. In both groups, the effects of FT3, FT4 and FT3/FT4 ratios on gestational age and birth weight were evaluated. Results: There was no significant difference in the gestational age between the GTT and control groups (39,3±1,0 weeks and 39,2±1,2 weeks, respectively). Birth weights were similar in both groups (3205,2±4899 g and 3196,6±309,3 g, respectively). When maternal weight was adjusted, a positive correlation was observed between maternal FT3/FT4 ratio and birth weight (r=0,317, p=0,017). Additionally there was a positive correlation between the gestational age and the birth weight in the control group (ρ=0,726, p=0,001). Conclusion: GTT had no significant effect on the gestational age and the birth weight. On the other hand an increase in the maternal FT3/FT4 ratio had a positive effect on the birth weight in the patient with GTT. Maternal characteristics (age, weight, BMI) and FT3/FT4 ratio should be taken into consideration in future impact assessment studies on this issue.

Hemiagenesia tiroidea: caso clínico y revisión de la literatura / Thyroid hemiagenesis: clinical case and review of the literature

La hemiagenesia tiroidea representa un trastorno congénito caracterizado por la ausencia de desarrollo de uno de los lóbulos tiroideos, asociado o no a ausencia del istmo. Es más frecuente en las mujeres y por lo general se presenta como falta del lóbulo izquierdo, con hipertrofia compensatoria del lóbulo contralateral. Su diagnóstico es generalmente incidental o por manifestaciones del lóbulo tiroideo presente. Se hizo una revisión bibliografía, en donde no se encontraron casos reportados en Venezuela de hemiagenesia o agenesia tiroidea, describiéndose el siguiente. Presentamos a una paciente de 50 años de edad, conocida con hipotiroidismo desde los 31 años, negando cualquier cirugía en el área de cabeza y cuello. Desde febrero 2019 presentó aumento progresivo de volumen en región anterior de cuello. Al examen físico se observó aumento de volumen en región anterior derecha del cuello, palpándose lóbulo tiroideo derecho aumentado de tamaño, de aspecto nodular, no doloroso. En ecosonograma tiroideo se concluyó como bocio tiroideo derecho de aspecto multinodular, con ausencia del lóbulo izquierdo. Perfil tiroideo dentro de límites normales. Se lleva a mesa operatoria corroborándose ausencia del lóbulo izquierdo y presentado en la biopsia definitiva hiperplasia nodular en el lóbulo derecho. Se discute su frecuencia, la forma de presentación y se hace revisión de la literatura(AU)

Thyroid hemiagenesis represents a congenital disorder characterized by the absence of development of one of thyroid lobes, associated or not with absence of isthmus. It is more frequent in women and generally presents as absence of the left lobe, with compensatory hypertrophy of the contralateral lobe. Its diagnosis is generally incidental or by manifestations of the present thyroid lobe. A bibliography review was made, where no cases reported in Venezuela of hemiagenesis or thyroid agenesis were found, describing the following. We present a 50-year-old patient, known with hypothyroidism since she was 31, denying any surgery in the head and neck area. Since February 2019, presented a progressive increase in volume in the anterior neck region. On physical examination, an increase in volume was observed in right anterior region of the neck, palpating an enlarged right thyroid lobe, with a nodular appearance and not painful. In a thyroid echo-sonogram, it was concluded as a right thyroid goiter with a multinodular appearance, with the absence of the left lobe. Thyroid profile within normal limits. It is taken to the operating table, confirming the absence of the left lobe and presented in the definitive biopsy nodular hyperplasia in the right lobe. Its frequency, form of presentation, and literature review are discussed(AU)

Incidencia del síndrome de baja triiodotironina en pacientes con shock séptico / Incidence of low-triiodothyronine syndrome in patients with septic shock

RESUMEN Objetivo: Se ha visto asociación entre los bajos niveles de hormonas tiroideas y malos resultados clínicos. Esta situación metabólica designada bajo el término de enfermedad eutiroidea, ha sido interpretada como un estado de adaptación a diferentes procesos patológicos, caracterizada por la disminución plasmática de triiodotironina T3. El presente estudio busca determinar la incidencia de este trastorno en los pacientes con shock séptico y su relación con otros índices de gravedad, y resultados clínicos. Métodos: Estudio de corte prospectivo analítico, evaluó a los pacientes que ingresaron con shock séptico a la unidad de terapia intensiva, durante el periodo abril 2018 - julio 2019. Se registraron variables asociadas al shock séptico, y el perfil tiroideo al momento del diagnóstico de shock séptico, a los 7, 14 y 21 días. Resultados: Se analizaron 27 pacientes que cumplieron con los criterios de inclusión. La incidencia de alteración del eje tiroideo fue del 96,3%s, con una mortalidad a los 28 días de 36,7%. Los pacientes sin alteración hormonal no presentaron desenlaces negativos. Entre los que presentaron baja triiodotironina, 42,3% recupero la función tiroidea dentro de los 28 días, con mortalidad del 0%. No recuperaron función tiroidea (57,7%), con una mortalidad del 66,7%. Comparativamente se observó que aquellos que presentaron alteración del eje y no normalizaron la función, requirieron más dosis de vasoactivos, y deterioro del clearence de lactato. Conclusión: Los pacientes con shock séptico presentan una alta incidencia de alteración del eje tiroideo y esta disfunción se asoció a mayor mortalidad.

ABSTRACT Objective: Low levels of thyroid hormones have been associated with poor clinical outcomes. This metabolic situation, designated euthyroid sick syndrome, has been interpreted as a state of adaptation to different pathological processes, characterized by the decrease in plasma triiodothyronine. The present study seeks to determine the incidence of this disorder in patients with septic shock and its relationship with other severity indices and clinical outcomes. Methods: This prospective analytical study evaluated patients admitted to the intensive care unit with septic shock between April 2018 and July 2019. Variables associated with septic shock and thyroid profile were recorded at the time of the septic shock diagnosis and 7, 14, and 21 days later. Results: A total of 27 patients who met the inclusion criteria were analyzed. The incidence of an altered thyroid axis was 96.3%, with a mortality at 28 days of 36.7%. Patients without hormonal alteration did not present negative outcomes. Among those with low triiodothyronine, 42.3% recovered their thyroid function within 28 days, in whom mortality was 0%; 57.7% did not recover their thyroid function, in whom mortality was 66.7%. Those whose thyroid axis was altered and who did not normalize its function required more doses of vasoactives and had deteriorated lactate clearance. Conclusion: Patients with septic shock have a high incidence of alteration of the thyroid axis, and this dysfunction is associated with higher mortality.

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)

Relationship of gender and age on thyroid hormone parameters in a large Chinese population

ABSTRACT Objective This study aimed to present the impact of age and gender on thyroid hormone levels in a large Chinese population with sufficient iodine intake. Subjects and methods A total of 83643 individuals were included and were stratified by age and gender. The median, 2.5th and 97.5th of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and FT3/FT4 ratio were calculated for both genders for every decade from 18 to over 80 years. TSH, FT3, FT4, FT3/FT4 distribution in each age group was evaluated for females and males using smoothing splines in the generalized additive models (GAM). TSH concentrations were compared in the different age groups in gender. Results In the over 80s age group, the TSH level (median: 2.57 mIU/L, 2.5th-97.5th: 0.86-7.56 mIU/L) was significantly higher than other age groups, irrespective to gender (P<0.001). Females had a higher TSH value than males in all age groups (P<0.001). Results of the smoothing curves showed that TSH increased with age, FT3 concentration was higher in males than in females and the tendency of the FT3/FT4 ratio was basically similar to that of FT3. TSH concentration in the 50s age group (median 2.48 mIU/L for females versus 2.00 mIU/L for males) was significantly higher than that in the 30s age group (median 2.18 mIU/L for females versus median 1.85 mIU/L for males). Conclusions In accord with increasing TSH values during aging, females and older adults have lower FT3 values and lower FT3/FT4 ratios, while the FT4 values remain stable.

Evaluation of the structure, autoimmunity, and functions of the thyroid gland in familial Mediterranean fever patients

ABSTRACT Objective Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder that is frequently seen in the eastern Mediterranean region. The thyroid gland can be affected in FMF patients through autoimmunity or amyloidosis. Here, we aimed to evaluate the structure and functions of the thyroid gland in addition to possible autoimmunity in FMF patients. Subjects and methods The study was conducted by the Endocrinology and Metabolism and Internal Medicine Departments. Thirty FMF patients and 30 age and gender-matched healthy controls were enrolled in the study. Free thyroxin (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone (TSH), and anti-thyroid peroxidase (anti-TPO) autoantibodies were investigated. Detailed thyroid grayscale and Doppler Ultrasonography examinations and shear-wave elastosonography (SWE) were performed in the patient and control groups. Results Anti-TPO was detected in 24% (n = 7) of the patients. On the grayscale US, mean thyroid volumes were similar between the FMF and the control groups (p > 0.05). By Doppler US, thyroid vascularity observed was detected in 10.3% (n = 3) of the patients. SWE revealed that the mean velocity value of right vs. left lobe in the patient group was 1.77 ± 0.45 m/s and 1.95 ± 0.51 m/s, respectively. Compared to the control group, the mean velocity values were significantly higher in the right (p = 0.004) and left (p = 0.01) lobes of the patient group. The mean stiffness value in the patient group was also significantly higher in the right and left lobes [10.13 ± 5.65 kPa (p = 0.005) and 12.24 ± 6.17 kPa (p = 0.02), respectively]. Conclusion Recognizing the complications of FMF early in the course of the disease is as important as the early diagnosis of the disorder. Based on this, thyroid functions and changes in its structure should be evaluated carefully for early diagnosis of a possible coexisting thyroid disorder. Arch Endocrinol Metab. 2020;64(1):66-70

Historia de las pruebas de función tiroidea / History of thyroid function tests

El desarrollo de las pruebas de función tiroidea no ha sido fácil, con múltiples retos para mejorar algunas características que son insatisfactorias, incluso en la actualidad. En 1960 se logró la medición de tiroxina total (T4 total), y aunque fue un gran avance, los investigadores sabían que era insuficiente para una evaluación precisa de la función tiroidea. Uno de los problemas importantes radica en que existen diferencias marcadas interindividuales en la composición y en las cantidades de las proteínas de transporte de la T4 y la triyodotironina (T3). Por lo tanto, los depósitos de T4 y T3 son muy diferentes a los valores de T4 libre (T4L) y T3 libre (T3L). Por ejemplo, la mujer embarazada tiene el doble de globulina fijadora de tiroxina (TBG) y tres cuartas partes de la cantidad de albúmina que tenía cuando no estaba embarazada. También se pierde transtiretina y albúmina en enfermedades graves o con traumas, como quemaduras o sepsis. Entre 1963 y 1965 se desarrolló una prueba para tratar de obtener una estimación de la T4L, con el método de absorción de la hormona tiroidea a partir de la T4 total. Sin embargo, este análisis no funcionó correctamente, especialmente teniendo en cuenta la variabilidad en la TBG

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

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

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

Tomar mate previo a la flebotomía no interfiere en las pruebas bioquímicas de rutina / Drinking mate prior to phlebotomy does not interfere with routine biochemical tests

En este estudio se evaluó el efecto de tomar mate en las pruebas bioquímicas de rutina. Se extrajo sangre a 32 mujeres voluntarias luego de 12 horas de ayuno y a la hora (T1), dos horas (T2) y tres horas (T3) posteriores a la toma de 5 mates. Se estudiaron parámetros hematológicos y analitos de química clínica. Los resultados se analizaron empleando pruebas estadísticas para muestras relacionadas. Se calculó la diferencia porcentual media (DM%) de cada analito en cada hora respecto del valor basal y se comparó con el valor de referencia del cambio (VRC). Una DM% mayor que el VRC se consideró clínicamente significativa. En T1, T2 y T3 los recuentos de neutrófilos, eosinófilos y linfocitos fueron más bajos que en T0, también los niveles de glucosa, urea, creatinina y cistatina C fueron más bajos que en T0, mientras que los valores de proteínas totales, colesterol transportado por lipoproteínas de baja densidad y la actividad enzimática de lactato deshidrogenasa fueron más altos que en T0. En todos los casos los cambios fueron estadísticamente significativos, aunque no lo fueron desde el punto de vista clínico. Tomar 5 mates antes de la flebotomía no interfiere en los resultados de las pruebas bioquímicas de rutina.

In the present study the effect of drinking mate in routine biochemical tests was evaluated. Blood was collected from 32 female volunteers after a 12 h fasting period. In addition, 1 hour (T1), 2 hours (T2), and 3 hours (T3) after drinking 5 mates, blood was collected again. Hematological parameters and clinical chemistry analytes were studied. The results were analyzed using statistical tests for related samples. Mean difference % (MD%) was calculated for each analyte and was further compared with reference change value (RCV). The MDs% higher than RCV were considered clinically significant. At T1, T2, and T3 the count neutrophils, eosinophils and lymphocytes were lower than at T0. Also glucose, urea, creatinine, and cystatin C values were lower than at T0 whereas total proteins, LDL-C, and LD enzymatic activity values were higher than at T0. In all cases, variability was statistically significant but not clinically significant. Drinking 5 mates prior to phlebotomy does not interfere with the results of routine biochemical tests.

Neste trabalho, o efeito de beber chimarrão foi avaliado em testes bioquímicos de rotina. O sangue foi extraído de 32 mulheres voluntárias após 12 horas de jejum, e uma hora (T1), duas horas (T2) e três horas (T3) após a tomada de 5 chimarrões. Parâmetros hematológicos e analitos de química clínica foram estudados. Os resultados foram analisados utilizando testes estatísticos para amostras relacionadas. A diferença percentual média% (DM%) de cada analito em cada hora foi calculada em relação ao valor basal e comparada com o valor de referência da modificação (VRM). Uma DM% maior que o VRM foi considerada clinicamente significativa. Em T1, T2 e T3 as contagens de neutrófilos, eosinófilos e linfócitos foram mais baixas que em T0, Também os níveis de glicose, ureia, creatinina e cistatina C foram mais baixos que em T0, ao passo que os valores de proteínas totais, colesterol transportado por lipoproteínas de baixa densidade e a atividade enzimática de lactato desidrogenase foram mais altos que em T0. Em todos os casos as alterações foram estatisticamente significativas, embora do ponto de vista clínico não o tenham sido. Tomar 5 chimarrões antes da flebotomia não interfere nos resultados dos testes bioquímicos de rotina.

Anticuerpos anti-estreptavidina: Confusión diagnóstica por interferencia bioquímica / Anti-estreptavidin antibodies. Diagnostic confusion by biochemical interference

Se presenta el caso de una paciente que, durante los estudios por búsqueda de fertilidad y posterior embarazo, mostraba un perfil tiroideo alterado con niveles elevados de T4 libre y TSH normal. Luego de descartar un adenoma tirotropo y ante la ausencia de sintomatología clínica de hipertiroidismo, se investigó la posibilidad de interferencias analíticas en los inmunoensayos utilizados para la medición de las hormonas. Se han descrito interferencias causadas por anticuerpos heterófilos, macro TSH, anticuerpos anti-tiroideos, biotina, y en menor medida anticuerpos anti-estreptavidina y anti-rutenio. Los análisis de la paciente se realizaron en autoanalizador cuya plataforma emplea el sistema estreptavidina-biotina que es muy susceptible a varios interferentes. Un algoritmo propuesto incluye una serie de pruebas simples de realizar e interpretar que permiten detectar o descartar la presencia de interferentes. De acuerdo al mismo, se efectuó la comparación con una plataforma analítica diferente (que no utiliza el sistema estreptavidina-biotina), diluciones seriadas, precipitación con polietilenglicol 6000 y tratamiento con micropartículas recubiertas con estreptavidina. Los resultados obtenidos confirmaron la presencia de anticuerpos anti-estreptavidina en el suero de la paciente. Ante discordancias entre las manifestaciones clínicas y los resultados de laboratorio, se debe investigar la posibilidad de interferencias metodológicas para evitar el riesgo iatrogénico potencial que implica una interpretación bioquímica errónea.

We present the case of a patient who, during studies for fertility and subsequent pregnancy, showed an altered thyroid profile with elevated levels of free T4 and normal TSH. After ruling out a thyrotropic adenoma and in the absence of clinical symptoms of hyperthyroidism, the possibility of analytical interference in the immunoassays used to measure hormones was investigated. Interferences caused by heterophile antibodies, macro TSH, anti-thyroid antibodies, biotin, and to a lesser extent anti-streptavidin and anti-ruthenium antibodies have been described. The analysis of the patient was carried out in a self-analyzer whose platform uses the streptavidin-biotin system that is very susceptible to several interferents. A proposed algorithm includes a series of simple tests to perform and interpret that allow detecting or ruling out the presence of interferents. Accordingly, a comparison was made with a different analytical platform (which does not use the streptavidin-biotin system), serial dilutions, precipitation with polyethylene glycol 6000 and treatment with microparticles coated with streptavidin. Results obtained confirmed the presence of anti-streptavidin antibodies in the patient's serum. In the case of disagreements between clinical manifestations and laboratory results, the possibility of methodological interferences should be investigated in order to avoid the potential iatrogenic risk involved in an erroneous biochemical interpretation.

Low triiodothyronine syndrome is associated with platelet function in patients with nephrotic syndrome

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.

RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.

Triiodothyronine (T3) upregulates the expression of proto-oncogene TGFA independent of MAPK/ERK pathway activation in the human breast adenocarcinoma cell line, MCF7

ABSTRACT Objective: To verify the physiological action of triiodothyronine T3 on the expression of transforming growth factor α (TGFA) mRNA in MCF7 cells by inhibition of RNA Polymerase II and the MAPK/ERK pathway Materials and methods: The cell line was treated with T3 at a physiological dose (10−9M) for 10 minutes, 1 and 4 hour (h) in the presence or absence of the inhibitors, α-amanitin (RNA polymerase II inhibitor) and PD98059 (MAPK/ERK pathway inhibitor). TGFA mRNA expression was analyzed by RT-PCR. For data analysis, we used ANOVA, complemented with the Tukey test and Student t-test, with a minimum significance of 5%. Results: T3 increases the expression of TGFA mRNA in MCF7 cells in 4 h of treatment. Inhibition of RNA polymerase II modulates the effect of T3 treatment on the expression of TGFA in MCF7 cells. Activation of the MAPK/ERK pathway is not required for T3 to affect the expression of TGFA mRNA. Conclusion: Treatment with a physiological concentration of T3 after RNA polymerase II inhibition altered the expression of TGFA. Inhibition of the MAPK/ERK pathway after T3 treatment does not interfere with the TGFA gene expression in a breast adenocarcinoma cell line.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

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

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

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

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.

Thyroid function in pediatric population with different nutritional status / Función tiroidea en población pediátrica con diferente estado nutricional

Abstract: Background: Thyroid dysfunction has been associated with the development of obesity. There are few studies describing their status in Mexican schoolchildren, in whom obesity and subclinical hypothyroidism (SCH) prevail. Methods: Levels of stimulating thyroid hormone (TSH) and thyroid hormones (TH) were correlated with anthropometric variables as indicators of nutritional status in schoolchildren residents of Mexico City. The thyroid status and prevalences of SCH were compared between all the nutritional conditions, considering the degree of pubertal development. Results: The mean of TSH was 2.96 ± 1.48 mIU/L, and the prevalence of SCH was 11.30%. TSH levels are higher in prepubertal (5.21 ±1.24 mIU/L (95% confidence interval [CI]: 3.72-6.69) versus pubertal children (2.96 ± 1.48 mIU/L [95% CI: 2.61-3.30), as well as in children with obesity (3.5 ± 1.13 mIU/L [95% CI: 2.98-4.02]) versus normal weight children (2.43 ± 1.37 mIU/L [95% CI: 1.88 - 2.97]). The TH is similar in the whole population, although triiodothyronine total levels tend to be lower in malnourished children. There is a positive correlation between TSH levels and all anthropometric variables. The prevalences of SCH were higher in groups of children with overweight and obesity. Conclusions: The body fat content is associated with thyroid status in Mexican schoolchildren. In addition, it is relevant to consider the degree of pubertal development for diagnosing hyperthyrotropinemia in children and adolescents.

Resumen: Introducción: La disfunción tiroidea se ha asociado con el desarrollo de obesidad. Existen pocos estudios descritos en población escolar mexicana, en quienes prevalece la obesidad y el hipotiroidismo subclínico (HSC). Métodos: Los niveles de hormona estimulante de tiroides (TSH) y hormonas tiroideas (HT) se correlacionaron con variables antropométricas indicadoras del estado nutricional de niños escolares residentes de la Ciudad de México. El estado tiroideo y las prevalencias de HSC se compararon entre todas las condiciones nutricionales, considerando el grado de desarrollo puberal. Resultados: La media de TSH fue 2.96 ± 1.48 mUI/L, y la prevalencia de HSC fue de 11.30%. Los niveles de TSH fueron mayores en los niños prepúberes (5.21 ± 1.24 mUI/L [intervalo de confianza (IC) 95%: 3.72-6.69]) vs. los niños púberes (2.96 ± 1.48 mUI/L [IC 95%: 2.61-3.30); así como en los niños con obesidad (3.50 ± 1.13 mUI/L [IC 95%: 2.98-4.02]) vs. los niños con peso normal (2.43 ± 1.37 mUI/L [IC 95%: 1.88-2.97]). Los niveles de HT son similares en toda la población, aunque los niveles de triiodothyronine total (T3) tienden a ser menores en niños desnutridos. Existe correlación positiva entre los niveles de TSH y todas las variables antropométricas. Las prevalencias de HSC fueron mayores en los grupos de niños con sobrepeso y obesidad. Conclusiones: El contenido de grasa corporal está asociado con el estado tiroideo en escolares mexicanos. Adicionalmente, es relevante considerar el grado de desarrollo puberal para el diagnóstico adecuado de hipertirotropinemia en niños y adolescentes.