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)

Clinical features and prognosis of patients hospitalized with heart failure and low T3 syndrome / 中华内科杂志

Objective: To investigate the association between triiodothyronine (T3) and inflammatory factors, and its potential effect on long-term outcomes in hospitalized patients with heart failure (HF). Methods: A total of 2 475 patients with HF admitted in Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018. Patients were divided into low T3 syndrome group (n=610, 24.6%) and normal thyroid function group (n=1 865, 75.4%). The median follow-up time was 2.9 (1.0, 5.0) years. A total of 1 048 all-cause deaths were recorded at the final follow-up. The effects of free T3 (FT3) and high-sensitivity C-reactive protein (hsCRP) on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis. Results: The age of the total population was 19-95 (57±16) years, 1 823 cases (73.7%) were male. Compared to those with normal thyroid function, albumin [(36.5±5.4) vs. (40.7±4.7) g/L], hemoglobin [(129.4±25.1) vs. (140.6±20.6) g/L], total cholesterol [3.6 (3.0, 4.4) vs. 4.2 (3.5, 4.9) mmol/L] (all P<0.001) were lower, Whereas age [(60.5±16.0) vs. (55.2±15.4) years], creatinine [105.0 (83.6, 137.0) vs. 87.8 (75.6, 106.3) mmol/L], log N-terminal B-type natriuretic peptide [(8.2±1.3) vs. (7.2±1.4) ng/L] were higher in LT3S patients (all P<0.001). In Kaplan-Meier survival analysis, patients with lower FT3 and higher hsCRP had significantly lower cumulative survival (P<0.001), lower FT3 combined with higher hsCRP subgroup had the highest risk of all-cause death (Ptrend<0.001). In multivariate Cox regression analysis, LT3S was an independent predictor of all-cause mortality (HR=1.40, 95%CI 1.16-1.69, P<0.001). Conclusion: LT3S is an independent predictor of poor prognosis in patients with heart failure. FT3 combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.

Risk factors of childhood systemic lupus erythematosus with thyroid dysfunction / 中华儿科杂志

Objective: To investigate the risk factors of childhood systemic lupus erythematosus (SLE) with thyroid dysfunction and to explore the relationship between thyroid hormone and kidney injury of lupus nephritis (LN). Methods: In this retrospective study, 253 patients who were diagnosed with childhood SLE and hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2021 were enrolled in the case group, and 70 healthy children were the control cases. The patients in the case group were divided into the normal thyroid group and the thyroid dysfunction group. Independent t-test, χ2 test, and Mann-Whitney U test were used for comparison between the groups, Logistic regression analysis was used for multivariate analysis, and Spearman correlation. Results: A total of 253 patients, there were 44 males and 209 females in the case group, and the age of onset was 14 (12, 16) years; a total of 70 patients, 24 males and 46 females were in the control group, and the age of onset was 13 (10, 13) years. The incidence of thyroid dysfunction in the case group was higher than that in the control group (48.2% (122/253) vs. 8.6% (6/70), χ²=36.03, P<0.05). Of the 131 patients, there were 17 males and 114 females in the normal thyroid group, and the age of onset was 14 (12, 16) years. Of the 122 patients in the thyroid dysfunction group, 28 males and 94 females were in the thyroid dysfunction group, and the age of onset was 14 (12, 16) years. Of the 122 had thyroid dysfunction, including 51 cases (41.8%) with euthyroid sick syndrome, 25 cases (20.5%) with subclinical hypothyroidism, 18 cases (14.8%) patients with sub-hyperthyroidism, 12 cases (9.8%) with hypothyroidism, 10 cases (8.2%) with Hashimoto's thyroiditis, 4 cases (3.3%) with hyperthyroidism, and 2 cases (1.6%) with Graves disease. Compared to patients with normal thyroid function, the serum level of triglyceride, total cholesterol, urine white blood cell, urine red blood cell, 24 h urine protein, D-dimer, and fibrinogen, ferritin and systemic lupus erythematosus disease activity Index-2000 (SLEDAI-2K) score were higher in patients with thyroid dysfunction (Z=3.07, 3.07, 2.48, 3.16, 2.40, 3.99, 2.68, 2.55, 2.80, all P<0.05), while the serum level of free thyroxine and C3 were lower in thyroid disfunction patients (10.6 (9.1, 12.7) vs. 11.3 (10.0, 12.9) pmol/L, and 0.46 (0.27, 0.74) vs. 0.57 (0.37, 0.82) g/L, Z=2.18, 2.42, both P<0.05). The higher level of triglyceride and D-dimer were the independent risk factors for childhood SLE with thyroid dysfunction (OR=1.40 and 1.35, 95%CI 1.03-1.89 and 1.00-1.81, respectively, both P<0.05). There were 161 patients with LN in the case group, all of which were conducted with renal biopsies, including 11 cases (6.8%) with types Ⅰ LN, 11 cases (6.8%) with typesⅡLN, 31 cases (19.3%) with types Ⅲ LN, 92 cases (57.1%) with types Ⅳ LN, and 16 cases (9.9%) with types Ⅴ LN. There were significant differences in the level of free triiodothyronine and thyroid stimulating hormone among different types of kidney pathology (both P<0.05); compared with types I LN, the serum level of free triiodothyronine was lower in types Ⅳ LN (3.4 (2.8, 3.9) vs. 4.3 (3.7, 5.5) pmol/L, Z=3.75, P<0.05). The serum level of free triiodothyronine was negatively correlated with the acute activity index score of lupus nephritis (r=-0.228, P<0.05), while the serum level of thyroid stimulating hormone was positively correlated with the renal pathological acute activity index score of lupus nephritis (r=0.257, P<0.05). Conclusions: There is a high incidence of thyroid dysfunction in childhood SLE patients. The higher SLEDAI and more severe renal damage were found in SLE patients with thyroid dysfunction compared to these with normal thyroid functions. The risk factors of childhood SLE with thyroid dysfunction are the higher level of triglyceride and D-dimer. The serum level of thyroid hormone is possibly related to the kidney injury of LN.

Use of combination of Oral Levothyroxine and Liothyronine in severe Hypothyroidism with Massive Pericardial Effusion / Journal of the ASEAN Federation of Endocrine Societies

@#Thyroid hormone plays an important role in cardiovascular function. Pericardial effusions are commonly seen in cases of severe hypothyroidism. However, large to massive pericardial effusions with cardiac tamponade are exceptionally rare. Herein, we present two cases of severe hypothyroidism with massive pericardial effusion. Our first case demonstrates that a patient with large pericardial effusion can be managed conservatively with aggressive thyroid hormone replacement therapy. In our second case, pericardiocentesis was performed in addition to thyroid hormone replacement therapy as the underlying aetiology of effusion could not be reasonably limited to hypothyroidism. These two cases served to highlight and demonstrate rapid normalisation of thyroid function test by using aggressive oral thyroid hormone replacement therapy using liothyronine, in combination with levothyroxine, which led to resolution of pericardial effusion and prevent its re-accumulation.

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)

Clinical characteristics of Graves / 中南大学学报(医学版)

OBJECTIVES@#A variety of causes can lead to cholestasis, however, cholestasis caused by Graves' disease is usually overlooked clinically. Here we analyze the clinical characteristics of Graves' disease associated cholestasis so as to have a better understanding for the disease.@*METHODS@#We retrospectively collected 13 inpatients' data who suffered from the Graves' disease associated cholestasis in the Department of Infectious Disease of Xiangya Hospital from January 2000 to December 2018. The characteristics of the patients' age, gender, liver function, thyroid function, coagulation function, the special cardiac examination, treatment, and follow-up data were analyzed.@*RESULTS@#Thirteen patients, including 10 males and 3 females with the age range from 33 to 55 (median 43) years old presented cholestasis, pruritus, and hypermetabolic symptoms. The levels of total bilirubin (TBIL), direct bilirubin (DBIL), glutamic-pyruvic transferase, glutamic-oxaloacetic transferase, alkaline phosphosphatase, and gamma glutamyl transpeptidase were 170.4-976.7 (median 388.8) µmol/L, 93.2-418.1 (median 199.2) µmol/L, 25.1-182.1 (median 106.4) U/L, 38.2-265.7 (median 59.7) U/L, 105.3-332.0 (median 184.5) U/L, and 20.7-345.1 (median 47.6) U/L, respectively. The levels of free triiodothyronine (FT@*CONCLUSIONS@#Graves' disease can cause cholestasis, with the low incidence. The symptoms of cholestasis can be improved or even eradicated with the cure of the Graves' disease. The cholestasis may be idiopathic. For patients with cholestasis and hyperthyroidism, Graves' disease should be considered for differential diagnosis.

Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study / 中华医学杂志(英文版)

BACKGROUND@#Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).@*METHODS@#The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.@*RESULTS@#The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.@*CONCLUSION@#Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

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.