Hyperthyroidism keeps immunoglobulin levels but reduces milk fat and CD11b/c+ cells on early lactation.

Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T4 (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRß1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45+ and CD3+ cells and decreased CD11b/c+ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.

Thyroid lesions in a population of domestic cats submitted to necropsy without clinical suspicion of thyroid disease.

Although hyperthyroidism is the most common endocrine disorder in elderly cats, systematic studies investigating the prevalence of thyroid lesions in feline animals are scarce. Our objective was to evaluate morphological changes in the thyroid glands of 61 cats submitted to necropsy without clinical suspicion of hyperthyroidism. Thirteen (13/61 [21.3%]) cats had thyroid enlargement and 54/61 (88.5%) had some histological thyroid changes. Proliferative lesions were histologically seen in 33/61 (54%) cats while non-proliferative lesions were observed in 48/61 (78.7%) cats. Thyroid hyperplasia (18/33 [54.5%]) and cystic adenoma (6/33 [18.2%]) were the most prevalent proliferative changes and lesions with little or no clinical significance (37/61 [60.6%]), degenerative (31/61 [50.8%]) and inflammatory changes (12/61 [19.7%]) were the most common non-proliferative changes. Among cats with proliferative lesions, 16/33 (48.4%) had a proliferation grade ≥A4, a grade previously associated with clinical hyperthyroidism. Although the cats from this study did not have any clinical diagnosis of thyroid disease, it is possible that one or more had some degree of clinically unnoticed thyroid dysfunction. The high prevalence of follicular lesions in this study highlights the importance of a more careful clinical and pathological investigation regarding thyroid diseases in mature and elderly cats.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Cardiac hypertrophy that affects hyperthyroidism occurs independently of the NLRP3 inflammasome.

Cardiac hypertrophy (CH) is an adaptive response to maintain cardiac function; however, persistent stress responses lead to contractile dysfunction and heart failure. Although inflammation is involved in these processes, the mechanisms that control cardiac inflammation and hypertrophy still need to be clarified. The NLRP3 inflammasome is a cytosolic multiprotein complex that mediates IL-1ß production. The priming step of NLRP3 is essential for increasing the expression of its components and occurs following NF-κB activation. Hyperthyroidism triggers CH, which can progress to maladaptive CH and even heart failure. We have shown in a previous study that thyroid hormone (TH)-induced CH is linked to the upregulation of S100A8, leading to NF-κB activation. Therefore, we aimed to investigate whether the NLRP3 inflammasome is involved in TH-induced CH and its potential role in CH pathophysiology. Hyperthyroidism was induced in NLRP3 knockout (NLRP3-KO), Caspase-1-KO and Wild Type (WT) male mice of the C57Bl/6J strain, aged 8-12 weeks, by triiodothyronine (7 µg/100 g BW, i.p.) administered daily for 14 days. Morphological and cardiac functional analysis besides molecular assays showed, for the first time, that TH-induced CH is accompanied by reduced NLRP3 expression in the heart and that it occurs independently of the NLRP3 inflammasome and caspase 1-related pathways. However, NLRP3 is important for the maintenance of basal cardiac function since NLRP3-KO mice had impaired diastolic function and reduced heart rate, ejection fraction, and fractional shortening compared with WT mice.

Nebivolol in oral subacute treatment prevents cardiac post-ischemic dysfunction in rats, but hyperthyroidism reduces this protection: mechanisms involved.

Nebivolol could prevent dysfunction in patients suffering myocardial ischemia. However, influence of hyperthyroidism is not known. Consequences and mechanisms of nebivolol treatment were investigated in isolated hearts from euthyroid (EuT) and hyperthyroid (HpT) rats. Rats were orally treated during 1 week with 20 mg/kg/day nebivolol (O-Neb), 30 mg/kg/day atenolol (O-Ate), or not treated (C). Isolated perfused hearts were exposed to global ischemia and reperfusion (I/R) inside a flow calorimeter. Left diastolic ventricular pressure, developed contractile pressure (P), and total heat rate (Ht) were continuously measured, while infarct size was measured after 2-h R. EuT-C and HpT-C hearts developed similarly low post-ischemic contractile recovery and economy (P/Ht). Nebivolol totally prevented dysfunction and reduced infarction size in EuT hearts, but partially improved recovery in HpT rat hearts. Contrarily, oral atenolol totally prevented dysfunction in HpT hearts but partially in EuT hearts. Nebivolol effects were reversed by perfusing L-NAME in both conditions, but partially reduced by aminoguanidine in HpT. However, L-NAME increased P and P/Ht recoveries in EuT-C and HpT-C rat hearts, as well as melatonin. Oral nebivolol prevented post-ischemic dysfunction and infarction in EuT hearts due to adrenergic ß1 blockade and activation of iNOS and/or eNOS, but the effect was attenuated in HpT hearts by excessive iNOS-dependent nitrosative pathways.

Manejo del paciente con Hipertiroidismo en consulta externa de la Unidad Técnica de Endocrinología del Hospital Carlos Andrade Marín / Management of the patient with hyperthyroidism in the outpatient clinic of the Technical Unit of Endocrinology of the Endocrinology Technical Unit of the Carlos Andrade Marín Hospital

El hipertiroidismo es un trastorno caracterizado por el exceso de hormonas tiroideas. El déficit de yodo es un factor clave en dicha patología y en lugares con suficiencia del mismo se asocian a au-toinmunidad tiroidea. La prevalencia de hipertiroidismo mani-fiesto varía del 0,2% al 1,3% en áreas con suficiencia de yodo, sin embargo, esto puede variar en cada país por diferencias en umbrales de diagnóstico, sensibilidad de ensayo y población se-leccionada. Un reporte de The Third National Health and Nutri-tion Examination Survey (NHANES III) mostró que el hiperti-roidismo manifiesto se presenta en 0,7% de la población general e hipertiroidismo subclínico en el 1,7%1,2.En incidencia, la patología se asocia con la suplementación de yodo, con la mayor frecuencia en áreas de deficiencias, por au-mento de nódulos tiroideos en la población anciana, teniendo a regiones de áreas montañosas como América del Sur, África Central y suroeste de Asia dentro de este grupo. Un meta aná-lisis de estudios europeos mostró una incidencia general de 50 casos por 100000 personas/años1. En Ecuador, según los datos del Instituto Nacional de Estadísticas y Censos (INEC) del 2017, se reportaron 157 casos de hipertiroidismo, de los cuales la En-fermedad de Graves (EG) fue la causa más común, seguida por el bocio multinodular tóxico (BMNT) y finalmente el adenoma tóxico (AT) con una incidencia de 61 %, 24 % y 14 % respecti-vamente3.Los pacientes con esta patología tienen aumento de riesgo com-plicaciones cardiovasculares y mortalidad por todas las causas, siendo falla cardíaca uno de sus principales desenlaces, así el diagnóstico precoz evita estos eventos, principalmente en pobla-ción de edad avanzada.El presente protocolo se ha realizado para un correcto trata-miento de esta patología en el Hospital de Especialidades Carlos Andrade Marín (HECAM).

Hyperthyroidism is a disorder characterized by an excess of thyroid hormones. Iodine deficiency is a key factor in this pa-thology and in places with iodine deficiency it is associated with thyroid autoimmunity. The prevalence of overt hyperthyroidism varies from 0,2% to 1,3% in iodine-sufficient areas; however, this may vary from country to country due to differences in diag-nostic thresholds, assay sensitivity, and selected population. A report from The Third National Health and Nutrition Examina-tion Survey (NHANES III) showed that overt hyperthyroidism occurs in 0,7% of the general population and subclinical hyper-thyroidism in 1,7%1,2.In incidence, the pathology is associated with iodine supplemen-tation, with the highest frequency in areas of deficiencies, due to increased thyroid nodules in the elderly population, having regions of mountainous areas such as South America, Central Africa and Southwest Asia within this group. A meta-analysis of European studies showed an overall incidence of 50 cases per 100000 person/years1. In Ecuador, according to data from the National Institute of Statistics and Census (INEC) in 2017, 157 cases of hyperthyroidism were reported, of which, Graves' di-sease (GD) was the most common cause, followed by toxic mul-tinodular goiter (BMNT) and finally toxic adenoma (TA) with an incidence of 61 %, 24 % and 14 % respectively3.Patients with this pathology have an increased risk of cardiovas-cular complications and all-cause mortality, with heart failure being one of the main outcomes, so early diagnosis avoids these events, mainly in the elderly population.The present protocol has been carried out for the correct treat-ment of this pathology at the Carlos Andrade Marín Specialties Hospital (HECAM).

Human T-cell leukemia virus type 1 is associated with dysthyroidism in the French Amazon.

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus known to cause two major diseases: adult T-cell leukemia/lymphoma and a progressive neuromyelopathy-tropical spastic paraparesis. Many viruses may be involved in the pathogenesis of thyroiditis; however, few studies have focused on the role of HTLV-1. We aimed to investigate the association between HTLV-1 and biological thyroid dysfunction. Methods: We included 357 patients with a positive HTLV-1 serology and thyroid-stimulating hormone assay data between 2012 and 2021 in a hospital in French Guiana; we compared the prevalence of hypothyroidism and hyperthyroidism in this group with that in an HTLV-1-negative control group (722 persons) matched for sex and age. Results: The prevalence of hypothyroidism and hyperthyroidism in patients with HTLV-1 infection was significantly higher than that in the control group (11% versus 3.2% and 11.3% versus 2.3%, respectively; p < 0.001). Conclusion: Our study shows, for the first time, the association between HTLV-1 and dysthyroidism in a large sample, suggesting that thyroid function exploration should be systematically implemented in this population as this may have an impact on therapeutic management.

La Insuficiencia Cardíaca Aguda como Manifestación de la Tirotoxicosis. A Propósito de un Caso / Acute heart failure as a manifestation of thyrotoxicosis. A case report

Introducción: La tirotoxicosis se considera una emergencia endocrinológica. Suele ser la complicación más grave y menos frecuente de una patología relativamente frecuente como es el hipertiroidismo. Tiene afectación a nivel sistémico, con especial hincapié en el sistema cardiovascular, por lo que una de las manifestaciones prevalentes y a considerar en este trabajo, es la insuficiencia cardiaca aguda. Caso clínico: Paciente femenina de 40 años con antecedente de tabaquismo e hipertiroidismo, con abandono de medicación (Metimazol) y de controles en contexto de pandemia. Consultó en reiteradas ocasiones por evento sincopal asociado a palpitaciones, agregando en esta consulta episodio tos con expectoración hemoptoica y náuseas. Laboratorio con TSH<0.01mU/L y T4 7.77pmol/L. Troponinas 19.3ng/L. Evolucionó con hipotensión sin respuesta a cristaloides y mayor disnea. Se decidió intubación orotraqueal. Se realizó ecocardiograma que informaba función sistólica con deterioro severo. Realizó tratamiento con Metimazol y solución de Lugol con mejoría de los parámetros de laboratorio. A los diez días evolucionó con abdomen agudo perforado con posterior shock séptico refractario y falleció. Discusión y conclusiones: Luego de examinar la bibliografía disponible, y contrastarla de forma retrospectiva con la evolución de la paciente, se puede observar la relación entre el hipertiroidismo y los cambios hemodinámicos. En el caso presentado, la paciente tuvo como antecedente el diagnóstico de hipertiroidismo y se consideró que el factor desencadenante fue la suspensión del metimazol; a su vez, la insuficiencia cardíaca aguda que presentó durante los primeros días de internación fue consecuencia del efecto cardiovascular directo de las hormonas tiroideas.

Introduction: Thyrotoxicosis is considered an endocrinological emergency; It is usually the most serious and least frequent complication of a relatively frequent pathology such as hyperthyroidism. It has systemic involvement, with special emphasis on the cardiovascular system, which is why one of the most prevalent manifestations to be considered in this work is acute heart failure. Clinical case: A 40-year-old female patient with a history of smoking and hyperthyroidism, with abandonment of medication (Methimazole) and controls in the context of a pandemic. She consulted repeatedly due to a syncopal event associated with palpitations, adding to this consultation an episode of coughing with bloody sputum and nausea. Laboratory with TSH <0.01mU/L and T4 7.77pmol/L. Troponins 19.3ng/L. He evolved with hypotension without response to crystalloids and increased dyspnea. Orotracheal intubation was decided. An echocardiogram was performed, which reported severely impaired systolic function. She underwent treatment with Methimazole and Lugol's solution with improvement in laboratory parameters. Ten days later, he developed an acute perforated abdomen with subsequent refractory septic shock and died. Discusion. Conclusion: After examining the available bibliography, and contrasting it retrospectively with the evolution of the patient, the relationship between hyperthyroidism and hemodynamic changes can be observed. In the case presented, the patient had a history of a diagnosis of hyperthyroidism, and it was considered that the triggering factor was the suspension of methimazole; In turn, the acute heart failure that she presented during the first days of hospitalization was a consequence of the direct cardiovascular effect of thyroid hormones.

Hipertiroidismo y falla cardíaca una asociación silente / A Silent Association Hyperthyroidism and Heart Failure

Los trastornos tiroideos se han ligado a manifestaciones multiorgánicas y/o sistemáticas; sin embargo, es importante conocer el rol de las alteraciones tiroideas en el tejido miocárdico, puesto que se conoce su implicación directa en el funcionamiento del mismo y sus alteraciones conllevan efectos deletéreos en el tejido miocárdico a nivel intracelular. Es necesario reconocer la función de la triyodotironina (T3) que actúa a nivel de los receptores nucleares los cuales, se unen a elementos sensibles de las tiroides en el promotor de genes diana. Además la función de la triyodotironina (T3) influye en genes claves específicos de miocitos, que regulados bajo este mecanismo, se pueden generar a nivel cardíaco, aumento de la contractilidad cardíaca, alto gasto cardíaco, hipertensión sistólica con presión de pulso amplia...(AU)

Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

Prediction for recurrence following antithyroid drug therapy for Graves' hyperthyroidism.

Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves' disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves' hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusion: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Maternal hyperthyroidism alters the immunological mediators profile and population of natural killers cells in decidua of rats.

Decidual immunological mediators modulate placental formation, decidualization and fetal development. However, the effect of maternal hyperthyroidism on decidual immunology needs further research. The aim of this study was to evaluate the population of uterine natural killer cells (uNKs) and the expression of immunological mediators in the decidua of female rats throughout pregnancy. Wistar rats were used and hyperthyroidism was induced by daily administration of L-thyroxine (T4) throughout pregnancy. The population of uNK cells in decidua was evaluated by immunostaining Lectin DBA, as well as the expression of interferon γ (INFγ), macrophage migration inhibitory factor (MIF), interleukin 15 (IL-15) and inducible nitric oxide synthase (iNOS) at 7, 10, 12, 14 and 19 days of gestation (DG). Maternal hyperthyroidism reduced the DBA+ uNK cell population in the decidua at 7 (P < 0.05) and 10 (P < 0.01) DGs compared to that in the control group, while it increased in the basal decidua (P < 0.05) and metrial gland (P < 0.0001) at the 12th DG. Hyperthyroidism also increased immunostaining of IL-15 (P < 0.0001), INFγ (P < 0.05), and MIF (P < 0.05) in the 7th DG, and increased immunostaining of IL-15 (P < 0.0001) and MIF (P < 0.01) in the 10th DG. However, excess thyroxine reduced IL-15 expression in the metrial gland and/or basal decidua in the 12th (P < 0.05), 14th (P < 0.01), and 19th (P < 0.001) DGs, as was also observed for INFγ in the basal decidua (P<0.001) and metrial gland (P < 0.0001) in the 12th DG. Regarding iNOS, an antiinflammatory cytokine, lower expression was observed in the basal decidua of hyperthyroid animals at 7 and 12 DGs (P < 0.05), whereas an increase occurred in the 10th DG (P < 0.05). These data demonstrate that maternal hyperthyroidism in female rats, particularly between 7 and 10 DGs, reduces the population of DBA+ uNKs in the decidua and increases the expression of inflammatory cytokines, suggesting a more proinflammatory environment in early pregnancy caused by this gestational disease.

Dolor y edema de miembros inferiores por dermopatía tiroidea: presentación inusual de la enfermedad de Graves en una paciente adolescente / Lower limb pain and edema due to thyroid dermopathy: an unusual presentation of Graves disease in an adolescent patient

La enfermedad de Graves es un proceso inmunomediado en el que autoanticuerpos se dirigen contra el receptor de tirotrofina. Por su acción estimulante sobre la glándula tiroides, se genera crecimiento glandular difuso y aumento de la hormonogénesis. Se caracteriza por el comienzo subagudo de síntomas constitucionales, neuromusculares, cardiovasculares, gastrointestinales y oculares, seguidos en algunos casos de la aparición de manifestaciones cutáneas como la dermopatía tiroidea o mixedema. En pediatría la enfermedad de Graves es infrecuente (aunque es la causa más frecuente de hipertiroidismo), pero la cronología de aparición de los síntomas está bien descrita; es rara la aparición de dermopatía en ausencia de otros síntomas de hipertiroidismo y sin afectación ocular. Se presenta el caso de una paciente de 15 años con dermopatía tiroidea por enfermedad de Graves sin oftalmopatía ni otros síntomas de hipertiroidismo clínico asociados.

Graves disease is an immune-mediated process characterized by the presence of autoantibodies to thyrotropin receptors. Its stimulating action on the thyroid gland causes diffuse glandular growth and increased hormone production. Graves disease is characterized by a subacute onset of non-specific, neuromuscular, cardiovascular, gastrointestinal, and eye symptoms, sometimes followed by skin manifestations, such as thyroid dermopathy or myxedema. In pediatrics, Graves disease is rare (although it is the most frequent cause of hyperthyroidism). However, the chronology of symptom onset has been well described; the development of dermopathy in the absence of other symptoms of hyperthyroidism and without eye involvement is rare. Here we describe the case of a 15-year-old female patient with thyroid dermopathy due to Graves disease without eye disease or other associated clinical symptoms of hyperthyroidism.

Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis.

Background and aims: Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD. Methods: A meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597). Results: We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively. Conclusions: Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422).

Prevalence of hypersomatotropism and hyperthyroidism in cats with diabetes mellitus from referral centers in Buenos Aires (2020-2022).

OBJECTIVES: The aim of this study was to estimate the prevalence of hypersomatotropism (HST) and hyperthyroidism in cats with diabetes mellitus (DM) from referral centers in Buenos Aires, Argentina. METHODS: This was a prospective study. Systematic screening of serum insulin-like growth factor 1 (IGF-1) and total thyroxine was performed in all cats diagnosed with DM at referral centers in Buenos Aires between February 2020 and February 2022. RESULTS: In total, 154 diabetic cats were evaluated (99 males and 55 females; median age 12 years [range 3-21]; mean body weight 5 kg [range 2-12]). Altogether, there were 115 (75%) domestic shorthairs and one domestic longhair; the remaining 38 cats were purebred (mainly Siamese, n = 25 [16%]). Twenty (12.9%) cats had IGF-1 concentrations >1000 ng/ml, and three (1.9%) had IGF-1 concentrations between 800 and 1000 ng/ml along with pituitary enlargement on CT, resulting in a 14.9% HST prevalence rate in diabetic cats. Intracranial imaging was performed in all cats with HST; median pituitary dorsoventral height was 5.8 mm (range 3.1-9.5). Fourteen of 23 (61%) cats had phenotypic changes consistent with acromegaly at the time of diagnosis of HST. Four of 154 (2.5%) cats had concurrent hyperthyroidism. CONCLUSIONS AND RELEVANCE: To date, this is the first study outside of Europe to have evaluated the prevalence of HST and hyperthyroidism in cats with DM. In Buenos Aires referral centers, feline HST is the most common concurrent endocrinopathy in cats with DM but with a lower prevalence than has previously been reported. Hyperthyroidism is a rare concurrent endocrinopathy in diabetic cats from referral centers in Buenos Aires.

Efficacy of methimazole before the administration of radioactive iodine in the management of Graves' disease: a systematic review and meta-analysis.

BACKGROUND: The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. OBJECTIVE: To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease. DESIGN AND SETTING: A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria. METHODS: A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021. RESULTS: Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58). CONCLUSIONS: The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease. PROSPERO REGISTRATION: CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.

Placental leukocyte infiltration accompanies gestational changes induced by hyperthyroidism.

In brief: The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Abstract: Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal-fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.