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1.
Int J Mol Sci ; 25(18)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39337701

RESUMEN

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.


Asunto(s)
Autoinmunidad , Ferritinas , Zinc , Humanos , Femenino , Masculino , Zinc/sangre , Estudios de Casos y Controles , Persona de Mediana Edad , Ferritinas/sangre , Adulto , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipotiroidismo/inmunología , Glándula Tiroides/metabolismo , Glándula Tiroides/inmunología , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Hipertiroidismo/sangre , Hipertiroidismo/epidemiología , Hipertiroidismo/inmunología , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/inmunología
2.
J Med Life ; 17(2): 236-238, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38813368

RESUMEN

The present report describes for the first time a case of diffuse hyperthyroidism in a 30-year-old female patient who had normal levels of thyroid-stimulating hormone receptor antibodies (TSHR-Ab), slightly elevated plasma levels of thyroid hormones, and slightly increased thyroid blood flow. Seven years before, after severe stress, she had Graves' disease with elevated plasma levels of TSHR-Ab. The patient's recent medical history included mental stress and autonomic dysfunction. This report describes a mild form of hyperthyroidism in terms of elevated plasma levels of thyroid hormones and Doppler ultrasonography data; this condition was first defined as 'minor hyperthyroidism'. The examination data suggest a probable secondary role of the immune system and primary role of the autonomic nervous system in the pathogenesis of Graves' disease.


Asunto(s)
Hipertiroidismo , Receptores de Tirotropina , Humanos , Femenino , Adulto , Hipertiroidismo/sangre , Hipertiroidismo/inmunología , Receptores de Tirotropina/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Enfermedad de Graves/inmunología , Enfermedad de Graves/sangre , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Hormonas Tiroideas/sangre
3.
Endokrynol Pol ; 72(1): 14-21, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32944926

RESUMEN

INTRODUCTION: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves' disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients. MATERIAL AND METHODS: This study included 440 patients [326 (74%) female, 114 (26%) male]. All patients were classified according to gender, age, smoking habit, and TRAb levels. RESULTS: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goiter size, male gender, cigarette smoking, Graves' orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAb-negative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD. CONCLUSIONS: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.


Asunto(s)
Autoanticuerpos/sangre , Enfermedad de Graves/sangre , Hipertiroidismo/sangre , Receptores de Tirotropina/sangre , Femenino , Enfermedad de Graves/complicaciones , Enfermedad de Graves/inmunología , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/inmunología , Masculino , Persona de Mediana Edad , Receptores de Tirotropina/inmunología , Pruebas de Función de la Tiroides
4.
Thyroid ; 31(6): 950-963, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33208049

RESUMEN

Background: Antigen-specific lymphocytes are increasingly investigated in autoimmune diseases and immune therapies. We sought to identify thyrotropin receptor (TSHR)-specific lymphocytes in mouse models of Graves' disease, including Graves' patient-specific immunotype human leukocyte antigen (HLA)-DR3, and in frozen and thawed Graves' patient blood samples. Methods and Results: Splenic lymphocytes of adenovirus (Ad)-TSHR-immunized BALB/c mice were stimulated with TSHR-specific peptides C, D, or J. Furthermore, CD154-expressing cells were enriched, expanded in vitro, and analyzed for binding of peptide-major histocompatibility complex (MHC) II multimers ("tetramers," immunotype H2-IAd). Only peptides C and J were able to elicit increased expression/secretion of CD154 and interferon-γ, and tetramers which were loaded with peptide C resulted in antigen-specific signals in splenic lymphocytes from Ad-TSHR-immunized mice. Accordingly, TSHR-specific HLA-DR3-MHC class II tetramers loaded with peptide p10 specifically bound to human HLA-DR3-(allele B1*03:01)-transgenic Bl/6 mouse splenic T lymphocytes. In addition, we fine-tuned a protocol to reliably measure thawed human peripheral blood mononuclear cells (PBMCs), which resulted in reliable recovery after freezing and thawing with regard to vitality and B and T cell subpopulation markers including regulatory T cells (CD3, CD4, CD25, FoxP3, CD25high, CD127low). TSHR-specific HLA-DR3-MHC class II tetramers loaded with peptide p10 identified antigen-specific T cells in HLA-DR3-positive Graves' patients' thawed PBMCs. Moreover, stimulation-dependent release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha from thawed PBMCs occurred at the expected levels. Conclusions: Novel MHC II tetramers identified TSHR-specific T lymphocytes in Ad-TSHR-immunized hyperthyroid BALB/c or HLA-DR3-transgenic mice and in thawed human PBMCs from patients with Graves' disease. These assays may contribute to measure both disease severity and effects of novel immune therapies in future animal studies and clinical investigations of Graves' disease.


Asunto(s)
Enfermedad de Graves/inmunología , Antígeno HLA-DR3/genética , Hipertiroidismo/inmunología , Receptores de Tirotropina/inmunología , Linfocitos T Reguladores/inmunología , Animales , Linfocitos B/inmunología , Ligando de CD40/inmunología , Modelos Animales de Enfermedad , Epítopos/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunización , Inmunofenotipificación , Interferón gamma/inmunología , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Ratones , Ratones Transgénicos , Péptidos , Factor de Necrosis Tumoral alfa/inmunología
5.
Int Immunopharmacol ; 91: 107296, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360368

RESUMEN

BACKGROUND: Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood. MATERIALS AND METHODS: We conducted a single center, retrospective study of advanced NSCLC patients who were treated with PD-1 inhibitors between 10 October 2016 and 1 April 2020. TFA was characterized as new onset subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism. Frequency of development of TFA-irAEs, and its relationship with overall survival (OS) and progression free survival (PFS) were evaluated. RESULTS: In our study, 191 patients were treated with PD-1 inhibitors. Among them, forty patients (20.9%) developed TFA, of whom 10 (5.2%) presented with subclinical hypothyroidism, 15 (7.9%) with overt hypothyroidism, 6 (3.1%) with subclinical hyperthyroidism and 9 (4.7%) with overt hyperthyroidism. Survival analysis showed that the OS (16.8 months vs. 11.1 months, p < 0.001) and PFS (10.4 months vs. 5.5 months, p < 0.001) were significantly longer in patients with TFA-irAEs than in those without TFA-irAEs. In subgroup analysis of hypothyroidism and hyperthyroidism groups, similar trends were also obtained for both OS and PFS. After adjusting for potential confounding variables, patients with TFA-irAEs had a lower mortality risk (HR 0.334, 95%CI 0.196-0.571) than those without TFA-irAEs. CONCLUSIONS: TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Hipertiroidismo/inducido químicamente , Hipotiroidismo/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Glándula Tiroides/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Hipertiroidismo/diagnóstico , Hipertiroidismo/inmunología , Hipotiroidismo/diagnóstico , Hipotiroidismo/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Glándula Tiroides/inmunología , Factores de Tiempo
6.
Rev Gastroenterol Peru ; 40(3): 274-277, 2020.
Artículo en Español | MEDLINE | ID: mdl-33181816

RESUMEN

Wilkie's syndrome or superior mesenteric artery syndrome is an unusual cause of proximal intestinal obstruction, primarily attributed to recent weight loss. We report the case of a 19-year-old woman comes to our clinic and reports weight loss, abdominal pain, nausea, and vomiting. Laboratory tests revealed anemia, hypoalbuminemia, hypomagnesemia, and a suppressed thyroid stimulating hormone secondary to levothyroxine. A barium swallow test showed gastric dilatation, delayed gastric emptying and an axial computed tomography revealed an aortomesenteric angle of 11.7°. Conservative management with total parenteral and enteral nutrition was initiated, being the first-line treatment. In refractory cases surgery is a safe and effective option.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Hipertiroidismo/complicaciones , Hipertiroidismo/inmunología , Síndrome de la Arteria Mesentérica Superior/etiología , Femenino , Humanos , Adulto Joven
7.
BMJ Case Rep ; 13(11)2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-33148577

RESUMEN

We report a case of a 21-year-old young woman who was initially diagnosed with hyperthyroidism secondary to Graves' disease and spontaneously switched to hypothyroidism in a year. While most autoimmune hypothyroidism is due to Hashimoto's disease, in her case, we suspect that her hypothyroidism is due to a switch of antibody dominance from thyroid stimulating hormone (TSH) receptor-stimulating antibody (TS Ab) to TSH receptor-blocking antibody (TB Ab). Switching from dominant TS Ab activity to dominant TB Ab activity is a rare phenomenon. Optimal management of this condition is not known. Loss of follow-up and medication non-adherence has made medical management in this young woman of reproductive age further challenging.


Asunto(s)
Autoanticuerpos/inmunología , Enfermedad de Graves/complicaciones , Enfermedad de Hashimoto/etiología , Tiroiditis Autoinmune/etiología , Diagnóstico Diferencial , Femenino , Enfermedad de Graves/inmunología , Enfermedad de Hashimoto/inmunología , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/inmunología , Tiroiditis Autoinmune/inmunología , Adulto Joven
8.
Int Arch Allergy Immunol ; 181(12): 956-965, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32942281

RESUMEN

BACKGROUND: Predisposition to hyperthyroidism may be influenced by functional gene polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). However, the results of the studies published so far remain discrepant, so we conducted a meta-analysis to more robustly investigate relationships between TNF-α/IL-1/IL-4/IL-6/IL-10 polymorphisms and predisposition to hyperthyroidism. METHODS: A comprehensive literature retrieval from PubMed, Embase, Web of Science, WanFang, VIP, and CNKI was endorsed by the authors, and 38 studies were found to be eligible for pooled meta-analyses. RESULTS: We found that genotypic frequencies of TNF-α -308 G/A, IL-1A -889 C/T, IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 C/T, and IL-10 -1082 A/G polymorphisms among cases were significantly different from those among controls. Moreover, we also found that genotypic frequencies of TNF-α -308 G/A and IL-6 -174 G/C polymorphisms among cases of Caucasian origin were significantly different from those among Caucasian controls, and genotypic frequencies of IL-1A -889 C/T, IL-1B -511 C/T, IL-6 -174 G/C, IL-6 -572 G/C, and IL-10 -1,082 A/G polymorphisms among cases of Asian origin were also significantly different from those among Asian controls. CONCLUSIONS: This meta-analysis suggests that TNF-α -308 G/A, IL-1A -889 C/T, IL-1B -511 C/T, IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 C/T, and IL-10 -1,082 A/G polymorphisms may influence predisposition to hyperthyroidism in certain ethnic groups.


Asunto(s)
Genotipo , Hipertiroidismo/genética , Interleucina-10/genética , Interleucina-1/genética , Interleucina-6/genética , Factor de Necrosis Tumoral alfa/genética , Etnicidad , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipertiroidismo/inmunología , Polimorfismo de Nucleótido Simple
9.
Transplant Proc ; 52(9): 2854-2857, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32694060

RESUMEN

BACKGROUND: Hyperthyroidism after hematopoietic stem cell transplantation (HSCT) is rare, and only a few cases have been reported. What is more important, the fundamental mechanisms of hyperthyroidism after HSCT remained unclear. CASE: A 28-year-old man received an HLA haploidentical related-donor HSCT for acute myeloid leukemia and developed hyperthyroidism 31 months after HSCT. He presented with periodic paralysis as the initial symptom, his serum levels of free triiodothyronine (fT3), free thyroxine (fT4), and anti-thyroid autoantibodies increased, and thyroid-stimulating hormone level decreased. As a result, he was diagnosed with hyperthyroidism. Although systemic symptoms, signs, and laboratory findings of graft-vs-host disease (GVHD) were absent, thyroid histopathologic examination revealed thyroid follicular destruction and infiltrations of lymphocytes, which mainly consisted of CD20+ B lymphocytes and CD4+ and CD3+ T lymphocytes by immunohistochemistry. These were in accordance with the pathologic features of GVHD. The symptom of periodic paralysis resolved after treatment with prednisolone and methimazole for 1 month. The treatments lasted for 4 months, and the plasma levels of fT3, fT4, TSH, and anti-thyroid peroxidase normalized. He did not relapse after drug withdrawal with observation for 24 months to date. CONCLUSIONS: To the best of our knowledge, the present case was the first to be confirmed with thyroid-specific GVHD-induced hyperthyroidism after allogeneic HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hipertiroidismo/etiología , Adulto , Enfermedad Injerto contra Huésped/inmunología , Humanos , Hipertiroidismo/inmunología , Leucemia Mieloide Aguda/terapia , Masculino
10.
Rev. gastroenterol. Perú ; 40(3): 274-277, Jul-Sep 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1144676

RESUMEN

RESUMEN El síndrome de Wilkie o de arteria mesentérica superior es una causa poco común de obstrucción intestinal proximal, relacionada a pérdida de peso reciente. Reportamos el caso de una mujer de 19 años que se presenta a la clínica con pérdida de peso, dolor abdominal, nausea y vomito. Los exámenes de laboratorio reportaron anemia, hipoalbuminemia, hipomagnesemia y una hormona estimulante de la tiroides suprimida secundario al uso con levotiroxina. Se realizó una serie esofagogastroduodenal con datos compatibles con dilatación gástrica severa, gastroparesia y una tomografía axial computada reveló un ángulo aortomesentérico de 11,7°. Se inicio manejo conservador a base de nutrición enteral y parenteral total, siendo este el tratamiento de elección. En casos refractarios, la cirugía es una opción segura y efectiva.


ABSTRACT Wilkie's syndrome or superior mesenteric artery syndrome is an unusual cause of proximal intestinal obstruction, primarily attributed to recent weight loss. We report the case of a 19-year-old woman comes to our clinic and reports weight loss, abdominal pain, nausea, and vomiting. Laboratory tests revealed anemia, hypoalbuminemia, hypomagnesemia, and a suppressed thyroid stimulating hormone secondary to levothyroxine. A barium swallow test showed gastric dilatation, delayed gastric emptying and an axial computed tomography revealed an aortomesenteric angle of 11.7°. Conservative management with total parenteral and enteral nutrition was initiated, being the first-line treatment. In refractory cases surgery is a safe and effective option.


Asunto(s)
Femenino , Humanos , Adulto Joven , Enfermedades Autoinmunes/complicaciones , Síndrome de la Arteria Mesentérica Superior/etiología , Hipertiroidismo/complicaciones , Hipertiroidismo/inmunología
11.
Eur J Endocrinol ; 182(1): 1-9, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31648184

RESUMEN

OBJECTIVE: Our study aimed to identify and characterize thyroid dysfunctions associated with immune checkpoint inhibitors (ICIs). DESIGN: Data were obtained from VigiBase, between January 1, 2011 to March 6, 2019. METHODS: All thyroid drug-adverse events are classified by group queries according to the Medical Dictionary for Regulatory Activities. Information component (IC) and reporting odds ratio (ROR) were considered as measures of disproportionality for the assessment of association between ICIs and thyroid dysfunctions. We used IC to identify meaningful drug-adverse events while using ROR to compare differences in the reporting of drug-adverse events caused by different ICI subgroups. Positive IC values are deemed significant. RESULTS: Compared with the full database, the following ICI-associated thyroid dysfunctions were over-reported: hypothyroidism (1125 reports for ICIs vs 12495 for all drugs; Information Component 4.28 (95% CI: 4.18-4.35)), hyperthyroidism (926 vs 7538; 4.66 (95% CI: 4.55-4.74)), thyroiditis (294 vs 1237; 5.40 (95% CI: 5.21-5.54)), thyrotoxic crisis (11 vs 288; 3.55 (95% CI: 2.61-4.20)). Hypothyroidism was over-reported for patients treated with ICI combination therapy versus those treated with ICI monotherapy (ROR 1.3 (95% CI: 1.1-1.7)), and the same was observed for hyperthyroidism (ROR: 1.9 (95% CI: 1.5-2.4)), thyroiditis (ROR: 3.3 (95% CI: 2.3-4.8)), thyrotoxic crisis (ROR: 11.5 (95% CI: 2.4-53.8)). All 11 thyrotoxic crisis cases were malignant melanoma patients, of which seven occurred under ICI combination therapy. CONCLUSIONS: Thyroid dysfunction may occur after ICI therapies, and severe thyrotoxic crisis may even occur. Raising awareness of ICI-associated thyroid dysfunction can improve the detection and treatment of these diseases.


Asunto(s)
Bases de Datos Factuales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/patología , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Hipertiroidismo/inmunología , Hipertiroidismo/patología , Hipotiroidismo/inmunología , Hipotiroidismo/patología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Adulto Joven
12.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31512728

RESUMEN

CONTEXT: The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation. OBJECTIVE: Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. DESIGN: Open-label, phase II proof-of-concept study. SETTING: Multicenter. PATIENTS: Fifteen with GD. INTERVENTION: Patients received 5 doses of iscalimab at 10 mg/kg intravenously over 12 weeks. MAIN OUTCOME MEASURES: Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed. RESULTS: The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks. A clinical response and biochemical euthyroidism was observed in 7 of 15 (47%) patients. Free and total triiodothyronine and thyroxine normalized in 7 patients who did not receive any rescue medication with antithyroid drugs (ATD), and 2/15 (13.3%) showed normal thyrotropin. Six (40%) patients required ATD. Four of 7 responders relapsed after treatment completion. Serum concentrations of thyrotropin receptor autoantibodies (TSH-R-Ab) significantly declined in all patients (mean 15.3 IU/L vs 4.0 IU/L, 66% reduction; P < 0.001) and TSH-R-Ab levels normalized in 4 (27%). Thyroperoxidase and thyroglobulin autoantibodies significantly decreased in responders. Iscalimab rapidly reduced serum CXCL13 concentrations (P < 0.001). Twelve (80.0%) patients reported at least 1 adverse event (AE). All treatment-related AE were mild or moderate and resolved by end of the study. CONCLUSION: Iscalimab was generally safe and clinically effective in a subgroup of hyperthyroid GD patients. The potential therapeutic benefit of iscalimab should be further tested.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD40/antagonistas & inhibidores , Antígenos CD40/inmunología , Hipertiroidismo/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Hipertiroidismo/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Prueba de Estudio Conceptual , Pruebas de Función de la Tiroides , Distribución Tisular , Adulto Joven
13.
Actual. SIDA. infectol ; 28(104): 123-126, 2020 dic.
Artículo en Español | LILACS, BINACIS | ID: biblio-1349139

RESUMEN

La epidemia por COVID-19, causada por el nuevo coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2) ha enfrentado al equipo de salud a un abanico de presentaciones clínicas y alteraciones de las funciones órganicas a las que diagnosticar y tratar. Dentro de estas se encuentra la disfunción tiroidea.En este reporte se presenta el caso de una paciente con taquicardia persistente luego de pasado el cuadro de COVID-19, que derivó en múltiples consultas hasta que se arribó al diagnóstico de tirotoxicosis de etiología autoinmune.La tirotoxicosis asociada a COVID-19 es infrecuente, pero agrega morbilidad a la convalecencia de los pacientes, por lo que su sospecha clínica y diagnóstico rápido serían beneficiosos


The infection by the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged the health care system with a new spectrum of clinical manifestations and organ disfuntions, that require proper diagnosis and treatment.In this case we report a patient with persistent tachycardia after COVID-19 acute illness. This finding led to multiple medical visits until final diagnosis of thyrotoxicosis of autoimmune etiology.Thyrotoxicosis is an unusual complication of COVID-19, that results in higher morbility in patients during the convalescent phase of the disease. Opportune clinical suspicion and early diagnosis seems to be beneficial in terms of clinical outcome


Asunto(s)
Humanos , Femenino , Adulto , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/tratamiento farmacológico , Tirotoxicosis/diagnóstico , Morbilidad , Diagnóstico Precoz , COVID-19 , Hipertiroidismo/inmunología
14.
Medicina (B Aires) ; 79(5): 419-423, 2019.
Artículo en Español | MEDLINE | ID: mdl-31671397

RESUMEN

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.


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.


Asunto(s)
Adenoma/diagnóstico , Anticuerpos Antiidiotipos/inmunología , Hipertiroidismo/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Estreptavidina/inmunología , Adenoma/inmunología , Adulto , Errores Diagnósticos , Femenino , Humanos , Hipertiroidismo/inmunología , Neoplasias Hipofisarias/inmunología , Embarazo , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre
15.
Medicina (B.Aires) ; Medicina (B.Aires);79(5): 419-423, oct. 2019. graf, tab
Artículo en Español | LILACS | ID: biblio-1056744

RESUMEN

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.


Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Neoplasias Hipofisarias/diagnóstico , Adenoma/diagnóstico , Anticuerpos Antiidiotipos/inmunología , Estreptavidina/inmunología , Hipertiroidismo/diagnóstico , Neoplasias Hipofisarias/inmunología , Tiroxina/sangre , Triyodotironina/sangre , Tirotropina/sangre , Adenoma/inmunología , Errores Diagnósticos , Hipertiroidismo/inmunología
16.
Endocr J ; 66(11): 1001-1009, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31308303

RESUMEN

It is known that there is a relationship between some diseases and blood groups. The objective of our study is to investigate how often ABO and Rh blood groups are seen in benign thyroid diseases, especially in autoimmune-mediated thyroid diseases, and hence whether there is an association between blood groups and thyroid diseases. A total of 958 patients who were followed due to any benign thyroid disease were included in the study. The study population comprised 958 patients, 550 with Hashimoto's hypothyroidism, 160 with non-Hashimoto's hypothyroidism, 103 with iatrogenic hypothyroidism, 93 with central hypothyroidism, and 28 with Graves' and 24 with non-Graves' hyperthyroidism. Of the patients, 47.1% belonged to the O blood group, 30% to the A blood group, 15.2% to the B blood group, and 7.7% to the AB blood group while 90% were Rh-positive. The ratio of those with the O blood group was determined to be significantly higher in the Hashimoto's hypothyroidism group compared to the other disease groups. In the non-Hashimoto's hypothyroidism group, however, the ratio of the AB blood group was statistically significantly higher. While autoimmune diseases were more common in those with the O blood group, they were significantly lower in the AB blood group (p < 0.001). In our study, we determined that the ratio of the O blood group was significantly higher among patients with hypothyroidism due to Hashimoto's thyroiditis. These findings imply that there might be a relation between O blood group and Hashimoto's thyroiditis.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Enfermedad de Graves/sangre , Enfermedad de Hashimoto/sangre , Hipotiroidismo/sangre , Sistema del Grupo Sanguíneo Rh-Hr , Adulto , Anciano , Autoanticuerpos/inmunología , Femenino , Enfermedad de Graves/inmunología , Enfermedad de Hashimoto/inmunología , Humanos , Hipertiroidismo/sangre , Hipertiroidismo/inmunología , Hipotiroidismo/inmunología , Inmunoglobulinas Estimulantes de la Tiroides/inmunología , Yoduro Peroxidasa/inmunología , Masculino , Persona de Mediana Edad , Turquía
17.
Horm Metab Res ; 51(6): 347-352, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31207655

RESUMEN

Various cut-offs have been proposed for thyroid peroxidase antibodies (TPOAb) positivity. Considering that the long-term trend of TPOAb levels and its positivity incidence is not clearly understood, we conducted the current study to determine the longitudinal variations of TPOAb in a population-based cohort study. We followed 5783 individuals of Tehran Thyroid cohort Study (TTS) for 10 years (4 phases). After exclusions, data of 3493 euthyroid participants remained for analyses. The baseline prevalence rates of TPOAb positivity were 19.8, 17, and 11.4% and the annual incidence rates (95% CI) of TPOAb positivity were 8.53 (8.29-8.77), 7.59 (7.37-7.80) and 6.79 (6.60-6.98) per 1000 persons for the 3 proposed cut-offs of 14.77, 18.38, and 40 U/l; respectively. Although a slightly increasing trend was observed for TPOAb levels (p=0.001) and its conventional positivity (TPOAb>40U/l), the recently proposed cut-offs of 14.77 and 18.38 U/l showed constant TPOAb positivity over 10 years. The time trends of the TPOAb levels among younger participants were significantly different from older participants (time×age effect p=0.004), with the former having an increasing trend and the latter, a relatively decreasing trend. Although the prevalence of TPOAb positivity was significantly (p<0.001) higher among women as compared to men, the longitudinal changes of TPOAb were similar in men and women. TPOAb positivity along with TSH values between 2.5 and 5.0 mU/l or free T4 values between 0.93 and 1.7 ng/dl exerted a significantly increased risk of subclinical or overt hypothyroidism. In an iodine sufficient population, an increasing trend in TPOAb levels was observed in line with the increasing incidence of subclinical and overt hypothyroidism.


Asunto(s)
Autoanticuerpos/sangre , Hipertiroidismo/diagnóstico , Hipertiroidismo/epidemiología , Hipotiroidismo/diagnóstico , Hipotiroidismo/epidemiología , Yoduro Peroxidasa/inmunología , Glándula Tiroides/inmunología , Adulto , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Hipertiroidismo/sangre , Hipertiroidismo/inmunología , Hipotiroidismo/sangre , Hipotiroidismo/inmunología , Incidencia , Irán/epidemiología , Masculino , Pronóstico , Estudios Prospectivos , Pruebas de Función de la Tiroides
18.
Endocr J ; 66(9): 827-835, 2019 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-31217394

RESUMEN

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.


Asunto(s)
Modelos Animales de Enfermedad , Enfermedad de Graves/etiología , Enfermedad de Graves/patología , Inmunización , Receptores de Tirotropina/inmunología , Adenoviridae/genética , Animales , Femenino , Enfermedad de Graves/inmunología , Humanos , Hipertiroidismo/inmunología , Hipertiroidismo/patología , Inmunización/métodos , Esquemas de Inmunización , Ratones , Ratones Endogámicos BALB C , Receptores de Tirotropina/genética , Glándula Tiroides/inmunología , Glándula Tiroides/patología
19.
BMJ Case Rep ; 12(4)2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-30954956

RESUMEN

We report two women who were diagnosed with hypothyroidism due to what was thought to be Hashimoto's thyroiditis 18 and 16 years ago, respectively. They had been euthyroid on stable doses of levothyroxine for many years, and they presented to our clinic with clinically and biochemically overt hyperthyroidism that persisted even after stopping levothyroxine. Immunological and imaging workups were consistent with Graves' disease. Both patients were treated medically and then received definitive treatment. To our knowledge, the intervals for these two conversions are among the longest conversion intervals reported in the medical literature.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Antitiroideos/uso terapéutico , Enfermedad de Graves/fisiopatología , Enfermedad de Hashimoto/fisiopatología , Hipertiroidismo/inmunología , Hipotiroidismo/inmunología , Femenino , Enfermedad de Graves/complicaciones , Enfermedad de Graves/inmunología , Enfermedad de Graves/terapia , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/terapia , Humanos , Hipertiroidismo/etiología , Hipertiroidismo/fisiopatología , Hipertiroidismo/terapia , Hipotiroidismo/etiología , Hipotiroidismo/fisiopatología , Hipotiroidismo/terapia , Metimazol/uso terapéutico , Persona de Mediana Edad , Propranolol/uso terapéutico , Tiroidectomía , Tiroxina/efectos adversos , Tiroxina/uso terapéutico , Resultado del Tratamiento
20.
Bull Exp Biol Med ; 166(6): 751-753, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31028578

RESUMEN

In vivo experiments showed that antibodies to OmpC and OmpF porins of Yersinia pseudotuberculosis increased thyroxine (T4) level in the blood of experimental animals. The mice were immunized with different antigens: recombinant OmpF porin in a soluble monomeric form, trimers of OmpC and OmpF porins isolated from the outer membrane, or antibodies to them. The level of thyroxine in the blood of mice immunized with OmpF and OmpC porins increased by 5.47 and 22.3 times, respectively; after immunization with antibodies to these proteins, blood thyroxine increased by 9.28 and 14.29 times. Immunization with recombinant OmpF porin induced no reliable increase in thyroxine level. Hence, the serum to recombinant OmpF porin contains no antibodies specific to conformational antigenic determinants that are present in the protein trimer and, according to our previous findings from molecular docking studies, determine cross-reactions between OmpF porin of Y. pseudotuberculosis and thyroidstimulating hormone receptor.


Asunto(s)
Antígenos Bacterianos/inmunología , Hipertiroidismo/inducido químicamente , Porinas/inmunología , Yersinia pseudotuberculosis/química , Animales , Anticuerpos Antibacterianos/administración & dosificación , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/química , Femenino , Hipertiroidismo/inmunología , Hipertiroidismo/metabolismo , Inmunización , Ratones , Ratones Endogámicos BALB C , Porinas/administración & dosificación , Porinas/química , Multimerización de Proteína , Receptores de Tirotropina/inmunología , Receptores de Tirotropina/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Tiroxina/biosíntesis , Yersinia pseudotuberculosis/inmunología
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