RESUMEN
Impaired sensitivity to thyroid hormones encompasses disorders with defective transport of hormones into cells, reduced hormone metabolism, and resistance to hormone action. Mediated by heritable single-gene defects, these rare conditions exhibit different patterns of discordant thyroid function associated with multisystem phenotypes. In this context, challenges include ruling out other causes of biochemical discordance, making a diagnosis using clinical features together with the identification of pathogenic variants in causal genes, and managing these rare disorders with a limited evidence base. For each condition, the present guidelines aim to inform clinical practice by summarizing key clinical features and useful investigations, criteria for molecular genetic diagnosis, and pathways for management and therapy. Specific, key recommendations were developed by combining the best research evidence available with the knowledge and clinical experience of panel members, to achieve a consensus.
Asunto(s)
Hormonas Tiroideas , Humanos , Hormonas Tiroideas/sangre , Hormonas Tiroideas/metabolismo , Europa (Continente) , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/terapia , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/metabolismo , Sociedades Médicas , Síndrome de Resistencia a Hormonas Tiroideas/genética , Síndrome de Resistencia a Hormonas Tiroideas/diagnóstico , Síndrome de Resistencia a Hormonas Tiroideas/terapiaRESUMEN
Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.
Asunto(s)
Enfermedades Autoinmunes , Enfermedad de Graves , Enfermedad de Hashimoto , Enfermedades de la Tiroides , Femenino , Humanos , Embarazo , Placenta/metabolismo , Enfermedades de la Tiroides/metabolismo , Enfermedades Autoinmunes/genética , Enfermedad de Graves/genética , Inmunidad InnataRESUMEN
Objective: Autoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI). Methods: We collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis. Results: We characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+ GZMK+, T CD8+ Cytotoxic and ILC3 CD3E - cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased. Conclusion: Immune imbalance exists in endometrium during WOI, which may impact embryo implantation.
Asunto(s)
Infertilidad Femenina , Enfermedades de la Tiroides , Humanos , Femenino , Infertilidad Femenina/genética , Infertilidad Femenina/metabolismo , Transcriptoma , ARN/metabolismo , Implantación del Embrión/genética , Endometrio/metabolismo , Enfermedades de la Tiroides/metabolismoRESUMEN
Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves' orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto's thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.
Asunto(s)
Oftalmopatía de Graves , Selenio , Enfermedades de la Tiroides , Humanos , Selenio/uso terapéutico , Calidad de Vida , Enfermedades de la Tiroides/tratamiento farmacológico , Enfermedades de la Tiroides/metabolismo , SelenoproteínasRESUMEN
BACKGROUND: Thyroglobulin (Tg) is considered a sensitive indicator of iodine deficiency. However, the usefulness of Tg as a biomarker of excess iodine is uncertain. The present study aimed to determine the influence of different iodine intake on serum Tg levels, evaluate the influence of thyroid diseases on the distribution of Tg, and identify the factors that may affect Tg levels. METHODS: A cross-sectional survey with a total of 1208 adults was conducted in different water iodine areas in China. Urinary iodine concentration (UIC), water iodine concentration (WIC), serum Tg, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. The thyroid volumes and nodules were measured by B-scan ultrasound. RESULTS: Based on the WIC data, subjects were divided into three groups. Based on the median urinary iodine concentration (MUIC) data, the iodine levels were adequate, more than adequate, and excess for the WIC < 10 µg/L group, 10 µg/L ≤ WIC ≤ 100 µg/L g, and WIC > 100 µg/L groups, respectively. The median Tg was significantly higher in the excess iodine group than in the adequate iodine group and the more than adequate iodine group (14.6 µg/L vs.12.7 µg/L, P = 0.042; 14.6 µg/L vs.12.5 µg/L, P = 0.004). Multiple linear regression analysis showed that excess iodine intake, goitre, thyroid nodules, and hypothyroidism were significantly related to higher serum Tg levels. CONCLUSION: Serum Tg level can be a promising biomarker of excessive iodine intake, but other factors, especially the presence of thyroid disease, should be considered when using this parameter.
Asunto(s)
Yodo , Tiroglobulina , Enfermedades de la Tiroides , Adulto , Humanos , Biomarcadores , Estudios Transversales , Tiroglobulina/sangre , Tiroglobulina/química , Nódulo Tiroideo , Tirotropina , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/metabolismoRESUMEN
Transcription factor FOXP3 is a crucial regulator in the development and function of regulatory T cells (Treg) that are essential for immunological tolerance and homeostasis. Numerous studies have indicated the correlation of tumor infiltrating FOXP3+ Treg upregulation with poor prognostic parameters in thyroid cancer, including lymph node metastases, extrathyroidal extension, and multifocality. Most immune-checkpoint molecules are expressed in Treg. The blockage of such signals with checkpoint inhibitors has been approved for several solid tumors, but not yet for thyroid cancer. Thyroid abnormalities may be induced by checkpoint inhibitors. For example, hypothyroidism, thyrotoxicosis, painless thyroiditis, or even thyroid storm are more frequently associated with anti-PD-1 antibodies (pembrolizumab and nivolumab). Therefore, Targeting FOXP3+ Treg may have impacts on checkpoint molecules and the growth of thyroid cancer. Several factors may impact the role and stability of FOXP3, such as alternative RNA splicing, mutations, and post-translational modification. In addition, the role of FOXP3+ Treg in the tumor microenvironment is also affected by the complex regulatory network formed by FOXP3 and its transcriptional partners. Here we discussed how the expression and function of FOXP3 were regulated and how FOXP3 interacted with its targets in Treg, aiming to help the development of FOXP3 as a potential therapeutic target for thyroid cancer.
Asunto(s)
Enfermedades de la Tiroides , Neoplasias de la Tiroides , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Humanos , Linfocitos T Reguladores/metabolismo , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Microambiente TumoralRESUMEN
Network pharmacology was used to illuminate the targets and pathways of polybrominated diphenyl ethers (PBDEs) causing thyroid dysfunction. A protein-protein interaction (PPI) network was constructed. Molecular docking was applied to analyze PBDEs and key targets according to the network pharmacology results. A total of 247 targets were found to be related to 16 PBDEs. Ten key targets with direct action were identified, including the top five PIK3R1, MAPK1, SRC, RXRA, and TP53. Gene Ontology (GO) functional enrichment analysis identified 75 biological items. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 62 pathways mainly related to the regulation of the thyroid hormone signaling pathway, MAPK signaling pathway, PI3K-Akt signaling, pathways in cancer, proteoglycans in cancer, progesterone-mediated oocyte maturation, and others. The molecular docking results showed that BDE-99, BDE-153, 5-OH-BDE47, 5'-OH-BDE99, 5-BDE47 sulfate, and 5'-BDE99 sulfate have a good binding effect with the kernel targets. PBDEs could interfere with the thyroid hormone endocrine through multiple targets and biological pathways, and metabolites demonstrated stronger effects than the prototypes. This research provides a basis for further research on the toxicological effects and molecular mechanisms of PBDEs and their metabolites. Furthermore, the application of network pharmacology to the study of the toxicity mechanisms of environmental pollutants provides a new methodology for environmental toxicology.
Asunto(s)
Éteres Difenilos Halogenados/toxicidad , Enfermedades de la Tiroides/inducido químicamente , Bases de Datos de Compuestos Químicos , Bases de Datos Genéticas , Bases de Datos de Proteínas , Evaluación Preclínica de Medicamentos , Contaminantes Ambientales/química , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Ontología de Genes , Redes Reguladoras de Genes/efectos de los fármacos , Éteres Difenilos Halogenados/química , Éteres Difenilos Halogenados/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/genética , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/metabolismoRESUMEN
Possible links between periodontitis and various cardiometabolic and autoimmune diseases have been advocated on the basis of chronic inflammation or oxidative stress. However, the association between periodontitis and thyroid dysfunction is under-researched. Participants without previous thyroid disease or ongoing thyroid-related medication were included from a nationwide population-level survey. Participants were categorized into tertiles of thyroid stimulating hormone (TSH) levels (first tertile < 1.76 mIU/L; second tertile 1.76-2.83 mIU/L; third tertile > 2.83 mIU/L), and periodontal condition was assessed using the Community Periodontal Index. Of the total of 5468 participants, 1423 had periodontitis (26%). A significant difference in the weighted prevalence of periodontitis according to TSH tertiles was observed, with the highest prevalence in the first tertile (26.5%) and the lowest prevalence in the third tertile (20.9%, p = 0.003). Subjects in the first TSH tertile had higher odds for periodontitis than those in the third tertile (OR 1.36, 95% CI 1.10-1.68; p for trend = 0.005) after adjusting for covariates. This association was consistent across subgroups and within sensitivity analyses among subjects without specific factors affecting thyroid function or diseases reported to be related to periodontitis. The present study demonstrated that low TSH levels were associated with significantly higher odds for periodontitis.
Asunto(s)
Periodontitis/patología , Glándula Tiroides/patología , Adulto , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodontitis/metabolismo , Prevalencia , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/patología , Pruebas de Función de la Tiroides/métodos , Glándula Tiroides/metabolismo , Tirotropina/metabolismoRESUMEN
To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.
Asunto(s)
Biomarcadores , Enfermedades de la Tiroides/diagnóstico por imagen , Enfermedades de la Tiroides/metabolismo , Tiroiditis Autoinmune/diagnóstico por imagen , Tiroiditis Autoinmune/metabolismo , Ultrasonografía , Adolescente , Adulto , Autoanticuerpos/inmunología , Autoinmunidad , Niño , Preescolar , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Pruebas de Función de la Tiroides , Ultrasonografía/métodos , Adulto JovenRESUMEN
The association between second to fourth finger ratio and thyroid diseases is unexplained. There is a possible interaction between prenatal exposition to sex hormone and thyroid functions in the adulthood. The study included 175 adults investigated in Lódz in the central Poland. It consisted of two main parts: a survey including questions about occurrence of thyroid gland dysfunction and anthropometric measurements (body mass and height and length of the second and fourth finger, waist and hip circumferences). The women who had thyroid disease had higher 2D:4D digit ratio (left hand) (mean = 1.004; SD = 0.036) than healthy ones (mean = 0.989; SD = 0.030) (t = - 2105; p = 0.038; d = 0.707). The association between thyroid diseases occurrence and prenatal steroid hormone exposition is noticed. Only females who had thyroid diseases tend to have higher 2D:4D digit ratio, for left hand.
Asunto(s)
Ratios Digitales , Efectos Tardíos de la Exposición Prenatal/epidemiología , Enfermedades de la Tiroides/epidemiología , Adulto , Anciano , Femenino , Hormonas Esteroides Gonadales/efectos adversos , Hormonas Esteroides Gonadales/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Embarazo , Medición de Riesgo/métodos , Factores de Riesgo , Factores Sexuales , Enfermedades de la Tiroides/metabolismo , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismoRESUMEN
To investigate the prognostic factors of extraocular muscle restriction in patients with thyroid eye disease (TED), 65 patients with TED and restrictive myopathy were evaluated. Demographics, clinical activity score (CAS), smoking status, thyroid disease status, thyroid hormone status, thyroid autoantibody status, orbital computed tomography (CT) scan at initial presentation, and treatment regimens were assessed. The movements of the most severely affected extraocular muscles were categorized into five grades. The patients were divided into the improved and the not-improved group based on the improvement in the limitation of the extraocular muscle excursion (LOM) throughout the follow-up, and the groups were compared using clinical factors. The mean LOM significantly improved from 2.3 ± 1.1 to 1.7 ± 1.2 after 1 year of follow-up. The excursion of the most restricted muscle improved in 32 patients but not in 33 patients during the follow-up. The initial concentration of the thyroid-stimulating antibody (TSAb) was significantly lower in the improved (229.3 ± 114.1) than in the not-improved group (345.0 ± 178.6) (P = 0.02) Age, sex, smoking status, CAS, thyroid status, and muscle thickness on the CT scan did not significantly differ in the groups. This study showed that the initial concentration of TSAb is a factor affecting the recovery of restrictive myopathy.
Asunto(s)
Oftalmopatías/diagnóstico , Enfermedades Musculares/diagnóstico , Enfermedades de la Tiroides/diagnóstico , Hormonas Tiroideas/metabolismo , Adulto , Anciano , Oftalmopatías/complicaciones , Oftalmopatías/metabolismo , Oftalmopatías/patología , Femenino , Humanos , Inmunoglobulinas Estimulantes de la Tiroides/administración & dosificación , Masculino , Persona de Mediana Edad , Enfermedades Musculares/complicaciones , Enfermedades Musculares/metabolismo , Enfermedades Musculares/patología , Músculos Oculomotores/metabolismo , Músculos Oculomotores/patología , Pronóstico , Fumar/efectos adversos , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/patología , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Tomografía Computarizada por Rayos XRESUMEN
Maternal thyroid hormone crosses the placenta to the fetus beginning in the first trimester, likely playing an important role in fetal development. The fetal thyroid gland begins to produce thyroid hormone in the second trimester, with fetal serum T4 levels gradually rising to term. Full maturation of the hypothalamic-pituitary-thyroid (HPT) axis does not occur until term gestation or the early neonatal period. Postnatal thyroid function in preterm babies is qualitatively similar to term infants, but the TSH surge is reduced, with a corresponding decrease in the rise in T4 and T3 levels. Serum T4 levels are reduced in proportion to the degree of prematurity, representing both loss of the maternal contribution and immaturity of the HPT axis. Other factors, such as neonatal drugs, e.g., dopamine, and non-thyroidal illness syndrome (NTIS) related to co-morbidities contribute to the "hypothyroxinemia of prematurity". Iodine, both deficiency and excess, may impact thyroid function in infants born preterm. Overall, the incidence of permanent congenital hypothyroidism in preterm infants appears to be similar to term infants. However, in newborn screening (NBS) that employ a total T4-reflex TSH test approach, a higher proportion of preterm babies will have a T4 below the cutoff, associated with a non-elevated TSH level. In NBS programs with a primary TSH test combined with serial testing, there is a relatively high incidence of "delayed TSH elevation" in preterm neonates. On follow-up, the majority of these cases have transient hypothyroidism. Preterm/LBW infants have many clinical manifestations that might be ascribed to hypothyroidism. The question then arises whether the hypothyroxinemia of prematurity, with thyroid function tests compatible with either non-thyroidal illness syndrome or central hypothyroidism, is a physiologic or pathologic process. In particular, does hypothyroxinemia contribute to the neurodevelopmental impairment common to preterm infants? Results from multiple studies are mixed, with some randomized controlled trials in the most preterm infants born <28 weeks gestation appearing to show benefit. This review will summarize fetal and neonatal thyroid physiology, thyroid disorders specific to preterm/LBW infants and their impact on NBS for congenital hypothyroidism, examine treatment studies, and finish with comments on unresolved questions and areas of controversy.
Asunto(s)
Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/terapia , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/terapia , Hormonas Tiroideas/metabolismo , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Enfermedades del Recién Nacido/metabolismo , Recien Nacido Prematuro , Embarazo , Pronóstico , Enfermedades de la Tiroides/metabolismo , Pruebas de Función de la TiroidesRESUMEN
PURPOSE: The close association among thyroid metabolism, mood disorders and behavior has long been known. The old and modern uses of thyroid hormones to modulate the expression of depression and bipolar disorder and to improve clinical outcome when used in conjunction with psychotropic medications. METHODS: A literature search was performed to identify studies investigating the effects of thyroid hormone treatment in patient s with mood disorders. RESULTS: The successful modification of mood disorders with thyroid hormone underscores the association between endocrine and cerebral systems in these disorders. Thyroid hormones have a profound influence on behavior and appear to be capable of modulating the phenotypic expression of major mood disorders. In fact, there is evidence that triiodothyronine (LT3) may accelerate the antidepressant response to antidepressants, and studies suggest that LT3 also may augment the response to antidepressants in refractory depression. Add-on treatment with supraphysiologic doses of levothyroxine (LT4) has shown efficacy in open-label and in placebo-controlled studies, including in rapid cycling and prophylaxis-resistant bipolar disorder, and with acute refractory uni- or bipolar depression. Functional brain-imaging studies (PET) demonstrated that administration of supraphysiologic LT4 improves depressive symptoms in patients with bipolar depression by modulating cerebral activity in the anterior limbic network. CONCLUSION: The add-on administration of supraphysiologic doses of LT4 is a promising strategy in patients with refractory bipolar and depressive mood disorders.
Asunto(s)
Antidepresivos/farmacología , Trastorno Bipolar , Trastorno Depresivo , Enfermedades de la Tiroides , Hormonas Tiroideas , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Interacciones Farmacológicas , Humanos , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/psicología , Hormonas Tiroideas/metabolismo , Hormonas Tiroideas/farmacología , Tiroxina/farmacologíaRESUMEN
CONTEXT: Genetic risk factors play a major role in the pathoetiology of autoimmune thyroid diseases (AITD). So far, only common risk variants have been identified in AITD susceptibility genes. Recently, rare genetic variants have emerged as important contributors to complex diseases, and we hypothesized that rare variants play a key role in the genetic susceptibility to AITD. OBJECTIVE: We aimed to identify new rare variants that are associated with familial AITD. METHODS: We performed deep sequencing of 3 previously mapped AITD-linked loci (10q, 12q, and 14q) in a dataset of 34 families in which AITD clustered (familial AITD). RESULTS: We identified 13 rare variants, located in the inositol polyphosphate multikinase (IPMK) gene, that were associated with AITD (ie, both Graves' disease [GD] and Hashimoto's thyroiditis [HT]); 2 rare variants, within the dihydrolipoamide S-succinyltransferase (DLST) and zinc-finger FYVE domain-containing protein (ZFYVE1) genes, that were associated with GD only; and 3 rare variants, within the phosphoglycerate mutase 1 pseudogene 5 (PGAM1P5), LOC105369879, and methionine aminopeptidase 2 (METAP2) genes, that were associated with HT only. CONCLUSION: Our study demonstrates that, in addition to common variants, rare variants also contribute to the genetic susceptibility to AITD. We identified new rare variants in 6 AITD susceptibility genes that predispose to familial AITD. Of these, 3 genes, IPMK, ZFYVE1, and METAP2, are mechanistically involved in immune pathways and have been previously shown to be associated with autoimmunity. These genes predispose to thyroid autoimmunity and may serve as potential therapeutic targets in the future.
Asunto(s)
Enfermedades Autoinmunes/patología , Biomarcadores/metabolismo , Carga Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Polimorfismo de Nucleótido Simple , Enfermedades de la Tiroides/patología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Femenino , Genotipo , Humanos , Masculino , Pronóstico , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/metabolismoRESUMEN
BACKGROUND: Thyroid disorders, both overt and subclinical, are highly prevalent conditions in the general population. Although a clear relationship between overt thyroid dysfunctions and cardiovascular complications has long been established, data regarding subclinical thyroid dysfunction are by far more controversial. PURPOSE: The present review will be aimed at providing a summary of most recent evidence coming from meta-analyses regarding the complex relationship between thyroid dysfunction and cardiovascular disease. CONCLUSIONS: The review will summarize, in the first part, the physiopathological link between thyroid hormone imbalances and the cardiovascular system. In the second part the review will outline the evidence coming from meta-analyses regarding the cardiovascular risk related with both overt and subclinical thyroid dysfunctions. Particular attention will be put towards studies showing data stratified for patient's age, TSH levels and pre-existing cardiovascular disease. Finally, an overview regarding the effects of specific therapy for subclinical thyroid diseases in terms of amelioration of cardiovascular outcomes will be included.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedades de la Tiroides , Hormonas Tiroideas/fisiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Enfermedades de la Tiroides/clasificación , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/fisiopatologíaRESUMEN
Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on to describe the main effects of the metabolites and their potential use in medicine. One section addresses thyroid hormone levels in corona virus disease 19 (COVID-19). It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed.
Asunto(s)
COVID-19/epidemiología , SARS-CoV-2 , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/metabolismo , Hormonas Tiroideas/fisiología , COVID-19/sangre , Comorbilidad , Diyodotironinas/fisiología , Humanos , Yoduro Peroxidasa/metabolismo , SARS-CoV-2/fisiología , Enfermedades de la Tiroides/virología , Hormonas Tiroideas/sangre , Hormonas Tiroideas/uso terapéutico , Tiroxina/fisiología , Triyodotironina/fisiología , Triyodotironina Inversa/fisiologíaRESUMEN
INTRODUCTION: Iodine deficiency disorder a common problem in sub-Saharan Africa (SSA). It affects not only the health of the affected individual but also the economic development of the country. However, to the best of our knowledge, there is a scarcity in literature about the associated factors of iodized salt utilization in sub-Saharan Africa. Therefore, this study aimed to identify both individual and community level determinants of iodized salt utilization in sub-Saharan Africa. METHODS: This study used the appended datasets of the most recent demographic and health survey from 31 sub-Saharan countries. A total weighted sample of 391,463 households was included in the study. Both bivariable and multivariable multilevel logistic regression were done to determine the associated factors of iodized salt utilization in SSA. P value ≤ 0.05 was used to declare statistically significant variables. RESULTS: Those households with primary (AOR = 1.53, 95% CI = 1.50-1.57), secondary (AOR = 1.81, 95% CI = 1.76-1.86) and higher education level (AOR = 2.28, 95% CI = 2.17-2.40) had higher odds of iodized salt utilization. Households with middle (AOR = 1.05, 95% CI = 1.02-1.08), richer (AOR = 1.13, 95% CI = 1.09-1.17) and richest wealth index (AOR = 1.23, 95% CI = 1.18-1.28) also had an increased chance of using iodized salt. Households from high community media exposure (AOR = 2.07, 95% CI = 1.71-2.51), high community education level (AOR = 3.78, 95% CI = 3.14-4.56), and low community poverty level (AOR = 1.29, CI = 1.07-1.56) had higher odds of using salt containing iodine. CONCLUSION: Both individual and community level factors were found to be associated with use of salt containing iodine in sub-Saharan Africa. Education level, media exposure, community poverty level, wealth index, community education, and community media exposure were found to be associated with use of salt containing iodine in SSA. Therefore, to improve the use of iodized salt in the region, there is a need to increase access to media sources and develop the socioeconomic status of the community.
Asunto(s)
Yodo/deficiencia , Modelos Teóricos , Cloruro de Sodio Dietético/uso terapéutico , Enfermedades de la Tiroides/epidemiología , Adulto , África del Sur del Sahara/epidemiología , Anciano , Composición Familiar , Femenino , Encuestas Epidemiológicas , Humanos , Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multinivel , Clase Social , Factores Socioeconómicos , Enfermedades de la Tiroides/tratamiento farmacológico , Enfermedades de la Tiroides/metabolismo , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , Hormonas Tiroideas/genéticaRESUMEN
The patho-mechanism of changes in the thyroid gland, including carcinogenesis, is a complex process, which involves oxidative stress. The goal of our investigation was to verify the extent of stress in the thyroid gland related to glycation. The study samples were comprised of blood sera, thyroid, and adipose tissue sections probed from 37 patients diagnosed with thyroid cancers and goiter. Using immuno-enzymatic and fluorometric assays we analyzed the content of advanced glycation end-products (AGEs), pentosidine, receptors for advanced glycation end-products (RAGE), scavenger receptor class (SR)-A, SR-B, glutathione, malondialdehyde and nitric oxide synthase. In addition to classic AGEs, a recent study detected the melibiose-derived glycation (MAGE) product. We demonstrated the presence of AGEs, MAGE and their receptors of the RAGE and SR-A. In addition, in the control samples of thyroid glands SR-B groups were detected as well as of pathological groups without noticeable tendency to antigen concentration in the area of carcinogenesis. Fluorescent AGEs correlate positively with glutathione, which supports the assumption that glycation stress leads to augmentation of oxidative stress and increase of the intensity of antioxidant mechanisms.
Asunto(s)
Productos Finales de Glicación Avanzada/metabolismo , Estrés Oxidativo , Enfermedades de la Tiroides/metabolismo , Glándula Tiroides/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Melibiosa/metabolismo , Persona de Mediana Edad , Óxido Nítrico Sintasa/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Enfermedades de la Tiroides/patología , Glándula Tiroides/patologíaRESUMEN
The most known effects of endogenous Cushing's syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus-pituitary-thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the "central hypothyroidism". These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus-pituitary-thyroid axis activity. During active Cushing's syndrome, the "immunological tolerance" guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing's syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing's syndrome patients, both during the active disease and after its remission.