RESUMEN
OBJECTIVE: To explore the causal relationship between thyroid dysfunction and sepsis based on the bidirectional two-sample Mendelian randomization (MR) method. METHODS: The genome-wide association study (GWAS) dataset were selected to screen single nucleotide polymorphisms (SNP) associated with thyroid dysfunction as instrumental variable (IV) for genetic variation, using hypothyroidism and hyperthyroidism as exposure factor and sepsis as outcome factor. Potential causal relationship between thyroid dysfunction and sepsis was analyzed using a bidirectional two-sample MR method primary analysis method of inverse-variance weighted (IVW). Potential pleiotropic analysis of SNP was performed using the MR Egger regression intercept test. Sensitivity analysis was performed using the "leave one out" test. Reverse MR method was used to prove the causal relationship. RESULTS: The GWAS data were screened based on the three main assumptions of MR, resulting in 101 SNP strongly associated with hypothyroidism and 10 SNP strongly associated with hyperthyroidism entering the MR analysis. The results of the MR using the IVW method showed that the risk of sepsis in individuals with hypothyroidism was 2.293 times higher than those without hypothyroidism [odds ratio (OR) = 2.293, 95% confidence interval (95%CI) was 1.199-4.382, P = 0.012]. There was no significant difference in the risk of sepsis between hyperthyroid and non-hyperthyroid populations (OR = 1.049, 95%CI was 0.999-1.100, P = 0.560). MR Egger regression intercept test showed that the included SNP did not have pleiotropy, and the MR-PRESSO test did not find outliers. Sensitivity analysis suggested that the results of MR were stable. The results of the reverse MR analysis showed that the reverse causal relationship between hyperthyroidism and sepsis was not proved (OR = 0.996, 95%CI was 0.988-1.004, P = 0.338), which further confirmed the robust MR analysis result. CONCLUSIONS: The results of the bidirectional two-sample MR analysis show that hypothyroidism can increase the risk of sepsis onset, while there is no causal relationship between hyperthyroidism and sepsis.
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Estudio de Asociación del Genoma Completo , Hipertiroidismo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Sepsis , Humanos , Sepsis/genética , Sepsis/complicaciones , Hipertiroidismo/genética , Hipertiroidismo/complicaciones , Hipotiroidismo/genética , Factores de Riesgo , Enfermedades de la Tiroides/genéticaRESUMEN
Background: Globally, clinical hypothyroidism affects an estimated 0.5 to 5% of the population, while subclinical hypothyroidism affects 5-20%. Limited data is available on the prevalence of thyroid disease within the Mexican population. The objective of this study was to describe the characteristics of people screened for hypothyroidism in Mexico during 2022 using the Zulewski scale. Methods: A cross-sectional analysis was conducted using data obtained from a digital survey administered by an e-Health platform. This study included participants of all genders, aged 18 years and older (n = 31,449). Descriptive statistics (frequencies and percentages) were sued to describe the data. Differences between groups were assessed through the chi-square or Fischer's exact test. Information gathered was subjected to hierarchical segmentation analysis to explore trends and patterns. Statistical significance was set as <0.05. Results: Among the participants, 87.7% were women, and 80% fell within the age group 18 and 44 years. According to the Zulewski scale, 27% of the participants had a low risk of hypothyroidism, 37.4% were classified as having an intermediate risk, and 35.6% were at a high risk. In people at high risk of hypothyroidism, the most common symptom was constipation (29.2%) whereas the most common sign was decreased speed of movement (26.2%). Inquiry of slow movements, dry skin, and facial edema allowed the identification of 90.2% of participants at high risk of hypothyroidism. Conclusions: In Mexico, a significant portion of the population is at an intermediate or high risk of hypothyroidism, requiring confirmatory diagnostic tests.
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Hipotiroidismo , Humanos , Masculino , Femenino , Adulto , Hipotiroidismo/epidemiología , Hipotiroidismo/diagnóstico , Estudios Transversales , Persona de Mediana Edad , Adulto Joven , Adolescente , México/epidemiología , Prevalencia , Anciano , Factores de Riesgo , Medición de RiesgoRESUMEN
INTRODUCTION: Metabolic syndrome (MetS) and hypothyroidism are well-established forerunners of atherogenic cardiovascular disease (CVD). It is possible that patients suffering from both these disease entities may have a compounded risk. This study aimed at determining the prevalence of hypothyroidism in MetS. MATERIALS AND METHODS: This cross-sectional study was conducted from September 2017 to August 2018 in the department of medicine at a tertiary care hospital in Northern India. Ethical approval was obtained from the institutional ethical committee. The study subjects consisted of 157 patients with MetS, the diagnosis of which was based on the International Diabetes Federation criteria. After a detailed history and physical examination, relevant investigations including complete thyroid profile were done. The data were analyzed using appropriate statistical tests (P < 0.05). RESULTS: In our study, the age of subjects ranged between 14 and 92 years, with a mean ± standard deviation of 48.1 ± 17.01 years. There were more females than males with a male-to-female ratio of 1:1.3. The prevalence of hypothyroidism was 46.5%. Hypothyroidism was more common in females (58.9%) as compared to males (41.1%). Patients with hypothyroidism had significantly higher body weight and body mass index (BMI) in comparison to euthyroid patients. The rest of the anthropometric parameters were comparable. Waist circumference and BMI of overt hypothyroid patients were found to be higher as compared to subclinical hypothyroid patients. Total cholesterol and triglyceride were significantly higher (P = 0.001 and P < 0.001, respectively), while high-density lipoprotein levels were significantly lower in patients with hypothyroidism than the euthyroid group (P < 0.001). CONCLUSION: Hypothyroidism, especially subclinical hypothyroidism, is a common endocrine disorder in patients with MetS. As MetS and hypothyroidism are independent risk factors for CVD, hence there is a need for screening for hypothyroidism and the treatment of the same can be beneficial in reducing the cardiovascular morbidity and mortality in patients with MetS.
Résumé Introduction:Le syndrome métabolique (METS) et l'hypothyroïdie sont des précurseurs bien établis d'une maladie cardiovasculaire athérogène (MCV). Il est possible que les patients souffrant de ces deux entités maladie puissent avoir un risque composé. Cette étude visait à déterminer la prévalence de l'hypothyroïdie dans les Mets.Matériaux et méthodes:Cette étude transversale a été menée de septembre 2017 à août 2018 dans le Département de médecine dans un hôpital de soins tertiaires du nord de l'Inde. L'approbation éthique a été obtenue auprès du Comité éthique institutionnel. Les sujets de l'étude étaient composés de 157 patients atteints de MetS, dont le diagnostic était basé sur les critères internationaux de la Fédération du diabète. Après un historique détaillé et un examen physique, des enquêtes pertinentes, y compris un profil thyroïdien complet, ont été effectuées. Les données ont été analysées en utilisant des tests statistiques appropriés (P <0,05).Résultats:Dans notre étude, l'âge des sujets variait entre 14 et 92 ans, avec une moyenne ± standard déviation de 48,1 ± 17,01 ans. Il y avait plus de femelles que les hommes avec un rapport masculin à féminin de 1: 1,3. La prévalence de l'hypothyroïdie était de 46,5%. L'hypothyroïdie était plus fréquente chez les femmes (58,9%) par rapport aux hommes (41,1%). Les patients atteints d'hypothyroïdie avaient Indice de poids corporel et de masse corporelle significativement plus élevé (IMC) par rapport aux patients euthyroïdiens. Le reste des paramètres anthropométriques étaient comparables. Le tour de taille et l'IMC des patients hypothyroïdiens manifestes se sont révélés plus élevés par rapport à l'hypothyroïde subclinique patients. Le cholestérol total et les triglycérides étaient significativement plus élevés (P = 0,001 et P <0,001, respectivement), tandis que les lipoprotéines à haute densité Les niveaux étaient significativement plus faibles chez les patients atteints d'hypothyroïdie que le groupe euthyroïdien (P <0,001).Conclusion:hypothyroïdie, en particulier L'hypothyroïdie subclinique est un trouble endocrinien commun chez les patients atteints de Metts. Comme les Mets et l'hypothyroïdie sont des facteurs de risque indépendants Pour les MCV, il y a donc un besoin de dépistage pour l'hypothyroïdie et le traitement de la même chose peut être bénéfique pour réduire le cardiovasculaire morbidité et mortalité chez les patients atteints de MetS.
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Índice de Masa Corporal , Hipotiroidismo , Síndrome Metabólico , Humanos , Hipotiroidismo/epidemiología , Hipotiroidismo/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Prevalencia , India/epidemiología , Anciano , Factores de Riesgo , Adulto Joven , Adolescente , Triglicéridos/sangre , Circunferencia de la Cintura , Anciano de 80 o más Años , Colesterol/sangreRESUMEN
Hypothyroidism is one of the most common endocrinopathies worldwide, the treatment of which is based on replacement therapy with levothyroxine. However, this seemingly simple treatment method is fraught with many difficulties and frequent dissatisfaction among patients. In fact, differences in response to levothyroxine probably depend on a complex interaction between individual, environmental, genetic, and epigenetic factors that are still not sufficiently understood. Immunological disturbances, underlying Hashimoto's disease, the most common cause of hypothyroidism, probably play a significant role in these relationships. Indeed, a growing number of studies indicate that autoimmunity through activation of low-grade inflammation can lead to impaired absorption, transport, metabolism, and action of thyroid hormones. This review provides an up-to-date overview of the causes responsible for both the difficulty in achieving target thyrotropin levels and persistence of nonspecific symptoms despite adequate hormone replacement from an immunoendocrine perspective. Understanding these mechanisms points to a new direction in the approach to hypothyroidism, indicating the need for new personalized treatment strategies.
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Terapia de Reemplazo de Hormonas , Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Enfermedad de Hashimoto/tratamiento farmacológico , Enfermedad de Hashimoto/inmunología , Femenino , MasculinoRESUMEN
Regardless of the cause, hypothyroidism should be treated with levothyroxine. The objectives of management are the normalization of TSH levels and the relief of symptoms. In general, the vast majority of patients who achieve normalization of TSH levels show a resolution of symptoms; however, for a small number of individuals, symptoms persist (despite adequate control of TSH). This scenario generates a dilemma in the therapeutic approach to these patients, because even when excluding other causes or concomitant diseases that can explain the persistence of symptoms, pharmacological management strategies are scarce. Consequently, the efficacy of some less conventional approaches to therapy, such as the use of LT3 monotherapy, desiccated thyroid extracts, and LT4/LT3 combinations, in addressing persistent hypothyroid symptoms have been evaluated in multiple studies. The majority of these studies did not observe a significant benefit from these "nonconventional" therapies in comparison to results with LT4 monotherapy alone. Nevertheless, some studies report that a significant proportion of patients prefer an alternative to monotherapy with LT4. The most common approach has been to prescribe a combination of LT4 and LT3, and this review describes and analyzes the current evidence of the efficacy of LT4/LT3 combination therapy vs. LT4 monotherapy in addressing persistent hypothyroidism symptoms to provide suggested guidelines for clinicians in the management of these patients.
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Quimioterapia Combinada , Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , Triyodotironina/uso terapéutico , Tirotropina/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis. METHODS: Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MRâEgger regression, Cochran's Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism. RESULTS: Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80-7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93-77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21-3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction. CONCLUSION: The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure.
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Enfermedades Cardiovasculares , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hipotiroidismo , Análisis de la Aleatorización Mendeliana , Tiroxina , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/genética , Hipotiroidismo/epidemiología , Tiroxina/uso terapéutico , Medición de Riesgo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Terapia de Reemplazo de Hormonas/efectos adversos , Factores de Riesgo , Fenotipo , Femenino , Infarto del Miocardio/genética , Infarto del Miocardio/epidemiología , Infarto del Miocardio/diagnóstico , Polimorfismo de Nucleótido Simple , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Masculino , Variantes Farmacogenómicas , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: The thyroid gland is an endocrine gland that has an impact on the body's general metabolism. Thus, the secretions of the thyroid gland can modify the overall metabolism of the entire body. The prevalence of hypothyroidism is increasing quickly, with rates of 2%-5% in affluent countries and 11% in India. Individuals diagnosed with hypothyroidism need to take medication for the rest of their lives, resulting in significant stress. Therefore, conducting a study in this area is imperative. OBJECTIVE: This study aims to assess the effectiveness of the therapeutic enema (Kshar Basti) and oral Kanchanar Guggul in the treatment of hypothyroidism. METHODS: The trial group (n=45) will receive a therapeutic enema (Kshar Basti) followed by oral Ayurvedic drugs for 180 days. The control group (n=45) will be given levothyroxine tablets at a dosage of 1.6 µg/kg/day for the same duration. The objective is to examine the alterations in thyroid stimulating hormone (TSH) levels before and after the treatment. RESULTS: Any deviation of the serum TSH by more than 20% from the initial values, while keeping triiodothyronine (T3), and thyroxine (T4) levels within the normal range, will be deemed statistically significant. Consequently, we anticipate a statistically significant variation in serum TSH levels between the therapeutic enema and Kanchanar Guggul treatments. Presently, the drug preparation operations are in progress. We expect to start enrolling patients in June 2024, do data analysis in December 2025, and acquire results by early 2026, marking the end of this trial. CONCLUSIONS: This study will evaluate the efficacy of the therapeutic enema, specifically Kshar Basti, in treating hypothyroidism. Furthermore, more research can determine the efficacy of a therapeutic enema (Kshar Basti) in treating overt hypothyroidism and hypothyroidism during pregnancy. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/05/052389; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Nzk1NjY=&Enc=&userName=052389. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57287.
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Hipotiroidismo , Tiroxina , Humanos , Hipotiroidismo/tratamiento farmacológico , Tiroxina/uso terapéutico , India , Adulto , Femenino , Masculino , Medicina Ayurvédica , Enema , Gomas de Plantas/uso terapéutico , Commiphora/química , Ensayos Clínicos Controlados Aleatorios como Asunto , Extractos Vegetales/uso terapéutico , Extractos Vegetales/administración & dosificación , Persona de Mediana EdadRESUMEN
BACKGROUND: Many studies have investigated the association between hypothyroidism and frozen shoulder, but their findings have been inconsistent. Furthermore, earlier research has been primarily observational, which may introduce bias and does not establish a cause-and-effect relationship. To ascertain the causal association, we performed a two-sample bidirectional Mendelian randomization (MR) analysis. METHODS: We obtained data on "Hypothyroidism" and "Frozen Shoulder" from Summary-level Genome-Wide Association Studies (GWAS) datasets that have been published. The information came from European population samples. The primary analysis utilized the inverse-variance weighted (IVW) method. Additionally, a sensitivity analysis was conducted to assess the robustness of the results. RESULTS: We ultimately chose 39 SNPs as IVs for the final analysis. The results of the two MR methods we utilized in the investigation indicated that a possible causal relationship between hypothyroidism and frozen shoulder. The most significant analytical outcome demonstrated an odds ratio (OR) of 1.0577 (95% Confidence Interval (CI):1.0057-1.1123), P = 0.029, using the IVW approach. Furthermore, using the MR Egger method as a supplementary analytical outcome showed an OR of 1.1608 (95% CI:1.0318-1.3060), P = 0.017. Furthermore, the results of our sensitivity analysis indicate that there is no heterogeneity or pleiotropy in our MR analysis. In the reverse Mendelian analysis, no causal relationship was found between frozen shoulders and hypothyroidism. CONCLUSION: Our MR analysis suggests that there may be a causal relationship between hypothyroidism and frozen shoulder.
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Bursitis , Estudio de Asociación del Genoma Completo , Hipotiroidismo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Hipotiroidismo/genética , Hipotiroidismo/epidemiología , Bursitis/genética , Bursitis/epidemiología , Predisposición Genética a la EnfermedadRESUMEN
This study aimed to assess the prevalence of thyroid dysfunction, as measured by hormone levels, in Saudi women with type 2 diabetes mellitus (T2DM). The study will also assess thyroid hormones and leptin, angiopoietin like 8 (ANGPTL8), obesity, and cardiovascular diseases (CVD) in T2D patients. A total of 250 women aged 40 to 60 years with T2DM were retrospectively studied between 2021 and 2022. This research examined medical records for T2DM patients. In this investigation, no T2DM patients had thyroid autoantibodies in their medical records. These patients were chosen for their FT4 and TSH values. All participants were Saudi females with T2DM, aged 54.5 years. Of the 250 participants, 32% had hypothyroidism, 14.8% had hyperthyroidism, and 40.8% (102) had no thyroid disease. Hypothyroidism (7.8â ±â 0.67 mmol/L) exhibited greater fasting blood glucose (FBG) levels than hyperthyroidism (7.1â ±â 0.64 mmol/L) (Pâ <â .05). Hypothyroid and hyperthyroid females had significant differences in high density lipoprotein-cholestrol (HDL-C), triglycerides, triglyceride glucose (TyG) index, body mass index (BMI), waist circumstance (WC), high-sensitivity C-reactive protein (hs-CRP), leptin, ANGPTL8, insulin resistance (IR), and insulin levels (Pâ <â .05). Pearson's correlation test showed that T2DM patients' HDL-C levels were favorably but negatively correlated with leptin and ANGPTL8 levels. In hypothyroidism, thyroid stimulation hormone (TSH) is favorably linked with glycated hemoglobin (HbA1c), triglyscride (TG), TyG index, BMI, WC, leptin, ANGPTL8, hs-CRP, and IR. T2DM is linked to thyroid malfunction, notably hypothyroidism, which correlates positively with TSH. TSH variations due to increasing leptin, ANGPTL8, and TyG index may enhance the risk of insulin resistance diseases, such as obesity and CVD, in Saudi females with T2DM.
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Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Diabetes Mellitus Tipo 2 , Hipotiroidismo , Leptina , Hormonas Tiroideas , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Leptina/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Arabia Saudita/epidemiología , Adulto , Proteínas Similares a la Angiopoyetina/sangre , Hormonas Tiroideas/sangre , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipertiroidismo/sangre , Hipertiroidismo/epidemiología , Índice de Masa Corporal , Glucemia/análisis , Glucemia/metabolismo , Obesidad/sangre , Obesidad/epidemiología , Tirotropina/sangre , Hormonas PeptídicasRESUMEN
Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95-105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation.
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Personal de Salud , Tiroxina , Humanos , Tiroxina/administración & dosificación , Tiroxina/farmacocinética , Equivalencia Terapéutica , Comités Consultivos , Testimonio de Experto , Comunicación , Composición de Medicamentos/métodos , Composición de Medicamentos/normas , Hipotiroidismo/tratamiento farmacológicoRESUMEN
In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.
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Administración Cutánea , Ácido Oléico , Absorción Cutánea , Tiroxina , Ácido Oléico/química , Tiroxina/administración & dosificación , Tiroxina/farmacología , Tiroxina/farmacocinética , Animales , Absorción Cutánea/efectos de los fármacos , Parche Transdérmico , Piel/metabolismo , Piel/efectos de los fármacos , Liberación de Fármacos , Ratones , Permeabilidad , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/metabolismo , Humanos , Química Farmacéutica/métodos , MasculinoRESUMEN
BACKGROUND: This study evaluates the association between vitamin A levels, AIP (the atherogenic index of plasma), and subclinical hypothyroidism. METHODS: A cross-sectional analysis was conducted involving a representative sample of 3530 Chinese adults. Linear and logistic regression models were utilized to evaluate the associations between AIP and subclinical hypothyroidism, stratified by vitamin A levels. These analyses were further differentiated by sex and age groups to identify any demographic-specific associations. RESULTS: In the vitamin A-sufficient group, an increase in AIP was associated with elevated total triiodothyronine (TT3) levels (ß = 0.26, 95%CI: 0.09, 0.41, p = 0.003). Conversely, in the group with severe vitamin A deficiency, higher AIP levels were linked to increased free triiodothyronine (fT3) and TT3 levels and decreased free thyroxine (fT4) levels (ß = 0.12, 0.03, and -0.29, respectively). Additionally, severe vitamin A deficiency increased the risk associated with AIP and subclinical hypothyroidism (OR = 1.66, 95%CI: 1.07, 2.58, p = 0.025). This risk was notably more pronounced in women and older adults, with odds ratios of 2.44 (95%CI: 1.55, 3.86, p < 0.001) and 2.14 (95%CI: 1.36, 3.38, p = 0.001), respectively. CONCLUSIONS: Vitamin A deficiency may increase the risk of the association between AIP and subclinical hypothyroidism, particularly among women and the elderly.
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Hipotiroidismo , Deficiencia de Vitamina A , Vitamina A , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Femenino , Masculino , Estudios Transversales , China/epidemiología , Persona de Mediana Edad , Adulto , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , Vitamina A/sangre , Aterosclerosis/sangre , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Anciano , Triyodotironina/sangre , Factores de Riesgo , Tiroxina/sangre , Enfermedades AsintomáticasRESUMEN
Biallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism, and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in 5 patients, goiter and hypothyroidism reappeared in 3. In these 3 patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing biallelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin, and overt hypothyroidism when their iodine intake was low.
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Bocio , Hipotiroidismo , Linaje , Tiroxina , Humanos , Femenino , Masculino , Adolescente , Hipotiroidismo/genética , Niño , Preescolar , Tiroxina/uso terapéutico , Bocio/genética , Tiroglobulina/genética , Yodo/deficiencia , Alelos , Mutación Missense , SimportadoresRESUMEN
Minipuberty is a term describing transient postnatal activation of the hypothalamic-pituitary-gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.
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Hipotiroidismo , Humanos , Femenino , Hipotiroidismo/metabolismo , Embarazo , Adulto , Complicaciones del Embarazo/metabolismo , Pubertad , Ovario/metabolismo , Adolescente , Lactante , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.
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Fracturas de Cadera , Tirotropina , Humanos , Fracturas de Cadera/mortalidad , Fracturas de Cadera/cirugía , Fracturas de Cadera/sangre , Anciano , Masculino , Tirotropina/sangre , Femenino , Estudios Prospectivos , Anciano de 80 o más Años , Pruebas de Función de la Tiroides , Modelos de Riesgos Proporcionales , Periodo Preoperatorio , Factores de Riesgo , Hipotiroidismo/sangre , Hipotiroidismo/mortalidad , Hipertiroidismo/sangre , Hipertiroidismo/mortalidadRESUMEN
Introduction: The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of Aanat and Asmt in the pineal gland and gonads of rats with hypothyroidism at different times of the day. Methods: Female and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes (Aanat and Asmt) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs. Results: The results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in Aanat expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding Asmt expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and Asmt expression in the gonads. Conclusions: This study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes (Aanat and Asmt) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner.
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Acetilserotonina O-Metiltransferasa , Hipotiroidismo , Melatonina , Glándula Pineal , Ratas Wistar , Testículo , Animales , Femenino , Masculino , Ratas , Acetilserotonina O-Metiltransferasa/metabolismo , Acetilserotonina O-Metiltransferasa/genética , N-Acetiltransferasa de Arilalquilamina/metabolismo , N-Acetiltransferasa de Arilalquilamina/genética , Gónadas/metabolismo , Hipotiroidismo/metabolismo , Melatonina/sangre , Ovario/metabolismo , Ovario/patología , Glándula Pineal/metabolismo , Propiltiouracilo , Testículo/metabolismo , Testículo/patologíaRESUMEN
BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.
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Neoplasias de Cabeza y Cuello , Hipotiroidismo , Humanos , Hipotiroidismo/etiología , Hipotiroidismo/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/terapia , Factores de Riesgo , Incidencia , Anciano , Quimioradioterapia/efectos adversos , AdultoRESUMEN
BACKGROUND AND OBJECTIVE: Posthemithyroidectomy hypothyroidism (PHH) is a relatively common complication (22%-30%) for which we have no published information from our country. The objective of the study is to determine the prevalence of PHH and evaluate its predictive markers by comparing patients who had euthyroidism with those who had hyperthyroidism before hemithyroidectomy. PATIENTS AND METHOD: Retrospective observational cross-sectional study on 106 patients, 88 euthyroid before hemithyroidectomy and 18 hyperthyroid. RESULTS: Prevalence of PHH in euthyroid patients 42% (89.2% subclinical hypothyroidism; 10.8% manifest hypothyroidism) and in hyperthyroid patients 50% (77.8% subclinical hypothyroidism; 22.2% manifest hypothyroidism). Predictive markers in euthyroid patients: preoperative thyrotropin ≥ 2.2 mIU/L (OR: 4.278, 95% CI: 1.689-10.833; sensitivity: 54.1%, 95% CI: 38%-70.1%; specificity: 78.4%, 95% CI: 67.1%-89.7%), age ≥50 years (OR: 3.509, 95% CI: 1.438-8.563; sensitivity: 64.9%, 95% CI: 49.5%-80.3%; specificity: 64.7%, 95% CI: 51.6%-77.8%) and percentage of remainder lobe ≤ 19.6% (OR: 1.024, 95%: 1.002-1.046; sensitivity: 70.2%, 95% CI: 55.5%-84.9%; specificity: 48.6%, 95% CI: 34.9%-62.3%). Predictive marker in hyperthyroid patients: weight >70 kg (OR: 28, 95% CI: 2.067-379.247; sensitivity: 88.9%, 95% CI: 68.4%-100%; specificity: 88.9%, 95% CI: 68.4%-100%). CONCLUSIONS: This is the first study in our country that demonstrates a prevalence of PHH above the average in euthyroid patients, which is slightly higher and more intense in hyperthyroid patients, and that recognizes the classic predictive markers in euthyroid patients but highlights a novel predictive marker marker in hyperthyroid patients, useful to assess a different risk of PHH when indicating hemithyroidectomy and to establish closer control of postoperative hormonal evolution.
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Bocio Nodular , Hipertiroidismo , Hipotiroidismo , Tiroidectomía , Humanos , Estudios Transversales , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Hipotiroidismo/epidemiología , Hipotiroidismo/sangre , Hipotiroidismo/etiología , Prevalencia , Bocio Nodular/cirugía , Bocio Nodular/epidemiología , Hipertiroidismo/epidemiología , Hipertiroidismo/sangre , Hipertiroidismo/cirugía , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Anciano , Biomarcadores/sangre , Tirotropina/sangreRESUMEN
BACKGROUND: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L). OBJECTIVES: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes. MATERIALS AND METHODS: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed. RESULTS: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women. CONCLUSION: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women.
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Hipotiroidismo , Yoduro Peroxidasa , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Hipotiroidismo/sangre , Hipotiroidismo/epidemiología , Hipotiroidismo/inmunología , Adulto , Estudios Prospectivos , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/inmunología , Yoduro Peroxidasa/inmunología , Recién Nacido , Autoanticuerpos/sangre , Tirotropina/sangre , Primer Trimestre del Embarazo/sangre , Adulto Joven , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Diabetes Gestacional/sangre , Diabetes Gestacional/inmunología , Enfermedades AsintomáticasRESUMEN
PURPOSE: To assess the incidence of congenital hypothyroidism (CH) and acquired hypothyroidism (AH) between 2014 and 2019 in continental France. METHODS: New cases of CH and AH were identified using the French National Health Data System (Système Nationale des Données de Santé, SNDS). Temporal trends were studied using linear regression models. Spatial distributions were studied using Moran's global index (I) and the statistical method and local indicators of spatial association. RESULTS: The incidence of permanent CH in females increased by 8.9 % per year (2014: 36.9 [31.1-43.7] per 100,000 birth-years vs. 2019: 51 [43.9-59.3] per 100,000 birth-years, p < 0.01). The incidence of AH decreased between 2014 and 2019 for both females (2014: 535.7 [533.2-538.2] per 100,000 person-years vs 2019: 335.5 [333.6-337.4] per 100,000 person-years, p < 0.01) and males (2014: 197.5 [195.9-199] per 100,000 person-years vs 2019: 141.7 [140.4-142.9] per 100,000 person-years, p < 0.01). The incidence of hypothyroidism was high in the Nord-Pas-De-Calais and Lorraine regions (CH and AH). CONCLUSIONS: The incidence of permanent CH in females has increased over time. AH incidence decreased. It seems necessary to investigate environmental factors in the disparity of incidence distribution.