RESUMO
BACKGROUND: Prader-Willi syndrome (PWS) is a rare multisystemic hereditary illness. Recombinant human growth hormone (rhGH) therapy is widely recognized as the primary treatment for PWS. This study aimed to examine how different PWS genotypes influence the outcome of rhGH treatment in children with PWS. METHODS: A review was conducted on 146 Chinese children with PWS, genetically classified and monitored from 2017 to 2022. Unaltered and modified generalized estimating equations (GEE) were employed to examine the long-term patterns in primary outcomes (growth metrics) and secondary outcomes (glucose metabolism metrics and insulin-like growth factor-1 (IGF-1)) during rhGH therapy. The study also evaluated the prevalence of hypothyroidism, hip dysplasia, and scoliosis before and after rhGH treatment. RESULTS: Children with PWS experienced an increase in height/length standard deviation scores (SDS) following rhGH administration. The impact of rhGH therapy on growth measurements was similar in both the deletion and maternal uniparental diploidy (mUPD) cohorts. Nevertheless, the deletion group was more prone to insulin resistance (IR) compared to the mUPD group. No significant variations in growth metrics were noted between the two groups (P > 0.05). At year 2.25, the mUPD group showed a reduction in fasting insulin (FINS) levels of 2.14 uIU/ml (95% CI, -4.26, -0.02; P = 0.048) and a decrease in homeostasis model assessment of insulin resistance (HOMA-IR) of 0.85 (95% CI, -1.52, -0.17; P = 0.014) compared to the deletion group. Furthermore, there was a decrease in the IGF standard deviation scores (SDS) by 2.84 (95% CI, -4.84, -0.84; P = 0.005) in the mUPD group during the second year. The frequency of hip dysplasia was higher in the mUPD group compared to the deletion group (P < 0.05). CONCLUSIONS: rhGH treatment effectively increased height/length SDS in children with PWS, with similar effects observed in both deletion and mUPD genotypes. Children with mUPD genetype receiving rhGH treatment may experience enhanced therapeutic effects in managing PWS.
Assuntos
Genótipo , Hormônio do Crescimento Humano , Síndrome de Prader-Willi , Humanos , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/genética , Hormônio do Crescimento Humano/uso terapêutico , Criança , Feminino , Masculino , Pré-Escolar , Fator de Crescimento Insulin-Like I , Adolescente , Resultado do Tratamento , Proteínas Recombinantes/uso terapêutico , Lactente , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/genética , Resistência à InsulinaRESUMO
Most of the thalassemic children of Bangladesh are receiving repeated blood transfusion. But they do not receive chelation therapy due to financial constraints. As a result, iron overload occurs in various organs of these children. Extra iron that is loaded in thyroid gland causes thyroid dysfunction. This study was undertaken to evaluate thyroid status in children with transfusion dependent Thalassemia patient. This cross-sectional analytical study was conducted in the Department of Pediatrics, Mymensingh Medical College Hospital, Bangladesh from September 2016 to April 2018. Children having thalassemia diagnosed by Hb electrophoresis, aged 3-12 years of both sexes were included as study group. Children of same age and sex admitted in indoor of Mymensingh Medical College Hospital with minor illness and without thalassemia were taken as comparison group. Purposive Sampling technique was applied. Serum FT4, TSH and ferritin level were estimated in all children. Data analysis was done with Statistical Package for Social Science (SPSS) version 21.0. A total of 60 patients were enrolled as study group and another 60 patients were compared as comparison group. Mean ages of study group was 7.88±2.55 years and comparison group were 7.22±2.48 years. The mean pre-transfusion hemoglobin, serum ferritin, serum FT4 and serum TSH level were found 6.23±0.60 gm/dl, 2658.33±879.39 ng/ml, 15.14±4.40 fmol/mL, 4.29±4.60 µIU/mL respectively in study group. The mean serum FT4 was found significantly lower and mean serum TSH was significantly higher in thalassemic children in comparison to non-thalassemic children (p= <0.05). Frequency of subclinical hypothyroidism was found significantly higher in study group (25.0%) compared to comparison group (3.3%) (p=0.001). Mean serum ferritin level was found significantly higher in hypothyroid cases. Mean FT4 level was significantly lower and mean TSH level was significantly higher in hypothyroid thalassemic patients (p= <0.001). Significant positive correlation between serum ferritin level and serum TSH level was found. Higher serum ferritin level was found significantly associated with the development of hypothyroidism in thalassemic patients.
Assuntos
Ferritinas , Talassemia , Humanos , Feminino , Masculino , Criança , Estudos Transversais , Pré-Escolar , Talassemia/terapia , Talassemia/sangue , Talassemia/complicações , Ferritinas/sangue , Centros de Atenção Terciária , Hipotireoidismo/etiologia , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Bangladesh/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Tireotropina/sangue , Tiroxina/sangue , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/sangueRESUMO
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.
Assuntos
Doenças Cardiovasculares , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hipotireoidismo , Análise da Randomização Mendeliana , Tiroxina , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/genética , Hipotireoidismo/epidemiologia , Tiroxina/uso terapêutico , Medição de Risco , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Terapia de Reposição Hormonal/efeitos adversos , Fatores de Risco , Fenótipo , Feminino , Infarto do Miocárdio/genética , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/diagnóstico , Polimorfismo de Nucleotídeo Único , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Masculino , Variantes Farmacogenômicos , Fatores de Risco de Doenças CardíacasRESUMO
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.
Assuntos
Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Diabetes Mellitus Tipo 2 , Hipotireoidismo , Leptina , Hormônios Tireóideos , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Leptina/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Adulto , Proteínas Semelhantes a Angiopoietina/sangue , Hormônios Tireóideos/sangue , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hipertireoidismo/sangue , Hipertireoidismo/epidemiologia , Índice de Massa Corporal , Glicemia/análise , Glicemia/metabolismo , Obesidade/sangue , Obesidade/epidemiologia , Tireotropina/sangue , Hormônios PeptídicosRESUMO
OBJECTIVE: To investigate markers of systemic inflammation and the effect of thyroid dysfunction on these parameters in patients with Hashimoto's thyroiditis (HT). METHODS: Patients with HT and volunteer healthy individuals admitted to the general surgery outpatient clinic between January 2020 and June 2023 were enrolled into the study. Patients with HT were divided into euthyroid, hypothyroid, and hyperthyroid subgroups. All participant data were retrospectively extracted from the hospital database. RESULTS: A total of 268 patients (euthyroid, n = 131; hypothyroid, n = 83; and hyperthyroid, n = 54) and 124 controls were included. The platelet-to-lymphocyte ratio was lower in the euthyroid group versus control group, and the neutrophil-to-lymphocyte ratio was lower in controls than the three patient subgroups. Euthyroid and hypothyroid patients with HT exhibited a higher systemic inflammation index than the control group. The pan-immune inflammation index was lower in controls than in euthyroid, hypothyroid, and hyperthyroid patients with HT. In patients with HT, inflammation markers did not significantly differ between subgroups. CONCLUSIONS: Markers of systemic inflammation provide meaningful and reliable information in patients with HT, but do not differentiate between euthyroid, hypothyroid, or hyperthyroid patients.
Assuntos
Biomarcadores , Doença de Hashimoto , Inflamação , Humanos , Doença de Hashimoto/sangue , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Feminino , Masculino , Adulto , Biomarcadores/sangue , Inflamação/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Casos e Controles , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Neutrófilos/patologia , Linfócitos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Plaquetas/patologia , Plaquetas/metabolismoRESUMO
Addison´s disease can form part of type 2 autoimmune polyglandular syndrome. The article reports the case of a 41-year-old female patient with hypothyroidism and vitiligo, who came to the emergency department complaining of asthenia that had worsened in recent months, as well as anorexia, nausea, and weight loss (6 kg in a year). Cutaneous hyperpigmentation was the main finding on physical examination, together with vitiligo lesions on the face, hands, and armpits. Further study revealed a low serum cortisol level, normal urine-free cortisol, and an elevated adrenocorticotropic hormone (ACTH). Antiperoxidase antibodies and 17-alpha-hidroxylase antibodies were both positive. Treatment was started with prednisolone and fludrocortisone, and a good clinical response was obtained. This case report aims to draw attention to the high level of clinical suspicion required to diagnose Addison´s disease and the need to screen actively for other potentially associated autoimmune diseases that may be associated.
Assuntos
Doença de Addison , Glucocorticoides , Hiperpigmentação , Prednisolona , Vitiligo , Humanos , Feminino , Adulto , Vitiligo/diagnóstico , Doença de Addison/diagnóstico , Doença de Addison/tratamento farmacológico , Doença de Addison/complicações , Prednisolona/administração & dosagem , Hiperpigmentação/diagnóstico , Hiperpigmentação/etiologia , Glucocorticoides/administração & dosagem , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/tratamento farmacológico , Fludrocortisona/administração & dosagem , Fludrocortisona/uso terapêutico , Hidrocortisona/administração & dosagem , Hormônio AdrenocorticotrópicoRESUMO
Objective: Observational studies have shown positive associations between thyroid dysfunction and risk of sarcopenia. However, the causality of this association remains unknown. This study aimed to evaluate the potential causal relationship between thyroid dysfunction and sarcopenia using Mendelian randomization (MR). Methods: This study collected pooled data from genome-wide association studies focusing on thyroid dysfunction and three sarcopenia-related features: low hand grip strength, appendicular lean mass (ALM), and walking pace, all in individuals of European ancestry. The primary analytical method used was inverse-variance weighted, with weighted median and MR-Egger serving as complementary methods to assess causal effects. Heterogeneity and pleiotropy tests were also performed, and the stability of the results was evaluated using the Leave-one-out. Results: The MR analysis indicated that hyperthyroidism could lead to a significant decrease in ALM in the extremities (OR = 1.03; 95% CI = 1.02 to 1.05; P < 0.001). The analysis also found that hypothyroidism could cause a notable reduction in grip strength (OR = 2.03; 95% CI = 1.37 to 3.01; P < 0.001) and walking pace (OR = 0.83; 95% CI = 0.77 to 0.90; P < 0.001). There was a significant association between subclinical hyperthyroidism and a reduced walking pace (OR = 1.00; 95% CI = 0.99 to 1.00; P = 0.041). Conclusion: This study provides evidence that hyperthyroidism, hypothyroidism, and subclinical hyperthyroidism can all increase the risk of sarcopenia.
Assuntos
Estudo de Associação Genômica Ampla , Força da Mão , Hipertireoidismo , Análise da Randomização Mendeliana , Sarcopenia , Humanos , Sarcopenia/genética , Sarcopenia/epidemiologia , Força da Mão/fisiologia , Hipertireoidismo/genética , Hipertireoidismo/complicações , Hipotireoidismo/genética , Hipotireoidismo/epidemiologia , Hipotireoidismo/fisiopatologia , Feminino , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/complicações , MasculinoRESUMO
Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3'-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.
Assuntos
Di-Iodotironinas , Hipotireoidismo , Inflamação , Fígado , Proteínas de Membrana , Nucleotidiltransferases , Estresse Oxidativo , Animais , Ratos , Hipotireoidismo/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/patologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Nucleotidiltransferases/metabolismo , Masculino , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Di-Iodotironinas/farmacologia , Proteínas de Membrana/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tri-Iodotironina , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Ratos Wistar , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). METHODS: We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)-Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. RESULTS: MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00-1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. CONCLUSION: This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.
Assuntos
Análise da Randomização Mendeliana , Distúrbios do Início e da Manutenção do Sono , Doenças da Glândula Tireoide , Humanos , Distúrbios do Início e da Manutenção do Sono/genética , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/complicações , Hipertireoidismo/genética , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/epidemiologia , Hipotireoidismo/genética , Hipotireoidismo/epidemiologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/epidemiologiaRESUMO
BACKGROUND: Gestational outcomes are known to be negatively correlated with hypothyroidism. This study was designed to compare the maternal factors affecting gestational outcomes in women with and without hypothyroidism. METHODS: This retrospective analysis was carried out in a tertiary hospital in Karachi, Pakistan, between 2008 and 2016. A standardized form was used to collect information on the age of the mother, gestational duration at the prenatal appointment, gestational diabetes mellitus (GDM), hypertension, and past records of miscarriages in hypothyroid and healthy pregnant women. Gestational outcomes were recorded as live birth or pregnancy loss. Statistical analysis was performed to examine overt versus sub-clinical hypothyroidism and among those diagnosed before versus during gestation. RESULTS: A collective of 708 women were enlisted in the hypothyroid pregnant group and 759 were recruited in healthy controls. Pregnancy loss was 9.9% (n=70) in hypothyroid women, whereas it was 14.3% (n=108) in the control group. The age of the mother, gestational duration at the prenatal appointment, and past records of miscarriages were discovered to be related to a higher chance of pregnancy loss in a multivariable analysis, but GDM (OR 0.04, CI 0.06-0.32, P=0.002) and hypothyroidism (OR 0.62, CI 0.43-0.89, P=0.01) exhibited a protective effect. CONCLUSION: This study found the age of the mother, gestational duration at a prenatal appointment, and past records of miscarriages to be associated with negative outcomes in hypothyroidism. These factors remained significant in overt as well as subclinical hypothyroid women.
Assuntos
Aborto Espontâneo , Diabetes Gestacional , Hipotireoidismo , Complicações na Gravidez , Resultado da Gravidez , Humanos , Feminino , Hipotireoidismo/epidemiologia , Gravidez , Paquistão/epidemiologia , Estudos Retrospectivos , Adulto , Complicações na Gravidez/epidemiologia , Diabetes Gestacional/epidemiologia , Aborto Espontâneo/epidemiologia , Adulto Jovem , Estudos de Casos e Controles , Fatores de Risco , Análise Multivariada , Nascido Vivo/epidemiologiaRESUMO
Myxedema is a potentially life-threatening condition typically observed in severe hypothyroidism. However, localized or diffuse myxedema is also observed in hyperthyroidism. The exact cause and mechanism of this paradoxical situation is not clear. We report here the analysis of body fluid distribution by bioelectrical impedance analysis (BIA) in 103 thyroid patients, subdivided according to their functional status. All BIA parameters measured in subclinical thyroid dysfunctions did not significantly differ from those observed in euthyroid controls. On the contrary, they were clearly altered in the two extreme, opposite conditions of thyroid dysfunctions, namely overt hyperthyroidism and severe hypothyroidism, indicating the occurrence of a typical hormetic condition. Surprisingly, differences in BIA parameters related to fluid body composition were even more evident in hyperthyroidism than in hypothyroidism. A hormetic response to thyroid hormone (TH)s was previously reported to explain the paradoxical, biphasic, time- and dose-dependent effects on other conditions. Our results indicate that myxedema, observed in both hypothyroid and hyperthyroid conditions, represents another example of a hormetic-type response to THs. BIA offers no additional valuable information in evaluating fluid body composition in subclinical thyroid dysfunctions, but it represents a valuable method to analyze and monitor body fluid composition and distribution in overt and severe thyroid dysfunctions.
Assuntos
Hipertireoidismo , Hipotireoidismo , Mixedema , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/metabolismo , Hipertireoidismo/complicações , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Impedância Elétrica , Hormese , Idoso , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/sangue , Composição CorporalRESUMO
RATIONALE: Sjögren syndrome (SS) is a prevalent autoimmune disorder targeting exocrine glands, causing symptoms such as dry eyes and mouth. It often goes underdiagnosed due to its varied presentations, emphasizing the importance of early and accurate diagnosis. PATIENT CONCERNS: A 22-year-old female presented with atypical symptoms of hypokalemic paralysis and severe bone pain, which are not commonly associated with SS. DIAGNOSES: Extensive diagnostic workup, including serological tests, ophthalmological assessments, and a lip biopsy, confirmed the diagnosis of distal renal tubular acidosis as a complication of SS. INTERVENTIONS: The patient was treated with an intensive inpatient regimen designed to stabilize her potassium levels and alleviate her symptoms. OUTCOMES: The comprehensive therapeutic intervention was successful, with the patient's symptoms being alleviated within 2 weeks. LESSONS: This case underscores the importance of being aware of SS in younger demographics and the necessity for a prompt and multifaceted treatment approach to manage systemic effects and improve quality of life.
Assuntos
Hipotireoidismo , Osteomalacia , Síndrome de Sjogren , Humanos , Feminino , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Adulto Jovem , Osteomalacia/etiologia , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/diagnóstico , Acidose Tubular Renal/complicações , Acidose Tubular Renal/diagnóstico , Hipopotassemia/etiologiaRESUMO
INTRODUCTION: Liver diseases are increasingly recognized as significant public health concerns in India, prompting investigations into novel approaches for assessing disease severity and prognosis. Recognizing the potential utility of thyroid hormone levels in these assessments, we conducted an observational cross-sectional study at our tertiary care hospital. Our study included 89 patients aged 12 years and above, admitted to medicine wards with ultrasound-diagnosed liver cirrhosis, excluding pregnant women and those on thyroid-altering medications. OBSERVATIONS: Our findings revealed a male-to-female ratio of 4.23:1, with the majority of patients falling within the 40-60 age-group, averaging 46.93 years. Notably, 87.6% of patients exhibited thyroid abnormalities, primarily low free T3 (FT3) syndrome and subclinical hypothyroidism. Classifying patients according to Child-Pugh (CP) score, 2.2% were CP class A, 22.5% were CP class B, and the remaining 75.3% were CP class C. Across all CP classes, low FT3 syndrome was prevalent, particularly in CP class C. Correlations between thyroid hormone levels and liver disease severity, assessed via CP and model for end-stage liver disease (MELD) scoring systems, were observed. Specifically, FT3 levels demonstrated a negative correlation with liver disease severity (p = 0.001), while no significant correlations were found for free T4 (FT4) and thyroid-stimulating hormone (TSH) levels. Based on our findings, we recommend routine thyroid function testing for all liver cirrhosis patients, irrespective of disease severity, to facilitate early detection and intervention. However, our study had limitations, including a small sample size and a precision error of 10% due to resource constraints for thyroid function testing. Moreover, reliance solely on ultrasound for liver cirrhosis diagnosis may lead to missed diagnoses, highlighting the need for complementary noninvasive tests such as FibroScan and aspartate aminotransferase to platelet ratio index (APRI) scores. CONCLUSION: Our study underscores the importance of considering thyroid function in the management of liver cirrhosis patients and provides valuable insights for enhancing clinical practice in this context.
Assuntos
Cirrose Hepática , Índice de Gravidade de Doença , Humanos , Cirrose Hepática/diagnóstico , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Testes de Função Tireóidea/métodos , Tri-Iodotironina/sangue , Hormônios Tireóideos/sangue , Idoso , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Índia/epidemiologiaRESUMO
Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin-angiotensin-aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients.
Assuntos
COVID-19 , Hiponatremia , Sistema Renina-Angiotensina , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/metabolismo , Hiponatremia/etiologia , Hiponatremia/metabolismo , Doenças do Sistema Endócrino/etiologia , Doenças do Sistema Endócrino/metabolismo , Sódio/metabolismo , Hipotireoidismo/metabolismo , Hipotireoidismo/complicaçõesRESUMO
Background: The interinfluence of thyroid function and daily physical activity (PA) remains unclear. We examined the causal relationship between genetically proxied thyroid-related traits; hypothyroidism, hyperthyroidism, thyroid stimulating hormone (TSH) and free thyroxine (FT4), and daily PA measures; leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), using Mendelian randomisation (MR) analysis. Methods: We used genome-wide association study (GWAS) data from the ThyroidOmics Consortium and the most comprehensive meta-analysis on PA, comprising data on hypothyroidism (n = 53 423), hyperthyroidism (n = 51 823), TSH within the reference range (n = 54 288), fT4 within the reference range (n = 49 269), LST (n = 526 725), and MVPA (n = 608 595) to conduct a bidirectional two-sample MR analysis. The inverse variance weighted (IVW) method was employed as the primary result. Sensitivity analyses included MR-Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) regression. Similar investigations were conducted in the reverse direction. Finally, we analysed a multivariable MR using body mass index (BMI)-related traits GWAS data. Results: In the primary IVW analysis, an increase in genetically proxied TSH levels significantly increased LST (correlation coefficient (ß) = 0.040; 95% confidence interval (CI) = 0.020-0.061, P = 9.776 × 10-5). The multivariable MR analysis indicated that the positive causal effect still existed when considering the influence of BMI (MVMR-IVW: ß = 0.042; 95% CI = 0.011-0.073, P = 0.007). Conversely, there was no evidence to suggest that PA impacts thyroid function. Conclusions: The results of this MR analysis suggest that thyroid function influences daily PA. The positive association between TSH and LST is not confounded or mediated by BMI.
Assuntos
Exercício Físico , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Comportamento Sedentário , Humanos , Exercício Físico/fisiologia , Tireotropina/sangue , Testes de Função Tireóidea , Glândula Tireoide , Hipertireoidismo/genética , Hipotireoidismo/genética , Tiroxina/sangueRESUMO
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.
Assuntos
Hipotireoidismo , Tiroxina , Tri-Iodotironina , Humanos , Quimioterapia Combinada/métodos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Tireotropina/sangue , Tiroxina/uso terapêutico , Resultado do Tratamento , Tri-Iodotironina/uso terapêuticoRESUMO
Thyroid hormone regulates the rate of testis maturation in mammals. Manipulations of thyroid hormone levels in neonatal animals affect various aspects of testis biology. However, there have been no studies examining the effects of thyroid hormone on the rete testis (RT). Here, we used animal models of neonatal hyperthyroidism (injections of triiodothyronine, or T3) and hypothyroidism (goitrogen 6-propyl-2-thiouracil [PTU] treatment) and found that higher levels of thyroid hormone accelerate RT development, while lower levels of thyroid hormone delay it. T3 and PTU treatments influence RT size, proliferation of RT cells, and expression of DMRT1 and androgen receptor in the RT. T3 supplementation accelerates RT development in an organ testicular culture, which indicates the local action of thyroid hormone. Additionally, it was found that follicle-stimulating hormone could be involved in the regulation both of RT proliferation and RT size. The fact that RT cells in a cell culture do not respond to T3 suggests indirect action of thyroid hormone on the RT in vivo or the loss of the responsiveness to the hormone in vitro.
Assuntos
Animais Recém-Nascidos , Testículo , Hormônios Tireóideos , Tri-Iodotironina , Animais , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/crescimento & desenvolvimento , Tri-Iodotironina/farmacologia , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/farmacologia , Propiltiouracila/farmacologia , Proliferação de Células/efeitos dos fármacos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Hipotireoidismo/induzido quimicamente , Hormônio Foliculoestimulante/farmacologia , Receptores Androgênicos/metabolismoRESUMO
BACKGROUND: Previous studies have shown an association between acute respiratory distress syndrome (ARDS) and thyroid function. However, their causal relationship remains unspecified. Therefore, this study aims to explore the causal relationship between ARDS and thyroid function-related diseases with Mendelian Randomization (MR) analysis. METHODS: ARDS dataset finn-b-J10_ARDS, finn-b-E4_THYROID dataset of disorders of the thyroid gland (DTG) and finn-b-E4_HYTHYNAS of hypothyroidism were acquired from public database. In univariate MR (UVMR), causal effects between DTG, hypothyroidism and ARDS were investigated using 5 types of algorithms, and reliability was validated by sensitivity analysis. Moreover, multivariate MR (MVMR), enrichment and interaction network analyses of genes corresponding to SNPs of DTG and hypothyroidism were carried out. Significant level was chosen as p<0.05. RESULTS: UVMR identified DTG and hypothyroidism (P < 0.05, OR > 1) as risk factors, and were causally related to ARDS. Reliability of UVMR results was confirmed through sensitivity analysis, and results were stable and reliable. However, DTG and hypothyroidism had no effect on ARDS in MVMR, possibly because these factors had independent effects on ARDS. Ultimately, 96 and 113 genes corresponding to SNPs of DTG and hypothyroidism were found closely related to immune-related pathways. CONCLUSIONS: UVMR and MVMR analysis revealed a causal connection between DTG and hypothyroidism as risk factors with ARDS, providing robust evidence for investigation into relationship of hypothyroidism on ARDS and between DTG and ARDS.
Assuntos
Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/genética , Hipotireoidismo/genética , Hipotireoidismo/epidemiologia , Predisposição Genética para Doença , Glândula Tireoide/patologia , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Fatores de RiscoRESUMO
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.