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Frontiers in Genetics 2024Hypothyroidism is a common endocrine disorder whose prevalence increases with age. The disease manifests itself when the thyroid gland fails to produce sufficient...
Hypothyroidism is a common endocrine disorder whose prevalence increases with age. The disease manifests itself when the thyroid gland fails to produce sufficient thyroid hormones. The disorder includes cases of congenital hypothyroidism (CH), but most cases exhibit hormonal feedback dysregulation and destruction of the thyroid gland by autoantibodies. In this study, we sought to identify causal genes for hypothyroidism in large populations. The study used the UK-Biobank (UKB) database, reporting on 13,687 cases of European ancestry. We used GWAS compilation from Open Targets (OT) and tuned protocols focusing on genes and coding regions, along with complementary association methods of PWAS (proteome-based) and TWAS (transcriptome-based). Comparing summary statistics from numerous GWAS revealed a limited number of variants associated with thyroid development. The proteome-wide association study method identified 77 statistically significant genes, half of which are located within the Chr6-MHC locus and are enriched with autoimmunity-related genes. While coding GWAS and PWAS highlighted the centrality of immune-related genes, OT and transcriptome-wide association study mostly identified genes involved in thyroid developmental programs. We used independent populations from Finland (FinnGen) and the Taiwan cohort to validate the PWAS results. The higher prevalence in females relative to males is substantiated as the polygenic risk score prediction of hypothyroidism relied mostly from the female group genetics. Comparing results from OT, TWAS, and PWAS revealed the complementary facets of hypothyroidism's etiology. This study underscores the significance of synthesizing gene-phenotype association methods for this common, intricate disease. We propose that the integration of established association methods enhances interpretability and clinical utility.
PubMed: 38919955
DOI: 10.3389/fgene.2024.1409226 -
Frontiers in Endocrinology 2024The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance.
RESEARCH METHODS AND PROCEDURES
Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114.
RESULTS
Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], =0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity ( = 0.08, ² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], =0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], =0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], =0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], =0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], =0.05)], and there was no difference from the healthy controls.
CONCLUSION
Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com, identifier (INPLASY202440114).
Topics: Humans; Hypothyroidism; Heart; Adaptation, Physiological; Magnetic Resonance Imaging; Ventricular Function, Left; Stroke Volume
PubMed: 38919487
DOI: 10.3389/fendo.2024.1334684 -
Frontiers in Endocrinology 2024Previous observational studies have shown conflicting results of vitamins supplementation for thyroid diseases. The causal relationships between vitamins and thyroid...
BACKGROUND
Previous observational studies have shown conflicting results of vitamins supplementation for thyroid diseases. The causal relationships between vitamins and thyroid diseases are unclear. Therefore, we conducted a two-sample bidirectional Mendelian randomization (MR) study to explore association of circulating vitamin levels with thyroid diseases.
METHODS
We performed a bidirectional MR analysis using genome-wide association study (GWAS) data. Genetic tool variables for circulating vitamin levels include vitamins A, B, B, C, D, and E, Genetic tool variables of thyroid diseases include autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid nodules (TNs), and Thyroid cancer (TC). Inverse-variance weighted multiplicative random effects (IVW-RE) was mainly used for MR Analysis, weighted median (WM) and MR Egger were used as supplementary methods to evaluate the relationships between circulating vitamin levels and thyroid diseases. Sensitivity and pluripotency were evaluated by Cochran's Q test, MR-PRESSO, Radial MR, MR-Egger regression and leave-one-out analysis.
RESULTS
Positive MR evidence suggested that circulating vitamin C level is a protective factor in autoimmune hypothyroidism (OR=0.69, 95%CI: 0.58-0.83, = 1.05E-04). Reverse MR Evidence showed that genetic susceptibility to autoimmune hyperthyroidism is associated with reduced level of circulating vitamin A(OR = 0.97, 95% CI: 0.95-1.00, = 4.38E-02), genetic susceptibility of TNs was associated with an increased level of circulating vitamin D (OR = 1.02, 95% CI: 1.00-1.03, = 6.86E-03). No causal and reverse causal relationship was detected between other circulating vitamin levels and thyroid diseases.
CONCLUSION
Our findings provide genetic evidence supporting a bi-directional causal relationship between circulating vitamin levels and thyroid diseases. These findings provide information for the clinical application of vitamins prevention and treatment of thyroid diseases.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Vitamins; Thyroid Diseases; Polymorphism, Single Nucleotide
PubMed: 38919472
DOI: 10.3389/fendo.2024.1360851 -
International Journal of Surgery Case... Jun 2024Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia,...
INTRODUCTION AND IMPORTANCE
Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia, burning sensations, and pruritus. These oral signs can serve as early indicators of systemic conditions such pernicious anemia.
CASE PRESENTATION
A 67 year old northern African female presented at the oral surgery service with complaints of a sore mouth and difficulty eating certain types of food. Her medical history revealed hypothyroidism and no history of gastrectomy. She was diagnosed with pernicious anemia in 2014 and is under hydroxocobalamin injection 5000μg/month since then. Dental history indicated extraction of all teeth, and in 2014, the patient was diagnosed with oral lichen planus. There were no contributory oral habits. Intraoral examination revealed a band like erythematous lesion on the palate with two superficial ulcerations, diagnosed as related to her pernicious anemia. The patient was prescribed a mouthwash containing sodium bicarbonate and corticosteroid to reduce inflammation and alleviate pain. A low level laser therapy was also considered to reduce the burning sensations.
CLINICAL DISCUSSION
Pernicious anemia (PA) is an autoimmune disease characterized by the gradual atrophy of the gastric mucosa, predominantly affecting the body and fundus of the stomach, leading to vitamin B12 deficiency. Its insidious onset often masks its presence. Patients have no anemic symptoms. However, they can present with oral manifestations related to vitamin B12 deficiency. Those oral signs can precede hematological symptoms helping in early diagnosis of PA.
CONCLUSION
Dentists and other oral health care providers must be aware of this condition and its oral manifestations. Investigating vitamin B12 levels should be considered in patients presenting with oral ulcers, oral erythema or burning sensations without an apparent origin.
PubMed: 38917702
DOI: 10.1016/j.ijscr.2024.109931 -
European Journal of Paediatric... Jun 2024NKX2-1-related disorder (NKX2-1-RD) is a rare disease characterized by a triad of primary hypothyroidism, neonatal respiratory distress, and neurological features,...
BACKGROUND
NKX2-1-related disorder (NKX2-1-RD) is a rare disease characterized by a triad of primary hypothyroidism, neonatal respiratory distress, and neurological features, including chorea.
OBJECTIVE
This study aimed to identify discrepancies in the management of NKX2-1-RD among European Union (EU) specialists.
METHODS
The ERN-RND Chorea & Huntington disease group designed a survey to conduct a cross-sectional multicenter study on the management of NKX2-1-RD. Descriptive analysis was performed, and total responses are presented for each item.
RESULTS
The study involved 23 experts from 13 EU countries with experience in evaluating hyperkinetic patients with NKX2-1-RD: 11 were adult specialists, and 12 were pediatric specialists. NKX2-1-RD diagnosis was made at different ages, with the most common initial symptoms being hypotonia and/or motor developmental delay (reported by 11 experts) and chorea (reported by 8 experts). Chorea involved various body parts and showed improvement as reported by 9 experts, stabilization by 12 experts, and worsening by 2 experts with age. The pharmacological treatment of chorea varied widely among the experts. Misdiagnosis was reported by 14 experts. NKX2-1 pathogenic variants or deletions were confirmed in >75 % of patients (reported by 12 experts). Pulmonary and endocrinology evaluations were requested by 7 and 12 experts, respectively. The management of psychiatric comorbidities also varied among the different experts.
CONCLUSIONS
This study highlights the need for a clinical practice guideline for the management of NKX2-1-RD to ensure that patients across the EU receive consistent and appropriate care. Such a guideline would benefit both doctors and healthcare practitioners.
PubMed: 38917695
DOI: 10.1016/j.ejpn.2024.06.007 -
Journal of Neural Transmission (Vienna,... Jun 2024Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In... (Review)
Review
Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.
PubMed: 38916623
DOI: 10.1007/s00702-024-02800-3 -
Journal of Gastrointestinal Surgery :... Jun 2024
PubMed: 38914257
DOI: 10.1016/j.gassur.2024.06.020 -
Military Medicine Jun 2024Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in...
INTRODUCTION
Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in patients taking levothyroxine for hypothyroidism and correlate it with biochemical thyroid function.
MATERIALS AND METHODS
This was a retrospective cohort study of patients aged 18 years and older who were treated with levothyroxine. Exclusion criteria were pre-existing diagnosis of AF and use of amiodarone in the prior year. Patients were followed 2012 through 2019 and stratified into 4 groups based on mean thyroid-stimulating hormone (TSH) value or mean fT4 value in 2012. Primary outcome was incidence of AF. Rates of AF between groups were assessed via Poisson regression with control of underlying confounders.
RESULTS
Of 21,035 patients, 1091 (5.2%) developed AF during follow-up. Thyroid-stimulating hormone at baseline was not significantly associated with incident AF. Higher fT4 levels at baseline were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio 1.22; 95% CI, 1.03-1.44) for the highest quartile versus the lowest quartile of fT4.
CONCLUSIONS
In hypothyroid patients treated with levothyroxine, higher circulating fT4 levels are associated with increased risk of incident AF. There is no association of serum TSH with risk of AF. In patients at risk for AF, consideration should be given to avoiding fT4 levels in the highest quartile.
PubMed: 38913449
DOI: 10.1093/milmed/usae324 -
The Canadian Journal of Urology Jun 2024Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based...
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based chemotherapy which is another frontline choice is often not a treatment option for older patients due to comorbidities that increase with age. Despite ICIs being better tolerated compared to traditional chemotherapy little is known about their efficacy and toxicity in patients ≥ 90 years due to the rarity of this population in clinical trials. Our objective was to analyze the efficacy and toxicity of immune checkpoint inhibitors in patients ≥ 90 years.
MATERIALS AND METHODS
We conducted a single center retrospective review of patients ≥ 90 years treated between July 2019 and September 2023 with standard of care ICIs for advanced urothelial cancer.
RESULTS
Six patients treated with pembrolizumab were identified. Four (66.7%) were male and mean age was 93.5 years at the time of treatment initiation. Response rate was 66.7% (4 patients) with 3 complete responses, which were durable off therapy. Median follow up was 18.2 months. Median progression free survival (PFS) was 10.2 months [95%confidence interval (95%CI): 1.77, not reached (NR)] and median overall survival (OS) was 18.2 months (95%CI: 12.1, NR). Side effects presented in 4 (66.7%) patients and included hypothyroidism, diarrhea, anemia, thrombocytopenia, rash, and bullous dermatitis. One patient developed grade 3 anemia and no patients experienced grade 4 events or required hospitalization due to treatment side effects.
CONCLUSIONS
Our experience in a small cohort of patients ≥ 90 years indicate that ICIs are well tolerated and effective for the treatment of advanced urothelial carcinoma in this patient population.
Topics: Humans; Male; Female; Retrospective Studies; Aged, 80 and over; Immune Checkpoint Inhibitors; Carcinoma, Transitional Cell; Neoplasm Staging; Urinary Bladder Neoplasms; Antibodies, Monoclonal, Humanized; Urologic Neoplasms; Treatment Outcome
PubMed: 38912939
DOI: No ID Found -
Plastic and Reconstructive Surgery.... Jun 2024Immunotherapy has transformed breast cancer management. However, it can be challenging to remain familiar with the adverse events, contraindications, and perioperative...
BACKGROUND
Immunotherapy has transformed breast cancer management. However, it can be challenging to remain familiar with the adverse events, contraindications, and perioperative recommendations for each agent.
METHODS
We used FDALabel to identify all Food and Drug Administration-approved immunotherapies indicated for the treatment of breast cancer. We extracted details regarding warnings and precautions, indications, and adverse events from each package insert.
RESULTS
We identified nine immunotherapies belonging to three classes: anti-human epidermal growth factor receptor 2 (HER2) agents, anti-programmed cell death protein 1 (PD-1) agents, and anti-trophoblast cell-surface antigen 2 (TROP-2) agents. Cardiotoxicity, including heart failure and cardiomyopathy, was common among those receiving anti-HER2 agents, and hypothyroidism was common among patients receiving the anti-PD-1 agent. The anti-TROP-2 agent was associated with diarrhea and neutropenia. Given the adverse event profile for each drug, we recommend preoperative evaluation components, including transthoracic echocardiography, liver function tests, and thyroid panels. We also indicate here which immunotherapies raise concern for venous thromboembolism, hematoma, and infection.
CONCLUSIONS
Using data from clinical trials, we recommend a preoperative evaluation tailored to the immunotherapeutic regimen of individual patients.
PubMed: 38911573
DOI: 10.1097/GOX.0000000000005915