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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 -
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 -
Annals of Translational Medicine Jun 2024Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and...
BACKGROUND
Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and potential association with thyroid gland dysfunction (TGD) remain poorly understood. This study aims to clarify these aspects and investigate the possible connection between keratoconus and TGD.
METHODS
We conducted a nationwide population-based cohort study using data from the Korean National Health Insurance Service database. A retrospective chart review was conducted on 4,059,021 patients aged over 20 without underlying corneal diseases in 2009. The end of the review period was at ten years, or until the onset of keratoconus. To evaluate the association with TGD, multivariate Cox regression analysis was used with adjustment of confounding variables such as sex and age.
RESULTS
During the review period, 2,334 patients developed keratoconus before the 10-year mark. Females exhibited a higher keratoconus incidence (7.101 per 100,000 person-years) compared to males (5.559) (P<0.001). After adjusting for age, the hazard ratio (HR) for keratoconus was 1.295 times higher [95% confidence interval (CI): 1.193-1.406] in females compared to males. Age groups were stratified in 10-year intervals. The highest incidence of keratoconus was observed in the 20 to 29-year age group (10.695 per 100,000 person-years). All other age groups had significantly lower HR values, with the lowest at 50-59 years (0.508, 95% CI: 0.447-0.577). Keratoconus incidence per 100,000 person-years was 6.227 in subjects without TGD, 6.019 in the hypothyroidism group and 8.287 in the hyperthyroidism group, respectively. Although not statistically significant, individuals with hyperthyroidism showed a higher HR (1.290, 95% CI: 0.939-1.771) for keratoconus when compared to those without TGD, after adjusting for age and sex.
CONCLUSIONS
This study emphasizes a female predominance in keratoconus incidence and suggests a possible connection between hyperthyroidism and keratoconus. Furthermore, it affirms a higher incidence of keratoconus among young individuals.
PubMed: 38911561
DOI: 10.21037/atm-23-1906 -
Indian Journal of Endocrinology and... 2024
PubMed: 38911110
DOI: 10.4103/ijem.ijem_406_23 -
Journal of Orthopaedic Case Reports Jun 2024Charcot arthropathy consists of a rapid and destructive complication of the joints following the loss of innervation caused by many complicated etiologies. Diabetic...
INTRODUCTION
Charcot arthropathy consists of a rapid and destructive complication of the joints following the loss of innervation caused by many complicated etiologies. Diabetic neuropathy has become the most common etiological factor.
CASE REPORT
We present a case of a 64-year-old female patient with a history of chronic renal failure on hemodialysis, hypertension, hypothyroidism, and Type 2 diabetes, complicated with neuropathy and Charcot disease, who referred to our department. Initially, the patient was managed with a restraint orthotic device due to a bimalleolar ankle fracture. An unsuccessful treatment and the presence of a pressure ulcer with pus-like drainage on the lateral malleolus 2 months later led to the decision for a below-knee amputation.
CONCLUSION
High clinical suspicion by the attending physician may reduce the risk of complications and lead to proper treatment with better outcomes.
PubMed: 38910990
DOI: 10.13107/jocr.2024.v14.i06.4498 -
Cureus May 2024Sinus bradycardia is defined as a heart rate of less than 60 beats per minute and can occur as an adaptive response but can also be pathologic. Sinus bradycardia can be...
Sinus bradycardia is defined as a heart rate of less than 60 beats per minute and can occur as an adaptive response but can also be pathologic. Sinus bradycardia can be a normal finding in children, individuals who exercise often, and as a physiologic response during sleep. Pathologic causes of sinus bradycardia include sinus node dysfunction, medications, acute myocardial infarction, heart failure, obstructive sleep apnea, exaggerated vagal activity, increased intracranial hypertension, infection, hypothyroidism, hypothermia, anorexia nervosa, and prolonged hypoxia. When pathologic, addressing the underlying cause will lead to an improvement in heart rate. Here, we present a case of sinus bradycardia in a 61-year-old female with hypothermia. Evaluation for common causes of bradycardia including cardiac evaluation was unremarkable. Treatment of hypothermia led to the resolution of bradycardia. The importance of the case is to help clinicians recognize hypothermia as a cause of bradycardia.
PubMed: 38910683
DOI: 10.7759/cureus.60991 -
The Korean Journal of Internal Medicine Jun 2024Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the...
BACKGROUND/AIMS
Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism.
METHODS
This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated.
RESULTS
The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity.
CONCLUSIONS
In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.
PubMed: 38910508
DOI: 10.3904/kjim.2024.085