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Thyroid : Official Journal of the... May 2024International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative... (Meta-Analysis)
Meta-Analysis
International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; < 0.001). The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.
Topics: Humans; Pregnancy; Female; Risk Factors; Pregnancy Complications; Hypothyroidism; Thyroid Function Tests; Adult; Autoantibodies; Body Mass Index; Iodide Peroxidase; Prospective Studies; Maternal Age; Thyrotropin
PubMed: 38546971
DOI: 10.1089/thy.2023.0646 -
The Journal of Clinical Endocrinology... Feb 2024With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.
OBJECTIVE
To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism.
DESIGN
Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial).
SETTING
Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.
PARTICIPANTS
The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.
MAIN OUTCOME MEASURES
Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.
RESULTS
In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.
CONCLUSION
Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.
Topics: Humans; Female; Aged; Thyrotropin; Incidence; Hypothyroidism; Thyroxine
PubMed: 37862463
DOI: 10.1210/clinem/dgad623 -
Neurological Research Jan 2024Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to...
OBJECTIVES
Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study.
METHODS
Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences ( ≤ 5 × 10) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results.
RESULTS
Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, = 0.170).
DISCUSSION
This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.
Topics: Humans; Genome-Wide Association Study; Hypothyroidism; Linkage Disequilibrium; Mendelian Randomization Analysis; Myasthenia Gravis
PubMed: 37695759
DOI: 10.1080/01616412.2023.2257458 -
Diabetes/metabolism Research and Reviews Feb 2024Increasing visceral fat deposition with raised prevalence of obesity and metabolic syndrome is associated with many adverse conditions, especially cardiovascular...
OBJECTIVES
Increasing visceral fat deposition with raised prevalence of obesity and metabolic syndrome is associated with many adverse conditions, especially cardiovascular diseases and diabetes. Although there are many studies that investigate hepatic steatosis in hypothyroidism and subclinical hypothyroidism, to the best of our knowledge, there is no study investigating its relationship with pancreatic steatosis. In the present study, the purpose was to investigate this relationship.
METHODS
Physical and biochemical characteristics of 30 hypothyroid, 30 subclinical hypothyroid, and 30 euthyroid volunteers were recorded in this cross-sectional study. Liver and pancreatic steatosis were evaluated with ultrasonography.
RESULTS
It was found that pancreatic steatosis was increased in hypothyroid and subclinical groups when compared to the control group, and hepatic steatosis was increased in the subclinical group when compared to the control group (steatosis; p = 0.002, p = 0.004, p = 0.001, p = 0.002, p = 0.002, p = 0.004). Pancreatic steatosis was positively correlated with age, hepatic steatosis, height, weight, BMI, waist circumference, hip circumference, hemoglobin, Insulin, alanine aminotransferase, Triglyceride, Creatinine, and gamma-glutamyltransferase and was negatively correlated with total cholesterol, high-density lipoproteins.
CONCLUSIONS
The prevalence of pancreatic steatosis was found to be increased in hypothyroidism and subclinical hypothyroidism when compared with the euthyroid control group.
Topics: Humans; Cross-Sectional Studies; Hypothyroidism; Metabolic Syndrome; Obesity; Fatty Liver; Lipid Metabolism Disorders; Pancreatic Diseases; Pancreas; Non-alcoholic Fatty Liver Disease
PubMed: 37691570
DOI: 10.1002/dmrr.3720 -
Frontiers in Endocrinology 2023Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with...
INTRODUCTION
Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes.
METHODS
This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia.
RESULTS
The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes.
CONCLUSION
Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.
Topics: Humans; Female; Polycystic Ovary Syndrome; Hyperprolactinemia; Retrospective Studies; Progesterone; Prevalence; Cross-Sectional Studies; Thyroid Diseases; Hypothyroidism; Thyrotropin
PubMed: 37854182
DOI: 10.3389/fendo.2023.1245106 -
Journal of Ayub Medical College,... 2023Obesity and hypothyroidism are two common clinical conditions that are often connected. This connection is now more important because of an exceptional rise in the...
BACKGROUND
Obesity and hypothyroidism are two common clinical conditions that are often connected. This connection is now more important because of an exceptional rise in the prevalence of obesity around the world. Both of these conditions have a noteworthy impact on human health and well-being. The main objective of this study was to determine the frequency of hypothyroidism in obese patients presenting at Ayub Teaching Hospital, Abbottabad.
METHODS
This cross-sectional study was carried out on 242 patients in the Department of Medicine of Ayub Teaching Hospital, Abbottabad from 1st March to 31st August 2022. SPSS version 23.0 was used for data analysis.
RESULTS
In this study, 242 obese patients were included. The mean age of the patients was 39.55±9.361 years. The mean BMI was 41.62±8.099kg/m2 ranging from 31 to 61kg/m2, the mean TSH level was 3.04±2.604mU/l, the mean T4 level was 8.53±2.215pmol/L and the mean T3 level was 1.2195±0.35795nmol/L. Out of a total of 242 patients, 34 (14.0%) were male and 208(86.0%) were female patients. Patients found with overt hypothyroidism were 11 (4.5%), subclinical hypothyroidism were 31 (12.8%) and euthyroid were 200 (82.6%).
CONCLUSIONS
The proportion of hypothyroidism among the obese patients was quite less in our setup and not significantly associated with age and gender of the patients.
Topics: Humans; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Hypothyroidism; Obesity; Thyrotropin
PubMed: 38406945
DOI: 10.55519/JAMC-04-12226 -
Deutsches Arzteblatt International Oct 2023Levothyroxine is a very commonly prescribed drug, and treatment with it is often insufficient or excessive. Nonetheless, there have been only a few reports on the... (Observational Study)
Observational Study
BACKGROUND
Levothyroxine is a very commonly prescribed drug, and treatment with it is often insufficient or excessive. Nonetheless, there have been only a few reports on the determinants of inadequate levothyroxine treatment.
METHODS
Data from 2938 participants in the population-based Rhineland Study were analyzed. Putative determinants of inadequate levothyroxine treatment (overtreatment, thyrotropin level <0.56 mU/L; undertreatment, thyrotropin level >4.27 mU/L) were studied with logistic regression. The determinants of the levothyroxine dose were assessed with linear regression.
RESULTS
Overall, 23% of the participants (n = 662) stated that they were taking levothyroxine. Among these participants, 18% were overtreated and 4% were undertreated. Individuals over 70 years of age and above were four times as likely to be overtreated (OR = 4.05, 95% CI [1.20; 13.72]). Each rise in the levothyroxine dose by 25 μg was associated with an increased risk of overtreatment (OR = 1.02, 95% CI [1.02; 1.03]) and of undertreatment (OR = 1.02, 95% CI [1.00; 1.03]). Well-controlled participants (normal thyrotropin levels 0.56-4.27 mU/L) received a lower levothyroxine dose (1.04 ± 0.5 μg/kg/d) than overtreated (1.40 ±0.5 μg/kg/d) or undertreated (1.37 ±0.5 μg/kg/d) participants. No association was found between sociodemographic factors or comorbidities and the levothyroxine dose. Iodine supplementation was associated with a lower daily dose (β = -0.19, 95% CI [-0.28; -0.10]), while three years or more of levothyroxine exposure was associated with a higher daily dose (β = 0.24, 95% CI [0.07; 0.41]).
CONCLUSION
Levothyroxine intake was high in our sample, and suboptimal despite monitoring. Our findings underscore the need for careful dosing and for due consideration of deintensification of treatment where appropriate.
Topics: Humans; Aged; Aged, 80 and over; Thyroxine; Hypothyroidism; Thyrotropin
PubMed: 37656481
DOI: 10.3238/arztebl.m2023.0192 -
Endocrine Mar 2024Previous studies have shown that the gut microbiota plays an important role in the maintenance of thyroid homeostasis. We aimed to evaluate the causal relationships... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have shown that the gut microbiota plays an important role in the maintenance of thyroid homeostasis. We aimed to evaluate the causal relationships between gut microbiota and hypothyroidism.
METHODS
Summary statistics for 211 gut microbiota taxa were obtained from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium. Summary statistics for hypothyroidism were obtained from two distinct sources: the FinnGen consortium R9 release data (40,926 cases and 274,069 controls) and the UK Biobank data (22,687 cases and 440,246 controls), respectively. A two-sample Mendelian randomization (MR) design was employed, and thorough sensitivity analyses were carried out to ensure the reliability of the results.
RESULTS
Based on the FinnGen consortium, we found increased levels of Intestinimonas (OR = 1.09; 95%CI = 1.02-1.16; P = 0.01) and Ruminiclostridium5 (OR = 1.11; 95%CI = 1.02-1.22; P = 0.02) may be associated with a higher risk of hypothyroidism, while increased levels of Butyrivibrio (OR = 0.95; 95%CI = 0.92-0.99; P = 0.02), Eggerthella (OR = 0.93; 95%CI = 0.88-0.98; P = 0.01), Lachnospiraceae UCG008 (OR = 0.92; 95%CI = 0.85-0.99; P = 0.02), Ruminococcaceae UCG011 (OR = 0.95; 95%CI = 0.90-0.99; P = 0.02), and Actinobacteria (OR = 0.88; 95%CI = 0.80-0.97; P = 0.01) may be associated with a lower risk. According to the UK Biobank data, Eggerthella and Ruminiclostridium5 remain causally associated with hypothyroidism. The sensitivity analysis demonstrates consistent results without evidence of heterogeneity or pleiotropy.
CONCLUSION
This study highlights the impact of specific gut microbiota on hypothyroidism. Strategies to change composition of gut microbiota may hold promise as potential interventions.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Hypothyroidism
PubMed: 37736821
DOI: 10.1007/s12020-023-03538-w -
Frontiers in Endocrinology 2023Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction...
BACKGROUND
Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work.
METHODS
A genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction. Hypothyroidism was linked to 22,687 cases and 440,246 controls. For hyperthyroidism, there were 3545 cases and 459,388 controls. A total of 3751 cases and 372016 controls were included in the genetic data for CMM from UK Biobank (http://www.nealelab.is/uk-biobank) (the Dataset: ieu - b - 4969). Among them, inverse variance weighting (IVW) is the main MR Analysis method for causality assessment. MR-Egger method, MR Pleiotropic residual and outlier test (MR-PRESSO), and simple and weighted median (VM) were used to supplement the IVW method. Sensitivity analyses, mainly Cochran's Q test, leave-one-out analysis, and MR Egger intercept test were performed to assess the robustness of the outcomes.
RESULTS
The two-sample MR Analysis results revealed a negative correlation between genetically predicted hypothyroidism and the probability of CMM (OR=0.987, 95%CI =0.075-0.999, =0.041). The supplemental MR Analysis did not reveal any statistically significant differences, although the direction of the effect sizes for the other approaches was consistent with the IVW effect sizes. The results of the causal analysis were relatively robust, according to a sensitivity analysis. The risk of CMM was unaffected by hyperthyroidism (>0.05). No correlation between CMM and thyroid dysfunction was seen in the reverse MR analysis.
CONCLUSION
Although the magnitude of the causal association is weak and further investigation of the mechanism of this putative causal relationship is required, our findings imply that hypothyroidism may be a protective factor for CMM.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Melanoma; Skin Neoplasms; Hypothyroidism; Hyperthyroidism
PubMed: 38093968
DOI: 10.3389/fendo.2023.1239883 -
Frontiers in Endocrinology 2023Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes...
BACKGROUND
Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes in gut microbiota after the onset of thyroid dysfunction are not clear.
METHODS
A two-sample Mendelian randomization (MR) study was used to explore the complex relationship between gut microbiota and thyroid dysfunction. Data on 211 bacterial taxa were obtained from the MiBioGen consortium, and data on thyroid dysfunction, including hypothyroidism, thyroid-stimulating hormone alteration, thyroxine deficiency, and thyroid peroxidase antibodies positivity, were derived from several databases. Inverse variance weighting (IVW), weighted median, MR-Egger, weighted mode, and simple mode were applied to assess the causal effects of gut microbiota on thyroid dysfunction. Comprehensive sensitivity analyses were followed to validate the robustness of the results. Finally, a reverse MR study was conducted to explore the alteration of gut microbiota after hypothyroidism onset.
RESULTS
Our bidirectional two-sample MR study revealed that the genera , , , and were the risk factors for decreased thyroid function, whereas the genera and and phyla Actinobacteria and Verrucomicrobia were protective. The abundance of eight bacterial taxa varied after the onset of hypothyroidism. Sensitivity analysis showed that no heterogeneity or pleiotropy existed in the results of this study.
CONCLUSION
This novel MR study systematically demonstrated the complex relationship between gut microbiota and thyroid dysfunction, which supports the selection of more targeted probiotics to maintain thyroid-gut axis homeostasis and thus to prevent, control, and reverse the development of thyroid dysfunction.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Hypothyroidism; Thyroxine; Clostridiales
PubMed: 38027113
DOI: 10.3389/fendo.2023.1267383