Abstract

BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.

Abstract

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.

Abstract

BACKGROUND It is important to consider biological sex as a variable that might influence exercise adaptation in order to optimize exercise prescription for men and women. OBJECTIVE The aim of this study was to quantify the impact of biological sex on maximal oxygen uptake ([Formula: see text]O2max) and performance outcomes after high-intensity interval training (HIIT). METHODS A systematic search and review was conducted by two independent reviewers up to 8 September 2022 using MEDLINE, SPORTDiscus, and Sports Medicine & Education Index in ProQuest. Trials including healthy adults were included if they presented data for or compared male and female [Formula: see text]O2max or performance outcomes in response to HIIT. Performance outcomes included measures of exercise performance and concurrently measured physiological adaptations. Where appropriate, a random-effects, pre-post meta-analysis was undertaken. Data were sub-grouped for men and women, baseline training level, mean age, intervention type, and intervention length. Heterogeneity was assessed using Chi2, Cochran's Q, and Higgins I2 and sensitivity analyses, where required. Study quality was assessed using the Newcastle-Ottawa Scale and publication bias was assessed through visual inspection of funnel plots. RESULTS Thirty-three references from 28 trials were included in the review (n = 965; 462 women and 503 men). Meta-analyses included 19 studies for [Formula: see text]O2max, eight for peak power output from [Formula: see text]O2max testing (PPO), and five for threshold power (powerAT). Meta-analyses revealed similar increases in [Formula: see text]O2max in women (g = 0.57; 95% CI 0.44-0.69) and men (g = 0.57; 95% CI 0.42-0.72), and powerAT in women (g = 0.38; 95% CI 0.13-0.64) and men (g = 0.38; 95% CI 0.11-0.64). Raw mean differences for change in [Formula: see text]O2max were Δ 0.32 L·min-1 and 3.50 mL·kg-1·min-1 in men, versus Δ 0.20 L·min-1 and 3.34 mL·kg-1·min-1 for women. No significant sex differences were present for the primary analysis of any outcome. After sub-grouping, significant differences were present for PPO where the effect size was higher for well-trained women (g = 0.37) compared with well-trained men (g = 0.17), and for [Formula: see text]O2max where interventions with a duration of 4 weeks or less had significantly smaller effect sizes compared with those longer than 4 weeks (p < 0.001). Unweighted mean percentage change in [Formula: see text]O2max, PPO, and powerAT across studies was 11.16 ± 7.39%, 11.16 ± 5.99%, and 8.07 ± 6.55% for women, and 10.90 ± 5.75%, 8.22 ± 5.09%, and 7.09 ± 7.17% for men, respectively. Significant heterogeneity was present for both [Formula: see text]O2max and PPO (I2, range: 62.06-78.80%). Sub-grouping by baseline training status and intervention length decreased heterogeneity in most groups. A qualitative synthesis of other outcomes indicated similar improvements in fitness and performance for men and women with some evidence suggesting differences in the mechanisms of adaptation. LIMITATIONS AND RISK OF BIAS Publication bias is unlikely to have significantly influenced results for [Formula: see text]O2max or powerAT, but the meta-analysis of PPO could have benefitted from additional study data to strengthen results. The overlap in age categories and sensitivity of the analysis limits the accuracy of the results of the sub-grouping by age. CONCLUSIONS Findings indicated no sex-specific differences for any fitness or performance outcomes. Baseline training status and intervention length accounted for most variability in outcomes. PROSPERO registration number: CRD42021272615.

Abstract

BACKGROUND Thyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta-analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD. METHODS We searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD. RESULTS A total of 13 studies were included in the analysis. Compared to non-PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD = -0.59, 95%CI = -1.04 to -.15, p = .009; FT3: SMD = -0.40, 95%CI = -.51 to -.30, p = .000) and higher serum FT4 levels (SMD = 0.33, 95%CI = .07-.59, p = .013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4. CONCLUSIONS Our results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

Abstract

BACKGROUND Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. METHODS The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. RESULTS Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. CONCLUSIONS Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. TRIAL REGISTRATION Registered number in PROSPERO CRD42023405052.

Abstract

BACKGROUND AND OBJECTIVE The prevalence of thyroid cancer (TC) has exhibited an upward trajectory in recent years. An accelerating amount of evidence shows a significant association between Hashimoto's thyroiditis (HT) and TC. The present study encompasses a meticulously designed systematic review and meta-analysis with the aim of scrutinizing the risk of TC and clarifying sex disparities in HT. METHODS A comprehensive search was conducted across reputable online databases, including PubMed, Cochrane Library, EMBASE, and Web of Science. English-language publications on the correlation between HT and TC were examined without temporal restrictions. Two authors independently screened the articles and extracted pertinent data. The collected data underwent statistical analysis using the STATA software, enabling the calculation of the pooled Odds Ratio (OR) and 95% confidence intervals (CI). Additionally, a supplementary analysis was conducted on studies incorporating sex-specific data to determine the OR (female vs. male) and the sex-based prevalence of TC in HT. RESULTS A total of 2,845 records were obtained, and 26 retrospective studies were included in this meta-analysis. The results indicated a significant role for HT in TC (OR: 2.22, 95% CI: 1.85-2.67). Supplementary analysis indicated that the prevalence of TC in HT patients was lower in women (0.31, 95% CI: 0.17-0.45) than in men (0.37, 95% CI: 0.21-0.53). However, the result was not statistically significant. CONCLUSION This systematic review and meta-analysis provide evidence that HT is associated with increasing odds of TC. Regular review of HT patients holds positive clinical significance.

Abstract

BACKGROUND Subclinical hypothyroidism (SCH) is characterized by elevated levels of thyroid hormone (TSH) and normal levels of free thyroxine (FT4). The outcomes of SCH patients are crucial for determining treatment plans; therefore, our aim is to summarize the existing prospective studies to understand the changes in thyroid function over time in SCH patients and the factors influencing these changes, providing references for clinical diagnosis and treatment. METHODS We searched PubMed, Embase, Cochrane Library, and Web of Science for prospective follow-up studies on natural outcomes of SCH published until September 2024. Results are presented as the overall risk ratio (RR) and 95% confidence intervals (CI). RESULTS We reviewed 8 prospective follow-up studies involving 1,859 individuals and extracted data from them for a meta-analysis. We found that when TSH levels are ≥ 10 mU/L, patients with SCH are more likely to progress to overt hypothyroidism (OH) (RR11.38, 95%CI 4.98-26.03, P<0.001) and were less likely to return to normal TSH levels (RR 0.20, 95%CI 0.09-0.42, P<0.001) compared to patients with TSH between 4.5 and 9.9 mU/L. In addition, patients who test positive for thyroid peroxidase antibodies (TPOAb) are more likely to progress to OH (RR 2.53, 95% CI 1.86-3.44, P < 0.001) and less likely to return to euthyroidism (RR 0.68, 95% CI 0.60-0.76, P < 0.001) compared to TPOAb-negative patients. CONCLUSION The results indicated that a large proportion of patients diagnosed with SCH will return to normal TSH levels or maintain SCH. Additionally, patients with TSH levels ≥ 10 mU/L or positive for TPOAb are more likely to experience progression and should be closely monitored. However, we did not find any gender differences in the natural outcome of SCH.

Abstract

PURPOSE The imbalance of thyroid hormones affects the metabolic activity of various tissues, including periodontium. Also, autoimmune diseases present an increased tendency to suffer from periodontal disease. Therefore, our systematic review was designed to answer the question "Is there a relationship between thyroid diseases and periodontal disease?". MATERIALS AND METHODS Following the inclusion and exclusion criteria, 10 studies were included in this systematic review using the databases PubMed, Scopus and Web of Science (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines). RESULTS Based on the meta-analysis, patients with thyroid diseases (especially with hypothyroidism) demonstrated significantly worse periodontal status than systemically healthy controls. Moreover, according to the cross-sectional studies, 5.74 ​% of periodontitis patients reported the concomitance of thyroid diseases. CONCLUSIONS In summary, the included studies suggest a potential relationship between thyroid diseases and periodontal disease. However, further research is necessary to reliably assess the oral health in patients with hypothyroidism and hyperthyroidism.

Abstract

BACKGROUND Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. METHODS We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per .1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. RESULTS The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity, .70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. CONCLUSION We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Abstract

BACKGROUND Thyroid hormones act on the cardiovascular system directly by modulating its function and indirectly by transcriptional regulation of gene expression in the heart and the vasculature. Studies have shown associations between overt and subclinical thyroid disorders and cardiovascular outcomes. The aim of this study was to perform a systematic review and meta-analysis to assess the potential relationships between subclinical hyper- and hypothyroidism and risk of atrial fibrillation (AF), and post-operative AF. METHODS MEDLINE and Scopus databases were searched from inception to 18th February 2023 for randomised controlled trials, case-control studies, and cohort studies which assessed the relationship between subclinical thyroid dysfunction and incident AF events. Risk of bias and the quality of evidence were assessed using the RoBANS tool and GRADE approach, respectively. Meta-analysis was conducted in Review Manager 5.4 using the Mantel-Haenszel statistical method and a random-effects model. Data are presented as risk ratios with 95% confidence intervals. Statistical heterogeneity amongst studies was assessed by the chi-squared (χ2) test and I2 statistic. p≤0.05 were considered significant. RESULTS A total of 6467 records were identified, of which 10 cohort studies met the inclusion criteria. Both subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of incident AF (risk ratio (RR), 1.99; 95% confidence interval (CI), 1.43-2.77; n = 5 studies; p<0.0001 and RR, 1.19; CI, 1.03-1.39; n = 7 studies; p = 0.02, respectively). Subgroup analysis for post-operative AF revealed marked heterogeneity between studies (I2 = 84%) and association with subclinical hypothyroidism was not significant (RR, 1.41; CI, 0.89-2.22; n = 3 studies; p = 0.15). CONCLUSIONS The current evidence suggests that both subclinical hyperthyroidism and subclinical hypothyroidism are associated with increased risk of incident AF. Further investigation is required to determine potential causal links that would guide future clinical practice.