Association between thyroid function and prognosis of severe COVID-19 among patients with SARS-CoV-2 infection: a retrospective cohort study in China.

Objective: This study aims to examine the thyroid hormone profile and its association with severe coronavirus disease 2019 (COVID-19) in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This retrospective cohort study enrolled patients admitted to a tertiary hospital due to SARS-CoV-2 infection between February 18 and May 18, 2022. Clinical data were collected retrospectively from the electronic medical record system. Based on the thyroid function, patients were divided into five groups: normal, non-thyroid illness syndrome (NTIS), hypothyroidism, thyrotoxicosis, and unclassified. The association between thyroid function and severe COVID-19 was detected using multivariable logistic regression and restricted cubic splines analysis. Results: This study included 3,161 patients, with 7.7% of them developing severe COVID-19. 44.9% of the patients had normal thyroid function, 36.5% had NTIS, 6.7% had hypothyroidism, and 1.0% had thyrotoxicosis on admission. After adjusting for age, sex, and relevant clinical characteristics, NTIS and hypothyroidism were associated with increased risks of severe COVID-19 (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.59-3.56 and OR 2.29, 95% CI 1.23-4.26, respectively), compared to normal thyroid function group. Among patients with NTIS or hypothyroidism, higher levels of total triiodothyronine (TT3) are associated with lower risks of severe COVID-19 (OR 0.73, 95% CI 0.64-0.82, for every 0.1nmol/L increase in TT3 level). Conclusion: Thyroid hormone profiles of NTIS or hypothyroidism are associated with increased risks of severe COVID-19. The decreased level of TT3 correlated with the increased risk of severe COVID-19 in patients with NTIS or hypothyroidism.

Risk factors of thyroid dysfunction in patients with rheumatoid arthritis.

Introduction: The study aimed to investigate the complicating thyroid dysfunction situation in patients with rheumatoid arthritis (RA) and to analyze the related risk factors of thyroid dysfunction in RA patients. Material and methods: The retrospective analysis of the clinical data and laboratory examinations of 290 cases of RA and 200 healthy individuals undergoing the physical examination was carried out. The thyroid function, anti-thyroid antibodies, and routine laboratory test items were measured. The RA disease activity score (DAS28) was determined in RA patients. Logistic analysis was used to identify risk factors associated with thyroid dysfunction in RA patients. Results: The detection rate of RA combined with thyroid dysfunction was 30.0%, which was higher than in the control group (7%, 14 cases). In the thyroid function test, levels of total triiodothyronine (T3) and free triiodothyronine (FT3) were lower, while thyrotropin (TSH), antithyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb) were higher in the RA group. There was a difference in hemoglobin (HGB) and total cholesterol (TC) in RA patients with and without abnormal thyroid function. Conclusions: Rheumatoid arthritis patients are more prone to develop thyroid dysfunction than healthy individuals, especially hypothyroidism. HGB and TC were correlated with thyroid hormones and antibodies and were risk factors correlated with thyroid dysfunction in RA patients. Clinical work should pay full attention to changes in thyroid function in patients with RA.

Early life air pollution exposures and thyroid function in children: a prospective cohort study.

Studies on early life ambient air pollution exposures and childhood thyroid function are scarce. This study aimed to evaluate the relationships between early life fine particulate matter (≤ 2.5 µm; PM2.5) and nitrogen dioxide (NO2) exposures and thyroid function in children. We measured the levels of thyrotropin, triiodothyronine, and free thyroxine in children (n = 684) residing in a rural Korean area at age 2, 4, 6, or 8 years from 2012 to 2020 in the Environment and Development of Children cohort. The relationship between residential average exposure levels of PM2.5 and NO2 during pregnancy and 1-year average levels before visit and thyroid function during childhood were analyzed. Inverse association between increases of 10 µg/m3 in PM2.5 during the first trimester and thyrotropin levels at aged 4 (ß, -0.12; 95% CI: -0.22, -0.02) and 6 years (ß, -0.16; 95% CI: -0.26, -0.06) were observed. No association was found between PM2.5 exposure during the second and third trimester and childhood TSH levels. Childhood PM2.5 exposure was positively associated with thyrotropin rise at aged 4 (ß, 0.2; 95% CI: 0.06, 0.35) and 6 years (ß, 0.16; 95% CI: 0.02, 0.29) and inversely related with free thyroxine levels at aged 8 years (ß, -0.04; 95% CI: -0.07, -0.01). No relationship between NO2 exposure and thyroid function was found. In conclusion, association between PM2exposure and childhood thyrotropin levels varied depending on exposure timing. Early gestational exposure showed an inverse relationship, whereas childhood exposures were positively associated with childhood thyrotropin levels. The long-term effects of early life air pollution exposure and underlying mechanisms should be investigated in future studies.

Thyroid function tests in overweight and obese children and adolescents with and without non-alcoholic fatty liver disease.

Background: Hypothyroidism can play an important role in the development of non-alcoholic fatty liver disease (NAFLD). This study compared the thyroid function tests in overweight and obese children and adolescents with and without NAFLD. Methods: This case-control study was conducted on 100 children and adolescents aged 4-18 years who referred to the endocrinology clinic of Amirkola Children's Hospital, Babol, Iran in 2021. 42 obese and overweight children with NAFLD were considered as case group and 56 persons without NAFLD as control group. They were selected after physical examination and body mass index (BMI) assessment. Then, TSH, T4, FBS, lipid profile, 25(OH) vit D3 (VD), AST and ALT levels were measured. Abdominal ultrasound was performed to survey fatty liver. T-test and Chi-score were used for analysis and p< 0.05 was considered significant. Results: The mean age in both group was 11.63±2.55 and 10.07±2.61 years, respectively (P=0.004). Hypothyroidism was not seen in the groups. Two groups in terms of mean TSH (P=0.92), T4 (P=0.87), FBS (P=0.33), cholesterol (P=0.44), LDL (P=0.35), VD (P=0.07) had no significant difference. However, difference was found between the two groups in terms of the mean level of AST (P=0.003), ALT (P=0.001), TG (P=0.02), HDL (P=0.01) and BMI (P0.001). Conclusion: This study showed that the mean level of thyroid hormones in both groups did not have significant difference and hypothyroidism was not seen. Other studies with larger sample size and longer periods of time are suggested.

Subclinical hyperthyroidism and the risk of dementia: A meta-analysis.

BACKGROUND: Accumulating evidence suggests that thyroid dysfunction may be related to the risk of dementia. However, previous studies evaluating the association between subclinical hyperthyroidism and the risk of dementia showed inconsistent results. This systematic review and meta-analysis were performed to evaluate the relationship between subclinical hyperthyroidism and the incidence of dementia in the general population. METHODS: Cohort studies relevant were retrieved by searching the electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Subgroup and meta-regression analyses were performed to investigate the source of heterogeneity. RESULTS: Nine cohort studies including 49,218 community-derived participants were included. Among them, 3177 (6.5%) had subclinical hyperthyroidism at baseline. During a mean follow-up of 10.2 years, 4044 participants developed dementia. The pooled results showed that compared to the participants with euthyroidism, those with subclinical hyperthyroidism had a higher incidence of dementia (risk ratio: 1.38, 95% confidence interval: 1.09 to 1.74, p = .006; I2 = 47%). Subgroup analyses according to study design, age of the participants, methods for diagnosis of dementia, or analytic model did not significantly change the results. The univariate meta-regression showed that the cutoff of thyroid-stimulating hormone for defining subclinical hyperthyroidism negatively affected the association between subclinical hyperthyroidism and dementia (coefficient: -1.44, p = .009), which completely explained the heterogeneity (residual I2 = 0%). CONCLUSION: Subjects with subclinical hyperthyroidism may have a higher risk of dementia compared to those with euthyroidism.

Association of maternal mild hypothyroidism in the first and third trimesters with obstetric and perinatal outcomes: a prospective cohort study.

BACKGROUND: Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy. OBJECTIVE: To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes. STUDY DESIGN: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes. RESULTS: Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group. CONCLUSION: This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Prenatal exposure to air pollution and maternal and fetal thyroid function: a systematic review of the epidemiological evidence.

BACKGROUND: Exposure to ambient air pollution is a top risk factor contributing to the global burden of disease. Pregnant persons and their developing fetuses are particularly susceptible to adverse health outcomes associated with air pollution exposures. During pregnancy, the thyroid plays a critical role in fetal development, producing thyroid hormones that are associated with brain development. Our objective is to systematically review recent literature that investigates how prenatal exposure to air pollution affects maternal and fetal thyroid function. METHODS: Following the Navigation Guide Framework, we systematically reviewed peer-reviewed journal articles that examined prenatal exposures to air pollution and outcomes related to maternal and fetal thyroid function, evaluated the risk of bias for individual studies, and synthesized the overall quality and strength of the evidence. RESULTS: We found 19 studies that collected data on pregnancy exposure windows spanning preconception to full term from 1999 to 2020 across nine countries. Exposure to fine particulate matter (PM2.5) was most frequently and significantly positively associated with fetal/neonatal thyroid hormone concentrations, and inversely associated with maternal thyroid hormone concentrations. To a lesser extent, traffic-related air pollutants, such as nitrogen dioxide (NO2) had significant effects on fetal/neonatal thyroid function but no significant effects on maternal thyroid function. However, the body of literature is challenged by risk of bias in exposure assessment methods and in the evaluation of confounding variables, and there is an inconsistency amongst effect estimates. Thus, using the definitions provided by the objective Navigation Guide Framework, we have concluded that there is limited, low quality evidence pertaining to the effects of prenatal air pollution exposure on maternal and fetal thyroid function. CONCLUSION: To improve the quality of the body of evidence, future research should seek to enhance exposure assessment methods by integrating personal monitoring and high-quality exposure data (e.g., using spatiotemporally resolved satellite observations and statistical modeling) and outcome assessment methods by measuring a range of thyroid hormones throughout the course of pregnancy.

Subclinical Hyperthyroidism and Cardiovascular Disease.

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology.

BACKGROUND: Low maternal urinary iodine concentration (UIC) during pregnancy is associated with adverse offspring neurodevelopment. Thyroglobulin (Tg) has been suggested as a more sensitive biomarker than UIC of long-term iodine status, but associations of Tg with neurodevelopment and the possible mediating role of thyroid function remain unknown. AIM: To study whether maternal Tg is associated with i) maternal and newborn thyroid function and ii) offspring IQ and brain morphology. METHODS: Participants were selected from two population-based prospective cohorts: Generation R (the Netherlands, iodine-sufficient) and INfancia y Medio Ambiente (Spain, mildly iodine-deficient) with maternal Tg and thyroid function data in the first half of pregnancy or in cord blood, early childhood IQ (age 4.5 and 6 years), late childhood IQ (age 9 and 13), or brain morphology at 10 years. Associations of Tg with TSH, FT4, IQ and brain morphology were studied with multivariable linear regression. RESULTS: i) Tg was associated with lower TSH (-0.12[-0.16; -0.08]) and higher FT4 (0.08[0.05;0.12]) in pregnancy (N=4,367), but not with cord blood TSH or FT4 (N=2,008). ii) Tg was associated with lower IQ in early childhood (ß[95% CI]:-0.06 [-0.10; -0.01], N=2,919), but not with IQ (N=2,503) or brain morphology (N=1,180) in later childhood. None of the associations of Tg with the studied outcomes differed by the iodine-to-creatinine ratio (i.e. effect modification) or changed when adjusted for thyroid function. CONCLUSIONS: Higher Tg is associated with lower IQ in early childhood and higher thyroid function during pregnancy, but not with IQ or brain morphology in later childhood. Further research should determine the value of Tg in addition to UIC for defining iodine status.

Myxedema in Both Hyperthyroidism and Hypothyroidism: A Hormetic Response?

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.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is associated with thyroid hormones and thyroid hormone sensitivity indices: a cross-sectional study.

BACKGROUND: Lipids and thyroid hormones (TH) are closely interrelated. However, previous studies have not mentioned the linkage encompassing the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) alongside TH level, as well as sensitivity indices. METHODS: This cross-sectional study leverages expansive datasets from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. Weighted multivariate linear regression, smoothed curve fitting and sensitivity analyses were used to investigate the associations of the NHHR with the thyroid. Subgroup analyses and interaction tests were conducted to determine the robustness of the findings across diverse segments of the population, ensuring the consistency and generalizability of the observed associations. RESULTS: The NHHR was significantly positively correlated with free triiodothyronine (FT3) levels, thyroid-stimulating hormone (TSH) levels, the FT3 to FT4 ratio (FT3/FT4), and the quantile-based thyroid feedback index for FT3 (TFQIFT3) and negatively correlated with free thyroxin (FT4) levels [0.17(0.07-0.27), P = 0.001; 0.60 (0.03-1.17), P = 0.040; 0.06 (0.04-0.08), P < 0.0001; 0.23 (0.16-0.30), P < 0.0001; and -0.65 (-1.05--0.24), P = 0.002]. Smoothed curve fitting revealed nonlinear correlations of the NHHR with thyroid function and thyroid hormone sensitivity indices. In subgroup analyses, interaction tests, and smoothed curve fitting analyses, different populations presented largely consistent statistical differences. CONCLUSION: Among American adults, the NHHR was significantly positively correlated with FT3 levels, TSH levels, the FT3/FT4 and the TFQIFT3. Conversely, a negative association was noted between the NHHR and FT4 levels.

Mendelian randomization analysis reveals no causal relationship between thyroid function and sarcopenia-related traits.

Background: Recent research has indicated a potential association between thyroid function and sarcopenia, but the specific mechanisms and a definitive causal relationship have yet to be established. Therefore, the objective of this study is to examine the potential causal connection between thyroid function and sarcopenia-related traits, including hand-grip strength, appendicular lean mass (ALM), and walking pace. Methods: The study used a bi-directional two-sample MR design, with thyroid function examined as the exposure and sarcopenia-related traits as the outcome in the first stage, and then reversed in the second stage. The genetic instruments for thyroid function were obtained from a comprehensive meta-analysis involving 271,040 participants. Data on sarcopenia-related traits based on GWASs were collected from the UK Biobank, which includes up to 461,026 European participants. The estimates for MR were calculated using the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed. Results: After applying the Bonferroni correction for multiple testing, our MR analyses revealed no significant impact of thyroid function liability on sarcopenia-related traits. Similarly, our reverse MR analysis did not provide evidence supporting the influence of liability to sarcopenia-related traits on thyroid function. The results of the primary IVW MR analyses were largely in line with those obtained from our sensitivity MR analyses. Conclusion: Our research findings do not suggest a link between thyroid function and sarcopenia-related traits. The associations identified in epidemiological studies may be influenced, at least in part, by shared biological mechanisms or environmental confounders.

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10-4), cataract (p = 3 × 10-3), and T1D (p = 1 × 10-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.

Subacute Thyroiditis: A Rare Cause of Pyrexia of an Unknown Origin.

Subacute thyroiditis is inflammation of the thyroid gland, classically presenting with neck pain or discomfort and sometimes with associated diffuse tender goiter and overt hyperthyroid symptoms. Only a few rare cases of subacute thyroiditis presenting as pyrexia of unknown origin (PUO) without any of the aforementioned clinical features have been reported in the literature. A 62-year-old male, with a past history of diabetes mellitus, presented with a history of intermittent fever lasting for one month duration. He did not have any significant localizing symptoms, except for a mild headache, and his examination findings were unremarkable as well. Investigations revealed a high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) levels, and a deranged thyroid profile, with high free T3 and T4 and suppressed thyroid-stimulating hormone (TSH) levels, suggestive of subacute thyroiditis. The diagnosis was further reinforced by the findings of a supportive ultrasound scan of the neck. The patient was started on steroids, to which he showed a significant clinical and biochemical response. Here, we aim to highlight atypical presentations of subacute thyroiditis and the importance of early consideration of endocrine diseases in the workup of PUO, sometimes even in the absence of suggestive clinical features.

Thyroid Function Trends in Dialysis: Unveiling Peritoneal and Hemodialysis Disparities.

BACKGROUND: The interplay between peritoneal dialysis (PD), residual kidney function (RKF), and thyroid function remains poorly understood, with limited prospective studies comparing thyroid function in PD versus hemodialysis (HD) patients. METHODS: This prospective single-center study assessed thyroid function in 18 PD patients over a 24-month follow-up period at the Department of Nephrology, Dialysis, and Kidney Transplantation, UHC Rijeka, Croatia. Data were compared to 24 concurrently treated HD patients. RESULTS: Initially, some PD patients exhibited elevated TSH levels, which normalized during follow-up despite longer dialysis duration. Compared to HD patients, PD patients demonstrated significantly higher T4 concentrations at baseline and higher FT4 concentrations at 12 and 24 months. Furthermore, FT3 levels were significantly higher in PD patients at baseline and at both 12 and 24 months, with T3 levels also within the reference interval after the beginning of the study. Additionally, a positive association was observed between T4 levels and 24-h diuresis after 12 months in PD patients. CONCLUSION: Recognizing additional risk factors and potential impacts on RKF and cardiovascular comorbidities in dialysis patients can enhance patient care, influence dialysis modality selection, and guide ongoing patient monitoring. Thorough evaluation of thyroid function in PD and HD patients is essential for optimizing clinical outcomes and overall well-being. This study contributes to understanding the complex interplay between thyroid function, RKF, and dialysis modality, emphasizing the need for further research to inform comprehensive patient care strategies.

Fetal sexual dimorphism of maternal thyroid function parameters during pregnancy, a single center retrospective real-world study.

Introduction: Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. Methods: This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. Results: A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. Discussion: We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy.

A Clinical Study of Thyroid Abnormalities and Autoantibodies in Patients Diagnosed With Anti-nuclear Antibody Positive Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

INTRODUCTION: Autoimmune connective tissue disorders (CTDs) are characterized by inflammation of the connective tissue structures and immune system aberrations, such as autoantibody production. This study investigates the prevalence and clinical significance of thyroid abnormalities in patients with anti-nuclear antibody (ANA)-positive autoimmune CTDs. METHODS: This prospective cross-sectional observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, from September 2022 to June 2024. Eighty patients diagnosed with ANA-positive CTDs were included. Comprehensive histories were collected from them and clinical examinations and routine investigations were performed. Blood samples were collected for thyroid function tests and autoantibody tests. Thyroid ultrasound investigations were also performed. Ethical approval and informed consent were obtained. RESULTS: The study revealed a significant prevalence of thyroid dysfunction among participants, with 39 (48.75%) exhibiting some form of thyroid abnormality. Subclinical hypothyroidism was the most common condition in 18 (22.50%) participants, predominantly affecting females. Thyroid autoantibodies were present in 32 (40%) participants, with thyroid peroxidase antibodies (anti-TPO Ab) being the most common seen in 17 (21.25%) participants. Systemic lupus erythematosus (SLE) was the most prevalent CTD among participants, seen in 44 (55%) participants, followed by Sjogren's syndrome (SS) seen in 19 (23.75%) participants. CONCLUSION: The study underscores the necessity of routine thyroid function screening in patients with ANA-positive CTDs to facilitate early detection and management of thyroid abnormalities, thereby preventing progression to overt hypothyroidism or hyperthyroidism. The findings highlight the significant association between thyroid dysfunction and autoimmune CTDs, advocating for a holistic approach to patient care.

The correlation between the thyroid function and urinary iodine/creatinine ratio of pregnant women attending a tertiary hospital in Beijing, China, during different trimesters.

OBJECTIVE: This study investigated the correlation between thyroid function and urinary iodine/creatinine ratio (UI/Cr) in pregnant women during different trimesters and explored potential influencing factors. METHODS: In this cross-sectional study, serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and UI/Cr were measured in 450 pregnant women. Correlations were analyzed using Pearson's correlation coefficient and multiple linear regression. Subgroup analyses were performed based on age, body mass index (BMI), parity, gestational age, education, occupation, and family history of thyroid disorders. RESULTS: UI/Cr was positively correlated with FT4 levels in the first and second trimesters, particularly in women with older age, higher BMI, multiparity, higher education, and employment. No significant correlations were found between UI/Cr and TSH or FT3 levels. CONCLUSION: UI/Cr is positively correlated with FT4 levels in early pregnancy, especially in women with certain risk factors. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health.