Abnormal Thyroid-stimulating Hormone Research Articles

Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study

BackgroundGraves’ disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.MethodsSingle-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed.ResultsThere were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025–1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870–1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D.ConclusionThere was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D.

The Association Between Hypothyroidism and Cognitive Function Change in Women across the Menopause Transition: The Study of Women's Health Across the Nation.

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. Methods: This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Results: Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; p value = 0.006; mean working memory scores: 6.8 vs 6.4; p value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. Conclusions: We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.

Anti-Müllerian Hormone Level Determinants among Non-Polycystic-Ovary-Syndrome Women Undergoing In Vitro Fertilization: A Retrospective Cross-Sectional Study.

Background and Objectives: The anti-Müllerian hormone (AMH) is a crucial biomarker in regulating ovarian follicle development and female fertility. AMH levels predict ovarian responses in in vitro fertilization (IVF) cycles, helping clinicians tailor treatment strategies. This study aims to determine whether thyroid autoimmunity, age, body mass index (BMI), sexual hormone levels, and 25-hydroxyvitamin D levels influence serum AMH in non-polycystic-ovary-syndrome (PCOS) euthyroid women. Materials and Methods: This retrospective cross-sectional study examined 52 female patients at Zygota Fertility Clinic between 2018 and 2022. Women aged 20-45 years with regular menstrual cycles were included, while conditions such as abnormal thyroid-stimulating hormone (TSH) levels, PCOS, and systemic autoimmune diseases were excluded. A number of parameters were measured in the study, including the subjects' age, BMI, 25-hydroxyvitamin D, serum free thyroxine (fT4), TSH, various antibodies, and a range of reproductive hormones. An analysis of the relationships between AMH and other variables was conducted using Spearman's correlation coefficient, and an assessment of the impact of confounding factors on AMH levels was conducted using a multivariable linear regression model. Results: The results revealed significant negative correlations between AMH levels and age (rho: -0.484, p < 0.001) and follicle-stimulating hormone (FSH) (rho: -0.550, p < 0.001), while positive correlations existed between AMH and estradiol (rho: 0.352, p = 0.011) and total testosterone (rho: 0.542, p < 0.001). No significant correlations were found between AMH levels and BMI, LH, or 25-hydroxyvitamin D. Conclusions: In this study, ovarian reserve was influenced by age, estradiol, and total testosterone in non-PCOS euthyroid women undergoing IVF. Conversely, BMI and vitamin D status did not significantly impact AMH levels. In order to better understand and possibly manage ovarian reserve, a holistic approach is absolutely essential, taking into account age, weight, hormonal balance, nutrition, and thyroid health.

Association Between Particulate Matter Exposure and Preterm Birth in Women With Abnormal Preconception Thyrotropin Levels: Large Cohort Study.

Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-μg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.

O-304 Is there any association between thyroid-stimulating hormone (TSH) levels and semen parameters? A retrospective study in a European fertility clinic

Abstract Study question Is there any association between TSH levels and semen parameters considering age, body mass index (BMI), and life style? Summary answer In line with the results of logistic regression, normal TSH values increase the probability of having a higher sperm count. What is known already To date, association between TSH levels, semen parameters and other hormones have not been thoroughly investigated in European andrology labs. However, while andrology guidelines do not support a systematic evaluation of thyroid function, some studies reported that men in infertility clinics have higher risks of presenting thyroid disorders than in the general population. Study design, size, duration Both partners investigated for sterility are routinely checked for TSH in the work up of our clinic. We examined for 2021 – 2023 all 347 male patients (infertile/fertile) with complete records of demographic data, semen analysis and hormone analysis. Patients suffering from azoospermia, genital tract infections, hormonal supplementation or heavy medical treatments (radiotherapy, chemotherapy), as well as those receiving iodine supplements or drugs that could potentially affect testicular or thyroid physiology, were excluded. Participants/materials, setting, methods Age, BMI, smoking and detailed alcohol intake were recorded. A blood sample was taken from each patient in connection with the sperm collection to measure TSH, FSH, LH, prolactin and testosterone levels. Spearman’s correlation coefficients were used to determine correlations among hormones. Statistical analyses were performed using semen parameters as dichotomized using WHO reference values. Men above the reference values for count, concentration and motility were used as comparison subjects in multivariate logistic regression. Main results and the role of chance The analysis explored relationships between age, BMI, smoking, alcohol consumption and semen parameters with TSH hormone levels. The mean age of the participants was 35.8 ±7.43 years and BMI was 27.2 ±4.54 kgm-2. Of all participants, 37% reported being smokers, alcohol consumption was 3% regularly, 35% occasionally, 44% rarely, 18% none. Considering a TSH level (0.4-4 mIU/l) as normal, the prevalence of thyroid dysfunction in the cohort was 0.9% (TSH &amp;lt;0.4) and 1.1% (TSH &amp;gt;4) implying that most patients had normal TSH levels. In this cohort, TSH levels were not found to be significantly affected by age, BMI, smoking or alcohol consumption despite being known as putative confounding factors influencing TSH levels. Among the various hormones evaluated, only one significant positive correlation was found between TSH and Prolactin (r = 0.199, p = 0.0001), while a trend towards a negative correlation between TSH and LH (r=-0.101, p = 0.073) was suggested. Multivariate logistic regression analysis showed, not surprisingly, that age was a factor influencing sperm count, sperm concentration as well as total and progressive sperm motility. Logistic regression also showed that when TSH values were within the normal range, sperm counts were significantly higher (OR:1.302, P = 0.043; CI95%:1.009-1.681). Limitations, reasons for caution Sperm morphology and viability were not recorded. Evaluation of thyroxine (T4) and triiodothyronine (T3) levels could be useful. The crucial role of iodine and the complex relationship between iodine and selenium status (which depends on geographical location) in affecting thyroid function should be taken into account in future studies. Wider implications of the findings Male patients with abnormal TSH levels are not very common in this region. Normal TSH level is associated with a higher sperm count. TSH assessment in infertile couples should be routine in both partners, given the recorded worldwide increase in thyroid dysfunction and iodine deficiency. Trial registration number not applicable

Prevalence and clinical correlates of suicide attempts in patients with first-episode drug-naïve major depressive disorder and comorbid autoimmune thyroiditis.

Autoimmune thyroiditis is closely associated with major depressive disorder (MDD) and suicide attempts. However, few studies have examined this relationship. The study aimed to assess the prevalence and correlates of suicide attempts in patients with first-episode drug-naïve (FEDN) MDD and autoimmune thyroiditis. We recruited 1718 out-patients with FEDN MDD and assessed depressive, anxiety and psychotic symptoms with the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety (HRSA) and Positive and Negative Syndrome Subscale positive subscale, respectively. The serum levels of free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), antithyroglobulin, thyroid peroxidase antibody (TPOAb) and several other metabolic parameters were assessed. Patients were divided into non-autoimmune thyroiditis, autoimmune thyroiditis only and autoimmune thyroiditis with abnormal TSH groups, based on autoimmune thyroiditis severity. Multiple logistic regression model was applied to identify the correlates of suicide attempts in patients with MDD and autoimmune thyroiditis with abnormal TSH. Compared with the non-autoimmune thyroiditis group, the autoimmune thyroiditis with abnormal TSH group had a nearly fourfold higher likelihood of reporting a suicide attempt, whereas no difference was found between the non-autoimmune thyroiditis and autoimmune thyroiditis only groups. HRSA score, lnTPOAb and lnTSH were independently associated with suicide attempts in patients with autoimmune thyroiditis with abnormal TSH. Patients with MDD and autoimmune thyroiditis with abnormal TSH are at higher risk for suicide attempt. TPOAb, TSH and anxiety are all independently associated with suicide attempts in this population, and regular thyroid checks are warranted.

Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study

Background Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.Methods This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.ResultsThis study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.ConclusionsBoth low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.

Relationship Between Urinary Iodine Concentration and the Prevalence of Thyroid Nodules and Subclinical Hypothyroidism.

The aim of the study was to investigate the iodine intake in the resident population in Xi'an and analyze the relationship between iodine nutritional status and the prevalence of subclinical hypothyroidism and thyroid nodules (TNs). A total of 2507 people were enrolled in Xi'an. Venous serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography were collected. Patients with abnormal TSH were checked for free thyroxine (FT4) and triiodothyronine (FT3). Adults in Xi'an had median UICs of 220.80 μg/L and 178.56 μg/l, respectively. A sum of 16.78% of people had subclinical hypothyroidism. Both iodine excess and iodine deficit increased the frequency of subclinical hypothyroidism. The lowest was around 15.09% in females with urine iodine levels between 200 and 299 μg/l. With a rate of 10.69%, the lowest prevalence range for males was 100-199 μg/l. In Xi'an, 11.37% of people have TNs. In comparison to other UIC categories, TN occurrences were higher in females (18.5%) and males (12%) when UIC were below 100 μg/l. In conclusion, iodine intake was sufficient in the Xi'an area, while the adults' UIC remains slightly higher than the criteria. Iodine excess or deficiency can lead to an increase in the prevalence of subclinical hypothyroidism. Patients with iodine deficiency are more likely to develop TNs.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study

PurposeThis study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). MethodsAmong patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. ResultsOf 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07–2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42–0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10–3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50–0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60–1.03) or landmark analyses (3-month HR=0.74, 0.51–1.07; 6-month HR=0.91, 0.66–1.24). ConclusionThyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation?

Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index?

Abstract Background: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. Objectives: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Methods: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of&lt;0.05. Results: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value &gt;1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional “abnormal” biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p&lt;0.001). Patients with three “abnormal” biomarkers had a threefold higher risk of AF recurrence compared with no “abnormal” biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). Conclusions: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Genetic Instability and Disease Progression of Indian Rett Syndrome Patients.

Rett syndrome (RTT) is the rare neurodevelopmental disorder caused by mutations in methyl CpG binding protein 2 (MECP2) gene with a prevalence of 1:10,000 worldwide. The hallmark clinical features of RTT are developmental delay, microcephaly, repetitive behaviours, gait abnormalities, respiratory abnormalities and seizures. Still, the understanding on the diagnosis of RTT among clinicians are less. The aim of our work was to study various clinical manifestations and a spectrum of MECP2 genetic heterogeneity in RTT patients from South Indian population. We screened 208 autistic patients and diagnosed 20 RTT patients, who were further divided into classical RTT (group I; N = 11) and variant RTT (group II; N = 9). The clinical severity of RTT was measured using RSSS, RSBQ, SSI, SSS and RTT gross motor scale. The biochemical analysis showed that thyroid-stimulating hormone (TSH), plasma dopamine and cholesterol levels were higher in group I when compared to group II, whereas the level of blood pressure, calcium, ferritin and high-density lipoprotein levels were significantly decreased in both RTT groups, when compared to the control group. The genetic mutational spectrum of MECP2 mutations were found in 12/20 of RTT patients, which revealed the occurrence of 60% pathogenic mutation and 20% unknown mutation and it was correlated with the clinical finding of respiratory dysfunction, scoliosis and sleeping problems. The significant results of this study provided clinical and genetic aspects of RTT diagnosis and proposed the clinicians to screen abnormal cholesterol, calcium and TSH levels tailed with MECP2 gene mutations for early prognosis of disease severity.

Thyroid Function Test Abnormalities in Children and Adolescents with COVID-19: A Case-Control Study

Background: There is a lack of conclusive evidence regarding thyroid function test (TFT) abnormalities in COVID-19, especially among children. Objectives: This study aimed to investigate TFT abnormalities in COVID-19 pediatric patients compared to healthy children. Methods: This study was conducted on 37 COVID-19-positive children who were admitted to Namazi Hospital from January 21 to March 1, 2022, compared with 37 healthy children. Within 48 h of positive real-time polymerase chain reaction (PCR) results for severe acute respiratory syndrome coronavirus 2, a blood sample was taken to measure serum levels of thyroid-stimulating hormone (TSH) and total thyroxine (tT4) in the two groups. Additional tests, including free and total triiodothyronine, free T4, and thyroperoxidase antibodies, were also conducted on cases. The chi-square, Pearson correlation coefficient, and analysis of variance tests were used for data analysis. Results: Twenty-five patients were male, and 49 were female, with a mean age of 7.99 ± 5.02. The abnormal TFT and TSH frequency was significantly higher in the case group than in the control group. Nevertheless, there was no significant difference between the case and control groups regarding tT4 abnormalities. We could not establish an association between the mean of TSH and tT4 and age groups in the two groups and between abnormalities of TFTs and COVID-19 severity. Conclusions: Although abnormalities of TFT were significantly more common among COVID-19 children, they were not associated with the disease severity. However, studies with larger sample sizes are recommended to evaluate thyroid abnormalities and their clinical course in COVID-19 children.

Monitoring Thyrotropin in Veterans With Thyroid Nodules.

After the initial thyroid nodule diagnosis, a patient's thyrotropin is often monitored. However, the American Thyroid Association guidelines do not offer recommendations for follow-up thyrotropin testing for patients with thyroid nodules who have no history of conditions or known medications that affect thyroid hormone levels. At the Veterans Affairs Dayton Healthcare System in Ohio, we conducted a retrospective chart review from January 2010 to December 2016 of 100 patients diagnosed with ≥ 1 thyroid nodule on imaging studies who had normal blood thyrotropin at the time of nodule diagnosis. The thyrotropin value was studied at and after diagnosis. A 95% CI was determined for the true population rate of patients with an abnormal thyrotropin at their most recent testing. χ2 tests for categorical variables and independent sample t tests for continuous variables were used to compare the abnormal and normal most recent thyrotropin groups. One hundred patients (male [83%], White race [82%]) with normal thyrotropin at nodule diagnosis had thyrotropin monitoring for a mean (SD) of 5.7 (2.5) years. Six of 100 patients (6%; 95% CI, 2.5%-12.7%) developed abnormal thyrotropin levels in a mean (SD) of 6.9 (3.1) years. When comparing the 6 patients with abnormal thyrotropin vs the 94 with normal thyrotropin, there were no significant differences in sex (P = .99), race (P = .55), age at diagnosis (P = .12), initial thyrotropin level (P = .24), most recent thyrotropin level (P = .98), or time from diagnosis to most recent thyrotropin level (P = .23). This study found no significant change in thyrotropin levels over time in patients with thyroid nodules and no history of medical conditions or medications known to affect thyrotropin levels. Monitoring thyrotropin over time may not be required in these patients. More studies are needed to provide additional data on thyrotropin monitoring for thyroid nodules so that clinicians can make evidence-based decisions.

SAT467 Monitoring TSH Over Time May Not Be Necessary in Patients With Thyroid Nodules

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: A substantial number of patients with thyroid nodules receive monitoring of blood thyroid stimulating hormone (TSH) levels after the initial diagnosis. There is not enough literature supporting long-term monitoring of blood TSH levels in these patients with thyroid nodules. The objective of this study was to evaluate the change in blood TSH level in patients with known thyroid nodules over time and to determine if repeat blood TSH testing is required in these patients. We hypothesized that monitoring of blood TSH level is not warranted in patients with thyroid nodules in the absence of a history of medical conditions or medications that are known to affect thyroid hormone levels. Methods: We studied 100 patients aged 18 to 99 years at the Dayton VA Medical Center with at least one thyroid nodule on imaging studies from January 2010 to December 2016 with normal blood TSH level at time of the diagnosis of the thyroid nodule. Subjects with abnormal thyroid hormone level, history of hot thyroid nodule, autoimmune thyroid disease (on imaging or blood work), thyroid or pituitary surgery, radioactive iodine treatment, neck irradiation, or usage of thyroxine or any other medications known to affect thyroid hormone levels were excluded. Blood TSH level at the time of diagnosis of thyroid nodule and after were retrospectively studied and analyzed for 100 subjects. Normal blood TSH level range at time of diagnosis was noted to be 0.35-5.50 uIU/mL or 0.35-4.00 uIU/mL depending on the assay method used. Normal repeat blood TSH level range was noted to be 0.35-5.50 uIU/mL, 0.35-4.00 uIU/mL, or 0.55-4.78 uIU/mL depending on the assay method used. Results: 100 subjects with normal blood TSH at the time of diagnosis of their thyroid nodule had blood TSH level monitoring for an average time period of 5.74 years. Out of the 100, six subjects (6%, 95% CI [2.52%, 12.73%]) developed an abnormal blood TSH level in a mean time period of 6.94 years. One subject’s initial blood TSH level increased from 3.38 uIU/mL to 7.76 uIU/mL after 8.52 years. This subject did not receive treatment with thyroxine. In the other five subjects, blood TSH level decreased to below normal range in a mean time period of 6.63 years and ranged from 0.25-0.52 uIU/mL. Blood TSH level remained within normal range for 94 subjects in a mean time period of 5.67 years. Conclusion: Monitoring of blood TSH level over time may not be required in most patients with thyroid nodules in the absence of symptoms, medical conditions, or medications that are known to affect thyroid hormone levels. Presentation Date: Saturday, June 17, 2023

THU231 Thyroid Function And Childhood Bone Mineral Density: Abnormal Thyrotropin Concentration May Be Another Predictor Of Pediatric Low Bone Mass

Abstract Disclosure: M. Ahn: None. Backgrounds: Thyroid hormone (TH) whose synthesis and secretion are mainly regulated by thyrotropin (TSH) play a critical role in the metabolism, growth, and development of human body. While TH is responsible for normal growth and differentiation of various organs, bone is known to be one of the major endocrine organs affected by the regulation of TH. Low bone mass or osteoporosis of child and adolescents can occur in numerous chronic conditions, however the influence of abnormal TH and TSH on low bone mineral density (BMD) of children and adolescents remains controversial. Investigating the effect of excessive or deficient TH and TSH on childhood BMD may unveil a better understanding of uncertain role of thyroid function in bone density of pediatric population. Objective: To elucidate the connection between thyroid function and childhood low bone mass. Methods: Serum T3, FT4 and TSH of 619 children aged between 10 to 18 years and previously diagnosed with hemato-oncologic, rheumatoid, gastrointestinal, endocrine conditions whose treatment was completed were assessed simultaneously with mineral density of lumbar spine and femur measured by dual energy x-ray absorptiometry. Serum T3, FT4, and TSH were subcategorized as either high/normal/low or normal/abnormal group with respect to age-matched reference range, then LSBMD data were compared. Comparison, correlation and regression analyses were performed to examine the association between the abnormality of thyroid function and low BMD. Results: Mean LSBMD z-scores of 619 children and adolescents were 0.49±1.28 and those who were less than -1.0 accounted for 37.7 % while serum T3, FT4, and TSH levels were 1.25±0.29 ng/mL, 1.28±0.19 ng/dL, and 2.76±1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were not significantly different in between subjects with either abnormal or normal serum T3 and FT4, however were lower in children with abnormal serum TSH. LSBMD (g/cm2) was negatively correlated with serum T3 whereas its z-scores showed no correlation with any of serum T3, FT4 and TSH. In linear regression, BMI z-scores were positively associated whereas serum T3, FT4, TSH were not directly associated with LSMBD z-scores. When the abnormality of T3, FT4, and TSH was considered as determinants for decreasing LSBMD z-scores, TSH abnormality was a significant risk factor having highest odds ratio as LSBMD z-scores decreased. Conclusion: Although serum T3, FT4, and TSH did not show a direct correlation with childhood LSBMD z-scores, abnormal TSH concentration could predict low LSBMD z-scores, therefore indicate low bone mass of children with various underlying conditions. Presentation: Thursday, June 15, 2023

The association between thyroid-stimulating hormone and thyroid nodules, goiter and thyroid antibody positivity.

The relationship between normal thyroid-stimulating hormone (TSH) levels and thyroid disease in adults remains controversial. This study aimed to investigate the correlation between serum TSH levels, particularly those falling within the normal range, and thyroid diseases in Chinese adults, including thyroid nodules (TN), goiter (GR), and thyroid antibody positivity. This research was a cross-sectional study conducted in an adult population in Tianjin, China. Thyroid volume (Tvol) and TN were assessed using thyroid ultrasonography. Fasting venous blood and spot urine samples were collected to evaluate thyroid function and iodine status. A total of 2460 subjects participated in the survey. The prevalence of thyroid dysfunction was 9.76%, and abnormal TSH levels were found to potentially increase the risk of GR and thyroid antibody positivity in adults. A total of 2220 subjects with TSH within the normal reference range were included in the further study. In these patients, Tvol decreased as TSH levels increased, in both men and women (P < 0.0001). Low TSH levels (0.27-1.41 IU/mL) were identified as a risk factor for TN (odds ratio [OR], 1.46; 95% CI: 1.14-1.87) and GR (OR 5.90, 95% CI 2.27-15.3). Upon stratification by sex and age, the risk of TN was found to be higher in women and elderly individuals (≥60 years old), while the risk of GR was found to be higher in men and younger individuals (<60 years old). High TSH levels (2.55-4.2 IU/mL) were identified as a risk factor for thyroid antibody positivity (OR, 1.53; 95% CI: 1.11-2.10). Men and younger individuals with high TSH levels exhibited a higher risk of thyroid antibody positivity. In adults with normal TSH levels, low TSH levels were associated with an increased risk of TN and GR, whereas high TSH levels were associated with thyroid antibody positivity. The research also suggests that adults whose TSH levels at upper or lower limits of the normal range should be reviewed regularly.

High-sensitive detection and quantitation of thyroid-stimulating hormone (TSH) from capillary/fingerstick and venepuncture whole-blood using fluorescence-based rapid lateral flow immunoassay (LFIA)

BackgroundIn the last decade, point of care testing (POCT) such as lateral flow immunoassays (LFIA) were developed for rapid TSH measurement. Most of these TSH-LFIAs are designed for qualitative measurements (i.e., if TSH values > 5, or >15 IU/L) and as screening tests for primary hypothyroidism in children and adults. Serum or plasma, but not venepuncture whole-blood or fingerstick/capillary, are usually used to quantify TSH accurately. Studies on performance evaluation of TSH-LFIAs POCT using venepuncture or fingerstick whole-blood are limited. Additionally, limited studies evaluated the performance and validity of TSH-LFIAs POCT compared to valid and reliable reference methods. To our knowledge, this is the first study to evaluate three different blood withdrawal techniques for evaluating POCT of TSH. AimWe aim to evaluate the performance of a new fluorescence-based LFIA and its Finecare™ fluorescent reader for quantitative measurement of TSH from a fingerstick, venepuncture whole-blood, and serum. Methods102 fingerstick, venepuncture whole-blood, and serum samples (with normal and abnormal TSH values) were analyzed by Finecare™ Rapid Quantitative LFIA test and Roche cobas® e 601 as a reference test. ResultsUsing serum, when compared to cobas® e 601 reference method, Finecare™ showed high sensitivity [90.5 % (69.6–98.8)] and specificity [96.3 % (89.6–99.2)] for diagnosis of thyroid abnormalities (<0.35 or >4.5 mIU/L). The actual test values (mIU/L) of Finecare™ showed excellent agreement (Cohen's Kappa = 0.85) and strong correlation (r = 0.93, p < 0.0001) with cobas® e 601. Using venepuncture whole-blood samples, Finecare™ showed similar results to serum with high sensitivity [95.2 % (76.2–99.9)], specificity [97.5 % (91.4–99.7)], excellent agreement (Cohen's Kappa = 0.91), and very strong correlation (r = 0.95, p < 0.0001) with cobas® e 601. These results suggest that Finecare™ can be used for quantitative measurement of TSH using serum or venepuncture whole-blood. These key performance indicators were slightly decreased when fingerstick whole-blood samples were used: sensitivity [85.7 %(63.7–97)], specificity [90.0 %,(81.5–96)], good agreement (Cohen's Kappa = 0.7) and very strong correlation (r = 0.9, p < 0.0001) with cobas® e 601. A subgroup analysis of abnormal TSH samples revealed a strong and significant correlation between the reference, Finecare™ whole-blood (r = 0.692; p = 0.0015), and fingerstick test Finecare™ (r = 0.66; p = 0.0025). A very strong correlation was also observed between cobas® e 601 serum and Finecare™ serum (r = 0.88; p < 0.0001). Conclusion: In comparison to the reference assay, our study demonstrates that Finecare™ exhibits high sensitivity, specificity, agreement, and a strong correlation. These findings provide evidence that Finecare™ is a reliable, valid, and accurate point-of-care test for TSH screening and quantitative measurement, especially in non- or small laboratory settings.

The correlation of lipid profile with subclinical and overt hypothyroidism: A cross-sectional study from Syria.

We proceeded with this study to investigate the relationship between hypothyroidism and lipid profile disturbance. A cross-sectional study at Al- Mowasat University Hospital in Damascus was conducted from March 2021 to March 2022, and included 324 adults. For each participant with abnormal thyroid stimulating hormone (TSH), free thyroxine (FT4) was requested. The participants were categorized into 3 groups: euthyroid (226 participants), subclinical hypothyroidism (SCH) (75 participants), and overt hypothyroidism (23 participants). Fasting lipid profile was tested as: cholesterol (Chol), triglycerides (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL). A significant relationship between hypothyroidism and dyslipidemia was noticed. LDL, TG, and Chol but not HDL showed a significant difference between study groups (euthyroidism, subclinical, and overt hypothyroidism). The lowest levels of these parameters were in euthyroidism and increased in subclinical and overt hypothyroidism subsequently. Overt hypothyroidism showed a significant difference in LDL, TG, and Chol compared to euthyroidism, however, we did not find a difference in lipid parameters in SCH compared to euthyroidism. LDL and Chol showed significant differences between subclinical and overt hypothyroidism. TSH had a positive weak correlation with LDL, TG, and Chol, however, there was no correlation with HDL. Also, FT4 had a negative weak correlation with LDL, TG, and Chol, however, there was a positive correlation with HDL. Our findings suggest a higher level of lipids (LDL, TG, and Chol) among SCH and overt hypothyroidism compared to general population. A weak correlations of lipid parameters with TSH and FT4 were detected. It is not well evident whether a restoration of euthyroidism might influence the morbidity and mortality, especially cardiovascular comorbidities, in this population, which mandates future studies.

Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis

Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24th March, 2021 to 23rd March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ2(1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations. Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening.What is Known:• Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances.• Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found.What is New:• TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome.• We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.