Establishing and Monitoring an Effective Management of Benign Nontoxic Multinodular Goitre in Kuwait "Utilizing Two Different Dose Levels of Recombinant Human TSH in Combination with Radioactive Iodine".

INTRODUCTION: rhTSH-assisted radioiodine therapy of multinodular goiter is not fully known and only a few studies, with a limited number of patients have evaluated the effect of rhTSH assisted radioiodine therapy beyond 1 year. Though there is an effective and safe management of benign non-toxic MNG available, it is not applicable to all patient categories in Kuwait covering the impact of the past environmental events (Gulf War) and the genetic relation. The proposed project aims to address those points raised, that is exclusive to the Kuwait population. MATERIALS AND METHODS: In this cohort study, 2 groups of patients, group one (G1) and group two (G2) patients (N=50, ≥18 years old) went undergo evaluated according to a proposed criteria followed by FNA to exclude cancer, toxicity and those who have refused surgery. All patients had a CT scan, TSH, T3, T4 and CBC and complete biomedical tests at a 6-months interval during the treatment period and the follow up. The Volumetric application of GE 670 SPECT/CT (i.e. Xeleris) and in-house developed MATLAB used for quantitative measurement. All patients had a 131-I uptake at baseline and 24 intervals post intramuscular a single dose of 0.3mg or 0.1mg (group 1, group 2) of rhTSH. RESULTS: There was no significant difference in TSH levels at 24-month follow-up between the two groups (p=0.327), whereas there was a statistically significant difference at the baseline and at the 6-months interval between the 2 groups for T4. Post treatment follow up at the 24-hour time point, Group 1 displayed significantly higher uptake than Group 2 (G1:41.74 ± 6.27 vs. G2:34.80 ± 3.84, p < 0.001). The change in I131 uptake from baseline to 24 hours was significantly greater in Group 1compared to Group 2 (p < 0.001). The ROC analysis (AUC) post treatment indicated an excellent discriminatory power for AUC (0.960) and (p < 0.001). There was a much better correlation posttreatment between BMI and thyroid volume for group 1 (R2=0.661) than for group 2 (R2=0.008). Our results suggest 42.1% thyroid volume reduction for group 1 and 20% for group 2. CONCLUSION: The study underscores the potential benefits of the higher rhTSH dose (0.3mg) in managing multinodular non-toxic goiter for the Kuwaiti population and the region considering the impact of dietary, and experience to the drastic environmental exposure.

Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study.

Backgroud: Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. Materials and methods: This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. Results: According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. Conclusions: In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (ß coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (ß coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by ß coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Introduction: Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. Aim: The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. Methods: This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Results: Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Conclusions: Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation? / Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index?

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<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 >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). 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.

FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos ­ 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.

[Hyperthyroidism - a classic disease]. / Hypertyreos är inte bara endokrinologens angelägenhet.

Hyperthyroidism presents with various forms of generalized symptoms. Primary care physicians as well as other specialists should have this in mind when meeting patients with symptoms such as palpitations, sweating, fatigue and weight loss. Thyroid-stimulating hormone (TSH) is a highly specific test and useful in ruling out hyperthyroidism. The severity of the disease determines the pace of management. Primary care is often involved in detection of hyperthyroidism but also takes part in the work of rehabilitation and the lifelong hormonal substitution that is necessary for 2/3 of all patients. Subclinical hyperthyroidism, characterized by low TSH levels but normal levels of T4 and T3, is associated with increased mortality by 24 percent and risks of cardiovascular disease, atrial fibrillation and osteoporosis. Treatment depends on age, presence of comorbidity and TSH-levels. In addition to specific endocrinological treatment, person-centered care is crucial during active disease and rehabilitation. The first Swedish care program for hyperthyroidism aims to enhance care efficiency and equity.

Subclinical hypothyroidism in Wales from 2000 to 2021: A descriptive cohort study based on electronic health records.

BACKGROUND: Subclinical hypothyroidism (SCH) is a biochemical thyroid disorder characterised by elevated levels of Thyroid Stimulating Hormone (TSH) together with normal levels of thyroid hormones. Evidence on the benefits of treatment is limited, resulting in persistent controversies relating to its clinical management. AIM: This study describes the demographic and clinical characteristics of patients identified as having subclinical hypothyroidism in Wales between 2000 and 2021, the annual cumulative incidence during this period and the testing and treatment patterns associated with this disorder. METHODS: We used linked electronic health records from SAIL Databank. Eligible patients were identified using a combination of diagnostic codes and Thyroid Function Test results. Descriptive analyses were then performed. RESULTS: 199,520 individuals (63.8% female) were identified as having SCH, 23.6% (n = 47,104) of whom received levothyroxine for treatment over the study period. The median study follow-up time was 5.75 person-years (IQR 2.65-9.65). Annual cumulative incidence was highest in 2012 at 502 cases per 100,000 people. 92.5% (n = 184,484) of the study population had TSH levels between the upper limit of normal and 10mIU/L on their first test. 61.9% (n = 5,071) of patients identified using Read v2 codes were in the treated group. 41.9% (n = 19,716) of treated patients had a history of a single abnormal test result before their first prescription. CONCLUSION: In Wales, the number of incident cases of SCH has risen unevenly between 2000 and 2021. Most of the study population had mild SCH on their index test, but more than a third of the identified patients received levothyroxine after a single abnormal test result. Patients with clinically recorded diagnoses were more likely to be treated. Given the expectation of steadily increasing patient numbers, more evidence is required to support the clinical management of subclinical hypothyroidism.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study.

PURPOSE: Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study. METHODS: Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates. RESULTS: Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029-1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy. CONCLUSIONS: This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Elevated thyroid stimulating hormone and metabolic syndrome risk in patients with first-episode and drug-naïve major depressive disorder: a large-scale cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients. METHODS: We recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust. RESULTS: The prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40-1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001). CONCLUSIONS: This study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive. Here we show that non-coding mutations in a (TTTG)4 short tandem repeat (STR) underlie dominantly inherited RTSH in all 82 affected participants from 12 unrelated families. The STR is contained in a primate-specific Alu retrotransposon with thyroid-specific cis-regulatory chromatin features. Fiber-seq and RNA-seq studies revealed that the mutant STR activates a thyroid-specific enhancer cluster, leading to haplotype-specific upregulation of the bicistronic MIR7-2/MIR1179 locus 35 kb downstream and overexpression of its microRNA products in the participants' thyrocytes. An imbalance in signaling pathways targeted by these micro-RNAs provides a working model for this cause of RTSH. This finding broadens our current knowledge of genetic defects altering pituitary-thyroid feedback regulation.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study.

OBJECTIVES: While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. METHODS: This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. RESULTS: There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors "Postoperative TSH level ≥ 2 mU/L", "Levothyroxine sodium tablet dose<1.4 µg/kg·d", and "Combined with Hashimoto thyroiditis" were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05). CONCLUSION: Optimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Thyroid function variations within the reference range and cognitive function: A two-sample Mendelian randomization study.

BACKGROUND: The causal relationship between thyroid function variations within the reference range and cognitive function remains unknown. We aimed to explore this causal relationship using a Mendelian randomization (MR) approach. METHODS: Summary statistics of a thyroid function genome-wide association study (GWAS) were obtained from the ThyroidOmics consortium, including reference range thyroid stimulating hormone (TSH) (N = 54,288) and reference range free thyroxine (FT4) (N = 49,269). GWAS summary statistics on cognitive function were obtained from the Social Science Genetic Association Consortium (SSGAC) and the UK Biobank, including cognitive performance (N = 257,841), prospective memory (N = 152,605), reaction time (N = 459,523), and fluid intelligence (N = 149,051). The primary method used was inverse-variance weighted (IVW), supplemented with weighted median, Mr-Egger regression, and MR-Pleiotropy Residual Sum and Outlier. Several sensitivity analyses were conducted to identify heterogeneity and pleiotropy. RESULTS: An increase in genetically associated TSH within the reference range was suggestively associated with a decline in cognitive performance (ß = -0.019; 95%CI: -0.034 to -0.003; P = 0.017) and significantly associated with longer reaction time (ß = 0.016; 95 % CI: 0.005 to 0.027; P = 0.004). Genetically associated FT4 levels within the reference range had a significant negative relationship with reaction time (ß = -0.030; 95%CI:-0.044 to -0.015; P = 4.85 × 10-5). These findings remained robust in the sensitivity analyses. CONCLUSIONS: Low thyroid function within the reference range may have a negative effect on cognitive function, but further research is needed to fully understand the nature of this relationship. LIMITATIONS: This study only used GWAS data from individuals of European descent, so the findings may not apply to other ethnic groups.

Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

[Acupoint application for Hashimoto's thyroiditis with liver-qi stagnation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of acupoint application for Hashimoto's thyroiditis (HT) with liver-qi stagnation. METHODS: One hundred and fifty patients of HT with liver-qi stagnation were randomly divided into an acupoint application group (75 cases, 11 cases were excluded, 5 cases dropped out) and a control group (75 cases, 12 cases excluded, 3 cases dropped out). Based on the health education combined with conventional western medicine treatment, the patients in the acupoint application group were treated with acupoint application, while the patients in the control group were treated with placebo acupoint application. Shenque (CV 8), bilateral Yongquan (KI 1), Yeshi, and ashi point were selected in both groups, with Yeshi treated once a week and the remaining acupoints treated every other day, for a total of 4 weeks. The serum levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), as well as the thickness of thyroid left lobe, right lobe, and isthmus, TCM symptom score, hospital anxiety and depression scale (HADS) score, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment. Adverse reactions in both groups were observed. RESULTS: Compared with before treatment, in the acupoint application group, the serum levels of TgAb and TPOAb were reduced after treatment (P<0.05), and the scores of role physical (RP), body pain (BP), vitality (VT), role emotional (RE), and mental health (MH) in SF-36 were increased after treatment (P<0.01, P<0.001). The thickness of the thyroid isthmus after treatment was smaller than that before treatment (P<0.05), and the TCM symptom scores and HADS anxiety (HADS-A) scores after treatment were lower than those before treatment (P<0.001, P<0.01) in both groups. In the control group, the scores of physical function (PF), RP, BP, VT, and RE in SF-36 after treatment were higher than those before treatment (P<0.05, P<0.01, P<0.001). There was no statistically significant difference in serum FT3, FT4, and TSH levels within the groups (P>0.05). There was no statistically significant difference in the above indexes between the two groups (P>0.05). The incidence of adverse reactions in the acupoint application group and the control group was 20.0% (15/75) and 10.7% (8/75) respectively, with skin allergy being the main adverse reaction. CONCLUSION: Acupoint application could reduce the serum levels of TgAb and TPOAb in patients of HT with liver-qi stagnation, alleviate thyroid enlargement, improve TCM symptoms and anxiety, and improve quality of life, with safe and reliable clinical efficacy.

MacroTSH: still a big problem for clinicians and clinical biochemists: lessons from a case report.

MacroTSH still interferes with TSH assays. We present here a case report illustrating the difficulties that can arise in such conditions and attempt to discuss the steps involved in diagnosis.

Lactose intolerance and levothyroxine malabsorption: a review of the literature and report of a series of patients treated with liquid L-T4 without lactose.

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 µg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels.

Total thyroxine, triiodothyronine, and thyrotropin concentrations during acute nonthyroidal illness and recovery in dogs.

BACKGROUND: Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. OBJECTIVES: To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. ANIMALS: Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. METHODS: Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. RESULTS: tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03-0.65] vs 0.11 ng/mL [range (0.05-0.26)], mean difference = 0.09 ng/mL; P = .03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. CONCLUSIONS AND CLINICAL RELEVANCE: In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs.

Possible association between subclinical hypothyroidism and age at menopause in Colombian women.

OBJECTIVE: To evaluate the association between subclinical hypothyroidism with early menopause, premature menopause, and last menstrual bleeding before the natural age of menopause. METHODS: This was a cross-sectional study conducted in 643 postmenopausal women aged 40-69 years. Groups were formed according to last menstrual episode: ≥45 [Natural age at menopause], 40-44 and [Early menopause], <40 [Premature menopause], and <45 [last menstrual episode before the natural age of menopause]. The Zulewski scale was applied to identify manifestations related to hypothyroidism and subclinical hypothyroidism, diagnosed with a serum TSH > 4.5 µIU/mL plus T4-free between 0.7 and 1.9 ng/dL. RESULTS: It was found that 24.4% had the last menstrual episode before the natural age of menopause, 18.6% had early menopause, and 5.7% had premature menopause. Subclinical hypothyroidism was diagnosed in 4.5% of patients. Among women with subclinical hypothyroidism, there was a higher frequency of early menopause, premature menopause, and last menstrual episode before the natural age of menopause, than in women without subclinical hypothyroidism (p < 0.05). Paresthesia (50%) and dry skin (40.7%) were the most reported hypothyroidism-related manifestations. Early menopause, premature menopause, and last menstrual episode before the natural age of menopause were associated with subclinical hypothyroidism, OR: 3.37 [95% CI: 1.40-8.10], OR: 4.31 [95% CI: 1.24-14.97], and OR: 3.57 [95% CI: 1.57-8.10], respectively. CONCLUSIONS: The last menstrual episode before the natural age of menopause, early menopause, and premature menopause were significantly associated with a higher chance of subclinical hypothyroidism.