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The article focuses on a case of simple virilizing congenital adrenal hyperplasia (CAH) in a newborn presenting with ambiguous genitalia and persistent hypoglycemia. Topics include the role of 21-hydroxylase deficiency in adrenal steroid biosynthesis, the diagnostic approach integrating biochemical and genetic evaluations, and the management strategies involving hormonal therapy and planned surgical correction.

In this study, we aimed to investigate the effects of antiseizure medications on serum thyroid-stimulating hormone (TSH), free thyroxin (fT4) levels, and the frequency of subclinical hypothyroidism in children with epilepsy. One hundred and eighty-one pediatric patients receiving valproate, phenobarbital, carbamazepine, and levetiracetam monotherapy were included. The serum TSH levels were significantly higher at 6th, 12th, and 18th months of the treatment compared with the pre-treatment levels in valproate-treated patients. Serum fT4 levels in carbamazepine group were significantly lower than levetiracetam, valproate, and phenobarbital groups at 12th and 18th months of the treatment. Serum fT4 and TSH levels in levetiracetam group showed no significant changes at any time point. The frequency of subclinical hypothyroidism at 18th month was 16% in valproate, 11% in phenobarbital, 7% in carbamazepine, and 0% in levetiracetam groups. Our data suggest that levetiracetam monotherapy does not cause thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of different thyroid hormone withdrawal (THW) duration before initial 131I therapy on the level of thyrotropin (TSH), biochemical parameters and prognosis in patients with differentiated thyroid cancer (DTC). Methods: DTC patients who underwent total thyroidectomy between January 2016 and August 2018 before initial 131I therapy were included. Patients undergoing two-week and three-week THW were categorized into groups A and B. Factors influencing TSH ≥ 30 mIU/L, changes in biochemical parameters before surgery and after THW, and prognosis after 131I therapy were evaluated and compared. Results: Totally, 95.3% (303/318) of patients had TSH ≥ 30 mIU/L after THW. The rate of TSH ≥ 30 mIU/L in groups A and B was 93.8% (152/162) and 96.8% (151/156), respectively (P = 0.212). Age was the only factor influencing TSH ≥ 30 mIU/L (hazard ratio [HR] 0.937, 95% confidence interval [CI] 0.882–0.997, P = 0.038). Changes of creatinine, alanine aminotransferase, aspartate aminotransferase, cholesterol, high-density lipoprotein and low-density lipoprotein before and after THW were higher in group B than in group A (all P < 0.05). After a median follow-up of 55 months, the rate of disease persistence/recurrence in groups A and B was 6.2% (7/113) and 2.3% (3/128), respectively (P = 0.241). Stimulated thyroglobulin before 131I therapy was the only predictor for disease persistence/recurrence (HR 1.028, 95%CI 1.012–1.043). Conclusions: Two-week THW was an effective strategy to achieve TSH ≥ 30 mIU/L before 131I therapy in patients younger than 50 years old and had less effect on changes in biochemical parameters, while there was no difference in the prognosis between two-week and three-week THW. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: A glucose homeostasis condition known as insulin resistance (IR) is characterized by a decreased sensitivity of adipose tissue, muscle fiber, liver, and other bodily tissues to insulin, even in the presence of normal or elevated blood concentrations of the hormone. Nevertheless, it is uncommon to evaluate the comorbidity of insulin resistance and thyroid discrepancies, particularly the order in which these indicators appear. This study emphasizes the association between hypothyroidism and insulin resistance. Material and Method: Eighty individuals with suspected thyroid illness or related problems were recruited for this cross-sectional study at the AVBR Hospital in Wardha between December 2020 and September 2022. The participants were categorized as having subclinical hypothyroidism, overt hypothyroidism, or controls based on the thyroid indicators detected in their serum. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used to perform the calculations. A Chi-square test was used in addition to control to examine the relationship between insulin resistance and thyroid function. Results are considered statistically significant only if the P value is less than 0.05. Results: Levels of HOMA-IR were lowest in the Controls (1.65), followed by the Subclinical Group (2.03), and highest in the Overt Group (5.00). HOMA-IR had a significant positive relationship with thyroid stimulating hormone, fasting insulin, and fasting blood sugar (FBS). The prevalence of insulin resistance was 64.3% in overt hypothyroid patients and 36% in subclinical hypothyroid patients. In contrast, it was 21% in the control group of hypothyroid patients on thyroxine therapy for over two months. Conclusion: Thyroid levels and the IR were significantly correlated. The prevalence of insulin resistance was 64.3% in overt hypothyroid and 36% in subclinical hypothyroid in this part of rural area. Therefore having awareness at the primary care physician level may prevent its morbid complications even assessed. [ABSTRACT FROM AUTHOR]

Objective: Infertile people undergoing assisted reproductive technology (ART) treatment in China may experience severe infertility-related stress and illness anxiety (IA). However, little relevant research has been conducted until now. Design: This study investigated the IA of 340 infertile people undergoing ART treatment, including 43 males, 292 females and 5 who preferred not to answer, in 2 tertiary general public hospitals in Wen Zhou, China. Main Outcome Measures: Blood samples for thyroid-stimulating hormone (TSH) levels were obtained from 107 women to explore the relationship between IA and TSH. The questionnaire contained the Mandarin version of the Fertility Problem Inventory, the Resilient Trait Scale for Chinese Adults and the Whiteley Index, measuring infertility stress, resilience and IA, respectively. Results: An incidence rate of 44.1% of IA among infertile people undergoing ART treatment in China was determined, and 30.2% of men and 46.6% of women had severe IA (χ2 = 4.05, p < 0.05). The risk of severe IA in women was around twice that in men (OR = 2.01, 95% CI: 1.01–4.01). Women's IA level was significantly associated with their TSH level (β = 0.27, p < 0.01). Resilience played a moderating role in the relationship between parenthood importance and illness anxiety. Conclusion: This study highlighted the importance and urgency of providing holistic care for illness anxiety of infertile people undergoing ART treatment in China, especially women. The findings of this study indicated that mind-body therapies and resilience empowerment workshops could be conducive to infertile people's holistic health. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is an autoimmune disorder, driven by the appearance of circulating autoantibodies (Ab) against the thyroid stimulating hormone (TSH) receptor, thus causing hyperthyroidism. While antithyroid drugs, the only available treatment for GD, carry a significant risk of relapse, advances in immunology could pave the way for more effective therapies. Natural killer (NK) cells, divided into cytotoxic CD56dim and cytokine-secreting CD56bright subsets, regulate immune responses through cytokine production and cell lysis and may play a role in the pathogenesis of GD. To investigate their involvement, we conducted flow cytometry on peripheral blood samples from 131 GD patients at various stages (disease onset, on antithyroid drugs, and in remission) and 97 age- and sex-matched healthy controls (HC). We analyzed NK cell subsets, activating (CD16, CD69, NKG2D, NKp30) and inhibitory receptors (CD161, NKG2A), degranulation (CD107a), and intracellular cytokines expression (interferon γ, tumor necrosis factor α). Statistical comparisons were made between GD patients and HC and across disease stages. GD patients had a higher frequency of total NK cells (p < 0.028) and CD56bright NK cells (p < 0.01) but a lower frequency of CD56dim NK cells (p = 0.005) compared to HC. NK cells in GD patients expressed activating receptors more frequently, except for NKG2D, but had decreased cytokine expression and degranulation ability. At GD onset, patients had higher frequencies of total NK cells, CD56bright NK cells, and NK cells expressing activating receptors compared to patients receiving ATD treatment and those in remission. CD161+ NK cells were lower at GD onset and returned to levels of HC following treatment. Correlation analysis revealed that free thyroxine (FT4) levels were inversely correlated with CD107a+ NK cells (p < 0.05) and positively correlated with CD69+ NK cells (p < 0.01). These findings suggest that hyperthyroidism impairs NK cell degranulation, with the increased frequency of NK cells potentially compensating for their reduced function. This dysfunction may contribute to the unregulated immune response in GD, highlighting NK cells as a potential target for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate changes in heart rate variability (HRV) and QT dispersion (QTd) in patients with differentiated thyroid cancer at different TSH suppression levels. Methods: The study included 125 DTC patients, who had been on TSH suppression treatment (TSHST) for at least 1 year. The patients were categorized into three groups: patients with TSH < 0.1 mIU/L (n:30), those with TSH 0.1 to 0.5 mIU/L (n:56), and those with TSH 0.5 to 2 mIU/L (n:39). The first two groups were classified as suppression groups, and the last as replacement (control) group. All patients underwent 12-lead electrocardiogram (ECG) recording and 24-hour rhythm holter echocardiography analysis. Results: The HRV results derived from a 24-hour rhythm holter did not exhibit any significant difference (p < 0.05). In dispersion evaluations, the QTd was significantly longer in the suppression groups (groups 1 and 2), than in the replacement group (group 3) (p < 0.001 and p:0.002, respectively). The same was found for corrected QT dispersion (QTcd) (p < 0.001 and p: 0.008, respectively). In multivariate linear regression analysis, TSH was found to affect QTd (β = -0.299; p = 0.002) and QTcd (β = -0.300; p = 0.002) values independently. Conclusion: In this study, it was shown that in patients with DTC receiving TSHST, QT dispersion prolonged as the TSH suppression level increased. Especially in high-risk DTC patients, evaluation of QTd may be useful in terms of evaluating cardiovascular risk and regulating TSHST level. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether there are differences in the biochemical blood parameters between individuals with Cognitive Disengagement Syndrome (CDS) and Attention Deficit Hyperactivity Disorder (ADHD), and to investigate the relationship between vitamin levels and these disorders, as well as their impact on symptom severity. The study included 35 patients with ADHD, 35 patients with both ADHD and CDS, and 35 healthy control subjects who presented to the child and adolescent psychiatry outpatient clinic between January 2022 and 2023, matched for age and gender. Children aged 7–15 were included in the study. Participants were administered a sociodemographic data form, DSM-IV Based Screening and Assesment Scale for Disruptive Behavior Disorders- Parent form (DBSAS-DBD) and the Barkley Child Attention Scale (BCAS). Hemogram parameters, iron, ferritin, Thyroid Stimulating Hormone (TSH), T3, T4, and vitamin levels (B12, folic acid, vitamin D) were analyzed for all participants. Of the participants, 78 (74.3%) were male, and 27 (25.7%) were female. In the analysis, Vitamin B12 and D levels were found to be significantly lower in the ADHD + CDS group compared to both the ADHD group and the control group (p = 0.04; p = 0.03; p = 0.009 p = 0.004 respectively). Hemoglobin levels did not significantly differ between the ADHD + CDS group and the ADHD group, but were significantly higher in the ADHD + CDS group compared to the control group (p = 0.004). Ferritin levels were significantly lower in both the ADHD + CDS group and the ADHD group (p < 0.001; p < 0.001, respectively). The significant decrease in vitamin B12 and vitamin D in the CDS + ADHD group may be related to daytime sleepiness and slow cognitive processes in the CDS clinic. Screening for nutritional deficiencies in individuals with CDS may be beneficial for clinical management, and identifying differences in blood parameters of CDS from ADHD will contribute to a better understanding of this clinical condition. This is an exploratory study with a rather small sample size, in which many outcomes were examined. Further studies with larger and more diverse samples will provide a more comprehensive understanding of the biochemical foundations of these two conditions. [ABSTRACT FROM AUTHOR]

As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8–77.3) years. We propose a RI of 0.34–3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data suggest the population distribution of thyrotropin (TSH) values is shifted toward lower values in self-identified Black non-Hispanic individuals compared with self-identified White non-Hispanic individuals. It is unknown whether genetic differences between individuals with genetic similarities to African reference populations (GSA) and those with similarities to European reference populations (GSE) contribute to these observed differences. We aimed to compare genome-wide associations with TSH and putative causal TSH-associated variants between GSA and GSE groups. Methods: We performed genome-wide association studies (GWAS) in 9827 GSA individuals and 9827 GSE individuals with TSH values between 0.45 and 4.5 mU/L. We compared effect sizes and allele frequencies of previously reported putative causal TSH-associated variants and our power to detect associations with these variants between the two groups. We additionally focused on variants in PDE8B and PDE10A, loci that have been most strongly associated with TSH in previous GWAS in GSE populations. Results: Four loci attained genome-wide significance in the GSA group compared with seven in the GSE group. PDE8B was not significantly associated with TSH in the GSA group, despite its strong association in the GSE group. Eight putative causal variants had significantly different effect sizes between groups. There was ≥80% power in the GSA group to detect significant associations with variants in PDE8B, PDE10A, NFIA, and LOC105377480, with higher expected power than in the GSE group for variants in PDE8B, NFIA, and LOC105377480 and similar power for other variants in PDE8B and PDE10A. No additional putative causal variants in PDE8B and PDE10A had effect sizes that differed significantly between the groups; power to identify associations with additional putative causal variants in PDE8B and PDE10A was similar between the groups. Conclusions: Patterns of genetic associations with TSH differed between identically sized GSA and GSE groups. Failure to replicate the strongest associations previously reported in GSE individuals in our GSA population was not fully explained by differences in allele frequencies or power, assuming similar effect sizes. Larger GSA population GWAS are necessary to confirm our findings and further investigate the contribution of genetic factors to population differences in the distribution of TSH values. [ABSTRACT FROM AUTHOR]

Background/Objectives: The interrelationship of thyroid volume and function with features of cardiovascular dysfunction has already been investigated but some aspects remain unclear, especially in terms of subclinical cardiovascular dysfunction in euthyroid patients. Intima-media thickness (IMT) measurement in ultrasound B-mode imaging in different vascular beds (most frequently within the common carotid artery) is one of the most important tools for the detection of subclinical atherosclerosis in both clinical practice and research. This article aimed to present the results of our research on the association between the thyroid evaluation parameters and the IMT measured in both the carotid and femoral arteries in euthyroid patients aged 18 to 65 years taking into account the influence of diabetes, hypertension, and excess body mass. Methods: We performed a retrospective cross-sectional analysis of data from patients with no thyroid disease who during planned hospitalization underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and Doppler ultrasound of carotid, vertebral, and lower extremities arteries with IMT measurement. Data from 45 people (females: 57.8%) were analyzed. Results: No significant correlations were found between biochemical parameters of thyroid function and IMT parameters. Thyroid volume was found to be significantly correlated with all parameters of the IMT within the superficial femoral artery (R = 0.407, p = 0.007 for the mean IMT calculated from the left side and the right side) and with minimal IMT within the common femoral artery taken from the left side and the right side (R = 0.342, p = 0.025). Selected IMT parameters were shown to be significantly higher in patients with arterial hypertension, diabetes, obesity, or metabolic syndrome in comparison to patients without the mentioned comorbidities. Using multiple linear regression, it was confirmed that parameters related to thyroid status do not significantly affect the IMT value. A significant effect of diabetes and, to a lesser extent, hypertension on the IMT value was confirmed, especially in the femoral arteries. Conclusions: In the population of euthyroid patients, thyroid volume correlates significantly with some parameters of femoral IMT. No significant correlations were found between thyroid biochemical parameters and IMT in both carotid and femoral arteries. A significant influence of diabetes and hypertension on the IMT value was confirmed, especially in the femoral arteries. [ABSTRACT FROM AUTHOR]

Vitiligo is a depigmenting disorder characterized by melanocyte loss, which results in pigment dilution of the skin. Vitiligo is commonly associated with thyroid disorders and thyroid stimulating hormone (TSH) is a sensitive marker to detect thyroid disorders. S100B is damage associated molecular pattern (DAMP) molecule released when there is melanocyte damage. In this study, we are estimating the serum TSH and S100B levels in vitiligo patients and controls and correlating them with disease activity. A cross-sectional study was conducted on 39 cases of vitiligo and controls. Demographic details were collected, the cases were examined and Vitiligo European Task Force (VETF) scoring was performed. Serum S100B was analyzed using an ELISA kit and serum TSH levels were estimated. Age of the participants ranged from 14 to 81 years with a mean and standard deviation of 44.08 ± 16.078 years. Female preponderance was noted. Vitiligo vulgaris was the most common presentation. Serum TSH (p = 0.32) and S100B (p = 0.22) levels between cases and controls were not statistically significant. Serum S100B level had a weak positive correlation with the spreading component of VETF score and it was statistically significant (p = 0.004). Mucosal vitiligo had higher levels of serum S100B levels compared to other types of vitiligo. In our study both serum TSH and S100B levels have demonstrated limited utility in distinguishing between vitiligo patients and controls. S100B showed a weak correlation with VETF scores indicating its potential (though limited) as a disease activity marker. Therefore, the potential of using this as a biomarker is debatable, and further multicentric studies with a larger sample size are required to establish the correlation. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a recurrent and persistent mental illness. However, there is a lack of research that distinguishes the severity of comorbid anxiety disorders in MDD, and insufficient evidence exists regarding the prevalence of MDD patients with comorbid moderate-to-severe anxiety in the Chinese population. Methods: The study included 1718 MDD patients (894 with moderate-to-severe anxiety symptoms and 824 without moderate-to-severe anxiety symptoms). Clinical symptoms and development were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale-14 (HAMA-14), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI). The blood pressure and thyroid hormone levels were measured. Results: We found that the incidence of MDD patients with moderate-to-severe anxiety symptoms was 52.04%. The prevalence of recent suicide attempts in MDD comorbid moderate-to-severe anxiety patients was 31.8%, which was 4.24 times higher than that in patients without moderate-to-severe anxiety. Additionally, suicide attempters had elevated levels of thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared to non-suicide attempters. We further identified CGI score, TSH, TPOAb, and DBP as influential factors for recent suicide attempts in MDD individuals who had moderate-to-severe anxiety symptoms. These indexes could distinguish between suicide attempts and non-suicide attempts in MDD patients with moderate-to-severe anxiety symptoms. Conclusions: Our findings mainly indicated a high prevalence of recent suicide attempts in MDD patients with moderate-to-severe anxiety. Several clinical correlates, thyroid hormones, and blood pressure might contribute to recent suicide attempts in MDD patients with moderate-to-severe anxiety symptoms. [ABSTRACT FROM AUTHOR]

Background: Despite TSH suppressive therapy improve the prognosis for the patient with differentiated thyroid cancer (DTC), there is an increasing concern regarding the potentially harmful effects of lifelong TSH suppression. Therefore, we aimed to examine the changes in body composition under TSH suppression in postmenopausal women with DTC. Methods: The body composition was assessed by the volumes as following; fat tissues of the epicardium and abdominal visceral and subcutaneous areas; bilateral psoas muscle or thigh muscle. Each volumetric measurements were performed using computed tomography (CT) scans using baseline and follow-up fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT)s for 2-year follow up period in Pusan National University Hospital, South Korea. Results: The 43 patients' median age was 50.0 years, and median body mass index (BMI) was 23.53 (interquartile range[IQR]: 22.19- 24.92) at the initial 18F-FDG PET/CT. The median follow-up period was 19.24 months (IQR: 17.24–21.79). No significant change in weight or BMI were observed during follow-up. Volumes of fat and muscles was not changed significantly except epicardial fat volume. The epicardial fat volume significantly increased during the follow-up period. The epicardial fat volumes were correlated with visceral fat volume, respectively, however, the changing ratio was only correlated with TSH suppression on multiple regression analysis. Conclusion: Both skeletal muscle and abdominal fat volumes did not change, whereas epicardial fat volume increased over less than 2 years of observation under TSH suppressive therapy. Further research is needed for the harmonization of benefits or losses with the optimal TSH concentration in postmenopausal women. [ABSTRACT FROM AUTHOR]

Introduction: Graves' disease and subacute thyroiditis (SAT) are two of the most common causes of thyrotoxicosis. free T3 to free T4 ratio (fT3/fT4), neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) have not been analysed in detail for diagnosis in previous studies. Materials and Methods: A total of 141 patients with subacute thyroiditis, 133 with Graves' disease and 126 healthy volunteers were included in the study. Thyroid stimulating hormone (TSH), fT3, fT4, C-reactive protein (CRP), MPV, NLR, erythrocyte sedimentation rate (ESR) and TSH receptor antibody (TRAb) levels were recorded. The laboratory parameters were compared between the two groups. ROC analysis was performed to evaluate fT3/fT4 ratio, ft4/TSH ratio, NLR and MPV to aid diagnosis, as well as cut-off values, sensitivity and specificity. Results: The fT3/fT4 ratio was significantly different between the subacute thyroiditis (SAT) and Graves' disease groups (2.45 ± 0.68 vs. 3.48 ± 1.8, p < 0.01). The MPV was lowest in the SAT group (8.83 ± 1.29). The NLR ratio was highest in the SAT group (2.84 ± 1.48 p < 0.01). The fT4/TSH ratio was highest in the Graves group (461.85 ± 536.2 p < 0.01).The AUC of ft3/ft4 ratio for estimating Graves' disease was 0.773, the specificity was 77.9%, the sensitivity was 66.2% (p < 0.01), and the cut-off value was 2.95. The AUC of the NLR ratio for the assessment of SAT was 0.742, the specificity was 80% and the sensitivity was 50% (p = 0.02). Conclusions: The ratio of fT3 to fT4, fT4/TSH ratio, MPV and NLR differ significantly between SAT and Graves' disease and can provide helpful information in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Thyroid hormones are essential for normal skeletal development and bone metabolism. Despite various studies, the effect of thyroid hormone on bone metabolism has not been clearly understood. We studied the bone formation markers (procollagen type 1 N-propeptide [P1NP] and osteocalcin [OC]) and bone resorption markers (C-terminal cross-linking telopeptide of type 1 collagen [CTX] and tartrate-resistant acid phosphatase [TRAP]) in patients with thyroid disorders and the effect of treatment on them. Furthermore, a study correlating these markers with thyroid-stimulating hormone (TSH) levels was done. Materials and Methods: This cross-sectional study recruited 60 cases (40 – hypothyroid and 20 – hyperthyroid) and 20 controls based on inclusion and exclusion criteria. To evaluate the effect of treatment, cases were further subdivided based on the duration of treatment received into 0-month (newly diagnosed), 1–6-month, and >6-month treatment subgroups. Both the cases and control underwent a thorough history, clinical examination, and detailed investigation based on a predesigned proforma. Results: In hyperthyroidism with 0-month treatment subgroup, both formation (OC, P1NP) and resorption (CTX) markers were significantly increased compared to control (P < 0.05), which became insignificant on treatment (1–6 months) with antithyroid medication despite low TSH value. Contrarily, in hypothyroidism, a statistically significant (P < 0.05) lower mean value of markers (OC, P1NP, and CTX) was observed only in the subgroup with levothyroxine supplementation. In hyperthyroidism, both the formation (OC and P1NP) and resorption markers (CTX and TRAP) showed a strong negative (P < 0.001) correlation with TSH, the strength of correlation decreased, and became insignificant on treatment. In hypothyroidism, only P1NP and CTX showed an overall significant positive (P < 0.05) correlation with TSH. Conclusion: Hyperthyroidism has high bone turnover markers, which showed early reversibility of markers on treatment with antithyroid medication despite low TSH, whereas in hypothyroidism, significantly lower mean value of markers is seen only in the subgroup with levothyroxine supplementation, probably owing to the suppressive effect of TSH. P1NP and CTX showed high sensitivity in both hypothyroidism and hyperthyroidism. The pattern of correlation between TSH and bone metabolism markers in hyperthyroidism suggests a direct negative effect of TSH on bone turnover, whereas in hypothyroidism, it either suggests TSH showing a positive correlation at a very high level which becomes negative as the TSH value decreases or TSH is not a dominant hormone regulating bone metabolism in hypothyroidism. [ABSTRACT FROM AUTHOR]

Adequate control of thyroid function is crucial for optimal pregnancy outcomes and neurodevelopment of the offspring, and testing for thyroid function is ideally performed using manufacturer- and gestation-specific reference ranges. While universal screening for thyroid dysfunction is not recommended, targeted case finding of women at risk of thyroid disease during pregnancy is advised. A number of controversies continue to fuel debate including: (i) the target range for thyroid stimulating hormone (TSH) in women with subfertility planning pregnancy, (ii) management of mild thyroid hypofunction before and during pregnancy, (iii) the treatment of thyroid peroxidase (TPO) antibody-positive euthyroid women with levothyroxine, (iv) the optimal choice of antithyroid treatment in women with hyperthyroidism. A significant body of evidence has accumulated in recent years, including large systematic reviews and meta-analyses of observational studies determining effects of thyroid dysfunction on pregnancy and fetal outcomes. In addition, outcomes from important randomised trials continue to inform current guidance on how to best care for women with thyroid dysfunction before and during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in patients taking levothyroxine for hypothyroidism and correlate it with biochemical thyroid function. Materials and Methods This was a retrospective cohort study of patients aged 18 years and older who were treated with levothyroxine. Exclusion criteria were pre-existing diagnosis of AF and use of amiodarone in the prior year. Patients were followed 2012 through 2019 and stratified into 4 groups based on mean thyroid-stimulating hormone (TSH) value or mean fT4 value in 2012. Primary outcome was incidence of AF. Rates of AF between groups were assessed via Poisson regression with control of underlying confounders. Results Of 21,035 patients, 1091 (5.2%) developed AF during follow-up. Thyroid-stimulating hormone at baseline was not significantly associated with incident AF. Higher fT4 levels at baseline were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio 1.22; 95% CI, 1.03-1.44) for the highest quartile versus the lowest quartile of fT4. Conclusions In hypothyroid patients treated with levothyroxine, higher circulating fT4 levels are associated with increased risk of incident AF. There is no association of serum TSH with risk of AF. In patients at risk for AF, consideration should be given to avoiding fT4 levels in the highest quartile. [ABSTRACT FROM AUTHOR]

We report a 31-year-old man with diarrhea and tachycardia. Diagnostic workup confirmed raised free thyroid hormones with unsuppressed thyroid stimulating hormone (TSH). Laboratory assay and medication interference were excluded. Consistent with a high glycoprotein hormone α-subunit (α-GSU), the α-GSU:TSH molar ratio was increased. However, anterior pituitary panel testing also confirmed an isolated, raised follicle stimulating hormone (FSH) (17.3 IU/L; reference range, 1.7-8.0). Therefore, interpretation of α-GSU was limited given the co-existent elevated FSH. There was no pituitary lesion on magnetic resonance imaging (MRI) and stimulated TSH was 232% of baseline levels following thyrotropin-releasing hormone (TRH) stimulation, making a diagnosis of TSH-oma less likely. Genetic analysis revealed no pathogenic variants in the thyroid hormone receptor β gene. Due to the persistently elevated FSH, a follow-up pituitary MRI was arranged, which identified a nasopharyngeal mass on the floor of the sphenoid sinus, raising the possibility of ectopic pituitary tissue. The patient underwent endoscopic resection of this lesion, with subsequent normalization of free T4, TSH, and FSH within a few weeks. Histology confirmed a plurihormonal pituitary adenoma with staining for TSH, growth hormone, luteinizing hormone, and FSH. This case highlights the biochemical and radiological challenges of diagnosing ectopic TSH-secreting pituitary tumors. [ABSTRACT FROM AUTHOR]

Objective: Basal metabolic rate (BMR) is an important factor in weight management and is influenced by fat‐free mass (FFM), fat mass (FM) and age. Current knowledge of the influence of hormonal levels on BMR is based on studies with small populations, studies that investigate exogenous administration and studies frequently lacking correction for body composition. Design: Cross‐sectional study. Patients: All men (n = 457) who were referred to our centre for a metabolic work‐up were eligible for inclusion. Median age was 47 (18–78) years and the vast majority had obesity (BMI ≥ 30 kg/m², 90.9%). Measurements: All men had a measurement of BMR, body composition and measurement of testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin‐like growth factor 1 (IGF‐1), thyroid‐stimulating hormone (TSH) and free thyroxine (fT4). Men with low, normal and/or high levels of each of these hormones were compared. The association between hormone levels and BMR was assessed through linear regression models. All analyses were controlled for FFM, FM and age. Results: In men with obesity, testosterone (total or free) was not associated with BMR. Linear regression analysis showed that DHEAS was positively associated with BMR in a sample of men with obesity and normal endogenous DHEAS levels, with the following equation: BMR (adjusted R² = 0.72): (BMR [kcal/d] = 513.402 + 18.940 × FFM [kg] + 9.507 × FM [kg] − 3.362 × age [years] + 0.307 × DHEAS [µg/dL]) (p < 0.01). TSH, fT4 and IGF‐1 were not associated with BMR. Conclusion: In men with obesity, endogenous DHEAS is positively associated with BMR. Testosterone, TSH, fT4 and IGF‐1 were not associated with BMR in men with obesity. Since we examined the specific population of men with obesity and only examined endogenous hormone levels, no extrapolation of results to other populations or the overall population can be made. [ABSTRACT FROM AUTHOR]

Background: Gestational Weight Gain (GWG) is an important indicator affecting pregnancy outcome, and thyroid hormones are also weight regulators. Researchers showed that thyroid hormones were correlated to prepregnancy Body Mass Index (BMI) and GWG. However, the normal ranges of thyroid parameters and GWG depend on the trimester of measurement. Therefore, we systematically reviewed the current knowledge on the association between thyroid function tests and prepregnancy BMI and GWG. Materials and Methods: This review was finally conducted on nine articles, while Google Scholar and databases such as Scopus, Medline, Cochrane Library, ISI Web of Science, Science Direct, and ProQuest were searched to find English articles from October 2022 to June 2023. Results: Thyroid-Stimulating Hormone (TSH) was positively correlated with prepregnancy BMI, while Free Thyroxine (FT4) was inversely correlated. TSH was positively related to weight gain and BMI in the first trimester, while the relationship was negative for FT4. Free Triiodothyronine (FT3) had a positive relationship with BMI in the first trimester (p = 0.004). Furthermore, TSH level was not associated with GWG in the second and third trimesters, while FT4 was inversely correlated with GWG. FT3 also increased with BMI in the second trimester and not in the third trimester (p < 0.001). Finally, there was a positive correlation between thyroid peroxidase autoantibodies values and prepregnancy BMI as well as maternal BMI, but the data were inconsistent. Conclusions: Determining the relationship between thyroid hormone levels and prepregnancy BMI and/or GWG may help researchers and clinicians manage weight gain and/or thyroid function in pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: We aim to investigate the predictive value of [99mTc] pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism (CH). Material and Methods: A retrospective analysis of [99mTc] pertechnetate thyroid scans performed for evaluation of CH at the Nuclear Medicine Unit of a hospital in Hong Kong between January 1, 2008, and December 31, 2018, was conducted. Scintigraphic findings and parameters at diagnosis, including thyroid stimulating hormone (TSH), free thyroxine (fT4), gender, and gestational age, were reviewed. The need for lifelong thyroxine replacement therapy was reviewed. Results: The study included 85 subjects, with 74 (87.1%) presenting with eutopic thyroid and 11 (12.9%) showing thyroid dysgenesis. Patients with scintigraphic evidence of thyroid dysgenesis required permanent thyroid hormone replacement therapy. Among the patients with eutopic thyroid, a higher TSH level was associated with the need for lifelong thyroid hormone replacement therapy (cutoff TSH value 18.72 mIU/L, sensitivity 77.3% and specificity 53.8%). Gender, gestational age, and fT4 did not show significant differences between the transient and permanent CH groups in patients with eutopic thyroid. Conclusion: Scintigraphic findings of thyroid dysgenesis indicate a high prevalence of permanent CH. In patients with eutopic thyroid, higher TSH levels predict the requirement for lifelong thyroid hormone replacement therapy. These results provide insights into the prediction of CH and aid in individualized treatment decisions for patients with CH. [ABSTRACT FROM AUTHOR]

Background: Altered thyroid function has been linked to insulin resistance (IR), but its relationship with the Metabolic Score for Insulin Resistance (METS-IR), a novel non-insulin-based index of IR, remains unclear. This study aimed to investigate the association between thyroid function status and METS-IR in a U.S. population. Methods: This cross-sectional study utilized data from 6,507 adults (aged ≥ 20 years) participating in the National Health and Nutrition Examination Survey from 2007 to 2012. Thyroid function status was categorized into five groups based on thyroid-stimulating hormone and free thyroxine levels. METS-IR was calculated from measures of fasting glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI). Multivariate regression analyzed the relationship between thyroid status and METS-IR after adjusting for potential confounders. Results: Higher thyroid-stimulating hormone levels were positively associated with METS-IR (β = 0.003, 95% CI 0.001–0.004, p = 0.021). Subclinical hypothyroidism in males and subclinical hyperthyroidism in females showed significant correlations with higher METS-IR. Thyroid peroxidase antibodies (TPO Ab) positivity strengthened the association between overt hypothyroidism and METS-IR. Conclusions: This study demonstrates significant associations between thyroid function status, particularly subclinical thyroid dysfunction, and insulin resistance as measured by METS-IR in a U.S. population. Thyroid status may serve as an early marker of insulin resistance risk. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions Trial Registration Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population‐based pregnancy‐specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population‐based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.A total of 800 healthy pregnant women aged 20–40 years in the Bhaktapur municipality were included. Population‐based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non‐pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.Median gestational age was 11 weeks. The reference interval was 0.05–3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89–15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody‐positive women. Compared with the current non‐pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.We found meaningful changes using population‐based pregnancy‐specific TSH and fT4 reference intervals and encourage further studies in other low‐ and middle‐income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.Clinical Trial Registration: U1111‐1183‐4093. [ABSTRACT FROM AUTHOR]

We report a case of a 60‐year‐old lady with metastatic follicular thyroid carcinoma (FTC) who was presented with thyrotoxicosis and heart failure symptoms after total thyroidectomy. Clinical features and investigations led to the diagnosis of functional metastatic FTC with concomitant thyrotoxicosis. Levothyroxine therapy was stopped, and she was treated with propylthiouracil (PTU) followed by serial radioiodine treatments (RAITs) with good control of thyrotoxicosis and metastases. Despite having a very high disease burden with metastatic FTC, she has been able to maintain her functional status thus far, 4.5 years after initial diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The main objective was to assess the therapeutic efficacy of selenium alone versus a combination of myo-inositol and selenium (MI + Se) in treating patients with autoimmune thyroiditis (AIT). The study aims to determine which treatment option is more effective in restoring euthyroid state, as indicated by changes in thyroid-stimulating hormone (TSH), T3, T4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) Methods: Google Scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies that reported outcomes of combined treatment (MI + Se) in restoring a euthyroid state, specifically comparing it with selenium-only (Se-only) treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined versus selenium-only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used for statistical analysis. Result: We pooled three studies, enrolling 151 participants in the MI + Se group and 137 participants in the Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD = −1.15, 95% CI: −1.60 to −0.69, P <.00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD = −0.51, 95% CI: −0.78 to −0.24, P =.0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD = −0.81, 95% CI: −0.44 to 0.09, P =.20), (SMD = 0.16, 95% CI: −0.09 to 0.42, P =.22), and (SMD = 0.30, 95% CI: −0.23 to 0.83, P =.26) respectively. Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with a non-significant reduction in TPOAB, T3, and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT. Plain Language Summary: Summary of Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis The study aimed to determine whether taking the supplementation therapy of myo-inositol and selenium (MI+Se) together is more effective than taking selenium alone for people suffering from autoimmune thyroiditis, a condition in which the immune system attacks the thyroid gland and often leads to hypothyroidism. Researchers reviewed relevant studies from Google Scholar and PubMed, focusing on randomized control trials (RCTs) and observational studies that compared the effects of selenium alone versus selenium plus myo-inositol. They analyzed changes in thyroid-related blood markers TSH, T3, T4, TPOAb, and TgAb levels) to assess effectiveness of the given therapy. The study included three RCTs with 288 participants that were assessed through the supplementation therapy of selenium alone and myo-inositol plus selenium (MI+Se). Findings suggest that the combination of selenium and myo-inositol significantly reduced TSH levels, which indicates thyroid activity and improvement in the condition, more than selenium alone. It also lowered TgAb levels, antibodies that attack the thyroid, more effectively than selenium alone. However, the two groups had no significant changes in other markers like TPOAb, T3, and T4. The results suggest that the combination treatment might be more effective in reducing harmful antibodies and improving thyroid function compared to selenium alone. This finding is particularly relevant for managing AIT and improving thyroid health, pointing to potentially better treatment strategies. Nevertheless, the study emphasizes the need for more extensive and longer-term research to confirm these benefits and fully understand the implications. This research highlights the promise of combining supplementation with selenium and myo-inositol as a more effective approach for people with autoimmune thyroiditis (AIT). This could lead to improved management and outcomes for this common thyroid condition. [ABSTRACT FROM AUTHOR]

Background: Thyroid stimulating hormone (TSH) has been proven to be closely associated with metabolic abnormalities, including obesity. The objective of this investigation was to scrutinize the intricate association between TSH concentration and obesity, within the adult population. The study focused on a comprehensive examination of the relationship, delving into specific adiposity parameters such as total percent fat (TPF), android percent fat (APF), and gynoid percent fat (GPF). Methods: This study included 809 participants aged 20 and above with normal TSH values from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Multivariable linear regression models examined the associations of TSH concentration with TPF, APF, and GPF. Subgroup analyses, stratified by sex, were performed using multivariable linear regression. Fitted smoothing curves and generalized additive models addressed non-linear relationships between TSH and TPF, APF, and GPF. Results: In fully adjusted models, a significant positive association was observed between TPF and TSH (β = 0.01, 95% CI: 0.00–0.02, p<0.05), while no such association was evident in APF and GPF. Upon sex stratification, females exhibited significant positive correlations between TSH and TPF, APF, and GPF (all p < 0.001), contrasting with males where no such correlations were found. Notably, a non-linear association was identified in males, specifically a U-shaped curve (inflection point: 32.6%) for TSH and APF. Conclusion: The study unveiled a statistically significant positive association between TSH and TPF in adults. Upon sex stratification, similar statistically significant relationships were observed between TSH and adiposity (TPF, APF, GPF) in females, while males exhibited a U-shaped non-linear relationship between TSH and APF. [ABSTRACT FROM AUTHOR]

Background: RNA-binding proteins (RBPs) modulate the synaptic proteome and are instrumental in maintaining synaptic homeostasis. Moreover, aberrant expression of an RBP in a disease state would have deleterious downstream effects on synaptic function. While many underlying mechanisms of synaptic dysfunction in Alzheimer's disease (AD) have been proposed, the contribution of RBPs has been relatively unexplored. Objective: To investigate alterations in RBP-messenger RNA (mRNA) interactions in AD, and its overall impact on the disease-related proteome. Methods: We first utilized RNA-immunoprecipitation to investigate interactions between RBP, DJ-1 (Parkinson's Disease protein 7) and target mRNAs in controls and AD. Surface Sensing of Translation – Proximity Ligation Assay (SUnSET-PLA) and western blotting additionally quantified alterations in mRNA translation and protein expression of DJ-1 targets. Finally, we utilized an unbiased bioinformatic approach that connects AD-related pathways to two RBPs, DJ-1 and FMRP (Fragile X messenger ribonucleoprotein 1). Results: We find that oligomeric DJ-1 in AD donor synapses were less dynamic in their ability to bind and unbind mRNA compared to synapses from cognitively unimpaired, neuropathologically-verified controls. Furthermore, we find that DJ-1 associates with the mRNA coding for FMRP, Fmr1, leading to its reduced synaptic expression in AD. Through the construction of protein-protein interaction networks, aberrant expression of DJ-1 and FMRP are predicted to lead to the upregulation of key AD-related pathways, such as thyroid hormone stimulating pathway, autophagy, and ubiquitin mediated proteolysis. Conclusions: DJ-1 and FMRP are novel targets that may restore established neurobiological mechanisms underlying AD. [ABSTRACT FROM AUTHOR]

Objective: There is a delicate interplay between thyroid hormones and thyrotropin (TSH) and metabolic homeostasis. However, the role of thyroid hormone sensitivity in metabolic health, particularly in relation to metabolic dysfunction-associated fatty liver disease (MAFLD) and associated complications such as elevated liver enzymes and free fatty acid (FFAs) has not been elucidated in euthyroid populations. Methods: A total of 3929 euthyroid adults from the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University were included in this study. Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI). Associations between thyroid hormones sensitivities and risk of MAFLD, MAFLD with elevated liver enzymes, MAFLD with elevated FFAs were assessed with logistic regression. Results: After adjustment for multiple risk factors, adjusted odds ratio (AOR) of the fourth versus the first TFQIFT4 quartile for MAFLD, MAFLD with elevated liver enzymes, and MAFLD with elevated FFAs were 1.778 (95% CI 1.378, 2.293), 1.466 (1.105, 1.945), and 1.936 (1.479, 2.534), respectively (all p<0.001). Per 1 SD in TFQIFT4, ORs increased 2.27 (95% CI 1.74, 2.97) for MAFLD, 2.05 (1.51, 2.78) for MAFLD with elevated liver enzymes, and 2.43 (1.82, 3.24) for MAFLD with elevated FFAs. The other sensitivity to thyroid hormones indices showed similar associations for MAFLD and MAFLD with elevated liver enzymes. Conclusions: These findings have important implications for understanding the role of thyroid hormone sensitivity in metabolic health, particularly in relation to MAFLD and associated complications such as elevated liver enzymes and FFAs. TFQIFT4, TFQIFT3, TSHI and TT4RI can be used as new indicators for predicting MAFLD and MAFLD with elevated liver enzymes. [ABSTRACT FROM AUTHOR]

The study examined effects of thyroid manipulation with propylthiouracil (PTU) on the metabolic adaptability of transitional dairy cows to early lactation. The study included 30 primiparous Holstein-Friesian cows, which were divided into two groups: PTU+ (n = 15; received orally 4 mg/kg PTU during 20 days before expected calving) and PTU− (n = 15; did not receive orally PTU). Blood was sampled from each cow consecutively from − 20, − 17, − 13, − 5, − 4, − 3, − 2, and − 1 days before the expected term of calving, calving day (0), and + 1, + 2, + 3, + 4, + 5, + 10, + 15, + 30 and + 60 days after the calving to measure thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), insulin, glucose, beta-hydroxybutyrate (BHB), bilirubin, total protein and albumin concentrations. Liver samples were biopsied at −7 ± 2 and +7 day relative to calving from both groups of cows to determine deiodinase (DIO) expressions and fat and glycogen content. Additionally, milk yield was monitored during the first 60 days of lactation. PTU successfully induced thyroid suppression by significantly reducing T3 and T4 concentrations and hepatic DIO1 expressions and caused PTU+ cows to have significantly higher insulin and glucose concentration in the precalving period. After calving, PTU+ cows had higher insulin and glucose concentration, liver glycogen content and overall milk production, lower BHB concentration, BCS loss, and liver fat deposits. Accordingly, cows treated with PTU have a more favourable energy balance and metabolic adaptation to early lactation. HIGHLIGHTS: PTU suppressed thyroid function before parturition in dairy cattle through the effect on T3 and T4 synthesis and DIO1 enzyme expression in liver. After parturition increase in the T3 and T4 concentration accompanied by changes in insulin, glucose, and BHB indicate more favourable energy status. Positive impact of PTU treatment appears in the period when control of energy metabolism is key factor for preserving the health and productivity [ABSTRACT FROM AUTHOR]

Thyroidectomy has been post-operatively managed by hormone replacement therapy in order to satisfy the reference ranges of thyroid stimulating hormone (TSH) and thyroxine (T4) levels. While medication and standardized reference ranges have proven to be effective, many patients continue to report unintentional weight gain despite adequate amounts of treatment and levels of TSH and T4. Physicians, over the years, have become complacent to these "normal" ranges, and have ignored the metabolic consequences that are affecting thyroidectomy patients. This paper aims to redefine the approach to post-thyroidectomy clinical care by challenging the current standardized hormonal range values, exploring the gaps in thyroid hormone conversion, investigating the metabolic pathways of T3, considering the influence of inflammatory markers, and proposing the future for patient-centered management. [ABSTRACT FROM AUTHOR]

Background: Although seasonal changes were suggested to be among the many factors that affect thyroid functions, this issue is still controversial. In this study, we aimed to investigate the possible relationship between seasonal changes and thyroid function. Methods: We retrospectively scanned all thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) values checked in our hospital between 2019 and 2023. Using the big data approach, we examined the relationship between TSH and thyroid hormones and monthly and seasonal recorded climatic changes, particularly the duration of daylight and temperature. Results: A total of 195,534 serum samples were analyzed for TSH, 195,491 for FT3, and 195,487 for FT4. There were significant differences in the values of TSH, FT3, and FT4 between months (p = 0.001 for TSH, p < 0.001 for FT3 and FT4). The months with the highest levels of TSH, FT3, and FT4 values were January, December, and June, while the months with the lowest levels were July, May, and March-April, respectively. The differences between the maximum and minimum median values were 14.5% for TSH, 4.9% for FT3, and 5.7% for FT4. From January to August, as the temperature rose, there was a decrease in TSH values. Between September and December, as the temperature decreased, an increase in TSH was observed. Conclusions: This study revealed that TSH, FT3, and FT4 show seasonal variability and change in temperature is an important factor that plays role in this variability. It would be appropriate to take these changes into consideration when interpreting thyroid function tests. [ABSTRACT FROM AUTHOR]

Background and purpose: Thyroid dysfunction can frequently be discovered in breast cancer patients during longterm follow-up after receiving post-operative radiation therapy (PORT). This study aimed to compare serum levels of thyroid transcription factors (TTFs) TTF-1 and paired box 8 (PAX-8) before and after PORT in breast cancer patients, combined with the results of serological thyroid indicators tests, and to analyze the relationship between the changes in serum levels of these two kinds of TTFs and thyroid dysfunction after breast cancer PORT. Methods: Female breast cancer patients without thyroid disease records who received PORT in Department of Radiation Oncology, Shanghai Ninth People’s Hospital Huangpu Branch, Shanghai Jiao Tong University School of Medicine from Jan. 2022 to Jun. 2022 were prospectively selected, and were divided into two groups according to being with or without supraclavicular radiation field. All the patients had given informed consent before joining the study. The study design was approved by the ethic committee of our hospital (Ethic Approval No. 2021-KY-2). Serum levels of TTF-1 and PAX8, serological thyroid indicators ［triiodothyronine (T3), tetraiodothyronine (T4), free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab)］ were recorded before PORT, at the end of PORT, 6, 12 and 24 months after the end of PORT, respectively. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was followed for this study. Results: Eighty patients were enrolled in this study (40 in each group). A total of 19 patients who had hypothyroidism were divided in two groups, 15 in supraclavicular field group (SC group) and 4 in non-supraclavicular field group (NSC group), respectively (P=0.004). Levels of TTF-1 ［5.70 (5.11, 7.13) vs 6.68 (5.15, 7.57), P=0.296］ and PAX-8 (5.26±1.01 vs 5.66±1.37, P=0.149) did not show statistically significant deference between two groups before PORT. In SC group, levels of TTF-1 and PAX-8 gradually rose in 12 months after the end of PORT. In NCS group, levels of TTF1 and PAX-8 did not change significantly during 24 months after the end of PORT. Test results of serum TTF-1 between two groups were statistically different at 6 months ［6.99 (4.73, 13.94) vs 5.79 (5.01, 6.28), P=0.049］, 12 months ［7.65 (5.02, 17.85) vs 5.43 (4.52, 6.22), P=0.005］ after the end of PORT, while test results of serum PAX-8 between two groups were statistically different at 12 months ［6.79 (4.86, 14.30) vs 5.81 (4.70,7.25), P=0.042］ after the end of PORT. The median values of TTF-1 and PAX-8 test results at 12 months after the end of PORT in SC group which were both significantly higher compared with NSC group were selected as the referent thresholds. Patients in SC group whose test results were higher than referent thresholds were defined as TTF-1/PAX8 elevating subgroups, and patients whose test results under the threshold defined as TTF-1/PAX-8 normal subgroups. The incidences of hypothyroidism were higher in elevation subgroups than in normal subgroups (65.0% vs 10.0%, 60.0% vs 15.0%, respectively, P=0.001, P=0.008, respectively). Positive correlations were observed between the elevation of TTF-1/PAX-8 at 12 months after the end of PORT and hypothyroidism after breast cancer supraclavicular field radiation (OR=9.702, 3.930, and P=0.020, 0.046, respectively) according to multivariate analysis. Conclusion: Thyroid dysfunction after breast cancer PORT was mainly manifested with hypothyroidism; supraclavicular field radiation may significantly increase the incidence of hypothyroidism; serum levels of TTF-1 and PAX-8 elevated obviously in breast cancer PORT patients who had hypothyroidism after receiving supraclavicular field radiation. [ABSTRACT FROM AUTHOR]

Chronic, mildly insufficient sleep is associated with increased cardiometabolic risk, but whether the regulation of thyroid hormones and related growth factors are mechanisms of this association is unclear. We investigated whether 6 wk of mild sleep restriction (SR) alters levels of free thyroxine (FT4), thyroid stimulating hormone (TSH), and fibroblast growth factor-21 (FGF-21), a modulator of FT4, in adults with adequate habitual sleep (AS; 7–9 h/night). Healthy adults participated in one of two randomized, crossover studies with identical 6-wk intervention phases: AS and SR (1.5 h/night < AS). Fasted blood samples were collected at baseline and endpoint of each phase. Outcomes were concentrations of FT4, TSH, and FGF-21 (women only). Linear mixed models tested the effects of SR vs AS on the outcomes, adjusting for baseline levels, week, sex, and sex-by-condition interaction. Thirty participants (20 women; 73% racial/ethnic minority; age 21–64 y [ M ± SD = 36.2 ± 12.8 y]) were included. In the full sample, no effects of SR on FT4 (β±SE = 0.02 ± 0.04, p = 0.654) or TSH (β±SE = −0.02 ± 0.04, p = 0.650) were observed; however, there were sex-by-condition interactions for both FT4 (p-interaction = 0.056) and TSH (p-interaction = 0.049). In sex-stratified analyses, TSH was reduced in SR vs. AS in women (β±SE = −0.11 ± 0.04, p = 0.011, Cohen's f 2 = 0.55) but not men (β±SE = 0.09 ± 0.08, p = 0.261). Among women (n = 17), FGF-21 was not significantly different between conditions (β±SE = 8.51 ± 17.70, p = 0.638). Prolonged mild SR reduces TSH in women, whereas FT4 and FGF-21 remain unaffected compared with AS. If sustained, disruptions to the thyrotropic axis in women may contribute to their more pronounced cardiometabolic risk in response to SR compared with men. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment. Methods: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile). Results: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21–2.36, p <.002) and low birth-weight (RR 1.72, 95% CI 1.13–2.62, p <.02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78–4.14, p =.16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93–1.65, p =.14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight. Conclusions: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery. [ABSTRACT FROM AUTHOR]

A 2‐year‐old cat was referred for suspected generalised seizure activity and reclusive behaviour, with a history of non‐resolving facial abscess. Magnetic resonance imaging (MRI) revealed a contrast enhancing lesion occupying the left calvarium and adjacent peripheral tissues. The intracranial lesion was causing significant mass effect, with oedema and transtentorial herniation. Nocardia nova was isolated from the lesion and identified by DNA sequencing. Treatment consisted of debridement via craniotomy and ventral bulla osteotomy, and combination antibiotic therapy with clarithromycin, amoxycillin and trimethoprim‐sulfonamide (sulfadoxine parenterally, then sulfadiazine orally). After several weeks of antibiotic therapy, the cat developed weakness, bicavitary effusion, myxoedema, non‐regenerative anaemia and azotaemia. Total thyroxine (TT4) was below the detectable limit and canine thyroid stimulating hormone (cTSH) assay was markedly elevated at 7.53 ng/mL (reference interval 0.15–0.3 ng/mL). Discontinuation of sulfonamides and administration of levothyroxine resulted in resolution of clinical signs. The cat was subsequently able to discontinue levothyroxine, with recovery of euthyroid state. To the authors' knowledge, this is the first report of clinical hypothyroidism in a cat treated with sulfonamide antibiotics and may influence antimicrobial selection and monitoring during therapy. This report also described the management of an atypical presentation of nocardiosis with intracranial extension. [ABSTRACT FROM AUTHOR]

Objective: To evaluate common endocrine responses of the patients hospitalized with COVID 19 Infection at Hayatabad Medical Complex Peshawar. Methods: This was a prospective cross sectional study which included 66 patients having age 18 years and above with positive COVID 19 PCR, who were reported in COVID OPD for hospitalization in Isolation Units and Intensive Care Unit of Hayatabad Medical Complex Peshawar between June 15, 2020 to December 15, 2020. Patients with preexisting kidney or liver disease, those who had used steroids before enrollment and pregnant and lactating females were excluded. Patients were clinically assessed, and investigations were performed which included C- reactive protein (CRP), complete blood count (CBC), Covid PCR, thyroid function tests (TFTs), and cortisol levels. Results: The mean age of the study participants was 54.38±15.81 years. At baseline, 75%, 17%, and 3% patients had mild, moderate, and severe COVID-19, respectively. Thyroid Stimulating Hormones (TSH) levels were suppressed in 25% of patients, more significant in those with more severe infection. Raised cortisol levels were found in 94% of patients at admission without any prior use of steroids. As per clinical outcome is concerned, mortality occurred in 20% of patients while 80% recovered healthy. Conclusion: The findings of the results suggest an appropriate response of endocrine system to covid infection. The amount of cortisol and TSH changes were also associated with the severity of sickness. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the difference in blood (serum/plasma) thyroid hormone (TH) levels, including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3), in bipolar disorder (BD) during different mood episodes (depression and mania) compared with healthy control (HC) and between manic episodes (BD-M) and depressive episodes (BD-D). Methods: As of September 1, 2024, the electronic databases PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, and Clinical Trials. Gov were systematically searched with no language limitations. Standardized mean differences (SMD) with 95% confidence interval (CI) were summarized using a random effects model. The chi-squared-based Q test and the I2 test assessed the size of heterogeneity. Results: The 21 studies included a total of 3696 participants, Of the 2942 BD patients, 1583 were in depressive episodes 1359 were in manic episodes. The status of measuring blood TH levels included 2 studies in plasma and 19 in serum. Combined with the results of the sensitivity analyses, we obtained the following relatively reliable results: serum T3 (SMD: -0.63, 95%CI: -1.09 to -0.17) and FT3 (SMD: -0.42, 95%CI: -0.83 to -0.00) levels decreased significantly in BD-D compared to HC; serum T3 (SMD: -0.91, 95%CI: -1.49 to -0.32) levels decreased significantly and serum FT4 (SMD: 0.37, 95%CI: 0.14 to 0.60) levels increased significantly in BD-M than in HC; serum T3 (SMD: 0.87, 95%CI: 0.24 to 1.49) and FT3 (SMD: 0.27, 95%CI: 0.13 to 0.42) levels demonstrated a significant elevation in BD-M compared to BD-D. In the group of euthyroidism, apart from serum FT4 (SMD: 0.21, 95%CI: -0.15 to 0.58) levels showed no significant difference between BD-M and HC, other results above remained consistent. Conclusion: Serum T3 and FT3 levels decreased significantly in BD-D compared to HC. Serum T3 levels decreased significantly and serum FT4 levels increased significantly in BD-M compared to HC. Serum T3 and FT3 levels increased significantly in BD-M than in BD-D. The temporality of changes in TH levels and BD progression demands further longitudinal studies to illustrate. Trial registration: Number and date of registration for prospectively registered trials No. CRD42022378530. [ABSTRACT FROM AUTHOR]

Background: Moderate‐to‐severe anxiety symptoms are severe and common in patients with major depressive disorder (MDD) and have a significant impact on MDD patients and their families. The main objective of this study was to develop a risk prediction model for moderate‐to‐severe anxiety in MDD patients to make the detection more accurate and effective. Methods: We conducted a cross‐sectional survey and tested biochemical indicators in 1718 first‐episode and drug naïve (FEDN) patients with MDD. Using machine learning, we developed a risk prediction model for moderate‐to‐severe anxiety in these FEDN patients with MDD. Results: Four predictors were identified from a total of 21 variables studied by least absolute shrinkage and selection operator (LASSO) regression analysis, namely psychotic symptoms, suicide attempts, thyroid stimulating hormone (TSH), and Hamilton Depression Scale (HAMD) total score. The model built from the four predictors showed good predictive power, with an area under the receiver operating characteristic (ROC) curve of 0.903 for the training set and 0.896 for the validation set. The decision curve analysis (DCA) curve indicated that the nomogram could be applied to clinical practice if the risk thresholds were between 13% and 40%. In the external validation, the risk threshold was between 14% and 40%. Conclusion: The inclusion of psychotic symptoms, suicide attempts, TSH, and HAMD in the risk nomogram may improve its utility in identifying patients with MDD at risk of moderate‐to‐severe anxiety. It may be helpful in clinical decision‐making or for conferring with patients, especially in risk‐based interventions. [ABSTRACT FROM AUTHOR]

Thyroid gland diseases remain clinical challenges due to the lack of reliable in vitro models to examine molecular pathways of thyrocytes development, maturation, and functional maintenance. This study aimed to develop in vitro thyrocytes model using a stem cell culture, P19 embryonal carcinoma which requires no feeder layer, differentiation into mature and functional thyrocytes that allow molecular and genetic manipulation for studying thyroid diseases. The procedure utilizes Activin A and thyroid stimulating hormone (TSH) to first induce embryoid body endoderm formation enriched in thyrocyte progenitors. Following dissociating embryoid bodies, thyrocyte progenitors are plated in Matrigel as monolayer cultures that allows thyrocyte progenitors mature to functional thyrocytes. These thyrocytes further maturate to form follicle-like structures expressing and accumulating thyroglobulin that can be secreted into the medium upon TSH stimulation. Thyrocyte differentiation-maturation process is monitored by the expression of essential transcriptional factors and thyrocyte-specific functional genes. Further, the applicability of this system is validated by introducing a siRNA control. Following molecular manipulation, the system can still be guided to differentiate into mature and functional thyrocytes. This system spans a time frame of 14 days, suitable for detailed molecular studies to dissect pathways and molecular players in thyrocytes development and functional maintenance. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder marked by chronic inflammation of the thyroid gland, predominantly affecting children and adolescents. In a previous study, we developed a "maximal" mathematical model of thyroid physiology to simulate the complex interactions within the thyroid gland. The present research introduces an enhanced version of the "maximal" model, integrating the pathophysiological impacts of HT. It specifically models the adverse effects of thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (TPOAb and TgAb) on TPO, Tg, sodium iodide symporter (NIS), albeit indirectly, and thyroid volume. Additionally, we present a new "minimal" model offering a streamlined interpretation of thyroid physiology and pathophysiology, designed for faster computational analysis while maintaining essential physiological interactions. Both models were fitted against longitudinal clinical data from patients with HT, assessing the concentrations of Thyroid Stimulating Hormone (TSH), Thyroxine (T4), and thyroid volume over 36 months, in both untreated patients and those receiving levothyroxine (LT4) treatment. The adaptation of the models to data shows that both of them accurately reproduce the available observed clinical outcomes, with the "maximal" model providing more detailed physiological insights but requiring extensive data and longer computation times. In contrast, the "minimal" model, despite exhibiting less realistic TSH oscillations, offers rapid parameter estimation and may be more feasible in clinical settings. These models hold significant potential as tools for detailed study and management of HT, enabling simulations of disease progression and therapeutic responses, thus paving the way for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusions and Clinical Relevance Knowledge about primary hypoadrenocorticism coexisting with immune‐mediated thyroiditis (Schmidt's syndrome) in dogs is limited.To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment.Sixty‐six client‐owned dogs.Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine.Thirty‐eight dogs were assessed before and 28 during treatment. Follow‐up data were available for 24/38 and 17/28 dogs, with median follow‐up duration of 3.8 years (range, <1.0‐8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow‐up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7‐15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6‐10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies.Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is a chronic, disabling mental illness with a high disease burden and is often comorbid with metabolic syndrome (MetS). The aim of this study was to determine the prevalence of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and to explore predictive factors affecting the development and severity of MetS. Methods: A total of 274 patients with SCZ who met the inclusion criteria were enrolled in this study, and their demographic data and general clinical information were collected. Concurrently, patients were assessed for psychopathology, illness severity, and antipsychotic drug–related adverse effects. Results: The prevalence of MetS in the target population was 35.77%, and the MetS subtype of abdominal obesity + high triglycerides + low level of high-density lipoprotein cholesterol accounted for the majority of patients in the MetS subgroup. Binary logistic regression showed that body mass index (BMI), uric acid (UA), thyroid-stimulating hormone, and QT-c interval could significantly and positively predict the development of MetS. Multiple linear regression showed that olanzapine concentration, BMI, and UA could significantly and positively predict higher MetS scores. Conclusion: This study reports the clinical patterns of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and identifies the correlations influencing the development and severity of MetS. These findings could potentially be applied toward the prevention of and intervention in MetS. [ABSTRACT FROM AUTHOR]

Background: Iron is an essential element for thyroid function. However, no study focuses on the association between iron and thyroid in individuals with obesity. Our research aimed to investigate the iron status in relation to baseline thyroid hormone levels and after laparoscopic sleeve gastrectomy (LSG). Methods: A total of 216 subjects with obesity were enrolled and divided into low and high iron groups depending on the median value. The association between iron and thyroid hormone was analyzed and compared before and after LSG at the 6-month follow-up in patients who underwent LSG. Results: 1) In all, Total Triiodothyronine (TT3) was significantly higher in high iron than low iron group (P = 0.008). TT3 and thyroid stimulating hormone (TSH) were significantly higher in high iron than low iron group (1.92 ± 0.61 vs. 1.69 ± 0.28 nmol/l, P = 0.029; 2.93 ± 1.66 vs. 1.88 ± 1.03 mU/l, P = 0.002) in females while not in males (all P > 0.05). 2) Iron was significantly positively associated with free triiodothyronine (FT3), free thyroxine (FT4), TT3 and TSH (all P < 0.05). Adjusted for body mass index (BMI), total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and homeostatic model assessment of insulin resistance (HOMA-IR), FT3, FT4 and TSH were still significantly associated with iron (all P < 0.05). 3). Regression analysis showed that iron was significantly associated with FT4 (β = 0.338, P = 0.038). 3) LSG led to decreased FT3, FT3, TT3, total thyroxine (TT4) and TSH at 6 months follow-up (all P < 0.05). Changed FT4 was significantly associated with changed iron (r = 0.520, P = 0.009). Subjects with iron decreased had more significant decreased TT4 than subjects without iron decreased (P = 0.021). Conclusion: Serum iron overload is significantly associated with impaired thyroid function in subjects with obesity. LSG led to improved thyroid function which is associated with a change in iron. Trial Registration: NCT04548232 registration date is on October 9, 2022, registered in https://register.clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Objective: The utilization of radioactive iodine‐131I (RAI) has long been established as a cost‐effective and conventional treatment for managing Graves' disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD. Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2‐h/6‐h/24‐h RAIU) prior to RAI treatment, the highest RAIU (RAIUmax), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established. Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p = 0.005), thyroid volume (p = 0.001), thyroid‐stimulating hormone (TSH, p = 0.042), ratio of RAIU at 6 h to 24 h (6‐h/24‐h RAIU, p = 0.048), total 131I activity (p = 0.026), and 131I activity per gram of thyroid tissue (p = 0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692–0.846), indicating that the model has good discriminatory ability. Conclusion: Calculated‐dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD. [ABSTRACT FROM AUTHOR]

Frequently, the serum concentrations of TSH (s-TSH) and free thyroxine (s-FT4) are interpreted together when a physician considers the patient's thyroid status. Then, each measurement is compared with its univariate reference interval. However, a pair of s-TSH and s-FT4 may be more appropriately assessed if compared with a bivariate reference interval. We constructed a bivariate reference interval for s-TSH and s-FT4 from their measurements in 495 healthy blood donors. After Box-Cox transformation, we estimated the Mahalanobis distances from each pair of s-TSH and s-FT4 to the center of the bivariate distribution. The 95 percentile in the distribution of the Mahalanobis distances was defined as the limit of the bivariate reference interval. Univariate reference intervals comprising the central 95% (2.5–97.5 percentile) and 97.5% (1.25–98.75 percentile) of reference values were estimated from the same data. Normal thyroid function was defined as both s-TSH and s-FT4 within their respective univariate reference intervals, or as a Mahalanobis distance within the 95% bivariate reference interval. In 177,514 specimens from adult individuals in out-patient care, 76.6% were classified as bivariate normal. The corresponding figures for the 95% and 97.5% univariate reference intervals were 68.9% and 76.2%, respectively. The kappa statistics for classification agreement between the bivariate 95% reference interval and the 95% and 97.5% univariate reference intervals were 0.790 and 0.881, respectively. We thought the bivariate reference interval to be clinically most accurate but were unable to prove it. [ABSTRACT FROM AUTHOR]

Biological variation is a relevant component of diagnostic uncertainty. In addition to within-subject and between-subject variation, preanalytical variation also includes components that contribute to biological variability. Among these, daily recurring, i.e., diurnal physiological variation is of particular importance, as it contains both a random and a non-random component if the exact time of blood collection is not known. We introduce four time-dependent characteristics (TDC) of diurnal variations for measurands to assess the relevance and extent of time dependence on the evaluation of laboratory results. TDC address (i) a threshold for considering diurnality, (ii) the expected relative changes per time unit, (iii) the permissible time interval between two blood collections at different daytimes within which the expected time dependence does not exceed a defined analytical uncertainty, and (iv) a rhythm-expanded reference change value. TDC and their importance will be exemplified by the measurands aspartate aminotransferase, creatine kinase, glucose, thyroid stimulating hormone, and total bilirubin. TDCs are calculated for four time slots that reflect known blood collection schedules, i.e., 07:00–09:00, 08:00–12:00, 06:00–18:00, and 00:00–24:00. The amplitude and the temporal location of the acrophase are major determinates impacting the diagnostic uncertainty and thus the medical interpretation, especially within the typical blood collection time from 07:00 to 09:00. We propose to check measurands for the existence of diurnal variations and, if applicable, to specify their time-dependent characteristics as outlined in our concept. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAEs. The study prospectively included 43 patients with metastatic disease scheduled for anti-PD-1/ L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta, and IL-17A were measured prior to ICI and during the endocrine-irAEs. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the non-irAE group (P < 0.05), whereas IL-1beta and IL-17A levels did not differ (P > 0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (P > 0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r = 0.706, P = 0.01) and negatively with baseline total testosterone level of men (r = 0.509, P = 0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Identifying physiological changes that occur in response to workload demands can help to elucidate athlete management and recovery strategies. The purpose of this study was to compare the physical and physiological demands between men and women throughout the course of a collegiate soccer season. Men (N 5 23) and women (N 5 26) soccer players participated in blood draws before preseason (T1) and every 4 weeks thereafter (T2-T4). Workload was determined at all practices and games via heart rate and global positioning satellite monitoring systems. Repeated measures multivariate analysis of variance and linear mixed models were used to assess workload and biomarker responses throughout the season (p, 0.05). Both teams experienced the highest workloads during the first 4 weeks of the season (p, 0.05), which was followed by several biomarker perturbations. Sex-by-Time interactions were observed for total cortisol, growth hormone, insulin-like growth factor-1, thyroxine, thyroid-stimulating hormone, vitamin D, and omega 3 fatty acid index (p, 0.05). Additional Sex effects were observed for free and total testosterone, estrogen, prolactin, sex-hormone binding globulin, creatine kinase, and iron levels (p, 0.05). Women soccer players experienced further Time effects for free cortisol, iron, ferritin, and percent transferrin saturation (p, 0.05). Male soccer players experienced additional Time effects for total testosterone, estrogen, creatine kinase, interleukin-6, triiodothyronine, and ferritin (p, 0.05). Despite similar patterns of change in workloads, differential fluctuations in physiological markers were observed between the sexes. Understanding sex differences in response to comparable workloads may enhance exercise prescriptions for better athlete management plans. Additional strategies to increase iron may be warranted in female athletes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the epidemiological, clinical, laboratory, and radiological characteristics of children diagnosed with Hashimoto’s thyroiditis and to present the experiences of a referral center. Materials and Methods: This study included 200 pediatric patients diagnosed with Hashimoto’s thyroiditis between January 2020 and May 2024 at a single center. The data were extracted and compiled from the participants’ medical records, including clinical information, physical examination findings, laboratory test results, and radiological imaging. Results: Mean age of the study population was 11.3 ± 3.2 years at diagnosis, with a female predominance. At the time of clinical presentation, 8.5% of the study participants were 6 years of age or younger. The majority of patients, comprising 39.5% of the cohort, exhibited euthyroid thyroid function. Additionally, 33.5% of the patients were classified as having subclinical hypothyroidism, 22% demonstrated overt hypothyroidism, and 5% presented with hyperthyroidism. Approximately one-third of the study participants were referred for further evaluation due to the identification of abnormal thyroid function test results during routine screening examinations. 48% of the patients had a documented family history of thyroid disease. At diagnosis, 39.5% were prepubertal. The rate of overt hypothyroidism was higher in prepubertal patients compared to pubertal patients (41.8% vs. 9.1%, P < .005). Mean gland volume SDS was 2.61 ± 3.69, and 45.5% had goiter. Thyroid nodular lesions were identified in 5.5% of the study participants. Fine-needle aspiration biopsy was performed on five patients, revealing benign findings in three cases and atypia of undetermined significance in the remaining two cases. Conclusion: Patints with subclinical hypothyroidism who have a baseline TSH level exceeding 8.5 mIU/L at initial presentation and do not receive treatment are likely to progress to overt hypothyroidism during subsequent follow-up. Prepubertal cases were more frequently observed compared to previous reports, and the course of hypothyroidism was more severe in prepubertal patients. These findings suggest a potential shift towards earlier onset of autoimmunity in children. Further studies are warranted to substantiate this observation. [ABSTRACT FROM AUTHOR]