Thyrotropin Research Articles

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

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

Gonadotropin releasing hormone - gonadotropes interactions revealed by pituitary single-cell transcriptomics in zebrafish.

Gonadotropin-releasing hormone (GnRH) governs reproduction by regulating pituitary gonadotropins. Unlike most vertebrates, gnrh-/- zebrafish are fertile. To elucidate the role of the hypophysiotropic-Gnrh3 and other mechanisms regulating pituitary gonadotropes, we profiled the gene expression of all individual pituitary cells of wild-type and gnrh3-/- adult female zebrafish. The single-cell RNA-Seq showed that Lh and Fsh gonadotropes express the two gonadotropin beta subunits with a ratio of 140:1 (lhb:fshb) and 4:1 (fshb:lhb), respectively. Lh gonadotropes predominantly express genes encoding receptors for Gnrh (gnrhr2), thyroid hormone, estrogen, and steroidogenic factor 1 (SF1). No Gnrh receptor transcript was enriched in Fsh gonadotropes. Instead, cholecystokinin receptor-b and galanin receptor-1b transcripts were enriched in these cells. The loss of Gnrh3 gene in gnrh3-/- zebrafish resulted in downregulation of fshb in Lh gonadotropes and upregulation of pituitary hormones like thyroid-stimulating hormone, growth hormone, prolactin and proopiomelanocortin-a. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+, lhb+ and fshb+/lhb+ cells. Our studies suggest that Gnrh3 directly acts on Lh gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression in both gonadotropes, most likely via a non-Gnrh receptor route. Altogether, while Lh secretion and synthesis are likely regulated in a Gnrh-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary. Moreover, the co-expression of lhb and fshb in both gonadotropes provides a possible explanation as to why gnrh3-/- zebrafish are fertile.

A Neglected Point: Frailty in Older Adults with Differentiated Thyroid Cancer.

This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty. This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE). The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05). Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Obesity-related subclinical hypothyroidism in childhood: Elevated triglycerides but not basal metabolicrate.

Studies on the associations between obesity-related subclinical hypothyroidism with basal metabolic rate and risk factors of cardiovascular disease in children and adolescents are scarce. Retrospective cohort study of children with obesity (n = 294) from the Uppsala Longitudinal Study of Childhood Obesity cohort. Differences in basal metabolic rate quantified by indirect calorimetry, and the cardiovascular risk factors; body mass index, blood lipids, fasting and 2 h oral glucose tolerance test glucose, glycated haemoglobin and insulin resistance, between subjects with and without subclinical hypothyroidism were investigated. The associations of baseline thyroid stimulating hormone (TSH) and ΔTSH with change in cardiovascular risk factors over time were assessed. Subjects with subclinical hypothyroidism had elevated triacylglycerides but no alterations in basal metabolic rate or other measured cardiovascular risk factors. ΔTSH was positively associated with Δtriacylglycerides, Δtotal-cholesterol and ΔLDL-cholesterol, independently of age, sex, Δbody mass index and ΔT4. In the subclinical hypothyroidism group, 92% of individuals normalised their TSH 0.9-2.9 years later. Children with obesity and subclinical hypothyroidism did not have an altered basal metabolic rate but elevated triacylglycerides. During the follow-up period, TSH changed in parallel with several blood lipids. Elevated TSH often normalised without pharmaceutical intervention within 3 years. The present study found that subclinical hypothyroidism in paediatric obesity is related to elevated triglycerides. The present study found that subclinical hypothyroidism is not associated to basal metabolic rate in paediatric obesity. TSH change over time correlated with the change in triglycerides and LDL and total cholesterol. Among subjects with subclinical hypothyroidism at baseline 92% normalised without pharmaceutical intervention within 3 years. This research adds to the knowledge of the longitudinal, natural course of elevated TSH in paediatric obesity which is expected to help to make informed decisions regarding follow-up and evaluation of this patient group.

Polycystic Ovary Morphology, Subclinical Hypothyroidism, and the Cutoff Value of Thyroid-Stimulating Hormone, a Population-Based Study.

Although numerous studies have explored the link between polycystic ovary syndrome (PCOS) and thyroid dysfunction, the relationship between polycystic ovary morphology (PCOM) and thyroid issues remains unclear. This study aimed to examine the association between PCOM and subclinical hypothyroidism (SCH) as well as the threshold for thyroid-stimulating hormone (TSH). Data were drawn from the Iranian PCOS prevalence study and the Khuzestan PCOS prevalence study. Eligible participants were divided into two groups: those with PCOM (n = 120) and a control group (n = 630). A logistic regression model was employed to assess the impact of PCOM on SCH, with odds ratios and 95% confidence intervals calculated. Additionally, a quantile regression model was used to evaluate the effect of PCOS on TSH levels. The results indicated no significant association between PCOM and SCH (adjusted OR: 1.38, 95% CI: 0.80-2.37; p = 0.243). Furthermore, after adjusting for confounding factors such as age, body mass index (BMI), and number of pregnancies, no significant differences were found in TSH levels between the PCOM and control groups. The prevalence of SCH and the TSH threshold were similar in both groups. Further comprehensive population-based studies with detailed thyroid evaluations are recommended.

The role of external-beam radiotherapy for differentiated thyroid cancer.

The treatment options for differentiated thyroid cancer (DTC) are surgery, thyroid stimulating hormone suppression, radioactive iodine, and multitargeted tyrosine kinase inhibitors. The role of external-beam radiotherapy (EBRT) for DTC is controversial because of the lack of randomized controlled trials, but prospective single-arm studies and propensity score matching analyses have shown its efficacy and safety. This review discusses the role of EBRT after resection of gross disease, when there is a high risk of locoregional failure, as well as its role for locoregionally gross recurrent and unresectable disease. As in other tumor sites, EBRT has an important role in the palliative management and local control of patients with metastatic DTC, especially with bone and brain metastases.

Clinicopathological and molecular markers for the identification of Hashimoto’s thyroiditis as a possible predisposing and prognostic factor of papillary thyroid carcinoma

Background: The papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, while Hashimoto’s thyroiditis (HT) is the most common inflam¬matory thyroid disease. The coincidental coexistence or the possible predisposing, protective or aggravating role of HT in the development of PTC have been repeatedly examined. Aim: The aim of the present study was to eval¬uate histopathological and clinical data obtained from pa¬tients with HT, PTC, and PTC+HT so as to investigate the possible association of HT with PTC. Methodology: The study’s cohort consisted of 114 patients (67 PTC, 29 PTC+HT, and 18 HT patients). A full record of their clini¬copathological and clinical laboratory data was followed by extensive statistical analysis in order to reveal possi¬ble correlations between the existence of each disease and various clinicopathological parameters. The study was conducted from 2019 to 2023 at the Hippokration General Hospital of Athens (Greece). Results: A signifi¬cant increase in the levels of thyroid-stimulating hormone (TSH; p=0.031), anti-thyroglobulin antibodies (Anti-Tg; p&lt;0.001), and anti-thyroid peroxidase antibodies (Anti-TPO; p&lt;0.001) was observed in the PTC+HT group. These patients also have smaller tumors (p=0.015) and a younger age of disease onset (p&lt;0.001), while the ma¬jority of PTC+HT patients were women (p=0.023) and had infiltrated lymph nodes (p=0.002). Furthermore, the majority of patients with infiltration of the capsule be¬longed to the PTC+HT group (57.1%; p=0.032). Conclu¬sion: PTC+HT represents a less aggressive clinical state, as good prognostic markers of PTC correlate with the presence of HT. In PTC+HT patients, the PTC tends to have early onset age and the primary tumor is often small, while the majority of PTC+HT patients are women.

Trends in the use of thyroid diagnostics and treatments between 2008 and 2019 in Germany

Following implementation of a national prevention program against iodine deficiency-related disorders in 1993 in Germany, the prevalence of thyroid disorders declined, but aggregated drug dispensation data suggested a recent increase in thyroid hormone use. We aimed to systematically investigate trends in the use of thyroid diagnostic and treatment measures between 2008 and 2019 in Germany. Using the GePaRD database (claims data from ~ 20% of the German population), we determined the annual age-specific and age-standardized prevalence of the use of thyroid diagnostics (thyroid-stimulating hormone (TSH) measurement, thyroid ultrasound, scintiscan, biopsy) and treatment (medication, surgery, radioiodine therapy) from 2008 to 2019 stratified by sex. Between 2008 and 2019, the age-standardized prevalence of TSH measurement increased by 44% in males (from 165 to 238 per 1,000 persons) and by 31% in females (from 134 to 176 per 1,000). The prevalence of thyroid ultrasound use showed no clear time trend, while there was a decrease in the prevalence of scintiscan use (males/females: decrease by 42/43%) and biopsy (males/females: decrease by 42/34%). The prevalence of levothyroxine use increased by ~ 31% both in males (from 36 to 47 per 1,000) and females (from 134 to 175 per 1,000), while the prevalence of thionamide use, iodine use, thyroidectomy, and radioiodine therapy decreased. Our study suggests a continued decline in the prevalence of clinically significant thyroid disorders between 2008 and 2019. The substantial increase in the prevalence of TSH measurement and levothyroxine use during this time period might indicate overuse of diagnostics and overtreatment, warranting further investigation.

Reference TSH intervals in children and adolescents

The determination of thyroid-stimulating hormone (TSH) is a reliable test in the diagnosis of thyroid dysfunction. When interpreting the results of quantitative studies, clinicians and laboratory specialists most often resort to assessing the compliance of the result with reference intervals (RI). At the same time, each laboratory must determine them for the analytes being measured itself, based on the characteristics of the examined contingent, the characteristics of the analytical systems used, achieving the necessary diagnostic effectiveness of the methodology, and its own practical and economic capabilities. A retrospective analysis of TSH results obtained from patients under the age of 19 years was performed for 54970 patients without hypothyroidism, thyrotoxicosis and pituitary disorders. For this work, reagent kits “Roche Cobas”, “Mindray” and “Beckman Coulter” (ICLA) were used. As a result, RI was established for the study of TSH for three sets of reagents with appropriate equipment and for four age groups: 1 day – 6 months, 6 months – 7 years, 7–14 years, 14–19 years. This makes it possible to use RI as a screening for possible developmental pathology in childhood and to determine the limits of clinical decisions.

Immune checkpoint inhibitors-related thyroid dysfunction: influencing factor analysis, prediction model development, and management strategy proposal

BackgroundWith the extensive utilization of immune checkpoint inhibitors (ICIs) across various cancers, ICIs-related thyroid dysfunction (ICI-TD) has become a growing concern in clinical practice. This study aimed to devise an individualized management strategy for ICI-TD to enhance the early identification and proactive management in cancer patients.MethodsWe designed and conducted a three-phase study. Initially, we analyzed the influencing factors through a systematic review and meta-analysis, which adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Moreover, the study protocol was registered with PROSPERO (CRD42019131133). Subsequently, prediction models for ICI-TD were developed utilizing 11 algorithms based on the real-world cohort data from July 20, 2018 (the approval date of the first ICIs, Pembrolizumab in China), to October 31, 2022. Considering discrimination, calibration, and clinical utility, we selected the model with the best performance for web calculator development. Finally, individualized management strategies for ICI-TD were proposed by combining evidence-based analysis with practical considerations.ResultsThe systematic review encompassed 21 observational studies involving 4,145 patients, revealing associations between ICI-TD and factors such as female gender, age, receipt of Pembrolizumab (versus other ICIs), and baseline levels of thyroid-stimulating hormone, free thyroxine, and antithyroid antibodies. In the prediction model development phase, 621 participants were enrolled, with 36 patients developing ICI-TD. The model based on the LightGBM algorithm demonstrated superior performance, leading to the development of a web calculator. Based on these findings and existing guidelines, individualized monitoring and treatment pathways for pharmacists were devised.ConclusionThis study offers comprehensive insights into managing ICI-TD, potentially enhancing tailored cancer immunotherapy management.

Clinical implications of dual therapy of acarbose plus myo-inositol on the thyroid profile in women with polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among PCOS women. Aims: To evaluate the benefits of acarbose plus myo-inositol therapy on the thyroid profile of PCOS. Methods: An open-labelled, parallel randomised clinical trial on 80 PCOS women based on inclusion and exclusion criteria was performed at the Department of Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur. Institutional ethics committee approval and prior informed consent were obtained. The trial was registered in CTRI (No: CTRI/2022/04/041877). Group A (n = 38) received metformin 500 mg TID, and group B (n = 39) received acarbose 50 mg TID along with myoinositol 1000 mg BID. Assessment of metabolic and hormonal profile was done at baseline and at the end of six months. Results: Both groups showed significant reductions in luteinising hormone (p &lt;0.0001), total testosterone (p&lt;0.05), thyroid stimulating hormone (p&lt;0.05), fasting insulin (p&lt;0.05), and homeostatic model assessment for insulin resistance (p&lt;0.0001). The follicle-stimulating hormone was increased only in the metformin group. No significant changes in body mass index, free triiodothyronine, free tetraiodothyronine, and fasting glucose were observed in any group. Both therapies were safe, and no side effects or hypoglycaemia were recorded. Conclusions: In consideration of the beneficial effects of the study, we conclude that the administration of acarbose plus myo-inositol exerts positive effects on the thyroid and other endocrinological profiles in PCOS women.

Thyroid and growth hormone endocrine disruption and mechanisms of homosalate and octisalate using wild-type, thrαa-/-, and dre-miR-499-/- zebrafish embryo/larvae

Homosalate (HS) and octisalate (OS), which are used in sunscreen for the purpose of blocking ultraviolet rays, are frequently detected in water environment. Although effects on estrogens and androgens have been reported, studies on thyroid and growth hormone endocrine disruption are limited. In the present study, larval mortality was compared in wild-type and two knockout fish (thyroid hormone receptor alpha a knockout (thrαa-/-) and dre-miR-499 knockout (dre-miR-499-/-)) after 96 h of exposure to HS and OS (0, 0.003, 0.03, 0.3, 3, 30 and 300 µg/L). To investigate the mechanisms of thyroid and growth hormone endocrine disruption, we measured the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), and insulin-like growth factor-1 (IGF-1), and the regulation of representative genes related to the hypothalamus-pituitary-thyroid (HPT) and GH/IGF axis in wild-type zebrafish exposed to target chemicals. The significantly lower larval survival rate of thrαa-/- and dre-miR-499-/- fish exposed to 300 μg/L of HS and OS suggest that thyroid hormone receptors and dre-miR-499 play a crucial role in the toxic effects of HS and OS. The finding of a significant increase in T3 and T4 in zebrafish larvae exposed to HS and OS supports a significant decrease in the crh gene. The reduction of GH and IGF-1 in fish exposed to HS and OS is well supported by the regulation of genes involved in the GH/IGF axis. Our observations suggest that exposure to HS and OS affects not only thyroid hormone receptors and their associated miRNAs, but also the feedback routes of HPT and GH/IGF axes, ultimately leading to growth reduction.

Association and interaction between overweight/obesity and suicide attempts in young first-episode and drug-naïve patients with major depressive disorder

AimsThis research's objective was to explore the correlation of overweight/obesity and suicide attempts in young patients with major depressive disorder (MDD) and the related factors of suicide attempts in patients with/without overweight/obesity. MethodsThis study included 520 young patients with MDD who were first-episode and drug-naïve (FEDN), with an average age of 20.50±2.36 years. Height and weight of each subject were measured, and overweight was classified as 24≤BMI<28, and obesity as BMI≥28.Biochemical indicators were detected including blood glucose, lipid, and thyroid function indicators. Depressive symptoms, anxiety symptoms, and psychotic symptoms were evaluated using Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. ResultsOverweight/obesity was a separate factor influencing suicide attempts in subjects(p<0.05, OR=0.57, 95%CI: 0.34-0.95). Higher HAMD, HAMA scores, levels of total cholesterol (TC), thyroid stimulating hormone (TSH), and prevalence of thyroid peroxidase antibody abnormalities were seen in overweight/obese individuals who attempted suicide(all p values < 0.01).While in patients without overweight/obesity, those who attempted suicide had higher HAMD, HAMA, PANSS positive subscale scores, levels of TSH, fasting blood glucose, TC, blood pressure, prevalence of TSH abnormalities, and lower levels of high-density lipoprotein cholesterol(all p values < 0.01). ConclusionsIn young FEDN patients with MDD, overweight/obesity might influence the incidence of suicide attempts and related influences.

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach.Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in in vitro cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, i.e. inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS).Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.

Interactions between pregnant women's nutrition habits, psychological well-beings, sleep quality and biochemical parameters.

Hormonal changes during pregnancy may cause various changes in biological, physiologic and psychosocial areas. The main objective of this study was to analyze the relationship between dietary habits, psychological well-being, sleep quality and biochemical parameters of pregnant women. The study was conducted on a total of 93 patients who applied to Ankara Koru Sincan Hospital Gynecology and Obstetrics Outpatient Clinic for routine pregnancy control between November-December 2023, were between the ages of 18-45, had a live singleton fetus, had no diagnosed psychiatric disease or chronic disease, and agreed to participate in the study. Anthropometric measurements and biochemical findings of the individuals were recorded with a questionnaire including the psychological well-being scale (PWBS) and Pittsburgh sleep quality index (PSQI). According to the study, PSQI scores during the second and third trimesters are significantly higher than the first trimester. It was observed that while individuals have bad sleep quality during the second and third trimesters, they have good sleep quality during the first trimester (χ2 = 14.736; P < 0.001). In the biochemical results, the thyroid-stimulating hormone (TSH) value in the second trimester was higher (P > 0.05). Weight gain during pregnancy, age and trimester have a negative effect on sleep quality. When the effects of lifestyles and eating habits of pregnant women on the process are considered, there is a relationship between smoking/alcohol consumption, less physical activity, poor eating habits, sleep quality and depressive symptoms. Factors such as age, educational background, trimester period and other basic sociodemographic variables are also involved.

Analysis of vitamin D metabolism, thyroid and autoimmune markers in the vitiligo pathways and their possible interaction with sleep.

Vitiligo is an autoimmune skin disease that can be influenced by stress, including that resulting from sleep deprivation and sleep disturbances. Sleep is essential in the regulation of several hormonal, metabolic and autoimmune pathways that may have important roles in vitiligo. This study aimed to investigate the potential interplay between hormonal, metabolic, and autoimmune markers in vitiligo patients, and the possible influence of sleep quality in these vitiligo pathways. A cohort of 30 vitiligo patients and 26 healthy controls were assessed for various laboratory markers, including thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), serum calcium, 1.25(OH)2D, 25(OH)D, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and antinuclear antibodies (ANA). The study evaluated sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Positive anti-TPO were found in the vitiligo group, but did not in the control group. Vitamin D 25(OH)D mean levels were clinically insufficient in both groups (< 30mg/dL). Reactive ANA was analyzed with 2 variables related to vitiligo: phototherapy and skin activity. No statistical correlation was found in the chi-square test on this relationship. Descriptive findings have shown that the positivity to anti-TPO and anti-TG, associated or not with reactive ANA, was higher in vitiligo group. Great part (85.7%) of vitiligo group were "poor sleepers" (PSQI > 5), which has increased (88.2%) when considering only individuals with signs of vitiligo activity. Autoimmune hypothyroidism and positive anti-TPO are expected in vitiligo, although this marker is not usually measured in the first laboratory screening to this disease. Adequate vitamin D levels may be a key adjuvant in skin pigmentation, and be related to sleep quality and immune regulation, as this vitamin can be related to better sleep and immunomodulation in autoimmune diseases. Evaluating ANA before phototherapy can be controversial, but it should be considered in cases with a poor response to this treatment, or when there is a higher risk of other autoimmune diseases. Poor sleep predominated in the vitiligo group, based on PSQI scores that reported worse subjective sleep in these patients. Worse sleep predominated in individuals with signs of skin activity and reactive autoimmune markers. Screening these components could be important in the management of vitiligo, as maintaining body homeostasis can help to improve the disease course. Sleep should be considered as a potential modulator of several multidirectional vitiligo pathways.

Application of composite reference intervals in the diagnosis of subclinical hypothyroidism in the elderly: a retrospective study.

Thyroid stimulating hormone releasing hormone (TSH) is a key indicator for diagnosing subclinical hypothyroidism (SCH). We evaluated factors affecting TSH levels in elderly SCH, establishing a composite reference interval, and comparing it with traditional one in diagnosis. We collected data on patients aged ≥60 undergoing physical examinations in Chengdu, screening the influencing factors associated with TSH. Then, a two-dimensional composite reference interval was established for TSH and FT4, and the differences between the new and traditional diagnosing methods were compared. The incidence of subclinical thyroid dysfunction was about 14%, with SCH accounting for 97%. Regression analysis found that TSH levels increase as FT4 and uric acid levels decrease. Compared with the two-dimensional composite reference interval, the traditional one has a higher incidence rate of SCH. Compared with the two-dimensional composite reference interval, the traditional one is more likely to overestimate the incidence rate of SCH, leading to excessive diagnosis and treatment.

THYROID DYSFUNCTION IN PATIENTS WITH TYPE 1 DIABETES AT A TERTIARY CARE HOSPITAL

Individuals with diabetes mellitus (DM) are reporting thyroid dysfunction at an alarming rate, and there's evidence that thyroid dysfunction—whether overt or subclinical—affects overall glycaemic control. 12.3% of individuals with Type 1 DM have overt hypothyroidism, while around 24.8% of patients have abnormal thyroid autoantibody levels. Objective: This study aimed to determine Thyroid dysfunction in patients with type 1 diabetes at a tertiary care hospital. Methods: The present descriptive study was carried out at Hayatabad Medical Complex Peshawar from January 2024 to June 2024 after obtaining permission from the ethical committee of the institute. A total of 110 participants were enrolled in the study. We included all T1DM patients of both genders. All participants with T1DM visiting the OPD were screened. The primary test for assessing thyroid function was TSH, which has an acceptable range from 0.5 to 5 mIU/ml. Triiodothyronine (T3) and free thyroxin (FT4) levels were also measured. On a Cobos 6000 machine (Roche), thyroid function tests (TFTs) were performed. Data was analyzed through SPSS version 22.0. Results: A total of 110 participants of both genders of different age groups were enrolled in this study. 63.63% of them were females and 36.36% were males. 18 individuals (16.36%) had subclinical hypothyroidism, 14 individuals (12.7%) were hypothyroid, and 78 of them (70.90%) were euthyroid. We did not identify any occurrences of hyperthyroidism in current research. In comparison to the rest of the population, individuals with hypothyroidism had significantly different mean Thyroid stimulating hormone, FT4 and FT3 levels (p &lt;0.0001). The mean differences for age, the period of diabetes, randomized blood sugar (RBS), and HbA1c were not statistically significant. When the data was examined for subclinical hypothyroidism, however, there was a substantial variance for mean Thyroid stimulating hormone (p &lt;0.0001) but not for FT4 or FT3. Likewise, there was no difference seen in age (p= 0.35) or gender (p= 0.63). Conclusion: Type 1 diabetes individuals often suffer from thyroid dysfunctions particularly hypothyroidism (12.7%) and subclinical hypothyroidism (16.36%). The analysis of thyroid-stimulating hormone levels and other hormonal markers for thyroid function is the most crucial approach.

Circulating Autoantibodies in Adults with Hashimoto’s Thyroiditis: New Insights from a Single-Center, Cross-Sectional Study

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Predictors for thyroid dysfunction after discontinuation of levothyroxine in children and adolescents with Hashimoto thyroiditis.

Few data on the clinical course after levothyroxine (L-T4) discontinuation in pediatric patients with Hashimoto thyroiditis (HT) are available. We investigated outcomes and predictors for successful withdrawal from L-T4 among children with HT. Among 168 patients diagnosed with HT between January 2000 and March 2021 at Seoul National University Children's Hospital and in whom L-T4 therapy was initiated during childhood, we attempted to discontinue this therapy in 47, 3 boys and 44 girls. L-T4 was restarted when patients developed overt or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels≥10 mIU/L) after L-T4 discontinuation. Median age at discontinuation was 15.4 years (12.7-18.4 years) with a median duration of L-T4 therapy of 47 months (20.3-80.3 months). During the median 30 months of follow-up (10.6-61.0 months) after L-T4 discontinuation, 33 (70.2%) developed thyroid dysfunction. Among these patients, 17 were eventually restarted on L-T4. TSH levels over 50 mIU/L at L-T4 initiation (hazard ratio, HR 3.5, P=0.002), age under 12 years at L-T4 discontinuation (HR 11.1, P=0.0001), and TSH levels higher than the upper 50% of normal (above 2.25 mIU/L in the present study) at L-T4 discontinuation (HR 2.7, P=0.014) were significantly predictive for overt hypothyroidism or subclinical hypothyroidism after L-T4 discontinuation. In addition, age under 12 years at L-T4 discontinuation was only predictive factor for restarting L-T4 medication (HR 4.3, P=0.012). L-T4 discontinuation in pediatric patients with HT resulted in thyroid dysfunction in 70.2% of cases; 36.2% of patients who attempted discontinuation required resumption of L-T4. Older age and lower TSH levels at L-T4 discontinuation were advantageous for successful withdrawal.