TSH Receptor Research Articles

Prevalence of Thyrotropin Receptor Antibodies and Clinical Profile of Patients with Alopecia Areata: A Cross-Sectional Study

Introduction: Alopecia areata (AA) is associated with thyroid dysfunction and abnormal levels of thyroglobulin and thyroid peroxidase autoantibodies. One study detected high prevalence of thyrotropin receptor antibodies (TRAbs) in AA patients. Our aim was to investigate the prevalence of TRAb levels in AA patients and to assess their association with thyroid hormones, other thyroid antibodies, AA severity, and other epidemiological variables. Methods: In this observational study, 139 patients (97 females, 42 males), aged 12 and above, with newly presenting, relapsing, or treatment-resistant AA were included. Medical histories were reviewed, alopecia severity was assessed using the Severity of Alopecia Tool (SALT), and blood tests measured thyroid hormones and autoantibodies. Results: The prevalence of TRAb was significantly higher in AA patients (23.6%) compared to the general population (1–2%) (p < 0.001). Elevated TRAb titers did not correlate with diagnosed thyroid dysfunction or treatment, abnormal thyroid function tests and autoantibodies, AA severity, duration, and onset. Male patients exhibited a significantly higher prevalence of abnormal TRAb titers compared to females (75.0% vs. 21.3%, p = 0.002). Conclusion: A significant proportion of AA patients presented with elevated TRAb levels, independent of thyroid hormone titers, other thyroid autoantibodies, or SALT score. Prevalence of abnormal TRAb levels was higher in males.

Identification and functionalization of thyrotropin receptor antibodies with different antigenic epitopes.

One of the sensitive markers for autoimmune thyroid disease (AITD) clinical identification is thyroid-stimulating hormone receptor antibodies (TRAbs). To quickly distinguish TRAb with distinct antigenic epitopes, a straightforward and uncomplicated technique has not yet been created. The objective of this study is to search for molecular diagnostic targets for different types of AITD {Graves' disease (GD), Graves' orbitopathy (GO), GD with third-degree goiter [GD(3)], hypothyroidism combined with positive TRAb [HT(TRAb+)]} as molecular diagnostic targets. Following action on thyroid cells, differential genes (DEGs) generated by TRAb with distinct antigenic epitopes were detected and identified by RNA sequencing (RNA-Seq), bioinformatics analysis, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) in the serum of patients with AITD. Using the 5-ethynyl-2'-deoxyuridine (EdU) assay, the effect of coculturing thyroid cells with different antigenic TRAb epitopes on the cells' capacity to proliferate was investigated. Bioinformatics analysis and RT-qPCR validation identified one GD key gene alpha 2-HS glycoprotein (AHSG), two GO key genes [adrenoceptor alpha 1D (ADRA1D) and H2B clustered histone 18 (H2BC18)], two GD(3) key genes [suppressor of cytokine signaling 1 (SOCS1) and cytochrome b-245 beta (CYBB)], and one HT(TRAb+) key gene (MASP2). Correlation analysis and ROC curves showed that the abovementioned genes could be used as molecular diagnostic targets for different types of AITD. Finally, EdU results showed that TRAb inhibited thyroid cell proliferation in the HT(TRAb+) group compared with the normal control group, whereas the remaining three groups promoted thyroid cell proliferation, with a statistically significant difference (P < 0.05). We identified six key genes for different types of AITD, which have diagnostic value for different types of AITD. Meanwhile, we found that TRAbs with different antigenic epitopes in AITD have different biological functions.NEW & NOTEWORTHY We identified six molecular targets of different types of AITD [GD, GO, GD(3), and HT(TRAb+)], which have diagnostic value for different types of AITD. Meanwhile, we found that TRAb with different antigenic epitopes extracted from the sera of patients with AITD had different biological functions, which also provided a new idea for further research on the mechanism of action of TRAb with different antigenic epitopes in AITD.

Graves disease: latest understanding of pathogenesis and treatment options.

Graves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). Although Graves hyperthyroidism is relatively common, no causal treatment options are available. Established treatment modalities are antithyroid drugs, which reduce thyroid hormone synthesis, radioactive iodine and surgery. However, emerging drugs that target the main autoantigen (monoclonal antibodies, small molecules, peptides) or block the immune pathway have been recently tested in clinical trials. Graves disease can involve the thyroid exclusively or it can be associated with extrathyroidal manifestations, among which Graves orbitopathy is the most common. The presence of Graves orbitopathy can change the management of the disease. An established treatment for moderate-to-severe Graves orbitopathy is intravenous glucocorticoids. However, recent advances in understanding the pathogenesis of Graves orbitopathy have allowed the development of new target-based therapies by blocking pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R), with several clinical trials providing promising results. This article reviews the new discoveries in the pathogenesis of Graves hyperthyroidism and Graves orbitopathy that offer several important tools in disease management.

Recombinant Human TSH Fails to Induce the Proliferation and Migration of Papillary Thyroid Carcinoma Cell Lines.

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients.

US-based, Prospective, Blinded Study of Thyrotropin Receptor Antibody in Autoimmune Thyroid Disease.

Bioassays provide information on the functionality of thyrotropin receptor antibodies (TSH-R-Ab) and thus may offer more clinical utility than binding assays. In this prospective, blinded, US-based study, the clinical performance of several TSH-R-Ab assays was compared. US endocrinology clinic. One hundred sixty-two unselected, consecutive, well-documented patients with various thyroid diseases and healthy controls. Blinded TSH-R-Ab measurements. Sensitivity and specificity of 4 TSH-R-Ab assays. The 4 TSH-R-Ab assays were negative in all 42 patients without autoimmune thyroid disease (AITD). In 104 patients with Graves' disease (GD), irrespective of the disease duration, TSH-R-Ab positivity was present in 65 (63%), 67 (65%), and 87 (84%) for the Cobas and Immulite binding assays and stimulatory TSH-R-Ab [thyroid-stimulating immunoglobin (TSI)] bioassay, respectively (TSI vs Immulite P < .0025, TSI vs Cobas P < .0009). Fifteen newly diagnosed GD patients were all positive in the TSI bioassay, but only 11 (73%) were positive in the Cobas and Immulite binding assays. Nine GD patients with biochemical subclinical hyperthyroidism were TSI-positive but Immulite- and Cobas-negative. Two GD patients were blocking TSH-R-Ab [thyroid-blocking immunoglobin (TBI)]-positive and TSI-negative, and the Immulite and Cobas were positive in both. Additional serum samples from AITD patients that consisted of 30 TBI-positive and 10 TSI-positive samples were blindly tested in the binding assays. Only 6 of the 10 TSI-positive samples were positive in both binding assays, and 30 and 28 of the TBI-positive samples were positive in the Cobas and Immulite assays, respectively. Binding TSH-R-Ab assays are less sensitive than TSI bioassays and are not specific for stimulating antibodies. Measuring the function of TSH-R-Ab in a bioassay can provide useful information to clinicians.

Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves' Disease.

Antithyroid drugs (ATD) are the treatment of choice for the majority of patients with Graves' hyperthyroidism worldwide. However, relapse of hyperthyroidism after withdrawal of arbitrarily chosen conventional 12 to 18 months of therapy is very common. In the last 2 decades, many studies have shown that treatment with long-term ATD (LT-ATD) is effective and safe in the maintenance of euthyroidism. In addition, it has been reported that serum TSH receptor antibody may not decrease permanently before 5 to 6 years of ATD treatment, and clinical trials have shown that ≥5 years of ATD treatment is accompanied by remission in the majority of patients with Graves' hyperthyroidism. The objective of this article is to discuss the optimal time to withdraw of conventional ATD therapy, to illustrate the decision-making of the management of recurrent hyperthyroidism, to review the proper management of LT-ATD, and to generate suggestions for lifelong ATD treatment by discussing 4 scenarios of decision-making in patients with Graves' disease.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, β+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Physiological Impacts of Cauliflower in Hyperthyroid Rabbits

This study aimed to investigate the effect of cauliflower extract as a remedy for hyperthyroid in rabbits. Twenty rabbits with mean weight 1700 ±95 g and age of 6-7 months were chosen. The animals were randomly divided into four groups (five in each group). The first group (GI) was the control and received normal diet and given tap water. The second and third groups (GII &amp; GIII) were received 30 μg/Kg BW sodium L-Thyroxin injected subcutaneously to induce hyperthyroidism for three weeks. After that, these groups (GII &amp; GIII) were administrated 20 &amp; 30 mg/kg of body weight cauliflower extract for four weeks. Blood samples were collected from hyperthyroid and treated groups after two and four weeks. Serum was centrifuged at 3000 rpm for 15 minutes. The collected serum was used in the assessment of the levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormones (TSH) by analytical kits which determined on ELISA method. Further, a molecular study was performed to estimate TSHR gene expression. The results of the present work showed that there was a significant (p&lt;0.05) decrease in T3 and T4 hormone levels means in rabbits treated with cauliflower extract as compared with hyperthyroid. It concluded from the present study that the natural products such as phenolic compounds, carotenoids, flavonoid, and ascorbic acid from cauliflower might be used as a remedy to recover from hyperthyroid states in order to reduce the intake of chemical drugs.

Subcutaneous Injections of Triamcinolone Acetonide for Upper Eyelid Retraction and Swelling Associated with Thyroid Eye Disease: A Retrospective Case Series Study.

To evaluate the efficacy of subcutaneous injection of triamcinolone acetonide (SCTA) in treating upper eyelid retraction and swelling in patients with thyroid eye disease (TED). This case series included consecutive patients (aged 16-69 years, monitored from June 2012 to December 2015) with TED-related eyelid symptom and without an enlarged extraocular muscle on magnetic resonance imaging (MRI). SCTA (0.5 mL, 40 mg/mL) was administered to target the orbital fat around the levator palpebrae superioris (LPS) muscle. Patients who did not exhibit improvement after the first trial received an additional injection. Follow-up was conducted for 12 months with 3-month intervals. Eyelid retraction, eyelid swelling, and eyelid lag were evaluated at each follow-up visit. In total, 116 eyelids of 102 patients were analyzed. SCTA led to significant improvement in 93% of eyes (108/116), disappearance of eyelid symptoms (74%, 87%, and 73% in retraction, swelling, and lag, respectively), and improvement of scores (from 1.64 to 0.12, 1.32 to 0.26, and 1.72 to 0.30, respectively). Improvement in eyelid symptoms was observed in eight eyes; however, additional steroid therapy was required in these cases due to the emergence of other extraocular muscle inflammation. Additional injection was required in 39.8% of patients. The clinical activity score was lower in the single SCTA group than in the multiple SCTA group (1.5 vs 0.9; p < 0.01). However, the levels of thyroid-stimulating hormone receptor antibody and MRI findings were not significantly different between the two groups. No elevation in intraocular pressure was observed. Eight female patients experienced menstrual disorder. SCTA effectively reduced LPS muscle enlargement and fat tissue swelling in patients with TED. A single SCTA was sufficient in almost 60% of the patients; nevertheless, follow-up is necessary to detect early signs of orbital inflammation even in eyelid-symptom-improved patients.

Stability analysis of a mathematical model for methimazole dosing in graves' hyperthyroidism: A dynamic approach

This study explores a novel mathematical model for analyzing methimazole (MMI) therapy in patients with Graves' disease, a common autoimmune cause of hyperthyroidism. The model leverages a system of ordinary differential equations to capture the interplay between key factors: methimazole concentration, thyroid-stimulating hormone (TSH), free thyroxine (FT4) concentration, thyroid-stimulating hormone receptor antibody (TRAb) concentration, and functional thyroid gland size (V). Thirteen parameters account for the underlying physiological processes. Stability analysis were employedby Lyapunov stability theory and LaSalle's principle, to demonstrate the model's asymptotic stability. This implies the system converges towards a steady state under defined conditions. Additionally, a clinically relevant chart is constructed based on FT4 levels and treatment duration.For model validation, patient data is utilized within SimBiology simulations implemented in MATLAB. These simulations offer valuable insights into the dynamic response of hyperthyroidism to MMI treatment. This approach holds promise for future applications in optimizing treatment strategies and facilitating personalized medicine approaches.

The Causes of Thyrotoxicosis, Clinical Features, and Treatment Strategies in a Former Iodine Deficient Area

Thyrotoxicosis is a hypermetabolic condition caused by excess thyroid hormones in the circulation with/without increased production from the thyroid gland. In this prospective study, we aimed to investigate the causes of thyrotoxicosis, clinical features, and treatment strategies in a former iodine-deficient area. Thyroid function tests, antithyroid and antithyroid receptor antibodies, and routine thyroid ultrasonography was obtained, and a thyroid scintigraphy/radioactive iodine uptake test was performed on need. A statistically significant difference was found between toxic multinodular goiter (TMNG) and Graves’ disease (GD) groups when mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values were analyzed. TSH levels were significantly lower in GD patients compared to those in TMNG and TNG patients, but free triiodothyronine (FT3) and free thyroxine (FT4) values were higher. A high level of TSH receptor antibody (TRAb) was observed in patients with normal antithyroid peroxidase (Anti-TPO). TRAb levels were found to be high. Anti-TPO and anti-thyroglobulin (Anti-Tg) levels were observed to be positively correlated with sT3 and sT4 levels. TMNG is the leading cause of thyrotoxicosis; despite sufficient iodide intake in our former iodine-deficient region, TMNG is characteristically seen in older patients with much lower thyroid hormone levels than GD. According to the study results, the diagnosis of patients with thyrotoxicosis, their clinical presentation, the treatment they will receive, early detection of postoperative complications were predicted

Low molecular inverse agonist of the thyrotropin receptor is active both intraperitoneal and oral administration

Autoimmune hyperthyroidism (Graves’ disease), which is caused by stimulating autoantibodies to the thyroid-stimulating hormone (TSH) receptor, and thyroid gland (TG) tumors, caused by constitutively increased activity of this receptor, are widespread and have a poor prognosis. The drugs used to treat them are not very effective and have many side effects. One of the approaches for the treatment of these thyroid diseases may be the use of allosteric regulators of the TSH receptor with the activity of inverse agonists. The purpose of the work was to study the effects of our previously developed compound TP48 and the new compound TPY5, belonging to the class of thieno[2,3-d]-pyrimidines, on the basal and thyrotropin-releasing hormone (TRH)-stimulated levels of thyroid hormones (THs) in the blood of rats and on the expression of genes responsible for the synthesis of THs in the TG. The effectiveness of TP48 and TPY5 was studied both with intraperitoneal (i.p., 20 mg/kg) and oral (40 mg/kg) administration. Using ELISA, the levels of free (fT4) and total (tT4) thyroxine and free (fT3) and total (tT3) triiodothyronine in the blood were assessed, including during TRH stimulation (intranasally, 300 μg/kg). The gene expression for thyroid peroxidase (Tpo), thyroglobulin (Tg), Na+/I–-symporter (Nis), type 2 deiodinase (Dio2) and TSH receptor (Tshr) in the TG was assessed using PCR. TPY5, with both routes of administration, reduced both basal and TRH-stimulated TH levels, while TP48 suppressed TH production only with i.p. administration. Orally administered TPY5 significantly reduced basal Tpo gene expression and TRH-stimulated Tg and Dio2 gene expression. I.p. administered TP48 reduced only TRH-stimulated expression of the Tg and Dio2 genes. Quite surprisingly, TPY5 (oral) and TP48 (i.p.) reduced basal Tshr gene expression and did not prevent its inhibition by TRH. Thus, the TPY5 compound we developed has the activity of an inverse agonist of the TSH receptor, is effective when administered orally, which is more in demand in medicine, and can be considered as a prototype of drugs to treat autoimmune hyperthyroidism and thyroid tumors.

Could effective iodine-131 half-life be extended by lithium carbonate in Graves' disease patients: Results from a retrospective analysis.

The effective iodine-131 (I-131) half-life (EHL) plays an important role in the evaluation of radioactive iodine therapy for Graves' disease (GD) patients. It has been observed that the EHL of GD patients varies after taking lithium carbonate. The purpose of this study is to investigate whether EHL can be extended and to identify the predictive factors associated with this outcome. The clinical data of 225 GD patients were retrospectively reviewed. Patients were divided into two groups based on whether the ΔEHL was ≥ 0.5 days. EHL tested after lithium carbonate was defined as Li-EHL. In the univariate analysis, age, sex, thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and baseline-EHL exhibited significant differences between the two groups (P < 0.05). Cutoff values of age and baseline-EHL to predict significant EHL extension were 40.5 years and 4.85 days, respectively, as determined by receiver operating characteristic (ROC) curve analysis. Multiple linear regression analysis further revealed that the regression equation, which included age, sex, baseline-EHL, and the FT3, free triiodothyronine (FT4)/free thyroxine(FT3) ratio, was statistically significant (P < 0.05). Li-EHL positively correlated with baseline-EHL and the FT4/FT3 ratio, but negatively correlated with age. Li-EHL was also increased in female individuals. In conclusion, age, sex, baseline-EHL and the FT4/FT3 ratio were associated with Li-EHL in GD patients.

Clinical Changes and Autoantibody Level Changes in Thyroid Eye Disease Patients after Intravenous High-dose Steroid therapy

Purpose: To evaluate the effects of intravenous steroid therapy on the clinical activity score (CAS), exophthalmos, margin-reflex distance 1 (MRD1), and autoantibody levels in patients with thyroid eye disease.Methods: In this retrospective observational study, we enrolled 83 patients diagnosed with thyroid eye disease treated with intravenous steroid therapy. We assessed exophthalmos, MRD1, CAS, thyroid-stimulating antibody (TSAb), and thyroid-stimulating hormone receptor antibody (TSHR Ab) levels at baseline, 6 and 12 weeks after initiating therapy, and 2 months after therapy termination. Additionally, baseline serum selenium levels were examined to determine their impact on treatment efficacy.Results: TSAb, TSHRAb, and CAS levels showed a continuous decline from 443.22 to 341.03 specimen-to-reference control ratio (SRR%), 22.18 to 7.91 IU/L, and 3.37 to 1.88, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001), up to 2 months following therapy termination. Exophthalmos did not show significant changes at any assessed time point up to 2 months after therapy termination. MRD1 decreased until 12 weeks after therapy initiation but showed no significant change 2 months later. No correlation was found between baseline serum selenium levels and changes in exophthalmos, MRD1, TSAb, TSHR Ab, or CAS.Conclusions: Intravenous steroid therapy was effective in reducing TSAb, TSHR Ab, and CAS levels up to 2 months after therapy termination. However, it had limited positive impact on exophthalmos or eyelid retraction. Baseline selenium levels did not correlate with the changes in any of the examined parameters.

STAT3 single-nucleotide variants in autoimmune thyroid disease in the Pakhtun population of Khyber Pakhtunkhwa, Pakistan

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases (AluI) and AciI respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease (p = 0.002, OR = 0.28, 95 % CI = 0.11–0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control (p = 0.032, OR = 0.29, 95 % CI = 0.09–0.86). Similarly, the G and C alleles showed a significant (p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease

BackgroundThe pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PurposeThis study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). MethodsHigh-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. ResultsA total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. ConclusionXKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

A survey on the management practices of graves’ disease by Egyptian physicians and a comparison to similar reports from USA, Italy, China, and Brazil

BackgroundGraves’ disease is the commonest cause of hyperthyroidism in iodine replete areas. Following universal salt iodization, most Egyptians are considered iodine sufficient. The present study aims to report a survey of real-life practices in the management of graves’ disease among Egyptian physicians and compare them to other similar reports.MethodsAn online survey was sent to members and affiliates of Alexandria thyroid association. Egyptian physicians were surveyed about initial diagnostics workup, management of an index case of uncomplicated graves’ disease not desiring pregnancy. Two modified scenarios were proposed to the index case to survey the impact on treatment preferences. Anonymous responses were collected, analyzed, presented, and compared to other published similar reports.ResultsSixty-eight participated out of 120 invited physicians (56.67%). Initial workup included TSH receptor antibodies 46/68 (67. 6%), thyroid ultrasound 45/68 (66.2%), and thyroid scintigraphy 25/68 (36.8%). Treatment preferences in the index case were antithyroid drugs (ATD’s) 52/68 (76.5%), radioiodine 12/68 (17.5%), and surgery 4/68 (6%). Compared to other reports, treatment preferences were almost identical to Italian ones, ATD’s (77.1%), radioiodine (16.2%), and surgery (4.5%). If the patient is complicated with graves’ orbitopathy, treatment preferences would change into ATD’s 37/67 (55%), radioiodine 1/67 (2%), radioiodine with corticosteroids 14/67 (21%), and surgery 15/67 (22%). If the patient is desiring pregnancy, treatment preferences would be ATD’s 32/68 (47%), radioiodine 5/68 (7.4%), and surgery 31/68 (45.6%).ConclusionA high participation rate was observed. Similar to other reports, medical treatment is the preferred modality of treatment in graves’ disease and surgery is the least utilized modality. Similar treatment preferences to Italians were observed in the index case.

Effect of progestin on thyroid function in female Wistar rats.

To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.

Hyperthyroidism in Pediatric Patients in a University Hospital: Ten Years of Experience

Although rare in childhood, hyperthyroidism is diagnosed by suppressed serum thyrotropin (TSH) levels and increased levels of free triiodothyronin (fT3) and free thyroxine (fT4) in addition to history and physical examination findings. In this study, we aimed to investigate the causes of hyperthyroidism and the clinical features of the disease in children and to evaluate the treatment. A total of 39 patients with hyperthyroidism diagnosed between 2010 and 2019 in the pediatric endocrinology department were included in the study.Thirty-one (79.5%) patients were female, and the mean age of admission was 14.4 (4.3-17.5) years. Of the cases, 33 (84.6%) were diagnosed with Graves’ diseases and 6 (16.7%) with Hashimoto thyroiditis. The most frequent complaints of patients diagnosed with hyperthyroidism were irritability (24, 61.5%), palpitation (22, 56.9%), and sweating (21, 53.8%). The most frequent findings were goiter in 31 (79.5%) patients and tachycardia in 27 (69.2%) patients. Serum TSH levels were suppressed in all patients, fT3 levels were increased in 94.4% of them, and fT4 levels were increased in 80.5% of them. In patients with Graves’ disease, TSH receptor antagonist was positive in 31 (93.9%) cases, and at least one of the thyroid autoantibodies was positive in all patients. Antithyroid drug treatment was initiated in all patients; 35 of them received methimazole and 4 of them received propylthiouracil. Radioactive iodine treatment was applied to three patients, and two patients were treated surgically who did not respond to antithyroid drug treatment. Antithyroid drug adverse effects were observed in 7 (21.2%) patients, requiring drug discontinuation in 1 patient. Although hyperthyroidism is rare in childhood, its treatment is difficult and requires close follow-up. Treatment options are different for adult patients. There is a need for multicenter studies to evaluate treatment efficacy and long-term outcomes in children.

Correlation between the thyroid computed tomography value and thyroid function in hyperthyroidism: a retrospective study

ObjectiveRadioiodine (I-131) therapy for hyperthyroidism is a well-established and safe treatment option. This study aimed to investigate the relationship between the computed tomography (CT) value and the function and volume of the thyroid gland by identifying the factors that induce changes in the CT value of patients with hyperthyroidism.MethodsThis retrospective study evaluated 38 patients with Graves’ disease and 10 patients with Plummer disease. To obtain the mean CT value and volume of the thyroid gland, the entire thyroid gland was set as the region of interest. A test dose of 3.7 MBq I-131 was administered before initiating I-131 therapy, and the radioiodine uptake (RIU) rate was assessed after 3, 24, 96, and 168 h. An approximate curve was plotted based on the RIU values obtained, and the effective half-life (EHL) was calculated. The correlation between the mean CT value and the volume of the thyroid gland, 24-h RIU, EHL, and the free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels was evaluated.ResultsThe CT value exhibited a significant positive correlation with EHL in patients with Graves’ disease (r = 0.62, p < 0.0001) as well as patients with Plummer disease (r = 0.74, p < 0.05). However, it did not display any correlation with the remaining parameters.ConclusionThe CT value is significantly correlated with EHL, suggesting that it reflects thyroid function and is mainly related to the factors associated with iodine discharge.