Graves' Disease Research Articles

The Gut Microbiota and Its Metabolites and Their Association with the Risk of Autoimmune Thyroid Disease: A Mendelian Randomization Study

Objectives: Observational research shows associations of the gut microbiota and its metabolites with autoimmune thyroid disease (AITD), but the causality is undetermined. Methods: Two-sample Mendelian randomization (MR) was employed to analyze the association of the gut microbiota and its metabolites with AITD. A total of 119 gut microbiotas and nine fecal/circulating metabolites were the exposures. AITD, Graves’ disease (GD), and Hashimoto’s thyroiditis (HT) were the outcomes. Inverse-variance weighting (IVW) was primarily used to assess causality; Cochran’s Q was used to assess heterogeneity. Sensitivity analyses (weighted median, MRPRESSO regression, MRPRESSO intercept, MRPRESSO global, Steiger filtering, leave-one-out) were conducted to assess causal estimate robustness. Multivariable MR (MVMR) was used to estimate the effects of body mass index (BMI) and alcohol consumption frequency on causality. Results: The outcomes were potentially causally associated with 22 gut microbiotas and three metabolites. After multiple-test correction, 3-indoleglyoxylic acid retained significant causality with AITD (IVW: odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.05–1.14, p = 2.43 × 10−5, FDR = 0.009). The sensitivity analyses were confirmatory (weighted median: OR = 1.06, 95% CI = 1.01–1.12, p = 0.025; MRPRESSO: OR = 1.09, 95% CI = 1.15–1.14, p = 0.001). MVMR revealed no confounding effects on this association (BMI: OR = 1.21, 95% CI =1.08–1.35, p = 0.001; drinks/week: OR = 1.22, 95% CI = 1.04–1.43, p = 0.014). Conclusions: MR revealed no significant causal effects of the gut microbiota on the outcomes. However, MR revealed the causal effects of 3-indoleglyoxylic acid on the risk of AITD.

Clinical efficacy of Chinese herbal medicine formula for Graves' hyperthyroidism: A multicentre, randomized, double-blind, placebo-controlled clinical trial.

According to the theory of traditional Chinese medicine,Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient. To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial. A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint. 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT3 levels (group A, p=0.0027; group B, p<0.0001; group C, p=0.0028) and FT4 levels (group A, p<0.0001; group B, p<0.0001; group C, p<0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p=0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p<0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p<0.0001), eye (p=0.0490), tiredness (p<0.0001), cognition (p<0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety. Pingkang granules significantly reduced serum FT3, FT4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism.

Static and dynamic pupillary features in graves disease without orbitopathy.

Pupillary contraction and dilatation are organized by the autonomic nervous system, which can also be affected by Graves' disease (GD). In this study, it was aimed to investigate the static and dynamic pupillary responses of Graves' patients in the hyperthyroid and euthyroid periods and to compare these results with the values obtained from healthy controls. 48 eyes of 24 newly diagnosed Graves' patients with clinical activity score ≤ 2 and 46 eyes of 23 age- and sex-matched healthy controls were included in the study. Patients with GD were evaluated separately in the hyperthyroid phase and after euthyroidism was achieved. After a detailed ophthalmological examination, patients undergone automatic quantitative testing to obtain static (scotopic, mesopic, low photopic, and high photopeak pupil diameters) and dynamic (pupillary contraction amplitude, latency, velocity and duration, and pupil dilation latency, velocity and duration) pupil measurements. A statistically significant difference was found between the control [4.7mm (3.7-6.9)] and hyperthyroid [5.1mm (3.6-7.8)] groups for mesopic pupil diameter (p = 0.003). Dynamic pupillometry measurements showed that hyperthyroid and euthyroid groups had greater pupil dilation delay and lower pupil dilation rate compared to the control group (p < 0.05 for all). Even in the absence of orbitopathy, patients with GD have autonomic dysregulation of pupillary functions. These changes, which prevail in the hyperthyroid phase, do not reverse when the TSH receptor antibody titer drops and the patient becomes euthyroid. Future studies are needed to elucidate the mechanism of these pupillary changes in GD.

Effect of methimazole withdrawl period on the I-131 uptake estimation using Tc-99m thyroid scanning in Graves' disease.

The effect of methimazole withdrawl period (MWP) on the estimation of 24 hour-radioiodine thyroid uptake (131IU24h) from 99mTc-pertechnetate thyroid uptake (99mTcTU) remains unclear for patients with Graves disease (GD) . This study aims to investigate the feasibility and reliability of 99mTcTU-based 131IU24h estimation with different MWPs. We enrolled 116 GD patients scheduled for 131I therapy at our hospital between April 2022 and April 2023. Based on MWP, the patients were categorized: standard (no methimazole or MWP>1 month), MWP1 (MWP≤1 week), MWP2 (MWP>1 week to ≤2 weeks) and MWP3 groups (MWP>2 weeks to <1 month). Fisher's exact test, one-way ANOVA or Kruskal-Wallis test were used to compare variables. Fitted curves of 99mTcTU20min versus 131IU24h were plotted for the standard group. Linear relationships and Bland-Altman plots were used to illustrate the relationship and consistency between estimated and measured 131IU24h. 131IU24h was higher in MWP1 group compared to MWP2 (70.22±7.95% vs 61.92±9.84%, P = 0.001), and thyroid masswas greater in MWP1 group (36.15±22.38g) versus MWP3 (21.25±11.90g, P = 0.005). The relationship between131IU24h and 99mTcTU20min in the standard group is described by the algorithm: estimated 131IU24h=11.3ln (99mTcTU20min)+39.4 (R2=0.62). Based on it, the correlation between estimated and measured 131IU24h was weak in MWP1 and MWP2 groups (both P>0.05) but strong in MWP3 (r=0.66, P=0.002). Additionally, the agreement between estimated and measured 131IU24h was highest in the MWP3 group (95% CI, -15.86 to 15.52%), compared to the MWP1and MWP2 groups. Estimated 131IU24h based on 99mTcTU is not suitable for GD patients with MWP less than 2 weeks at our institution, necessitating further prospective multi-center studies for validation.

Effect of Antithyroid Drugs Treatment Duration on The Remission Rates of Graves' Disease in Children and Adolescents: A Single-Arm Meta-Analysis and Systematic Review.

Antithyroid drugs (ATDs) are the preferred treatment option for Graves' disease (GD), yet there is a lack of systematic evaluations studying the relationship between treatment duration and therapeutic outcomes. This study aims to assess the remission rate (RR) in children with GD under ATDs therapy and to conduct an analysis of associated factors. Systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang database, with a search time limit from the establishment of the database to 23 November 2023. The primary outcome was the RR. The pooled RR was calculated and subgroup comparisons were performed. Meta-analysis was conducted using R Studio 2023.09.0 + 463 software. The study incorporated a total of 19 research projects, which collectively involved 3359 paediatric patients diagnosed with GD (comprising 2600 girls and 759 boys). The overall RR for paediatric GD treated with ATDs was 25.4% (95% Confidence Interval [CI]: 20.7%, 30.1%). The pooled RR following treatment durations of < 2 years, 2-5 years, and > 5 years were respectively 15.5%, 24.1% and 33.0%. Meta-regression results indicated that the duration of treatment and follow-up duration were significant sources of high heterogeneity among the studies. Specifically, for every additional year of ATDs treatment, there was an increase in the RR by 3.8% (Coefficient = 3.8%, 95% CI: 0.6%, 7.0%, p < 0.01). The overall RR for the treatment of paediatric GD with ATDs is 25.4%, and prolonging the treatment course can indeed lead to an increased RR.

Causal linkage of Graves’ disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes

BackgroundAging is an irreversible progressive decline in physical function. Graves’ disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated.MethodsWe used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes.ResultsF-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer’s disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004).ConclusionsGD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer’s disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

ANAESTHESIA MANAGEMENT IN A CASE OF HYPERTHYROID WITH PROPTOSIS FOR ENDOSCOPIC DECOMPRESSION

This article describes a case of a 65-year-old man with hyperthyroid and who underwent left orbit endoscopic decompression for left eye proptosis. The article also discusses the management of thyroid eye disease (TED) in general. Thyroid associated orbitopathy, also known as Graves orbitopathy, is the most common cause of proptosis ( bulging of the eye). It is an autoimmune disease that affects the muscles and fatty tissues around the eye. TED is most commonly associated with Graves disease, an autoimmune disease that causes an overactive thyroid gland. However, TED can also occur in people with normal thyroid function or an hyperactive thyroid gland. The article presents a case of a 65-year-old man with TED who underwent decompressive surgery to relieve pressure . The article also discusses the importance of maintaining euthyroid (normal thyroid function) in patients with TED.

Soluble immune checkpoints associated with disease activity and treatment response in GD and TED.

Soluble immune checkpoints play an important role in peripheral tolerance that has seldom been investigated in Graves' disease (GD) and thyroid eye disease (TED). The objective of this work is to examine the alteration of soluble immune checkpoints in GD and TED. We performed a quantitative multiplex analysis of 17 immune checkpoint proteins in serum from 50 GD patients without TED, 28 GD patients with TED and 40 healthy controls. The association with demographical, serological, clinical features and 27 cytokines was analyzed. A follow-up was conducted in GD patients without TED. Functional outcomes of sLAG-3 and sGITR were assessed in cell cultures using rh-LAG3, rh-GITR, an antagonistic LAG-3 antibody and an antagonistic GITR antibody. GD patients with TED had distinct sICP and cytokine profiles compared with GD patients without TED. Active TED patients exhibited elevation in the levels of sBTLA, sLAG-3, sGITR, sCD80, sCD86 and sPD-L1. Further, GD patients without TED with high sBTLA, sCD27 and sCD40 levels at baseline showed a better improvement in thyrotropin receptor antibody (TRAb) titers after antithyroid drug (ATD) treatment. Adding recombinant human GITR and LAG-3 to PBMC cultures resulted in increased inflammatory cytokine secretion and decreased anti-inflammatory cytokine secretion. The present study uncovers disturbed soluble immune checkpoints and cytokines in GD patients with and without TED, and may pave the way for novel immunological screening, allowing for identification of TED patients at higher risk of developing active disease and GD patients with better treatment response after ATD treatment.

Proangiogenic effect of thyrotropin receptor stimulating antibody in human umbilical vein endothelial cells.

This study aims to investigate the role of TRAb in the angiogenesis associated with Graves' disease (GD) and to elucidate its underlying mechanisms. Human thyroid follicular epithelial cells (Nthy-ori 3-1) and human umbilical vein endothelial cells (HUVECs) were treated with the monoclonal thyroid-stimulating antibody M22 and thyroid-stimulating hormone (TSH) at various concentrations. Cell viability, migration, and tube formation were evaluated using CCK-8, wound healing, and tube formation assays, respectively. Protein expressions of TSHR receptor (TSHR) and phosphorylated AKT (p-AKT) in M22-induced HUVECs were quantified via Western blotting. Proteomic analysis was employed to identify changes in protein expression profiles and relevant signaling pathways in GD specimens. Immunofluorescence assays were conducted to detect and localize the expressions of CD34 and PROX1 in GD specimens and normal thyroid tissues. M22 stimulated the proliferation of Nthy-ori 3-1 cells and HUVECs in a dose-dependent manner, while TSH exhibited an inverted U-shaped dose-response effect. M22 also dose-dependently promoted angiogenesis, and more effectively induced tube formation in HUVECs compared to TSH, although the difference was not statistically significant. A total of 16 proteins were significantly upregulated and 24 were downregulated in M22-induced HUVECs. Notably, PROX1, the most significantly upregulated protein, is closely associated with angiogenesis. Immunofluorescence confirmed that PROX1 was significantly more expressed in thyroid tissues from GD patients compared to normal tissues adjacent to papillary thyroid cancer (PTC), and it co-localized with CD34. TRAb enhances angiogenesis and upregulates PROX1 expression in HUVECs, suggesting a novel possible mechanism for goiter formation in GD.

The TSH Receptor Antibody Reactome Contributes to Retro-Orbital Inflammation.

The thyroid eye disease (TED) of Graves disease is associated with high titers of stimulating TSH receptor antibodies, retro-orbital inflammation, fibroblast release of cytokines and chemokines, and adipogenesis, which in turn leads to proptosis, muscle fibrosis, and dysfunction. Part of this scenario is the induction of fibroblast proliferation and autophagy secondary to synergism between the TSH receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). While TED is well associated with thyroid-stimulating antibodies to the TSHR, which is also well expressed on fibroblasts, in fact the TSHR reactome has a variety of TSHR antibodies with varying biological activity. Therefore, we have now evaluated the possible role of neutral TSHR antibodies (N-TSHR-mAbs), directed at the hinge region of the TSHR, which do not induce cell proliferation but are known to have effects on multiple proteins in thyroid cells including stress-related signaling molecules. We examined the consequences of an N-TSHR-mAb acting on TSHR-expressing fibroblasts and found marked cell stress, which initiated signaling pathways involving inflammasome activation. This response ended in widespread cell death by pyroptosis through activation of caspase 8 and gasdermin D. Hence, not only can stimulating TSHR autoantibodies influence TED inflammation but the N-TSHR antibodies, representing more of the reactome, may also exaggerate the retro-orbital inflammatory response seen in TED.

Genetically mimicked effects of thyroid dysfunction on diabetic retinopathy risk: a 2-sample univariable and multivariable Mendelian randomization study.

Thyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy. Using data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings. In UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10-1.19; P<0.025). However, MVMR analysis, after adjusting for Graves' disease (GD) and/or rheumatoid arthritis (RA), revealed no significant association between TOS and the four stages of diabetic retinopathy. The Meta-analysis demonstrated the collective effect of TOS on diabetic retinopathy across all stages [OR=1.11; 95% CI (1.08-1.15); P<0.01]. In UVMR analysis, the estimates for hypothyroidism (HPT) and GD were similar to those for TOS. In the MVMR analysis, after adjusting for RA, the significant effect of HPT on DR and non-proliferative diabetic retinopathy (NPDR) remained. Additionally, MVMR analysis suggested that the estimates for GD on DR were not affected by TOS, except for GD-proliferative diabetic retinopathy (PDR). However, no significant correlation persisted after adjusting for RA, including for GD-PDR. Our study demonstrated a significant association between thyroid dysfunction TD and DR, with the relationship being particularly pronounced in HPT-DR.

Use of rituximab in the of immunoinflammatory rheumatic diseases combined with Graves' disease (autoimmune polyglandular syndrome in adults): case report and literature review

Rituximab (RTM) is a chimeric (murine and human) monoclonal antibody against B-lymphocytes (CD20). RTM is widely used in hematology for lymphoproliferative diseases and in rheumatology for rheumatoid arthritis, Sjögren's disease, some types of vasculitis and systemic connective tissue diseases. The administration of RTM is associated with a depletion of B-cells mediated by the regulation of apoptosis and cytotoxic effects via complement-dependent and antibody-dependent mechanisms. Considering the pathogenesis of autoimmune damage in Graves' disease (GD), an autoimmune thyroid disease associated with thyrotoxicosis, the use of RTM could be effective in this pathology. We present three patients with a combination of diffuse toxic goiter and rheumatic pathology treated with RTM; different outcomes of GD were observed.

Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves' Hyperthyroidism with Potassium Iodide.

Graves' hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal 123I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves' disease (GD) with a large goiter (>40 g), 131I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves' Disease.

Previous studies of fixed-dose radioiodine therapy (RIT) for Graves' disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD. This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols. The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117). The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate.

New onset of Graves' disease after controlled ovarian stimulation: A case report and brief literature review.

De novo onset of Graves' disease (GD) after controlled ovarian stimulation (OS) is exceptional. Only one case of progression to GD after OS in a patient with pre-existing subclinical hyperthyroidism has been reported. We describe the case of a patient with neither previous thyroid disorders nor autoimmunity who developed GD after OS for primary infertility. A 40-year-old woman with primary infertility underwent four cycles of OS. Her thyroid function performed before the last cycle was unremarkable (thyroid stimulating hormone [TSH] 1.9 mU/L, fT4 1.3 ng/dL, fT3 2.4 pg/mL), and thyroid autoimmunity was negative (anti-thyroperoxidase antibodies and anti-thyroglobuline antibodies). Six weeks after the last cycle she developed overt thyrotoxicosis (TSH < 0.005 mU/L, fT4 4.79 ng/dL, fT3 15.6 pg/mL) with anti-thyrotropin receptor antibodies (TRAb) positivity (9.2 IU/L). She was diagnosed with GD and anti-thyroid therapy was instituted. After 1 year of treatment, thyroid function was still suboptimal (TSH 0.2 mU/L, fT4 1.04 ng/dL, fT3 2.2 pg/mL), and TRAb titer still elevated (8.75 IU/L). Despite her desire to achieve pregnancy, a further cycle of OS was postponed until complete remission of thyroid dysfunction and withdrawal of anti-thyroid therapy. Although TSH assay after OS is not recommended in euthyroid women without autoimmunity, in the presence of hyperthyroid symptoms throughout OS it is advisable to evaluate thyroid function and TRAb. It is advisable to carefully evaluate the course of GD before proceeding with further courses of OS that could lead to its exacerbation or recurrence. In cases where a strong desire for pregnancy persists, thyroidectomy may be proposed.

Surgical Outcomes in Thyroidectomy for Patients with Graves’ Disease: A Randomized Controlled Trial

Background: Thyroidectomy is a preferred protocol for patients with Graves’ disease. However, it may be a challenging option in post-surgical management of various factors. There, this study aims to compare the surgical outcomes of total thyroidectomy and subtotal thyroidectomy in patients with Graves’ disease to provide evidence-based surgical decision-making. Methods: This randomized controlled trial was conducted at Sheikh Zaid Hospital, Rahim Yar Khan, October 2023 to April 2024; enrolled 120 patients diagnosed with Graves’ disease using a simple random sampling technique were assigned to Group A (n=60) and B (n=60) who underwent total thyroidectomy, and subtotal thyroidectomy respectively. Preoperative assessments and surgeries were performed while postoperative outcomes, complications, and thyroid function tests were also monitored and represented using independent t-tests while a p&lt;0.05 was considered significant. Results: It was revealed that operative time was significantly higher for total thyroidectomy than subtotal thyroidectomy 125.60±14.56 and 97.54±12.56 respectively, suggesting significantly lower time consumption in subtotal thyroidectomy procedure (p=0.001). Patients who underwent subtotal thyroidectomy had a significantly shorter hospital stay compared to those who underwent total thyroidectomy (p=0.02). Moreover, levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were significantly different between the two groups. Patients who underwent subtotal thyroidectomy had significantly lower T3 and T4 levels and higher TSH levels compared to those who underwent total thyroidectomy (p&lt;0.05). Conclusion: Subtotal thyroidectomy demonstrated favorable outcomes, including shorter operative time, lower rates of postoperative complications, and thyroid function tests compared to total thyroidectomy. These findings help and support the consideration of subtotal thyroidectomy as a viable surgical approach for patients with Graves' disease. Keywords: Grave Disease, Thyroidectomy, Thyroxine, Triiodothyronine.

Unveiling the Role of Gut Microbiota and Metabolites in Autoimmune Thyroid Diseases: Emerging Perspectives.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.

Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease

Background &amp; Objective: Graves’ disease (GD) is an autoimmune condition that targets the thyroid gland, resulting in excessive stimulation and synthesis of thyroid hormones. Excessive synthesis of these hormones can lead to symptoms such as loss of body weight, accelerated heart rate, irritability, reduced tolerance to heat, and excessive perspiration. Alpha-Klotho (KL), a protein crucial for physiological processes, is also involved in GD. The defective immunological condition of GD patients may increase Klotho expression, and the enhanced expression of fibroblast growth factor-23 (FGF23) in GD may be linked to the disease pathophysiology. We investigated serum levels of KL and FGF23 in Iraqi patients with Graves’ disease, analyzing correlations with clinical status and evaluating their potential as biomarkers for disease activity. Methodology: We conducted this cross-sectional study at The National Diabetes Center, Mustansiriyah University, between December 2022 and April 2023. The study involved 103 patients diagnosed with GD, and 103 patients, aged 21-70 y, as a control group. Patients with multinodular goiter, single thyroid nodules, thyroiditis, pregnant women, and those on medications or oral contraceptives, were excluded. Result: clinical significance of FGF23 and Klotho (KL) levels in patients with Graves’ disease (GD) compared to a control group. Results indicate that the median of KL levels are significantly higher in GD patients (KL = 6.31) compared to the control group (KL = 2.40), with a highly significant difference (P &lt; 0.001). In contrast, differences in median of FGF23 levels between GD patients (149) and controls (86.05) were not statistically significant (P = 0.07). Furthermore, KL levels were significantly higher in hyperthyroid patients compared to other thyroid statuses (P = 0.023), while FGF23 levels did not significantly differ across thyroid statuses (P = 0.255). Additionally, the study found a strong correlation between TRAb levels and both KL (r = 0.291, P &lt; 0.001) and FGF23 (r = 0.211, P = 0.003), and between KL and FGF23 directly (r = 0.412, P &lt; 0.001). These findings suggest that while KL may be a significant biomarker in GD, FGF23 relevance appears limited in this context. Conclusion: In Graves’ Disease patients have significantly higher levels of KL and FGF23 compared to controls, suggesting a distinct pathophysiological role for these biomarkers in mineral homeostasis and thyroid hormone regulation. Abbreviations: AITD - Autoimmune thyroid diseases; KL - Alpha-Klotho; FGF23 - fibroblast growth factor-23; GD - Graves’ disease; HT - Hashimoto's thyroiditis; IGF-1R - Insulin-like Growth Factor-1 Receptor; Keywords: Autoimmune Thyroid Disorders, Hyperthyroidism, Graves’ disease, Alpha-Klotho Citation: Rashid MF, Alammar HAJ, Rahmah AM. Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease. Anaesth. pain intensive care 2024;28(5):836−841. DOI: 10.35975/apic.v28i5.2567 Received: June 16, 2024; Reviewed: July 07, 2024; Accepted: July 18, 2024

6581 Case of Conversion from Hashimoto’s Thyroiditis to Graves’ Disease: An Unusual Sequence

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: The two most common autoimmune thyroid diseases are Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is a destructive thyroiditis, via autoantibodies most commonly against the thyroid peroxidase enzyme (anti-TPO), while GD results in hyperthyroidism, due to TSH-receptor stimulating antibodies (TSAb) and Thyroid Stimulating Immunoglobulin (TSI). Case Report: A 23-year-old male presented to the clinic with complaints of weight gain, dry skin and excessive hair loss. His physical examination was non-contributory and laboratory evaluation revealed a TSH of 130 uIU/ml (ref: 0.45-4.5), free T4 (fT4) 0.4 ng/dl (ref: 0.82-1.77), and positive anti-TPO antibodies, for which he was started on levothyroxine (LT4) supplementation for newly diagnosed HT. Over the first five months on treatment, his TSH and T4 progressively improved to 31.8 uIU/ml and 1.48 ng/dl, respectively. Six months later, his TSH rapidly decreased to 0.01 uIU/ml, with an fT4 elevation to 2.45 ng/dl, alongside developing hyperthyroid symptoms like weight loss, insomnia and palpitations. Due to persistently positive anti-TPO antibody titers, his hyperthyroidism was considered iatrogenic, and LT4 dose was gradually reduced, but eventually required to be discontinued. A thyroid ultrasound depicted generalized increase in vascularity, consistent with active thyroiditis. He continued to have a significantly suppressed TSH &amp;lt;0.005 uIU/ml and elevated fT4, off all medications, and was also found to have multiple positive antibody titers [TSI of 1.02 IU/L (ref: &amp;lt; 0.55), thyroglobulin antibody of 351 IU/ml (&amp;lt; 0.9) and anti-TPO Ab &amp;gt;600 IU/ml (ref&amp;lt; 34)]. He was then diagnosed with new GD, and thyroid suppression therapy with 10mg/day of methimazole was initiated, to which he rapidly responded, with a TSH of 0.059 uIU/ml and reduced fT4 of 1.37 ng/dl. His diagnosis of GD was confirmed via an I-123 thyroid uptake scan which revealed a homogenous increased tracer uptake of 57% at 24 hours (ref 15-35%), following which he received definitive therapy for GD, with radio-active iodine (RAI) ablation with 20.6 mCi of I-131. Discussion: As HT and GD have a common autoimmunity-based pathophysiology, conversions between the two clinical states have been described, though HT to GD, as seen in our patient is much less common than the reverse conversion. Some described mechanisms include an antibody switch from thyrotropin receptor blocking to stimulating action, HT-induced thyrotroph destruction resulting in GD antibody formation, and treatment with LT4. Simultaneously elevated levels of both TSI and anti-TPO can occur, and therefore treatment and diagnosis should be based on thyroid function tests and clinical presentation. Patients with autoimmune thyroid disease require close monitoring, due to the potential risk of conversion from one clinical end of the spectrum to the other, and early recognition is important. Presentation: 6/1/2024

7729 Autoimmune Thyroid Disease And Risk of Premature Ovarian Failure - A Comprehensive Analysis Combining Observational Studies, Two-sample Mendelian Randomization Study, And Targeted Drug Forecast

Abstract Disclosure: R. Wang: None. T. Dou: None. L. Guan: None. X. Qi: None. X. Wang: None. C. Yu: None. Q. Guan: None. Premature ovarian failure (POF), a condition impacting women's fertility and physical well-being. Specifically, autoimmune thyroid disease (TAI) is recognized as an organ-specific autoimmune condition that may co-occur with POF in clinical scenarios, yet the precise nature of their relationship remains uncertain. The objective of this study is to investigate the influence of TAI on ovarian function, identify shared pathogenic genes, predict potentially effective drugs, and establish a foundation for clinical interventions. Firstly, a case-controlled study was conducted using the Nationwide Readmissions Database (NRD) in the United States. This involved identifying patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) as the study group, and those without deficiency as the control group, to explore the correlation with POF. Additionally, an Asian population-based case group comprising 897 patients with POF and a control group of 897 healthy women were gathered to analyze the association of POF with TAI-related antibodies, namely TGAb and TPOAb. Furthermore, a two-sample Mendelian randomization(MR) study was undertaken in European populations to investigate the causal relationship between TAI and POF. Lastly, genes associated with HT, GD, and POF were compiled from the GEO, GeneCards, and DisGeNET databases, and common genes were identified through intersection. Subsequent gene ontology and pathway enrichment analyses, protein-protein interaction analyses, and candidate drug predictions were performed based on the shared genes. The findings revealed a significant association between TAI and POF in the NRD, with patients exhibiting TAI being notably more prone to POF compared to the control group (OR 1.78, 1.34-2.35, P&amp;lt;0.001). Subgroup analysis further demonstrated an increased risk of POF in patients with HT (OR 1.51, 1.02-2.22, P&amp;lt;0.05) and GD (OR 2.18, 1.45-3.29, P&amp;lt;0.05). In the Asian population, a retrospective analysis indicated a positive correlation between TPOAB positivity and POF (OR 1.76, 1.24-2.51, P&amp;lt;0.05). MR analysis unveiled a causal relationship between GD and POF. Through a comprehensive examination of multiple gene databases, 47 common genes were identified between HT and POF, and 20 common genes between GD and POF. Enrichment analysis demonstrated relative similarities in cytokines and signal transduction, apoptosis, inflammatory response, and other aspects between HT and POF. GD was found to potentially influence ovarian function through pathways such as the PI3K-Akt signaling pathway and adhesive plaques. Dexamethasone, rapamycin, and other drugs emerged as potential therapeutic options for both diseases. In summary, our study suggests that TAI, particularly GD, may elevate the risk of POF. Additionally, we predict potential therapeutic drugs, and shed light on the potential biological mechanisms linking HT/GD and POF. Presentation: 6/3/2024