Treatment Of Graves' Disease Research Articles

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.

8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?

Abstract Disclosure: K.S. Hill: None. R. Osman: None. Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use. Presentation: 6/3/2024

STAT6 blockade ameliorates thyroid function in Graves' disease via downregulation of the sodium/iodide symporter.

Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous study demonstrated that blockading STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS. Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1cells were incubated with IL4, TSH (Thyroid stimulating hormone) or monoclonal TSAb (thyroid-specific stimulatory autoantibody) for 24h. Quantitative RT-PCR,Western blot and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used Luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene. NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves' disease (GD) patients and TSAb increased the expression of NIS. We show that STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation. In Graves' disease, TSAb induces STAT6 signaling to upregulate NIS expression and STAT6 blockade ameliorates thyroid function via downregulation of the sodium/iodide symporter. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment.

Approach to the Patient: Challenging Cases of Pediatric Thyrotoxicosis.

Graves' disease (GD) is the leading cause of hyperthyroidism in children. However, compared to adults GD in children is a rare condition. In a recent guideline issued by the European Thyroid Association the diagnostic evaluation and treatment of pediatric GD is described extensively. In this article we go beyond the guideline and describe the potential challenges of establishing the right etiology of thyrotoxicosis in children, illustrated by cases of thyroid hormone resistance, autonomous functioning thyroid nodules and subacute thyroiditis with a thyrotoxic phase. In addition, we report therapeutic challenges in pediatric GD such as recurrent immunological flare-ups under anti-thyroid drug (ATD) treatment, innovative ways to improve ATD compliance and the role of definitive treatment in persistent complaints of malaise under ATD treatment.

Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis.

Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions. In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit. A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217±444.24 v/s 214.74±55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference. The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.

Effects of low-dose methotrexate with MMI in patients with Graves' disease: results of a randomized clinical trial.

Supplemental methotrexate (MTX) may affect the clinical course of Graves' disease (GD). Evaluate efficacy of add-on MTX on medical treatment in GD. Prospective, open-label, randomized supplementation controlled trial. Academic endocrine outpatient clinic. One hundred and fifty-three untreated hyperthyroid patients with GD. Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients. Discontinuation rate at months 18 in each group. In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771). Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.

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.

Association between serum vitamin D level and Graves’ disease: a systematic review and meta-analysis

ObjectiveThis meta-analysis aims to analyze the relationship between serum vitamin D (VD) levels and Graves’ disease (GD).MethodsWe conducted a search for publications on VD and GD in the English language. Our search encompassed databases such as PubMed, Embase, Web of Science, and the Cochrane Library, covering publications available through August 2023. A meta-analysis was performed using Cochrane RevMan 5.4 software. The standardized mean difference (SMD) and 95% confidence interval (CI) were used for outcome calculation. We used R software to test for publication bias.ResultsTwelve studies were selected, comprising 937 (22.4%) cases with GD and 3254 (77.6%) controls. The overall meta-analysis revealed that patients with GD are significantly more likely to have low VD levels (SMD = − 0.66; 95% CI: −1.05, − 0.27; p = 0.001) than those in the control group. Egger’s test results indicated no publication bias (p = 0.0791). These studies exhibited a high degree of heterogeneity (chi-square = 205.86, p < 0.00001; I2 = 95%). Subgroup analysis was conducted based on assay method, geographic location, and mean age of the case group to explore the heterogeneity sources. Assay methods and geographic locations were identified as potential heterogeneity sources. Based on the mean age, there were no statistically significant differences found in the subgroup analysis of the included studies.ConclusionThere is promising evidence that low serum VD levels may increase the risk of GD. Further rigorous and long-term trials are needed to explore the role of VD in the onset and treatment of GD.

Graves' disease in children with Down syndrome.

While subclinical or overt hypothyroidism are common in Down syndrome (DS); Graves' disease (GD) is rare (ranges 0.6-3%). We aimed to evaluate the clinical features, course, and treatment of GD in children with DS and compare them with those without DS. Among 161 children with GD, 13 (8 female, 5 male) had DS (8%). Data were collected retrospectively from patients' medical records. The mean age at diagnosis was 10.6 ± 4.5 years, with a female-to-male ratio 1.6:1. The main symptoms were weight loss (n = 6), increased irritability (n = 3), and increased sweating (n = 3). None had orbitopathy. Seven of 11 patients with a thyroid ultrasound at diagnosis had a goitre. On admission, all had thyroid-stimulating hormone (TSH) <0.01 mU/L (normal range (NR): 0.51-4.30), free triiodothyronine, free thyroxine (mean ± s.d .), and thyrotrophin receptor antibodies (median, range) were 22.2 ± 10.2 pmol/L (NR: 3.5-8.1), 50.2 ± 18.7 pmol/L (NR 12.6-20.9), and 17.0 (2.89-159.0) U/L (NR <1), respectively. Patients were treated either with methimazole (n = 10) or carbimazole (n = 3), a dose of 0.54 ± 0.36 mg/kg/day. The treatment was 'block and replace' in ten patients and 'dose titration' in three patients, with a mean duration of 43.4 ± 11.0 months. Of 13 patients, four are still receiving primary treatment, three are in remission, one patient had two medically treated recurrences, three underwent surgery without complications, and two patients were lost to follow-up. Our data show that the clinical course of GD in patients with DS was similar to those without DS and suggest that a prolonged medical therapy should be the preferred option.

The main principles of managing patients with Graves’ disease in clinical practice

BACKGROUND: Graves’ disease (GD) is a common cause of persistent thyrotoxicosis. In regions with adequate iodine intake, the incidence is 20–30 cases per 100,000 people. Modern treatment of GD includes antithyroid drugs, radioactive iodine therapy (RAI), and thyroidectomy. The choice of treatment strategy is based on the severity of thyrotoxicosis, the frequency of potential side effects, the availability of treatment options, and the likelihood of achieving sustained remission. Previous studies have demonstrated differences in approaches to diagnosis, treatment, and follow-up between countries and individual specialists.AIM: To conduct a survey on the current clinical practice of treating Graves’ disease in Russia.MATERIALS AND METHODS: An online survey was conducted among physicians in 2022-2023. The questions covered the principles of diagnosis, treatment, and dynamic observation of adult patients with Graves’ disease.RESULTS: The study involved 104 physicians of various specialties who treat patients with Graves’ disease. Approximately 99% of respondents chose the determination of thyroid-stimulating hormone receptor antibodies (TSHR-ab) to clarify the etiology of thyrotoxicosis, while only 60.6% of them chose thyroid scintigraphy. As the first-line treatment method, antithyroid drug therapy is chosen by 88.5%, while 13.5% of physicians use radioactive iodine therapy (RAI), and less than 1% of respondents refer patients to thyroidectomy. Thiamazole is most commonly used (99%), while propylthiouracil (PTU) is used in cases of allergy to thiamazole or during the first trimester of pregnancy. The «block-replace» scheme is preferred over the «block» scheme, with 72.1% compared to 28.8%, respectively. The majority of physicians (95.2%) initiate therapy with moderate doses of thiamazole (20–30 mg) and PTU (200–300 mg). Most physicians conduct dynamic monitoring of liver transaminase levels (57.7%) and complete blood count (78.8%). Conservative therapy is prescribed for a period of 12–18 months (88.5%) or up to 24 months (10.6%). Before discontinuing antithyroid drug therapy, 89.4% of respondents monitor thyroid hormone levels, 82.7% monitor TSHR-Ab levels, and 47.1% perform thyroid ultrasound. Repeat courses of conservative therapy are prescribed for up to 61.5% of respondents. Approximately 63.5% of surveyed physicians reported difficulties in referring patients for radical treatment due to a limited number of specialized institutions. Physicians cited patient unwillingness and the need to postpone pregnancy (81.6% and 24.3% respectively) as the main inhibitory factors for RAI. Thyroidectomy was associated with patient unwillingness (69.2%), as well as physician fear of laryngeal paralysis (48.1%) and postoperative hypoparathyroidism (49%).CONCLUSION: The results of the study demonstrated that physicians in their practice generally adhere to international recommendations for the treatment of Graves’ disease.

Abstract 54: Engineering chimeric antigen receptor (CAR) T cells using autoantigen binding domains for treatment of B cell malignancies with increased specificity

Abstract Introduction: Chronic inflammation often leads to cancer, and many autoimmune diseases lead to a significantly increased risk of developing cancer. Though many autoimmune diseases, like Graves’ Disease (GD), don’t have treatments that address this risk. Chimeric antigen receptor (CAR) T cells are an effective treatment for hematological cancers by eliminating all B cells, but a more targeted form of CAR T cells could eliminate specific B cell populations in B cell malignancies, including GD. Methods: To allow our CAR T cells to target specific B cell populations that cause GD, we engineered chimeric autoantigen receptors (CAAR) with epitopes of thyroid stimulating hormone receptor (TSHR) as the binding domain. This acts as bait for the anti-TSHR B cells. Jurkat T cells were lentivirally transduced with these CAAR plasmids. Anti-TSHR B cell lines were engineered by transducing Nalm6 cells with lentivirus for anti-TSHR B cell receptors. Cytotoxicity assays were performed on primary human TSHR CAAR T cells incubated with the anti-TSHR B cell lines. Cytokine production, proliferation, and cytotoxicity assays were performed on these coincubated cells to determine the efficacy of our TSHR CAAR T cells. Results: Two of the three Jurkat TSHR CAAR T cells showed significant binding to anti-TSHR antibodies (TRAbs). They also showed significant activation, measured by CD69 expression, when incubated with plate bound TRAbs, but not soluble TRAbs. The B cell lines were validated by binding to TSHR. The primary TSHR CAAR T cells showed significantly increased proliferation and production of TNF, IFN-y, and IL-2, when compared with controls. The TSHR CAAR T cells also had significant cytotoxic action against the anti-TSHR B cell lines, but not Nalm6 B cells. The cytotoxic function was comparable to our CD19 CAR T cell with the same activation domains, though it demonstrated specificity to only anti-TSHR B cells. Conclusion: TSHR CAAR T cells are a potentially curative treatment for GD that will stop chronic inflammation and could reduce GD patient’s risk of developing thyroid cancer. This is also an important development in CAR T cell therapies that allows for specific targeting of certain B cell populations. Citation Format: Abiagil Cheever, Hunter Lindsay, MacKenzie Hansen, Chloe Kang, K. Scott Weber, Kim O'Neill. Engineering chimeric antigen receptor (CAR) T cells using autoantigen binding domains for treatment of B cell malignancies with increased specificity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 54.

The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial.

Graves' disease (GD) is characterized by thyroid overactivity. Anti-thyroid drugs (ATDs), such as propylthiouracil (PTU) and methimazole (MMI), are commonly used for GD treatment, and studies have suggested a link between these drugs and elevated lipoprotein levels. However, data on their effects on lipoproteins, insulin resistance, or low-density lipoprotein receptor (LDL-R) levels are lacking, both in Indonesia and in other countries. This study investigated changes in lipoproteins, LDL-R, and insulin resistance markers with ATD treatment. This study is a secondary analysis of a randomized clinical trial entitled "The Differential Effects of Propylthiouracil and Methimazole as Graves' Disease Treatment on Vascular Atherosclerosis Markers" conducted in Jakarta, Indonesia. Thirty-seven newly diagnosed GD patients received MMI or PTU for 3 months. After 3 months of ATD treatment, LDL-R levels significantly decreased compared to baseline (197 vs. 144 ng/mL, p<0.001), while most lipoproteins, including TC, LDL-C, HDL-C, non-HDL-C, the cholesterol ratio, and the LDL-C/HDL-C ratio, increased. Unexpectedly, neither the PTU nor MMI groups showed an increased dyslipidemia prevalence. Although body mass index increased significantly and fasting plasma glucose decreased slightly, no significant post-treatment change in insulin resistance was observed. The study received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (ref KET-784/UN.2.F1/ETIK/PPM.00.02/2019) and was registered on clinicaltrials.gov (NCT05118542). ATD treatment for GD led to a significant increase in total cholesterol, LDL-cholesterol, and high-density lipoprotein-cholesterol levels, along with a reduction in LDL-R levels. Both PTU and MMI showed similar effects. These findings provide valuable insights into the effects of ATDs on lipoproteins and insulin resistance in GD patients. ClinicalTrials.gov Identifier: NCT05118542.

Significance of Gut Microbiota on Graves' Disease.

Growing research proves gut microbiota and thyroid autoimmunity are linked. Graves' disease (GD), as an autoimmune thyroid disease (AITD), is attributed to the production of thyroid-stimulating hormone receptor (TSHR) autoantibodies that bind to the thyroid follicular endothelial cells. It is well known that genetic factors, environmental factors, and immune disorders count for much in the development of GD. So far, the pathogenesis of GD is not elucidated. Emerging research reveals that the change in gut microbiota composition and its metabolites are related to GD. The gut microbial diversity is reduced in GDs compared with healthy controls (HCs). Firmicutes and Bacteroidetes account for a large proportion at the genus level. It is found that phyla Bacteroidetes increased while phyla Firmicutes decreased in Graves' Disease patients (GD patients). Moreover, gut microbiota modulates the immune system to produce cytokines through bacterial metabolites. This article aims to find out the relation between gut microbiota dysbiosis and the development of GD. As more molecular pathways of bacterial metabolites are revealed, targeting microbiota is expected to the treatment of GD.

Evaluation of YouTube As A Source For Graves' Disease Information: Is High-Quality Guideline-Based Information Available?

To understand the quality of informational Graves' disease (GD) videos on YouTube for treatment decision-making quality and inclusion of American Thyroid Association (ATA) treatment guidelines. Cross-sectional cohort. Informational YouTube videos with subject matter "Graves' Disease treatment." The top 50 videos based on our query were assessed using the DISCERN instrument. This validated algorithm discretely rates treatment-related information from excellent (≥4.5) to very poor (<1.9). Videos were also screened for ATA guideline inclusion. Descriptive statistics were used for cohort characterization. Univariate and multivariate linear regressions characterized factors associated with DISCERN scores. Significance was set at P < .05. The videos featured 57,513.43 views (SD = 162,579.25), 1054.70 likes (SD = 2329.77), and 168.80 comments (SD = 292.97). Most were patient education (52%) or patient experience (24%). A minority (40%) were made by thyroid specialists (endocrinologists, endocrine surgeons, or otolaryngologists). Under half did not mention all 3 treatment modalities (44%), and 54% did not mention any ATA recommendations. Overall, videos displayed poor reliability (mean = 2.26, SD = 0.67), treatment information quality (mean = 2.29, SD = 0.75), and overall video quality (mean = 2.47, SD = 1.07). Physician videos were associated with lower likes, views, and comments (P < .001) but higher DISCERN reliability (P = .015) and overall score (P = .019). Longer videos (P = .015), patient accounts (P = .013), and patient experience (P = .002) were associated with lower scores. The most available GD treatment content on YouTube varies significantly in the quality of medical information. This may contribute to suboptimal disease understanding, especially for patients highly engaged with online health information sources.

GRAVES’ DISEASE IS ASSOCIATED WITH INCREASED RISK OF CLINICAL ALZHEIMER’S DISEASE

Abstract Identification of modifiable risk factors for Alzheimer’s Disease (AD) onset is an important aspect of controlling the burden imposed by this disease on an increasing number of older U.S. adults. Graves’ disease (GD), the most common cause of hyperthyroidism in the U.S., has been hypothesized to be associated with increased AD risk, but there is no consensus. In this study, we explore the link between GD and risk of clinical AD. Cox and Fine-Grey models were applied to a retrospective propensity-score-matched cohort of 15,505 individuals with GD drawn from a nationally representative 5% sample of U.S. Medicare beneficiaries age 65+ over the 1991-2017 period. Results showed that the presence of GD was associated with a higher risk of AD (Hazard Ratio [HR]:1.15; 95% Confidence Interval [CI]:1.07-1.23). Magnitude of associated risk varied across subgroups: Males (HR:1.19; CI:1.01-1.41), Females (HR:1.09; CI:1.02-1.18), Whites (HR:1.13; CI:1.04-1.20), Blacks (HR:1.33; CI:1.04-1.20). Competing risk estimates were consistent with these findings. A potential mechanism connecting GD and AD may involve shared etiological factors between the two diseases. Although replication of our findings is needed, they suggest that GD prevention and treatment may contribute to reducing the burden of AD in U.S. older adults.

Antithyroid drug-induced leukopenia and G-CSF administration: a long-term cohort study

Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves’ disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.

FRI564 Thymic Hyperplasia In Graves' Disease: An Under-recognized Association

Abstract Disclosure: S. Nachum: None. A. Rivadeneira: None. K.N. Kobaly: None. Association of thymic hyperplasia (TH) with Graves’ disease (GD) is rare and underrecognized. In an era of increased diagnostic imaging, incidental findings of thymic masses in patients with GD may be increasingly identified and awareness of this association may reduce unnecessary interventions. We report three cases of GD with TH at presentation, one of which includes resolution of TH. CASE 1: 56 year-old man with unintentional weight loss, palpitations and eye discomfort was diagnosed with GD (TSH &amp;lt;0.015, FT4 4.47, TRAB 8.18, TSI 8.51). He had an incidental 3x3 cm anterior mediastinal mass on a chest CT. MRI chest suggested TH. Myasthenia gravis antibodies were negative. I-123 uptake and scan showed diffusely increased uptake within the thyroid gland and no increased uptake in the upper chest corresponding to mediastinal mass. Initiation of methimazole normalized thyroid function. CT chest at 9 months showed near resolution of the anterior mediastinal soft tissue density compatible with resolving TH. CASE 2: 23 year-old woman presented with insomnia, palpitations, and neck pain and was found to have GD (TSH &amp;lt;0.01, FT4 2.75, TRAB 9.16, TSI 8.84). CT neck obtained due to pain showed diffuse enlargement of the thyroid and a soft tissue density in the partially imaged superior mediastinum. Methimazole was started. Further evaluation of mass is pending. CASE 3: 35 year-old man presented with atrial fibrillation and was diagnosed with hyperthyroidism (TSH &amp;lt; 0.01, FT4 5.55). Tc-99m pertechnetate scan showed diffuse uptake consistent with GD. Methimazole was started. CT chest obtained due to concern for pulmonary embolism showed a 12.6 x 3.0 cm anterior mediastinal mass. HCG was undetectable. Further evaluation of mass is pending. Discussion: TH is thought to occur due to hormonal excess stimulating the thymic cortex and immunological mechanisms that result in formation of medullary lymphoid follicles.1 The incidence of TH in GD is unknown as diagnostic imaging is not routinely obtained. A study of thymic biopsies in patients undergoing thyroidectomy found 38% of patients with thyrotoxicosis had histological evidence of TH.2 This benign condition improves with treatment of GD, with decreased thymic size after 5-24 months of treatment with antithyroid drugs.3 In the absence of a discrete mass, invasion of other tissues or calcifications, repeat imaging after 6 months with regression of TH by 50% obviates the need for biopsy.1 Biopsy and thymectomy should be deferred when thyrotoxic due to risk of precipitating thyroid storm4 and be reconsidered if thymus fails to regress on repeat imaging. Additional guidance for observation is needed as the differential diagnosis for mediastinal mass includes diseases warranting more urgent diagnosis and intervention. Identification of high-risk patient characteristics or imaging findings may be of clinical utility in this circumstance. Presentation: Friday, June 16, 2023

FRI542 Long-term Metabolic Outcomes In Graves’ Disease: Is There A Difference Between Oral Anti-thyroid Medications And Radioactive Iodine Treatment?

Abstract Disclosure: E. Shemesh: None. T. Kolitz: None. A. Nathan: None. K.M. Tordjman: None. Y. Greenman: None. E. Izkhakov: None. Introduction: The treatment of hyperthyroidism in patients with Graves’ disease (GD) is associated with various metabolic comorbidities, including weight gain and an increased risk of cardiovascular and cerebrovascular diseases. Few studies have assessed the potential differences in metabolic outcomes between radioactive iodine (RAI) and oral anti-thyroid drug (ATD) therapies. Aim: We sought to investigate the long-term (&amp;gt;10 years) metabolic effects of RAI versus ATD therapy in GD. We also compared the occurrence rates following long-term use to those with short-term (&amp;lt;5 years) use in order to explore a potential "legacy effect". Hypothesis: RAI and oral ATD treatment will differ in their associated risk of metabolic sequelae, including the occurrence of hypertension, dyslipidemia, obesity, and diabetes. Methods: Patients attending the Institute of Endocrinology at the Tel Aviv Sourasky Medical Center filled in a questionnaire on post-RAI or post-ATD treatment for GD. Results: In total, 143 participants had been followed-up for 5 years, and 87 of them (age range 31-88 years, 65 females [74.7%]) had completed &amp;gt;10 years of follow-up (mean follow-up period 14±1 years). During the initial 5-year follow-up period, RAI treatment was associated with a significantly increased rate of obesity and dyslipidemia in the short-term, but no comparable differences persisted into the &amp;gt;10-year follow-up period. However, mean fasting glucose concentrations were higher among RAI recipients compared to ATD recipients (106 and 91 mg/dL, respectively, p=0.037) even after 10 years, and the mean triglyceride concentration was also higher in the former (127 and 88 mg/dL, respectively, p=0.02). There were no significant group differences in the rates of diabetes mellitus or dyslipidemia in the &amp;gt;10-year follow-up period. Conclusions: RAI therapy is associated with long-term higher glucose and triglyceride levels compered to ATD therapy in patients with GD. Clinical metabolic diagnosis are comparable. The significant group differences in the occurrence of metabolic morbidities that had been observed after the first 5 years of follow-up persisted to a greater or lesser extent into the extended &amp;gt;10-year follow-up period, as evidenced by fasting glucose and triglycerides concentrations Presentation: Friday, June 16, 2023

FRI572 Teprotumumab In Unexplored Presentation Of Thyroid Eye Disease

Abstract Disclosure: M.T. Torres Torres: None. A.N. Gonzalez Bossolo: None. M.M. Mangual Garcia: None. Thyroid eye disease (TED) is an autoimmune disease of the orbital soft tissue associated with facial disfigurement, diminished quality of life, and potentially vision-threatening consequences that can occur in 40% of patients with Graves’ disease (GD). All the therapies for this condition were off-label with questionable long-term effects until 2020 when the Federal Drug Administration approved teprotumumab, a human monoclonal antibody against insulin-like growth factor-1 receptor, for the treatment of TED. Randomized placebo-controlled trials have demonstrated that teprotumumab reduces proptosis, diplopia, and Clinical Activity Score (CAS) in patients with active TED of less than 1.3 years of duration who were treatment-naïve or previously treated with &amp;lt; 1g of methylprednisolone equivalent therapy. Data on the efficacy of teprotumumab on cases of longer TED duration or previously treated with eye surgery or &amp;gt; 1g of methylprednisolone equivalent therapy for TED is limited as these patients were excluded from the trials. A 76-year-old nonsmoker male with long-standing hyperthyroidism due to GD, glaucoma, and type 1 diabetes mellitus was referred by ophthalmologist due to TED. He received radioactive iodine (RAI) for treatment of GD after failure to Methimazole therapy. After RAI, he reported progressively worsening bilateral eye edema, redness, pain, vision loss, and diplopia requiring hospitalization for an emergent orbital decompressive surgery and intravenous steroid therapy due to sight-threatening Grave’s orbitopathy. He was discharged home with oral prednisone taper down until it was discontinued 6 months later with mild improvement of symptoms. Physical exam was remarkable for bilateral strabismus, orbital chemosis, conjunctival injection and redness, eyelid swelling, limited eye motion, severely impaired visual acuity and color vision, no proptosis, and a CAS of 5 suggesting active TED. Laboratories showed biochemical euthyroidism and controlled glycemia. Teprotumumab was started 2 years and 8 months after symptom onset with marked improvement of inflammatory signs and symptoms, eye motion, visual acuity, diplopia, intraocular pressure, and CAS score decrease to 1 point suggesting inactive disease within 4 weeks of therapy without adverse side effects. This case describes the positive effects of teprotumumab in a patient with characteristics not previously studied such as active TED of longer duration than in clinical trials, previous treatment with orbital surgery or &amp;gt; 1g of methylprednisolone equivalent therapy, and increased IOP. Rather than drawing conclusions, our goal is to create awareness and promote further research of teprotumumab and novel agents in patients with TED with previously uncharacterized presentations as it may have important implications for their management including significant improvement in their quality of life. Presentation: Friday, June 16, 2023

FRI561 The Thyroid Trifecta

Abstract Disclosure: P. Kachhadia: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. Introduction: Autoimmune Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) may co-exist or may occur alternatingly, known in many case reports as Graves’s Alternans. Hyperfunctioning (Toxic, hot) thyroid nodules (TN) may also co-exist with GD, a rare condition called Marine-Lenhart syndrome. However, the co-existence of HT, GD and TN is perceivably rarer. Case Presentation: The patient is a 45 year old female with a prior history of HT for 20 years, who presented to the clinic with symptoms of minimal eye pain, tremors, fatigue, diarrhea and anxiety. She was not on thyroid replacement, with normal thyroid function tests (TFTs). Physical exam showed bilateral proptosis, a moderate goiter, hand tremors, mild anxiety and tachycardia. Labs showed high TPO (3995.0 IU/mL, n &amp;lt;18 IU/mL), Thyrotropin receptor antibody (5.25 IU/L, n&amp;lt;1.75 IU/L), and Thyroid-stimulating immunoglobulins (1.8 TSI index, n&amp;lt;1.3 TSI index) with low-normal TSH of 0.42 uIU/mL (0.35-4.01 uIU/mL) , mid-range free triiodothyronine (FT3) at 3.6 pg/mL (2.8-4.4 pg/mL) and normal free thyroxine (FT4) at 0.80 NG/dL (0.61-1.37 NG/dL). Thyroid US showed a 2.4 cm left lobe inferior nodule classified as TI-RADS 3. Fine needle aspiration of this nodule was benign. Radioactive Iodine-123 Uptake Scan showed a hot nodule in the left inferior lobe and with visible uptake in the rest of the gland (uptake was mid-normal). She was started on methimazole 5mg once daily and propranolol 10mg BID with improvement in her symptoms. Subsequent TFTs showed stable T4 and T3 and normalization of TSH to 1.78 uIU/mL (0.35-4.01 uIU/mL). Discussion: Marine-Lenhart syndrome was described in 1911 by surgeons David Marine and Carl Lenhart. Graves’ Alternans has been described in the literature, with variable time separation. Though thyroid nodules occur in up to 35% of those with GD, only 1-4.1% are deemed functional nodules. Nuclear medicine imaging via Tc-99m pertechnetate or I-123 iodine at diagnosis of GD generally shows such nodules as cold nodules lacking uptake, while the rest of the gland has diffuse uptake. However, with normalization of TSH through treatment, these cold nodules may alternate uptake and present as hot nodules. Conclusion: In conclusion, this case presents the co-existence of HT, GD and HN, a term we are calling “Thyroid Trifecta”. It is imperative that HNs should be identified if RAI treatment is planned in such patients. Literature review portrays cases in which if thyrotoxicosis persists post RAI treatment for GD, careful examination and repeat RAIU may show a hot nodule consistent with Marine-Lenhart Syndrome. These patients may benefit instead from thyroidectomy. In the case of our patient, definitive treatment options have been discussed and she has been referred for thyroidectomy due to the presence of the TN. RAI ablation will be avoided in view of mild but active thyroid eye disease. Presentation: Friday, June 16, 2023