Autoimmune Thyroid Disease Research Articles

Case study of thyroid dysfunction associated with polycystic ovarian syndrome (PCOS)

Background: In recent times, there's a noticeable rise in endocrine dysfunctions, with increasing clinical resemblance between PCOS and autoimmune thyroid disease. The exact cause of this association remains uncertain, but these conditions share a reciprocal relationship. While they exhibit common clinical features, risk factors, and pathophysiological abnormalities, the root causes differ. Polycystic ovaries can be a manifestation of hypothyroidism, making it necessary to rule out hypothyroidism before diagnosing PCOS. Common factors like increased adipose tissue, insulin resistance, high leptin, and abnormal autoimmunity play a vital role in linking these conditions. These shared signs and symptoms emphasize the association between PCOS and hypothyroidism, though the etiopathological basis of this complex relationship is not fully established. Methodology: Cross-Sectional study of 200 patients involved after history, examination. Statistical analysis by SPSS v.22. Result: In this study, we aimed to evaluate thyroid function in PCOS patients using serum TSH levels and estimate the prevalence of hypothyroidism. We also examined prolactin levels in diagnosed PCOS patients, considering criteria like age distribution, BMI, clinical manifestations, fertility status, and thyroid status. Conclusion: Our findings suggest that PCOS is more prevalent in patients with thyroid disorders such as autoimmune thyroiditis and subclinical hypothyroidism compared to the general population. Additionally, PCOS increases the risk of cardiovascular diseases like hypertension and dyslipidemia. Subclinical hypothyroidism with PCOS further elevates the risk of hypertension compared to euthyroid PCOS patients. The study reveals that thyroid dysfunction occurs in 29.0% of PCOS patients, emphasizing importance of screening for thyroid abnormalities in PCOS patients.

Thyroid Disease and Systemic Lupus Erythematosus.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21-79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p < 0.05, chi-square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.

Tumor Inflammatory Microenvironment of the Thyroid Cancer: Relationship between Regulatory T-Cell Imbalance, and p-NFΚB (p65) Expression—A Preliminary Study

Background: Inflammatory microenvironment is an essential component of all tumors, including thyroid cancer. Autoimmune thyroid diseases are often associated with thyroid cancer. CD25, expressed in Treg cells and B cells, has been found to be associated with autoimmune thyroid diseases and the NFkB pathway is critical to tumor formation, regulating immune-related genes, and pro-inflammatory cytokine. Methods: Protein expression of CD25 and NFkB and its phosphorylated form was analyzed by immunohistochemistry in 80 patients with thyroid cancer (10 cases of cancers with Hashimoto’s thyroiditis and 70 cases without). Results: CD25 was mainly detected in the nucleus of the inflammatory cells such as in the thyrocytes and neoplastic cells. Protein staining was detected in the T-lymphocytes of the outermost zone of the lymphoid follicles. Moreover, in all cancer alterations, there were a higher level of p-NFkB than in the surrounding tissues. Again, p-NFkB staining was evident in neoplastic cells but not evident in inflammatory cells. Conclusions: Strong inflammatory infiltrate in the tumor microenvironment is correlated with an invasive phenotype. CD25 and p-NFkB levels were statistically significantly overexpressed in cancer cells.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Exploring the role of gut microbiota in autoimmune thyroid disorders: a systematic review and meta-analysis.

Autoimmune thyroid diseases (AITDs) are characterized by unique immune responses against thyroid antigens and persist over time. The most common types of AITDs are Graves&apos; disease (GD) and Hashimoto&apos;s thyroiditis (HT). There is mounting evidence that changes in the microbiota may play a role in the onset and development of AITDs. The purpose of this comprehensive literature study was to answer the following query: Is there a difference in microbiota in those who have AITDs? According to the standards set out by the PRISMA statement, 16 studies met the requirements for inclusion after being screened for eligibility. The Simpson index was the only diversity measure shown to be considerably lower in patients with GD compared to healthy participants, whereas all other indices were found to be significantly greater in patients with HT. The latter group, however, showed a greater relative abundance of Bacteroidetes and Actinobacteria at the phylum level, and consequently of Prevotella and Bifidobacterium at the genus level. The strongest positive and negative relationships were seen for thyroid peroxidase antibodies and bacterial load. Overall, both GD and HT patients showed significant changes in the gut microbiota&apos;s diversity and composition. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432455.

Rituximab in the treatment of Graves’ disease and endocrine ophthalmopathy. Opportunities and limitations

Rituximab is a chimeric (mouse and human) monoclonal antibody against B-lymphocytes (CD20). This drug is widely used in rheumatology in the treatment of rheumatoid arthritis, Sjogren’s syndrome, some systemic connective tissue diseases and vasculitis, as well as in hematology in lymphoproliferative diseases. Administration of rituximab leads to depletion of B-lymphocytes through various mechanisms, including antibody-dependent and complementdependent cytotoxic effects, as well as the regulation of apoptosis. Considering the mechanism of autoimmune damage in Graves’ disease, an autoimmune thyroid disease accompanied by thyrotoxicosis and endocrine ophthalmopathy (an autoimmune lesion of the accessory apparatus of the eye), the use of rituximab may be effective in these diseases. The review considers the currently available results of studies on the use of various doses of rituximab in these diseases.

Height, Autoimmune Thyroid Disease, and Thyroid Cancer: A Mendelian Randomization Study.

Background: Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association between height and hypothyroidism or thyroid cancer has not been thoroughly explored. Autoimmune thyroid disease (AITD) mainly presents as hypothyroidism, thus we aim to evaluate the causal relationship between height as exposure and its association with AITD or thyroid cancer. Methods: Mendelian randomization (MR) analyses were performed by using genetic instruments associated with height, which were selected from the largest genome-wide association meta-analysis for height in up to 5.4 million individuals. Summary-level data for AITD and thyroid cancer (including 30,234 and 3001 cases, respectively) were collected from the large number of available genome-wide association studies. Bidirectional MR was performed to test for reverse causal association between AITD and adult height. Results: MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], p-value = 1.99E-03) per 1-standard deviation (SD) increase in genetically predicted height. The bidirectional MR did not show any causal association between AITD and adult height. Additionally, increased genetically predicted height was associated with 15% increased risk of thyroid cancer ([CI 1.07 to 1.23], p-value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. Conclusions: This MR study showed that 1-SD increase in genetically predicted height was associated with increased risk of AITD and thyroid cancer. In contrast, there was no evidence of a causal association of genetically predicted AITD with height. These results could further aid in investigation of height-related pathways as a means of gaining new mechanistic insights into AITD and thyroid cancer.

Association between rheumatoid arthritis and autoimmune thyroid disease: evidence from complementary genetic methods.

To assess the causal association of Rheumatoid Arthritis (RA) with Autoimmune thyroid disease (AITD). Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between RA and AITD using summary statistics from large-scale genome-wide association studies (GWASs). Various sensitivity analyses had been conducted to assess the robustness and the consistency of the findings. The linkage disequilibrium score regression revealed a shared genetic structure between RA and AITD, with the significant genetic correlation between RA and autoimmune hyperthyroidism and autoimmune hypothyroidism estimated to be 0.3945 (P = 2.83 × 10-6) and 0.2771 (P = 1.04 × 10-6) respectively. The results of MR analysis showed that RA had a positive causal relationship with autoimmune hypothyroidism and autoimmune hyperthyroidism. The odds ratio (OR) were 1.29 (95% CI, 1.17-1.42; P = 1.08 × 10-7) and 1.47 (95% CI, 1.25-1.72; P = 1.85 × 10-6), respectively. In reverse MR analysis, autoimmune hypothyroidism had a positive causal relationship with RA, OR was 1.51 (95% CI, 1.37-1.66; P = 1.10 × 10-16); autoimmune hyperthyroidism had no causal relationship with RA relationship (P = 0.22). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between RA and AITD. Our study suggested a potentially causal effect of genetically predicted RA on autoimmune hyperthyroidism and a bidirectional causal relationship between RA and autoimmune hypothyroidism was also observed with complementary genetic approaches, which supports the importance and necessity of thyroid function screening and monitoring in RA patient management in clinical practice.

Diabete mellito dopo trattamento con ocrelizumab per sclerosi multipla primariamente progressiva

Objectives: immune reconstitution therapies, which include antibody-based cell-depleting therapies targeting CD20+ (ocrelizumab, ofatumumab) or CD52+ (alemtuzumab) leukocytes, are approved for the treatment of multiple sclerosis. Autoimmune thyroid disease is the most common adverse effect of treatment with alemtuzumab, but some cases of autoimmune diabetes have been reported. To date, diabetes mellitus has not been reported after CD20-targeting monoclonal antibodies therapy. Case Report: a 41-year-old man with primary progressive multiple sclerosis was diagnosed with diabetes mellitus six months following the first ocrelizumab infusion. He experienced polyuria and polydipsia, but not other symptoms as visual loss or weight loss. We started a basal-bolus insulin therapy, with progressive and relatively rapid improvement of glycemic control. To note, C-peptide resulted indicative of a preserved beta-cell activity and autoantibodies were negative. To present date, the patient reached an excellent control with metformin. Conclusions: this is the first case of diabetes mellitus reported after ocrelizumab administration. The timing of onset and course are similar to alemtuzumab-induced autoimmune diseases, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion appears inferior in duration and cell population affected. This case suggests the need for screening and follow-up of glycemic status in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to elucidate the correlation between hyperglycemia and ocrelizumab.

Innate Immunity in Autoimmune Thyroid Disease during Pregnancy.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.

Genetic link between primary sclerosing cholangitis and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study.

Observational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship between PSC and TD remains uncertain. The purpose of this study is to investigate the causal associations and specific direction between these two conditions. Gaining insight into the potential causal relationship between PSC and TD is valuable for elucidating the pathogenesis of PSC and for devising innovative approaches for the prevention and treatment of PSC and its associated complications. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between PSC and TD, such as autoimmune thyroid disease (AITD), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), among others. PSC was the exposure variable, while TD was the outcome variable. To identify suitable instrumental variables (IVs), we utilized genome-wide association study (GWAS) datasets to select potential candidate single-nucleotide polymorphisms (SNPs). The primary statistical approach employed was the inverse-variance weighted (IVW) method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy. We found that the causal associations between genetically predicted PSC and Graves' disease (GD), hyperthyroidism (IVW OR=1.230, 95%CI: 1.089-1.389, P=0.001; IVW OR=1.001, 95%CI: 1.000-1.002, P=0.000) were statistically significant. The reverse MR analysis indicated that genetic susceptibility to hyperthyroidism (P=0.000) and hypothyroidism (p=0.028) might be the risk of PSC. There was no statistically significant causal association observed between PSC and other TD (IVW P>0.05), with the exception of GD, hyperthyroidism, and hypothyroidism as determined through bidirectional two-sample analysis. To ensure the reliability of our findings, additional sensitivity analyses were conducted, including the leave-one-out (LOO) test, heterogeneity test, and pleiotropic test. In this study, we conducted an investigation into the causal association between PSC and TD. Our findings indicate that PSC significantly elevates the susceptibility to GD and hyperthyroidism from a statistical perspective. These results shed light on the etiology of PSC and have implications for the management of patients with PSC.

HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression.

Recent studies have shown that thyrocytes are permissive to HHV-6A infection and that the virus may contribute to the pathogenesis of autoimmune thyroiditis. Thyroid autoimmune diseases increase the risk of papillary cancer, which is not surprising considering that chronic inflammation activates pathways that are also pro-oncogenic. Moreover, in this condition, cell proliferation is stimulated as an attempt to repair tissue damage caused by the inflammatory process. Interestingly, it has been reported that the well-differentiated papillary thyroid carcinoma (PTC), the less aggressive form of thyroid tumor, may progress to the more aggressive follicular thyroid carcinoma (FTC) and eventually to the anaplastic thyroid carcinoma (ATC), and that to such progression contributes the presence of an inflammatory/immune suppressive tumor microenvironment. In this study, we investigated whether papillary tumor cells (BCPAP) could be infected by human herpes virus-6A (HHV-6A), and if viral infection could induce effects related to cancer progression. We found that the virus dysregulated the expression of several microRNAs, such as miR-155, miR-9, and the miR-221/222 cluster, which are involved in different steps of carcinogenesis, and increased the secretion of pro-inflammatory cytokines, particularly IL-6, which may also sustain thyroid tumor cell growth and promote cancer progression. Genomic instability and the expression of PTEN, reported to act as an oncogene in mutp53-carrying cells such as BCPAP, also increased following HHV-6A-infection. These findings suggest that a ubiquitous herpesvirus such as HHV-6A, which displays a marked tropism for thyrocytes, could be involved in the progression of PTC towards more aggressive forms of thyroid tumor.

Autoimmune thyroid status in subclinical thyroid disorders in patients attending a tertiary care center in Nepal: a hospital-based cross-sectional study

BackgroundThyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles.MethodsThis hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman’s correlation was done to determine the association between variables.ResultsOut of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal.ConclusionThe rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.

FRI544 Serological Profile In Rheumatoid Arthritis And Its Interplay With Autoimmune Thyroid Diseases

Abstract Disclosure: T. Kolitz: None. S. Kivity: None. I. Tessler: None. Y. Marcus-Perlman: None. E. Izkhakov: None. I. Yaish: None. Y. Greenman: None. Objective: Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders, with an estimated prevalence of 5%. AITD encompass the clinical scope of Hashimoto’s thyroiditis (HT) and Graves’s disease (GD). Rheumatoid arthritis (RA) is a relatively common non-organ-specific autoimmune disease with an estimated global prevalence of 0.5-1%. Numerous studies have investigated the association of thyroid disorders and RA in various populations, but results were inconsistent. This study is aimed to assess the rate of AITD in RA patients and to further investigate these rates in subgroups of patients with seronegative RA, seropositive RA and dual-positive RA antibodies [i.e., positive anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF)]. Methods: We used a big-data platform (MDClone Ltd., Israel) to create a cohort of RA patients with and without coexistent AITD. The cohort included 1316 patients who were treated in the Tel Aviv Sourasky Medical Center for any diagnosis between January 2008 and December 2022. Results: There were 340 men (25.8%) and 976 (74.2%) women in the cohort. The mean age at time of initial coding of RA diagnosis in our referral center was 62.5±15 years. AITD was found in 15.5% of the entire RA cohort. Hypothyroidism was the most common thyroid-associated diagnosis (in 95.8% of patients with RA and AITD). When RA patients were further sub-classified to seronegative, seropositive, and dual-positive RA, the rates of AITD were 11.8%, 17.6% and 25%, respectively (p=0.007). AITD rates in seropositive women and men were 20.6% and 8%, respectively (p&amp;lt;0.001). In the RA-seronegative subgroup, the rate of AITD was 15.6% in women and 2.7% in men (p&amp;lt;0.001). The mortality rates in RA-seronegative patients, RA-seronegative patients with AITD, RA-seropositive patients and RA-seropositive patients with AITD were 5.5%, 8.3%, 21.6% and 29.5%, respectively (p=0.05). Conclusion: Our findings suggest that the prevalence of AITD in patients with RA is associated with the specific serological profile, with highest rates in RA patients who are positive for both anti-CCP and RF. Randomized prospective studies are required to explore any cause-and-effect correlation and to delineate the impact of AITD on RA outcome and mortality rates. Presentation: Friday, June 16, 2023

The association between thyroid dysfunction, autoimmune thyroid disease, and rheumatoid arthritis disease severity

BackgroundRheumatoid Arthritis (RA) and autoimmune thyroid disease (AITD) are the two most prevalent coexisting autoimmune diseases due to their similar pathogenesis. Considering the potential effect of AITD on the severity of RA disease, this study aimed to determine the association between thyroid dysfunction, anti-thyroid peroxidase (anti-TPO) positivity, AITD, and RA disease severity in the Iranian population.MethodsThree hundred and fifty RA patients who presented to Shahid Beheshti tertiary care center, Qom, Iran, were included in this cross-sectional study. The data were collected through the patient’s medical records, interviews, physical examinations, and laboratory tests. The RA disease activity score in 28 joints for RA with erythrocyte sedimentation rate (DAS-28-ESR) was used to divide patients into three subgroups, remission (DAS-28-ESR ⩽ 2.6), mild-to-moderate (2.6 < DAS-28-ESR ⩽ 5.1), and severe disease activity (DAS-28-ESR > 5.1).ResultsUsing the aforementioned method, 111, 96, and 138 patients were put into remission, mild-to-moderate, and severe disease activity groups, respectively. Anti-TPO antibody positivity rate was 2.93 times more prevalent among patients with severe disease compared to the remission subgroup (OR: 2.93; P-value < 0.001). Patients suffering from a more severe disease were almost 2.7 times more probable to have AITD (OR = 2.71; P-value < 0.001) and they were 82% more likely to have thyroid dysfunction compared to patients in remission (OR = 1.82; P-value = 0.006).ConclusionsIt was demonstrated that thyroid dysfunction, anti-TPO antibody positivity, and AITD were significantly more common among RA patients with more severe disease activity.

FRI540 A Novel, Rapid, Sensitive Bioassay For Thyrotropin Receptor Stimulatory Antibodies Improves Diagnosis &amp; Management Of Autoimmune Thyroid Disease

Abstract Disclosure: G.J. Kahaly: None. M.A. Lupo: None. A.T. Bossowski: None. L. Frommer: None. B. Hatun: None. A. George: None. J. Wolf: None. Background: Autoantibody mimicry of hormone action at the thyrotropin receptor (TSH-R) and aberrant signaling of TSH-R by autoantibodies (TSH-R-Ab) causes autoimmune thyroid disease (AITD), hyperthyroidism and hypothyroidism, both of which affect millions of patients worldwide. In this multicenter, single blind study, the specificity, sensitivity and performance of a novel bioassay for stimulatory TSH-R-Ab were tested. Methods: TSH-R-Ab were measured in a blinded manner with a TSH-R binding immunoassay (Cobas e411, Roche), and both stimulatory (TSAb) and blocking (TBAb) bioassays with luciferase release as readout (Thyretain®, Quidel) according to manufacturer’s instructions. TSH-R-Ab was also measured using the new TSAb bioassay (TurboTM). TurboTM utilizes a cAMP biosensor that is an engineered form of firefly luciferase in which the cAMP-binding domain of protein kinase A is fused between the N- and C-termini such that the luciferase is inactive until cAMP binds to the cAMP binding site. Using this biosensor, luciferase activity is proportional to intracellular cAMP levels. TurboTM detects TSAb in serum at room temperature, in a real-time homogeneous format, which delivers results in 60 minutes. It does not require cell culture, sample dilution, washing or cell lysis steps. Results: Eight-hundred forty-four samples of unselected, consecutive AITD patients and control subjects, devoid of autoimmune endocrine and thyroid disorders, were included. Mean age (SD) was 49 (14.7) years, range 1-89 years. Female: male sex ratio was 3.7:1. The four TSH-R-Ab assays were negative in all 174 controls. In contrast, the Turbo TSAb, Thyretain® TSAb and the binding assays detected TSAb in 557 of 670 (83%), 526/670 (78%) and 430/637 (67%) AITD samples, respectively (TurboTM bioassay versus binding immunoassay, chi-square test p&amp;lt;0.001). The results of the Turbo bioassay highly correlated with both thyroid function in Graves’ hyperthyroidism as well as with the clinical activity and severity of associated thyroid eye disease (p&amp;lt;0.001). Inter- (two users) and intra- (two lots) assay comparison for the Turbo bioassay showed coefficient of variations of only 4%, 3%, and 2%, respectively. The two TSAb bioassays, TurboTM and Thyretain®, correlated (Spearman’s r =0.7, p&amp;lt;0.001). Furthermore, the magnitude of serum levels in both TSAb bioassays correlated with TSH-R-Ab binding (both p&amp;lt;0.001). Finally, seventeen AITD samples showed dual TSH-R-Ab positivity in the TBAb and TSAb bioassays. Conclusions: The novel, rapid, easy-to-perform, sensitive and specific TurboTM bioassay performs better than the established TSH-R-Ab binding immunoassay and the Thyretain® bioassay. It provides clinically useful information for the accurate diagnosis and management of AITD patients. Presentation: Friday, June 16, 2023

THU364 A Rare Case Of Concurrent Diabetic Ketoacidosis And Grave’s Thyrotoxicosis

Abstract Disclosure: A.D. Teixeira: None. E. Ukponmwan: None. P. Kachhadia: None. S. Aldasouqi: None. A. Abu Limon: None. Introduction: Type 1 Diabetes Mellitus (T1DM) is marked by deranged glycemic control due to the autoimmune destruction of insulin producing β cells in the pancreas. It affects 1.5 million adults in the United States. Approximately one-third of these patients may develop autoimmune polyglandular syndrome (APS). Autoimmune Thyroid Disease (AITD) is the most commonly associated autoimmune disease, with Hashimoto’s Thyroiditis more commonly observed than Graves Disease (GD). Patients with AITD and T1DM meet criteria for APS type 3A. Here, we present a case of a patient hospitalized for T1DM with diabetic ketoacidosis (DKA) who was also found to have concurrent GD. Case Presentation: Our patient was a 50 year old male who presented to the hospital with complaints of nausea and vomiting for a two day duration. He had symptoms of unintentional weight loss, polyuria and polydipsia for about two months prior to presentation. He was found to have blood sugar level of 438 mg/dL, with pH of 7.05 (7.35-7.45), anion gap of 30, bicarbonate level of 7.0 mmol/L (20-30 mmol/L), Beta-hydroxybutyrate level of 82mg/dL (n&amp;lt;4.10 mg/dL). Hemoglobin A1C was 15.1% . EKG revealed atrial fibrillation with RVR, and therefore thyroid function tests (TFTs) were ordered and showed a thyroid stimulating hormone (TSH) level of 0.01uIU/mL (0.35-4 uIU/mL), free thyroxine (FT4) of 1.29 ng/dL (0.61-1.37 ng/dL) and free triiodothyronine (FT3) levels of 4.4 pg/mL (2.8-4.4 pg/mL). Endocrinology evaluation of the patient’s Thyroid US showed some mild vascularity. Cardiac evaluation of patient’s atrial fibrillation did not reveal any other causes of arrythmia. Further labs showed TSI of 2.6 (n&amp;lt;1.3 TSI index) with normal TRAb and TPO levels. T1DM antibody testing revealed GAD-65 antibody (Ab) level of 51.3 nmol/L (n &amp;lt;0.02 nmol/L), Zinc Transporter 8 Ab level of &amp;gt;500 U/mL (n&amp;lt;15 U/mL). He was started on methimazole with good tolerance and was discharged upon resolution of his DKA with multiple daily injections of insulin. Discussion: AITD is the most prevalent autoimmune disease associated with T1DM, with GD being a less common association compared to Hashimoto’s thyroiditis. Many patients diagnosed with T1DM may develop other autoimmune conditions. On rare occasions these diseases can present concurrently, as it did with our patient. Recognition and awareness of APS types helps physicians recognize and screen for other autoimmune conditions that have previously been seen together. Literature search shows very few cases with both diseases presenting at the same time on hospitalization. However, with the recent COVID-19 pandemic, 5 cases were reported of simultaneous disease following vaccination. Our patient had no known exposure to COVID-19 virus or vaccine when he developed symptoms. Presentation: Thursday, June 15, 2023

FRI258 A Diagnostic Journey To Autoimmune Polyendocrine Syndrome Type 2

Abstract Disclosure: S. Amankwah: None. H.K. Driscoll: None. C. Muojieje: None. M. Sanati: None. Background: Approximately 50-65% of patients with autoimmune adrenal insufficiency have one or more autoimmune endocrine disorders. This case demonstrates the importance of considering autoimmune polyendocrine syndrome (APS) when a patient presents with more than one autoimmune endocrine disorder. Case: A 29-year-old woman with history of idiopathic intracranial hypertension, hypothyroidism on levothyroxine 50 mcg daily, endometriosis, and chronic migraines complained of fatigue, word finding difficulty, misspeaking of words, and staring spells. An MRI of the brain w+wo IV contrast revealed hypo-enhancing appearance of the pituitary gland. The patient was referred to endocrinology by neurology. Hormonal work up was performed checking for prolactin, ACTH, morning cortisol, TSH, Free T4, FSH, LH, IGF-1 and a serum chemistry panel. Thyroid antibodies were also ordered to help understand the etiology of her hypothyroidism. Pituitary hormones were normal except elevated TSH and borderline low serum cortisol. Subsequently a co-syntropin stimulation test resulted in inadequate cortisol rise. ACTH level measured inappropriately low normal. The patient then started steroid replacement therapy. Thereafter, 21-hydroxylase antibodies, serum renin and aldosterone were checked to screen for Addison Disease. Her 21-hydroxylase antibody was positive, aldosterone level low, and renin elevated pointing to autoimmune adrenalitis etiology. Her thyroid antibodies were also positive indicating autoimmune thyroid disease. Considering these results, the condition of APS came into question. Hence, the patient was screened for type 1 diabetes mellitus which was positive for glutamic acid decarboxylase 65 antibody but negative for insulin and pancreatic islet cell antibodies. Her hemoglobin A1c was 5.0%. Due to her history of gluten intolerance, she was screened for celiac disease which was negative for t-Transglutaminase antibody. The patient’s fatigue improved on steroid replacement therapy. She became euthyroid after increasing her levothyroxine dose to 75 mcg daily, and repeated MRI a year later did not show pituitary abnormalities. Discussion: APS type 2 is a polygenic inherited disorder associated with HLA-DR3 and DR4 that affects adult females more than males. The syndrome is characterized by type 1 diabetes mellitus, autoimmune thyroid disease and Addison disease. Associated nonendocrine autoimmune syndromes include celiac disease, pernicious anemia, and atrophic gastritis. These characteristics overlap with APS type 1 except for autoimmune thyroid disease that presents with type 2. It should be noted that thyroxine therapy can precipitate a life-threatening Addison crisis in a patient with untreated adrenal insufficiency and hypothyroidism. Therefore, it is necessary to evaluate adrenal function in all hypothyroid patients in whom APS is suspected. Presentation: Friday, June 16, 2023

FRI537 Thyrotropin Receptor Blocking Antibodies - A Multicenter, 4-Assay Comparison

Abstract Disclosure: A. George: None. A.T. Bossowski: None. B. Hatun: None. J. König: None. M.A. Lupo: None. L. Frommer: None. J. Wolf: None. G.J. Kahaly: None. Background: Thyrotropin receptor (TSH-R) blocking autoantibodies (TBAb) are present in 10-15% of patients with autoimmune thyroid disease (AITD). TBAb are functional, impact thyroid function, and are clinically relevant. This multicenter study compares, in a large collective of AITD subjects, the sensitivity and specificity of four immunoassays for the measurement of TBAb and introduces a novel and ultra-rapid TBAb bioassay. Methods: Serum samples from AITD patients were tested with a TSH-R binding immunoassay (Cobas e411, Roche, Penzberg, Germany), an established cell-based TBAb reporter bioassay (Thyretain®, Quidel, San Diego, USA) with expression of a Luciferase transgene as readout and a new “TurboTM” TBAb bioassay (Quidel) with a readout that is based on a cyclic AMP-activated luciferase. A Passing-Bablok regression and intra- and inter-assay validations were performed. All samples were also tested for stimulating TSH-R-Ab (TSAb, Thyretain®, Quidel). Results: Of 1011, unselected, consecutive AITD patients (Graves’ disease and Hashimoto thyroiditis), 132 patients and 212 samples were TBAb positive. Median age was 32 years (25/75 percentile 13.25/46.5 years) and female: male ratio was 2.86:1. Of 212 samples, 149 (70.3%), 47 (23,1%) and 16 (7,5%) were hypothyroid, euthyroid and hyperthyroid, respectively. Thyroperoxidase and thyroglobulin antibodies were present in 136 (64.15%) and 70 (33.02%) samples, respectively. The four TSH-R-Ab assays were negative in 90 control subjects devoid of autoimmune thyroid and endocrine disorders. In contrast, the TurboTM cAMP TBAb, Luciferase TBAb and the Cobas binding assays detected TBAb in 212 (100%), 168 (79%) and 137/180 (76%) samples, respectively (Chi-square test p&amp;lt;0.001). The TurboTM TBAb bioassay highly correlated with thyroid function (p=0.007). Furthermore, the magnitude of percentage inhibition in both TurboTM and Luciferase TBAb bioassays correlated with TSH-R-Ab binding assay positivity (both p&amp;lt;0.001). Seventeen of 212 (8%) samples showed dual TSH-R-Ab positivity in the Turbo TBAb and TSAb bioassays, while 13 (6.1%) samples showed dual positivity for TSAb and TBAb in all three bioassays. The two TBAb bioassays correlated (Spearman’s r =0.59, p&amp;lt; 0.001). Single-user testing and intra-assay validation demonstrated adequate precision with very low coefficient of variation (CV 0.05) and low CV (0.14) at 92% and 44% inhibition (serum TBAb positivity), respectively. Conclusions: This is the largest reported collective of TBAb-positive samples in AITD patients, measured with four different immunoassays. TBAb markedly affects thyroid function. The novel, easy-to-perform, rapid and reliable TurboTM blocking bioassay detected significantly more TBAb than the established immunoassays demonstrating both its higher analytical performance and clinical utility in the management of AITD patients. Presentation: Friday, June 16, 2023

SAT467 Monitoring TSH Over Time May Not Be Necessary in Patients With Thyroid Nodules

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: A substantial number of patients with thyroid nodules receive monitoring of blood thyroid stimulating hormone (TSH) levels after the initial diagnosis. There is not enough literature supporting long-term monitoring of blood TSH levels in these patients with thyroid nodules. The objective of this study was to evaluate the change in blood TSH level in patients with known thyroid nodules over time and to determine if repeat blood TSH testing is required in these patients. We hypothesized that monitoring of blood TSH level is not warranted in patients with thyroid nodules in the absence of a history of medical conditions or medications that are known to affect thyroid hormone levels. Methods: We studied 100 patients aged 18 to 99 years at the Dayton VA Medical Center with at least one thyroid nodule on imaging studies from January 2010 to December 2016 with normal blood TSH level at time of the diagnosis of the thyroid nodule. Subjects with abnormal thyroid hormone level, history of hot thyroid nodule, autoimmune thyroid disease (on imaging or blood work), thyroid or pituitary surgery, radioactive iodine treatment, neck irradiation, or usage of thyroxine or any other medications known to affect thyroid hormone levels were excluded. Blood TSH level at the time of diagnosis of thyroid nodule and after were retrospectively studied and analyzed for 100 subjects. Normal blood TSH level range at time of diagnosis was noted to be 0.35-5.50 uIU/mL or 0.35-4.00 uIU/mL depending on the assay method used. Normal repeat blood TSH level range was noted to be 0.35-5.50 uIU/mL, 0.35-4.00 uIU/mL, or 0.55-4.78 uIU/mL depending on the assay method used. Results: 100 subjects with normal blood TSH at the time of diagnosis of their thyroid nodule had blood TSH level monitoring for an average time period of 5.74 years. Out of the 100, six subjects (6%, 95% CI [2.52%, 12.73%]) developed an abnormal blood TSH level in a mean time period of 6.94 years. One subject’s initial blood TSH level increased from 3.38 uIU/mL to 7.76 uIU/mL after 8.52 years. This subject did not receive treatment with thyroxine. In the other five subjects, blood TSH level decreased to below normal range in a mean time period of 6.63 years and ranged from 0.25-0.52 uIU/mL. Blood TSH level remained within normal range for 94 subjects in a mean time period of 5.67 years. Conclusion: Monitoring of blood TSH level over time may not be required in most patients with thyroid nodules in the absence of symptoms, medical conditions, or medications that are known to affect thyroid hormone levels. Presentation Date: Saturday, June 17, 2023