Hashimoto's Thyroiditis Research Articles

On Vascular Lesions of the Thyroid Gland with Emphasis on Intrathyroidal Hemangioma: Clinicopathologic Characterization of Two Cases and Review of the Literature

Mesenchymal neoplasms of the thyroid gland are exceptionally rare accounting for less than 0.5% of all intrathyroidal tumors with hemangiomas comprising merely 6% of them. The clinicopathologic characteristics of two additional examples of thyroid hemangioma together with a thorough review of the pertinent literature are presented. A 62-year-old man and an 18-year-old woman presented with asymptomatic, soft-to-palpation, mobile nodules of the right thyroid lobe classified as TI-RADS 5 and TI-RADS 4, respectively, on ultrasound imaging. Microscopically, lesions featured a circumscribed, unencapsulated, lobular proliferation of variably-sized, congested, vascular channels lined by a single layer of flattened, cytologically bland endothelial cells, together with interspersed residual follicles. Vascular endothelial cells were strongly positive for CD31, CD34 and ERG, and negative for pancytokeratin AE1/AE3, TTF1, and PAX8. A diagnosis of cavernous hemangioma was rendered in the clinical setting of Hashimoto thyroiditis and follicular adenoma, respectively. Following inclusion of the current cases, a total of 53 intrathyroidal hemangiomas were identified in the literature with a patient mean age of 48.9 years (range = 0.17-84) and a slight female predilection (F:M = 1.4:1). A proclivity for the right thyroid lobe (59.6%) was noted with the striking majority of cases exhibiting features of cavernous hemangioma (95.2%). Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.

Role of immune cells in mediating the effect of gut microbiota on Hashimoto's thyroiditis: a 2-sample Mendelian randomization study.

Hashimoto's thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT. In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures. There was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT. In conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT.

Vestibular Dysfunction in Euthyroid Children with Hashimoto's Thyroiditis.

A relationship exists between autoimmune thyroid disorders and vestibular dysfunction. This study aimed to analyze cervicalevoked myogenic potentials (cVEMP) and video head impulse test (vHIT) results between children with Hashimoto thyroiditis (HT) and healthy controls to determine vestibular end-organ problems. Thirty-six children with HT and 30 healthy subjects were recruited. The main inclusion criteria for the healthy group were the presence of normal thyroid function and no clinical history of vestibular problems. Each participant (both HT and healthy groups) was assessed using audiovestibular tests, cVEMP, and vHIT. There was no significant difference between the groups in terms of cVEMP (p1 and n1) latencies for both ears. There was no significant difference in cVEMP amplitudes (p1-n1 peak-to-peak) between the groups. There were statistically significant differences in the VOR gain of the right and left ears between the groups (P < .001, P < .001). When we considered lower cutoff value as 0.80 for VOR gain, 29 of 36 patients with HT (80.6%) had lower VOR gain scores. Only 1 of 30 healthy participants (3.3%) had a lower VOR gain score. This difference was statistically significant (P < .001). Subclinical vestibulopathy may occur in children with HT. The vHIT seems to be a valuable tool for identifying and screening preclinical vestibular pathologies in this patient group.

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

Causal relationship between antihypertensive drugs and Hashimoto's thyroiditis: a drug-target Mendelian randomization study.

Recent studies have indicated a potential association of hypertension with Hashimoto's thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genome-wide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies. Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10-5) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10-3). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10-5) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10-3) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications. The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT.

Adrenal hypoplasia congenita and hypogonadotropic hypogonadism due to a novel NR0B1 (DAX1) gene mutation associated with common variable immunodeficiency and Hashimoto's thyroiditis.

Not required for Clinical Vignette.

6644 Glycosylation Patterns of the IgG Variable Region in Thyroglobulin Antibodies and Their Impact on Antigen Binding Affinity

Abstract Disclosure: S. Wang: None. Y. Cao: None. C. Zhao: None. C. Huang: None. K. Zhao: None. Y. Li: None. Y. Huang: None. Z. Ying: None. Y. Zhang: None. Y. Gao: None. Objective: Thyroglobulin antibodies (TgAb), key serological markers in Hashimoto's thyroiditis (HT) patients, are predominantly in immunoglobulin G (IgG) form. Prior research has highlighted the importance of increased glycosylation in TgAb IgG from HT patients. This study investigates the unique glycosylation patterns of F(ab')₂ fragments in TgAb IgG in HT patients, compared to healthy individuals. It focuses on how these patterns differ and their impact on binding to thyroglobulin (Tg). Exploring the role of N-glycosylation in the F(ab')₂ segment of TgAb IgG is crucial for understanding its effect on immune responses in HT, potentially unveiling key mechanisms of the disease. Methods: To assess serum TgAb levels in HT patients (n≥28), we used an electrochemiluminescence immunoassay, dividing patients into medium-level (mHT, n≥14) and high-level (hHT, n≥14) groups. TgAb IgG was isolated from serum of both HT and control groups (n = 14) using affinity chromatography. TgAb IgG was then cleaved with Ides enzyme to yield TgAb IgG F(ab’)2 and Fc fragments. The F(ab')2 fragment of TgAb IgG underwent MALDI-QIT-TOF-MS mass spectrometry for glycosylation profiling. Additionally, mixed TgAb IgG was separated using columns that recognize mannose and terminal sialic acid, yielding high mannose and high terminal sialic acid TgAb IgG. Different TgAb IgG glycoforms were prepared through enzymatic treatment with peptide-N-glycosidase F, β1-4 galactosidase, and α2-3,6,8 neuraminidase. The binding affinity of these TgAb IgG to Tg antigen was measured using Tg specific ELISA and surface plasmon resonance (SPR). Results: Using MALDI-TOF MS, we identified 22 IgG glycan types in both HT and control (Con) groups. In the hHT group, six glycan types (G0F, G1F, G2F, M5A1, A3G1F, A3F) were upregulated compared to Con, with statistical significance (p &amp;lt; 0.05). The mHT group showed increased levels of G1F and G2F compared to Con (p &amp;lt; 0.05). Between hHT and mHT, only A3F was significantly elevated (p &amp;lt; 0.05). Removal of N-glycosylation from IgG TgAb F(ab)2 reduced binding to Tg antigen. Presence of both mannose and terminal sialic acid in TgAb enhanced the binding to Tg. Conclusions: Most TgAb IgG in the variable region of HT patients contain N-glycans. The glycosylation patterns of TgAb IgG F(ab)2 in HT differ significantly from healthy controls, affecting antibody binding affinity. Our findings reveal the complex role of glycosylation patterns in TgAb IgG, providing new insights into HT pathogenesis and potential research directions. 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

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

8229 Prevalence of Thyroid Cancer in Patients with Hashimotos Thyroiditis Presenting Concomitant Thyroid Nodular Disease

Abstract Disclosure: M.A. Alvarez Castillo: None. L. Sanchez Arriaga: None. A. Segovia Palomo: None. Introduction: Hashimoto's thyroiditis (HT) is the most frequent autoimmune thyroid disease and the main cause of goiter and hypothyroidism; it induces a process of aseptic autoimmune inflammation. Fibroinflammatory changes lead to the development of thyroid nodules (TN), additionally chronic inflammation is an important player in the development of cancer, although this association is controversial. The prevalence of thyroid cancer (TC) in patients with HT ranges from 0.61-58.4% (25.01%), being higher than in patients with TN without concomitant HT. Objective: To know the prevalence of malignancy in patients with HT who present thyroid nodular disease. Methodology: An observational, descriptive, retrospective, and longitudinal study was carried out. Patients with HT diagnosis were selected by measuring Ab TPO and/or Ab TG who presented an ultrasound diagnosis of TN and FNAB of the thyroid lesion had been performed. Descriptive statistics and linear regression were used. Results: 87 patients: 6 (6.9%) men and 81 (93.1%) women aged 47.9 (12.7) years. 4 (4.5%) required FNAB in 2 TN, for a total of 91 TN studied. 64% had a diagnosis of hypothyroidism and were taking LT4, TSH 4.40 (4.44) mUI/mL, FT4 1.00 (0.27) ng/dL. Mean Ab TPO was 794.7 ± 1354.6. Diagnosis time 19.5 (29.1) months. 39.6% the detection was made by the patient and 35.2% by the doctor. Major axis was 18.8 (12.1) mm. Ultrasound pattern of single TN 58.2% and multinodular 41.8%. Median TIRADS was 4, with a mode of 5. 81.3% reported Bethesda II and 18.7% malignant or suspected, were sent for surgery, malignancy was confirmed in 16/ 17 lesions. 14 (15.3%) were TPC and 2 lymphomas, the main subtypes were classic papillary and NHL, respectively. Mode of ATA risk was intermediate. Multivariate analysis only TIRADS represented risk factor (OR 2.08) Conclusions: The frequency of TC in our population was 15.3%, which reflects a higher prevalence of malignancy in thyroid nodules in patients with chronic thyroiditis, in accordance with what has been reported in other series. Presentation: 6/3/2024

6771 New onset Graves’ Disease in a Patient with Hashimoto's Thyroiditis and Positive Thyroid Peroxidase Autoantibodies. Case Report

Abstract Disclosure: M.M. Eid: None. J.L. Zapater: None. Introduction: Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) are the most common thyroid autoimmune disorders. Transition of GD to HT is common, but transition of HT to GD is rare. Case: A 55 year old, female with depression, HTN and fibromyalgia. She was referred for evaluation of chronic fatigue and reduction in functional capacity. Five years earlier, she had also been evaluated for fatigue. Labs at that time: TSH 3.80 µIU/ml (0.35-3.74 µIU/ml), free T4 0.8 ng/dl (0.76-1.46 ng/dl), thyroid peroxidase antibody (anti-TPO) 605.6 U/ml (0-60 U/ml), and anti-thyroglobulin antibody (anti-TG) 37.2 U/ml (0-60 U/ml). Subclinical hypothyroidism was diagnosed, but no levothyroxine was initiated. Her TSH was found to be normal in 2019 and 2021. At the current clinical encounter, other than fatigue she denies weight/voice change, tremor, palpitation, anxiety, recent flu like illness or radiation exposure, neck swelling/pain, heat intolerance, or difficulty swallowing. Her daily medications are amlodipine 10mg and duloxetine 20mg. She had menopause 2 years ago. She has no known allergy. She has a brother with rheumatoid arthritis. She denies smoking or alcohol consumption. On exam, vital signs are normal, and BMI is 28.1. There is diffuse, firm thyromegaly without a palpable nodule. There is no cervical lymphadenopathy, tremor, neck tenderness, exophthalmos, or lid lag. Creatinine, liver enzymes are normal but hemoglobin is 9gm/dl. Anti-tissue transglutaminase and anti-gliadin antibodies were negative. Her thyroid labs were: TSH &amp;lt;0.008 uIU/ml, free T4 1.06ng/dl, free T3 4.07 pg/ml (2.3-4.2 pg/ml), total T3 1.74 ng/ml (0.60-1.81 ng/ml), anti-TPO antibody 12,414 U/ml, anti-TG antibody 22 U/ml, thyrotropin receptor antibody (TRAB) 15.24 IU/L (0-1.75 IU/L), and thyroid stimulating immunoglobulin (TSI) 331% (&amp;lt;130%). Thyroid uptake scan showed 49% iodine-131 uptake in symmetric and homogenous uptake, and no hot or cold nodules. GD was diagnosed, methimazole 5mg daily was initiated. Conclusion: Our case had subclinical HT with positive anti-TPO antibodies 5 years preceding the onset of GD. Causes of autoimmune conversion are not well understood. Viral infection or radiation exposure in genetic susceptible patients have been assumed as triggers (1). The blocking and stimulating action of TRAB on TSH receptors is considered as a possible mechanism of switching between hypothyroidism and hyperthyroidism. Clinical and biochemical evaluation for possible conversion to GD in patients with HT is recommended (2).

8176 An Unusual Case of Thyroid Eye Disease (TED) Occurring in Autoimmune Hypothyroidism

Abstract Disclosure: K. Prasongdee: None. C.M. Tessier: None. Background: It is unusual for TED to present in patients with autoimmune thyroid disease who are euthyroid or hypothyroid. Clinician recognition of this rare presentation is important in ensuring proper treatment and improving patient outcomes. Clinical Case:Our patient is a 57-year-old female with a past medical history of COPD, hypothyroidism presenting with several months of blurry vision. She reports double vision when looking down, and eye pain at rest and with eye movement. She was diagnosed with hypothyroidism one year prior to presentation, and her TSH subsequently normalized after titration to levothyroxine of 112 mcg daily. She reported no history of head or neck radiation. No family history of thyroid disease. She smoked for 30 pack years but stopped 2 years prior. Physical exam showed eye lid swelling and redness, pain and diplopia on end-lateral gaze, no chemosis, no conjunctival injection, or inflammation of the caruncle, lids closed completely, proptosis with Hertel ophthalmometer measured 23 mm on the right eye and 22 mm in the left eye (normal range &amp;lt; 18 to 20 mm for Caucasians), thyroid not enlarged with no palpable nodules, no thyroid bruits. The initial Clinical Activity Score (CAS) was 4, which indicated active TED. A thyroid ultrasound showed Inhomogeneous echogenicity with increased vascularity consistent with autoimmune thyroiditis. An MRI of the orbits revealed diffuse extraocular muscle enhancement and enlargement with tendinous insertion sparing, increased T2 hyperintensity findings which favored thyroid eye disease. Further laboratory testing confirmed the presence of multiple thyroid autoantibodies: Thyrotropin binding inhibitory immunoglobulin 2.76 IU/L (normal range &amp;lt; 1.75 IU/L), Thyroid peroxidase antibody 1135 IU/mL (normal range &amp;lt;9 IU/mL), Thyroglobulin antibodies 157 IU/mL (normal range &amp;lt; 116 IU/mL), thyroid-stimulating immunoglobulin 447% (normal range &amp;lt;140 % Baseline). She was referred to ophthalmology for management of TED and was started on teprotumumab. Her CAS improved to 0 and her diplopia resolved. Her proptosis remained stable. This case illustrates an unusual clinical course in a patient who initially presented with autoimmune hypothyroidism, later developed Thyroid Eye Disease. A study by Kahaly GJ et al showed that in Hashimoto’s thyroiditis (HT), thyroid-stimulating autoantibodies are highly correlated with thyroid eye disease (TED) with positive thyroid-stimulating autoantibodies detected in 5.5% of the patients with HT and 68.2% in the patients with HT and TED. Even though it is less common, up to 6% of patients with HT may be affected by TED. Rare presentations such as this case emphasizes the need to be vigilant when evaluating eye symptoms in patients with autoimmune thyroid disease. Teprotumumab that showed improvement in patients with Grave’s and thyroid eye disease, was also successful in treating our patient symptoms. Presentation: 6/3/2024

8062 Uncommon Presentation of Multiple Myeloma as a Rapidly Growing Thyroid Goiter Initially Thought to be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (&amp;lt; 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (&amp;lt;1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

8806 A Case of Autoimmune Thyroid Switching

Abstract Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None. Autoimmune thyroid disease comprises both hyper- and hypothyroid states including Graves' disease and Hashimoto's thyroiditis, respectively. The predominant antibody activity, demonstrable by thyrotropin receptor antibody, predicts the clinical presentation and treatment; thyrotropin receptor antibodies may act as a stimulatory or inhibitory stimulus upon the thyroid gland recognized as thyroid stimulating antibody(TSAb) and thyroid blocking antibody(TBAb). Rarely patients may transition from a hyperthyroid to a hypothyroid state and vice versa if the predominant antibody activity shifts which may occur due to a variety of mechanisms and characteristics related to each individual patient and treatment course. A 29 year old female presented to establish care for autoimmune thyroiditis. She was diagnosed with Graves' disease at age 19 when pregnant and treated with propylthiouracil; she switched to methimazole for the next six years when her thyroid function normalized and therapy discontinued. Two years later she became concerned with weight gain and her thyroid function was reevaluated demonstrating hypothyroidism and she was treated with levothyroxine 25mcg daily until presentation. Further labwork revealed undetectable TSI, and TPO antibody elevated at 177 u/mL. She became clinically and biochemically euthyroid on levothyroxine 50mcg daily. Switching between hyper- and hypothyroid states is a rare occurrence among patients with may attributable factors. Both antithyroid drugs including methimazole as well as replacement therapy with levothyroxine may alter the antibody milieu and so the predominant ratio and activity among TSAb and TBAb thereby leading to a shift in clinical presentation and thyroid state. Pregnancy may lead to hemodilution contributing to lessening of autoimmune activity which may return following delivery leading typically to a shift from TSAb to TBAb. Uncontrolled hyper- and hypothyroidism may affect dendritic activity leading to altered presentation and increased immune reactivity. The unlikely occurrence of switching from a hyperthyroid to a hypothyroid state based upon autoimmunity as in this patient was likely affected these factors. Recognition of this potential transition and associated factors would lead to beneficial monitoring and possibly development of assays more attuned to this phenomenon with better capability in maintaining a euthyroid state and potentially predicting a transition. Presentation: 6/3/2024

7668 Rhabdomyolysis Associated with Severe Hypothyroidism

Abstract Disclosure: H. Soe: None. P. Mikkilineni: None. Background: Over 70% of the patients with newly diagnosed hypothyroidism can present with muscle complaints such as weakness, fatigability, cramps, myalgia. However, rhabdomyolysis, which is the rapid breakdown of skeletal muscle cells, is the rare presentation. Clinical Case: A 70-year old male patient with history of rheumatoid arthritis, hyperlipidemia, prior CVA (left hemispheric subcortical stroke) 6 months ago without residual deficit presented to the hospital with poor oral intake and generalized muscle weakness for 3 weeks. He was unable to get out of bed without assistance and also needed adult diapers. Found to have new-onset severe hypothyroidism with TSH 228 uIU/ml (Ref: 0.350-4.940) and FT4 &amp;lt;0.40 ng/dL (Ref: 0.70-1.50), positive TPO antibody 197 IU/ml (Ref: 0-34). No prior thyroid labs were available and no known history of thyroid disorder was recorded. He has never been on Amiodarone or Lithium before. On physical exam, he was alert and oriented. There was no goiter or palpable thyroid nodule. There was no focal neurological deficit and no peripheral edema. There were no other signs and symptoms pertinent to hypothyroidism except mild bradycardia (HR 56-60) and borderline low blood pressure. AM cortisol was 10.1 ug/dL (Ref: 3.7-19.4). EKG showed low-voltage sinus bradycardia. Echocardiogram was normal. Urinalysis was positive for large blood but only 3 RBCs were present which raised the suspicion of rhabdomyolysis. Creatinine kinase (CK) was 15,584 IU/L (Ref: 30-200). Other laboratory studies were significant for acute renal failure with mild hyperkalemia and mild hypocalcemia, also transaminitis; BUN 130 mg/dl (Ref: 8-26), Creatinine 9.51 mg/dl (Ref: 0.72-1.25), eGFR 5 ml/min/1.73 m2 (Ref: &amp;gt;59), AST 435 IU/L (Ref: 5-34), ALT 269 IU/L (Ref: &amp;lt;55), ALP 171 IU/L (Ref: 40-150). On medication review, he was started on Atorvastatin 80 mg daily during prior admission for CVA 6 months ago. He received IV fluids, s/p 1 dose of Hydrocortisone 100 mg IV, Levothyroxine IV 200 mcg, followed by Levothyroxine IV 50 mcg daily x 3 days and switched to Levothyroxine PO 100 mcg daily (weight-based dose). Atorvastatin was on hold. He became anuric during the hospital course and received 2-3 sessions of hemodialysis. 3-4 days later, CK was trending down to 3000 IU/L, FT4 improved to 0.54 ng/dl and there was also significant improvement in kidney and liver functions. The patient was diagnosed with acute renal failure secondary to rhabdomyolysis associated with severe hypothyroidism caused by Hashimoto's thyroiditis, in the setting of high dose statin use. Conclusion: Clinicians should raise the suspicion of rhabdomyolysis in a patient with severe hypothyroidism, especially in patients with recent high dose statin use as rhabdomyolysis can be a rare and fatal complication of severe hypothyroidism, in the presence of precipitating factors. Presentation: 6/2/2024

5039 Chronic Painful Hashimoto's Thyroiditis

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

6781 A Rare Case of Diffuse Large B Cell Lymphoma of the Thyroid

Abstract Disclosure: D. Deyar: None. M. Herrera: None. M. Ahmad: None. P. Ucciferro: None. Introduction: Primary thyroid lymphoma (PTL) is rare, comprising less than 5% of thyroid cancers. It is frequently seen in middle-aged women and 1.5% of patients with Hashimoto’s thyroiditis. PTL may present with rapidly growing mass, dysphagia, stridor, or hoarseness. We describe a case of a female patient presenting with a neck mass and new onset hypothyroidism who was found to have DLBCL of the thyroid. We aim to raise clinical awareness regarding PTL and elucidate its association with Hashimoto’s disease and discuss treatment strategies. Case presentation: The patient was a 62-year-old female with a past medical history of type 2 diabetes, hypertension, and hyperlipidemia, presenting for worsening neck swelling for the past four weeks. She reported tenderness around the mass along with voice hoarseness and difficulty swallowing. She also reported increased shortness of breath associated with the mass while lying flat and denied any heat intolerance, cold intolerance, weight changes or bowel habit changes. The patient’s vitals were as follows: blood pressure: 146/104 mmHg, heart rate: 58 beats per minute, temperature: 36.3 C, respiratory rate: 20 breaths per minute. Initial blood work demonstrated the following: sodium: 137 mmol/L, potassium: 4.2 mmol/L, 9.4 mg/dL, white blood cell count: 12.1 × 109/L, hemoglobin: 14.5 g/dL, platelets: 330 × 109/L, thyroid stimulating hormone: 17.1 uIU/mL, free T4: 0.4 ng/dL, and TPO antibodies: 300 IU/mL. A CT scan of her neck demonstrated a left sided mass measuring 6.6 cm, by 5.6 cm, by 11 cm. The patient was started on 50 mcg of levothyroxine and was assessed by otorhinolaryngology and underwent fine needle aspiration biopsy. The patient’s biopsy demonstrated diffuse large B cell lymphoma of the thyroid gland. The patient was started on R-CHOP chemotherapy for her lymphoma as an outpatient and had a significant decrease in the size of her neck mass and improvement in her compressive symptoms. She is scheduled for six cycles of R-CHOP therapy and continues to follow with oncology. Discussion: Diffuse Large B Cell Lymphoma (DLBCL) of the thyroid is rare and necessitates distinct therapeutic considerations. Patients with Hashimoto's thyroiditis have been found to be 60-fold times more likely to develop primary thyroid lymphoma as compared to those without thyroiditis. The pathophysiology regarding this association remains unclear, however some suggest it may be due to chronic lymphocytic inflammation of the thyroid gland leading to monoclonal lymphocyte growth. Treatment of DLBCL of the thyroid requires immunotherapy, most commonly with the R-CHOP therapy which distinguishes it from the conventional management of thyroid carcinomas. Physicians should be vigilant in considering these treatment differences and to consider PTL as an etiology of growing thyroid mass in patients with Hashimoto’s thyroiditis. Presentation: 6/2/2024