Elevated Antibody Research Articles

ЦИТОКИНЫ И МАРКЕРЫ ЩИТОВИДНОЙ ЖЕЛЕЗЫ В СЫВОРОТКЕ КРОВИ У ЖЕНЩИН С АУТОИММУННЫМ ТИРЕОИДИТОМ В ДИНАМИКЕ ЛЕЧЕНИЯ

The study involved 147 women aged 31-47 with newly diagnosed AIT and hypothyroidism in the dynamics of replacement therapy with levothyroxine (before and after 6 months). The control group consisted of 63 conditionally healthy women, examined once at the beginning of the study. In peripheral blood serum, the concentrations of TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, RANKL, OPG, TSH and TPOAb were determined.
 It was found that the initially increased values (p<0,001) of IL-1β and IL-6 remained in patients after substitu- tion therapy at higher levels than in the control group (p<0,001). The tendency to an increase in the levels of IL-10 (p=0,056) and IL-17A (p=0,067) revealed at the beginning of therapy was leveled out (p>0,05) by the end of the ob- servation. TNF-α values did not significantly differ from those of the control group both at baseline and after 6 months
 (p=0,166 and p=0,184, respectively). The concentrations of IL-4 (p=0,376 and p=0,179, respectively), IL-8 (p=0,102 and p=0,116, respectively) and OPG (p=0,988 and p=0,661, respectively) remained at the level of the results of healthy women before and after treatment. RANKL concentrations before treatment were elevated (p=0,029), having lost their significant significance after therapy (p=0,096). The initially decreased values of the OPG/RANKL index (p=0,017) also did not differ on repeated examination from the indicators of the control group (p=0,253). After 6 months of taking levo- thyroxine in women with AIT, a significant (p<0,001) decrease in initially elevated TSH levels to the values characteris- tic of the control group was recorded against the background of a significant (p<0,001) increase in the concentrations of initially elevated autoimmune antibodies (p<0,001).
 When examining women with AIT and confirmed hypothyroidism, it was found that replacement therapy with levothyroxine for 6 months did not significantly affect the production of most of the studied cytokines against the back- ground of a decrease in the initially increased TSH values to the values of the control group and a significant increase in the initially increased TPOAb.

PSAT348 Falsely Elevated TSI Antibody Without Causing Hyperthyroidism, in a Hypothyroid Patient

Abstract Introduction Hashimoto's thyroiditis and Graves’ disease are the most common causes for Hypothyroidism and Hyperthyroidism respectively. There are case reports of co-existence of these two disorders in the same patient (1) which causes an alternating clinical course of both hypothyroidism and hyperthyroidism. The Graves’ disease specific Thyroid Stimulating Immunoglobulin (TSI) antibody is reported to have a very high sensitivity and specificity. However, the presence of TSI antibody in a long-standing hypothyroid patient without developing hyperthyroidism, is of extreme rare occurrence. Case Description Our patient is a 58-year-old Caucasian female who has a history of hypothyroidism that was diagnosed in 1990. She was initiated on levothyroxine and had maintained a stable dose of 100 mcg daily for many years. During the initial visit at our endocrinology clinic in December 2020, the patient's labs were consistent with iatrogenic thyrotoxicosis due to a low TSH 0.233 (0.30-4.00 uIU/ml), normal Free T4 1.33 (0.80-1.80 ng/dl) and normal Free T3 2.28 (2.0-4.40 pg/ml). TPO antibody was negative at 11 (0-34 IU/mL). The levothyroxine dose was reduced to 88 mcg daily, but patient did not obtain follow-up labs for many months. In August 2021, the TSH was noted to be normal at 2.29. Patient was also diagnosed with multinodular goiter with the presence bilateral sub centimeter thyroid nodules which had remained stable over the years. However, thyroid ultrasound in December 2020 showed a 1.8 cm left mid to lower pole nodule that was biopsied and reported to be Bethesda category III with benign Afirma Genomic sequencing classifier. Subsequently, patient reported experiencing swelling and pain of bilateral fingers and underwent evaluation by rheumatologist who ordered a panel of blood tests to assess for autoimmune conditions. Interestingly, thyroid antibodies were also assessed, and it came back remarkable for elevated the Graves’ disease specific TSI antibody level 221% (< 140%) and elevated anti-thyroglobulin (TG) antibody 40.6 (<4.1). Patient's medication list was verified, and she was not on any high-dose biotin supplementation, and she denied experiencing any hyperthyroid symptoms. The corresponding thyroid labs were unremarkable with normal TSH 2.2, normal free T4 1.33 and normal free T3 2.28. Patient was reassured about the normal thyroid labs and advised that her symptoms are not thyroid related. The repeat TSH level continues to remain normal and was 2.18 in December 2021. Conclusion Although the presence of TSI antibody has a high positive predictive value for diagnosing Graves’ disease, a falsely elevated TSI antibody, can rarely occur without causing any clinical consequences. Reference (1) Alvin Mathew A, Papaly R, et al. Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi: 10.7759/cureus.19448 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT355 A Case Report Identifying Graves’ Ophthalmopathy in a Myasthenia Gravis Crisis and Response to Teprotumumab

Abstract Background Thyroid disease is relatively common in patients with Myasthenia Gravis (MG), affecting 5%–10% of patients, conversely, the prevalence of MG in patients with Graves’ disease is 0.14%. Of thyroid diseases seen in MG, Graves’ Disease (GD) is the most common. Graves ophthalmopathy (GO) is a known complication associated with GD, however, in patients with MG, its identification may be difficult, as both GD and MG may present with similar ocular signs and subtle differences. This case identifies GO in a MG crisis and its response to teprotumumab. Clinical Case A 53-year-old-woman with MG presented with one year of worsening bilateral eye and arm weakness, fatigue, eye pain, headaches and palpitations. Examination revealed bilateral ptosis, eyelid edema, and ⅘ bilateral upper extremity strength. Workup revealed suppressed TSH (<0.010, n 0.5-5.0 ml U/L) and elevated antibodies: Thyroid Stimulating Immunoglobulin (4.86, n <0.54 IU/L) and Thyrotropin Receptor Antibodies (TRAb) (8.08, n ≤1.75 IU/L). Thyroid ultrasound showed several bilateral cystic nodules and increased thyroid parenchyma vascularity without thyromegaly, suggestive of GD. Thyroid Uptake and Scan showed diffusely elevated 24-hour uptake (71%, n 10-30%) consistent with GD. Treatment was initiated with methimazole 5 mg daily. At follow up, she had symptoms of eyelid weakness, diplopia, headaches, and muscle weakness. Graves’ Ophthalmopathy Clinical Activity Score (CAS) was 5/10. Examination showed bilateral ptosis with eyelid edema, proptosis, conjunctival redness, and chemosis. Extraocular muscle movements intact without pain, normal pupils and visual fields. Ophthalmology review and orbital CT showed bilateral exophthalmos with extraocular muscle thickening consistent with thyroid eye disease (TED). The classic coke-bottle-sign of the anterior tendon of the inferior rectus muscles was noted. Given her presentation, clinical course and progression of TED, she commenced a teprotumumab treatment trial. Clinical improvement of GO was noted upon follow-up assessment after 5 doses of teprotumumab: CAS 2/10, decreasing proptosis on exam, and TRAb (3.86, n ≤1.75 IU/L). Conclusion This case highlights the potentially misleading clinical findings and difficult diagnoses of coexisting GO and MG. Although muscular weakness is common in GD, concomitant MG is rare and may cause profound additional morbidity. Ocular signs in both diseases may cause diagnostic confusion, although ptosis is more consistent with MG and lid retraction with GD alone. GO can mimic some of the neuromuscular and ophthalmologic signs of MG and can be easily missed or mistakenly attributed to either MG or GD. This may result in a delayed diagnosis/inappropriate treatment of GO, thus, clinicians should maintain suspicion for coexisting diagnoses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP635 A rare case of metastatic papillary thyroid carcinoma on NTRK inhibitor with thyrotoxicosis

Abstract We present a case of 26-year-old Hispanic female with neck enlargement and worsening dyspnea. She was noted to have enlarged thyroid nodules; biopsy revealed papillary thyroid carcinoma (PTC) with ETV6-NTRK fusion by next-generation sequencing (NGS). Further work up revealed extensive bilateral milliary pulmonary metastases and Graves’ disease with elevated thyrotropin receptor antibodies and thyroid-stimulating immunoglobulin titers. Tuberculosis work up was negative and bronchoalveolar lavage revealed metastatic PTC. The patient was initiated on larotrectinib (100mg administered twice daily) as well as block-and-replace regimen with levothyroxine and methimazole. Her dyspnea improved and she successfully underwent total thyroidectomy as well as bilateral neck dissections; methimazole and thyroid hormones were discontinued thereafter. Interestingly, patient developed thyrotoxicosis post-surgery even without being on levothyroxine with elevated free T3 at 18 pg/mL (normal range 2.3–4.2), compared to 5.8 pg/mL prior to surgery. Despite discontinuation of levothyroxine, patient continued to be biochemically and clinically hyperthyroid. She was treated with methimazole for 4 months after surgery, and subsequently underwent radioactive iodine (RAI) ablation with 30 mCi of I-131 of sodium iodide. After RAI, thyroid function started to improve, prompting re-initiation of very low dose levothyroxine about 5 months after surgery. Since then, she has remained clinically stable. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach

Abstract Introduction The two most common autoimmune disorders affecting the thyroid gland, namely Graves’ disease and Hashimoto's thyroiditis, represent opposite ends of the same spectrum. They can rarely co-exist in the same patient (1) leading to an unpredictable clinical course and pose a therapeutic challenge, necessitating close monitoring. We present a unique case of a female who switched multiple times between a hypothyroid and hyperthyroid state due to the co-existence of both Hashimoto's thyroiditis and Graves’ disease. Case Description A 78-year-old Caucasian female was diagnosed with hypothyroidism in 2011 by her primary care physician and was started on levothyroxine 50 mcg daily. The TSH level prior to initiation of levothyroxine therapy is unknown, but the first documented TSH level while on therapy in June 2012 was 0.347 uIU/ml (0.45-4.50), free T4 1.1 ng/dl (0.8-1.8) and free T3 3.4 pg/ml (2.3-4.2). Levothyroxine was lowered to 25 mcg daily but repeat TSH was 0.01 uIU/ml in February 2013 and the levothyroxine was discontinued. The TSH level rose to 7.35 uIU/ml in December 2014 and levothyroxine was restarted. However, subsequent dose reduction was required followed by discontinuation due to persistently suppressed TSH levels and the TSI antibody during that time was elevated at 24.10 IU/L (0.00-0.55). Patient established care at our endocrinology clinic in 2019. Initial laboratory findings showed suppressed TSH <0.005 uIU/ml (0.30-4.00), elevated free T3 4.72 pg/ml (2.00-4.40), normal free T4 1.70 ng/dl (0.80-1.80) and elevated TSI antibody 15.50 IU/L. Radioactive iodine uptake scan showed high normal 24 hour uptake at 32% (10-35%) with mild heterogeneous distribution of the radiotracer throughout both lobes of the gland with diminished uptake in the right lower lobe, which corresponded to a 1.3 cm nodule that was biopsied and reported to be Bethesda category II. Patient was initiated on methimazole 5 mg daily. In June 2019, labs showed elevated TSH 6.91 uIU/ml, low free T4 0.74 ng/dl and free T3 2.01 pg/ml. Methimazole was held, and labs repeated after a few weeks, did not change significantly. In September 2020, levothyroxine 25 mcg daily, was initiated due to fatigue symptoms and an elevated TSH 10.61 uIU/ml with low FT4 0.8 ng/dl. Patient did not follow up for a while after that. In December 2021, levothyroxine was increased to 50 mcg daily in response to an elevated TSH 12.91 uIU/ml. The TPO and TSI antibodies remain elevated at 210 IU/ml (0-34) and 9.08 IU/L respectively. Conclusion Our case highlights the diagnostic and therapeutic challenges encountered when both Hashimoto's thyroiditis and Graves’ disease co-exist in the same patient. Reference (1) Alvin Mathew A, Papaly R et al. Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi: 10.7759/cureus.19448 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Clinical Study of the Relationship between Sjögren Syndrome and T-Cell Large Granular Lymphocytic Leukemia: Single-Center Experience.

The relationship between Sjögren syndrome (SS) and T-cell large granular lymphocytic (T-LGL) leukemia remains unclear. In this paper, we report for the first time a large case series of 21 patients with primary and secondary SS associated with T-LGL leukemia. Our results suggest the importance of considering T-LGL leukemia in the diagnostic evaluation of SS patients, particularly when neutropenia occurs. We also postulate that elevated antinuclear antibody titers in patients with T-LGL leukemia indicate the need for the clinical assessment of SS. To assess whether SS affects the frequency of the signal transducer and activator of transcription 3 (STAT3) gene mutations in T-LGL leukemia, we examined STAT3 mutations by next-generation sequencing in two cohorts of patients: with SS-associated T-LGL leukemia and T-LGL leukemia in the setting of rheumatic diseases but without SS. While our results suggest that SS, per se, is not associated with an increased frequency of STAT3 mutations in T-LGL leukemia, further studies are needed to better assess the role of the STAT pathway in the development of concomitant SS and T-LGL leukemia.

X-LINKED INHIBITOR OF APOPTOSIS DEFICIENCY IN A PATIENT WITH ADULT-ONSET RECURRENT FEBRILE ILLNESSES

<h3>Introduction</h3> X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency caused by a mutation in the gene XIAP. It is commonly associated with hemophagocytic lymphohistiocytosis (HLH), recurrent splenomegaly, and inflammatory bowel disease (IBD), as well as hypogammaglobulinemia. We report a case of an adult with late diagnosis of XIAP deficiency in the setting of recurrent febrile illnesses. <h3>Case Description</h3> An 18-year-old Caucasian male presented with fever and generalized lymphadenopathy without other localizing symptoms, which was attributed to cytomegalovirus infection. He recovered without specific treatment, but throughout adulthood he had recurrent infections including pneumonia, appendicitis, cholecystitis, epididymitis, sinusitis, and aseptic meningitis. These infections were often associated with high fever, transaminase elevation, and inflammatory marker elevation. At age 41 he demonstrated persistent hypogammaglobulinemia (IgG 610-635, reference range 767-1590 mg/dl; IgM 28-33, reference range 37-286 mg/dl), elevated antinuclear antibodies, and poor Pneumovax response (adequate response to serotypes 9V, 2, 6B). He denied family history of similar issues. Common variable immunodeficiency (CVID) was considered, but subsequent genetic testing showed a pathologic variant in XIAP gene (c.712C>T/p.Arg238*), leading to a diagnosis of XIAP deficiency. The patient was started on IVIG and Anakinra with good response to treatment. <h3>Discussion</h3> This case highlights the importance of considering genetic testing even in adults with delayed onset of symptoms. The clinical phenotype and presentation of XIAP deficiency is variable and can often mimic more common diseases such as CVID. Even in patients without a history of IBD or HLH, genetic testing to detect XIAP deficiency should still be considered given its variable presentation.

ODP502 Nodular Pretibial Myxedema without Graves’ Orbitopathy: A Case Report

Abstract Background Nodular myxedema is an uncommon skin manifestation of autoimmune thyroid disease. Almost always associated with significant orbitopathy from the deposition of glycosaminoglycans by stimulated fibroblasts. Clinical Case A 57-year-old male presented to dermatology clinic with multiple, non-tender, non-erythematous, nodular lesions of the distal left leg, which had been increasing in size and number over the past one year. The initial clinical impression was lipoma, versus leiomyoma, versus pilomatricoma. The pathology report from punch biopsy of one of the lesions revealed diffuse dermal mucin deposition, consistent with pretibial myxedema. The patient was then referred to endocrinology. His symptoms included increasing fatigue and weight gain of 20.4 kilograms over the last 7 years. He had long-standing history of untreated hypothyroidism and tobacco use disorder. There was no known history of hyperthyroidism, neither thyromegaly, acropachy, nor any signs of orbitopathy were found on examination. Laboratory tests revealed a mildly elevated TSH (5.491 uIU/ml, reference 0.450-5.491 uIU/ml), normal free thyroxine (0.98 ng/dl, reference 0.45-1.80 ng/dl) and elevated anti-microsomal antibody (66. 0 IU/mL, reference &amp;lt;9. 00 IU/ml). Following the pathology report, thyroid stimulating immunoglobulin was requested and found to be elevated (322%, reference &amp;lt;140%). Thyroid ultrasound showed estimated volume of 5. 04 and 2.96 ml for the right and left thyroid lobes, respectively, and only one sub-centimeter nodule. Treatment with levothyroxine was started. Conclusion Thyroid dermopathy, including pretibial myxedema, is attributed to high serum concentrations of thyroid stimulating immunoglobulin leading fibroblasts to deposit mucopolysaccharides in the papillary and reticular dermis. The resulting nonpitting edema can occur anywhere in the skin, despite its notorious penchant for the anterior tibial region. Thyroid dermopathy is seen in 4.3% of patients with Graves’ disease in general, and 15% of patients with Graves’ orbitopathy 1 . Thyroid dermopathy is very rare in the absence of concurrent orbitopathy. Here we present a very unusual case of biopsy-confirmed nodular pretibial myxedema in the absence of current or remote history of known hyperthyroidism, and without any apparent orbitopathy. Presentation: No date and time listed

A REFRACTORY CASE OF HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS

<h3>Introduction</h3> Hypocomplementemic Urticarial Vasculitis (HUV) is a rare small vessel vasculitis. Patients present to allergy clinic with recurrent urticarial lesions. Proposed diagnostic criteria include 2 major criteria: recurrent urticarial lesions and hypocomplementemia, with at least 2 minor criteria: dermal biopsy showing leukocytoclastic vasculitis, arthralgias/arthritis, organ involvement, or elevated anti-C1q antibodies. We describe here the clinical presentation and therapeutic management of a refractory case of HUV. <h3>Case Description</h3> A 28-year-old female presented with a 2-year history of inflammatory arthritis and recurrent hives. Workup revealed hypocomplementemia: C3: 60, C4:10, decreased serum C1q<3.6, elevated anti-C1q antibody (102) and negative autoimmune markers. Cutaneous biopsy showed IgG/C3 at the basement membrane. She had been diagnosed with HUV and treated without benefit with different medications regimens including prednisone, hydroxychloroquine, colchicine, and dapsone all discontinued due to adverse effects/ineffectiveness. Patient was then tried on Methotrexate and Cyclosporine with limited benefit and later on Mycophenolate and omalizumab with minimal improvement. Over time, she developed pulmonary capillaritis, pericarditis, and episcleritis. She progressively developed a multi-organ, complex syndrome all of which was attributed to HUVS. After multiple failed therapies and poor control of urticaria multi-disciplinary decision was made to start Rituximab. <h3>Discussion</h3> Suspicion of HUVS should increase when hives do not respond to therapy, last>24 hours, and leave hyperpigmentation upon resolution. Differential diagnosis includes Muckle-Wells syndrome (hearing loss), Cogan syndrome (progressive hearing/vision loss), Sharp syndrome (positive U1-RNP antibodies), and SLE (positive ANA, normal levels of C1 esterase inhibitor). The case describes an aggressive form of HUV and highlights refractory disease with escalating therapies.

LBODP100 A Rare Case Of Pembrolizumab Induced Graves’ Disease

Abstract Cancer immunotherapies have recently changed the therapeutic armamentarium of anti-cancer treatments, particularly for melanoma and cancers of the kidneys, lungs, and colon. Immune checkpoint inhibitors (ICPis) act on various immune checkpoints. Of them, anti-PD-1 antibodies (such as pembrolizumab) are monoclonal antibodies that act against programmed cell death 1 protein. However, by counteracting the regulators of adaptive immunity, this class of drugs may cause immune-related adverse events that involve multiple organs and endocrine glands, such as the thyroid gland. The symptoms of thyroid dysfunction usually present during the first weeks of ICPis therapy. In the current report, we present a case of a 50-year-old male who presented to the emergency department complaining of fever, chills, nausea, and vomiting for one week. The patient had a history of colon cancer with lymph node metastasis status post tumor resection and colostomy. He began Keytruda® (pembrolizumab) treatment after tumor resection, and the presenting symptoms appeared after receiving the first immunotherapy infusion. His medical history was significant for psoriasis and rheumatoid arthritis. The patient's history was unremarkable for thyroid diseases, and he did not receive thyroid medications with no previous exposure to intravenous contrast media, over-the-counter iodine preparations, or biotin. At the emergency department, the patient had a temperature of 101.4°F, a heart rate of 110 bpm, and blood pressure of 130/70 mm Hg. On examination, tenderness was indicated upon palpating the anterior part of the neck. The patient was treated with intravenous fluids, steroids, beta-blockers, and broad-spectrum antibiotics. A workup for sepsis was requested, and it revealed negative blood culture and urine culture results. His laboratory indices demonstrated a suppressed level of TSH (0. 01 mIU/mL) and elevated Free T4 (3.16 ng/dl). Still, his TSH level reported at the Oncology clinic before Keytruda administration was (0.9 mIU/mL), and Free T4 was (1.7 ng/dl). Thyroid ultrasound revealed a heterogeneous thyroid gland consistent with thyroiditis. Antibody testing showed positive thyroid antithyroglobulin antibodies and elevated thyroid-stimulating antibodies (TSI). A radioactive iodine uptake test was ordered, revealing increased contrast uptake. These findings suggested that the cause of thyroid dysfunction was Graves’ disease. The patient was started on Methimazole 20mg per day and discharged home after scheduling an outpatient follow-up appointment with the endocrinologist. This case is one of the rare cases of thyrotoxicosis attributable to Graves’ disease related to pembrolizumab therapy. To the best of our knowledge, two studies in the literature reported three cases of ICPi-induced thyrotoxicosis with thyroid antibody positivity following anti-PD-1 antibody therapy. Presentation: No date and time listed

PSAT347 New Onset of Graves’ Disease after COVID-19 Vaccination

Abstract Introduction Adjuvants are substances that are commonly found in vaccines. They can enhance the efficacy and potency of a vaccine via an immunological response. However, in some susceptible individuals, these adjuvants can lead to a serious autoimmune response known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This can lead to the onset of autoimmune disorders following vaccination. There are many case reports of the onset of autoimmune disorders following COVID-19 vaccination. However, new onset of Graves’ disease within one day after COVID-19 vaccination, is of rare occurrence. Clinical Case We present the case of a 33-year-old Caucasian male who presented to his primary care physician with chief complaints of fever ranging between 99.2F to 101.3F, palpitations and hand tremors which started one day after he received his first dose of COVID-19 vaccine. Initial laboratory evaluation included a negative throat swab for Group A Streptococcus, a negative nasal swab for Influenza A &amp; Influenza B and a negative nasopharyngeal swab for SARS-COV-2 RNA. On physical examination, he was afebrile, pulse rate 101/min, blood pressure 125/74 mm Hg and oxygen saturation 98%. Due to persistence of tachycardia, an EKG was done which showed a normal sinus rhythm with no other abnormalities. Further laboratory testing was remarkable for a suppressed TSH 0.005 (0.300-4.00 uUI/ml), elevated FT4 2.36 (0.80-1.80 ng/dl) and an elevated TSH receptor Antibody (TRAb) 8.67 (0.00-1.75 IU/L), which confirmed the diagnosis of Graves’ disease. Subsequently, patient established care at our endocrinology clinic. Labs were repeated which showed persistence of hyperthyroidism with TSH &amp;lt;0.005, high normal FT4 1.56 and an elevated FT3 5.36 (2.00-4.40 pg/ml). Thyroid ultrasound was remarkable for mild thyromegaly with increased vascularity and no discrete nodules. Patient was initiated on Methimazole 10 mg daily and propranolol 10 mg twice daily. During the first follow-up visit, the dose of Methimazole was reduced to 5 mg daily based on improved labs. However, it had to be increased back to 10 mg daily due to subsequent worsening of labs. Since then, patient has been maintained on a stable dose of Methimazole 10 mg once daily and the beta-blocker has been discontinued. It has been almost 1 year since the diagnosis and the Graves’ disease specific Thyroid Stimulating Immunoglobulin (TSI) antibody is still elevated at 1.31 (0.00-0.55 IU/L). Conclusion Graves’ disease should be considered high in the differential diagnosis in a patient presenting with fever and tachycardia following COVID-19 vaccination. Our unique case supports the current literature available on the various autoimmune conditions caused by the autoimmune/inflammatory syndrome induced by adjuvants, also known as ASIA. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT283 Sclerosing Mucoepidermoid Cancer – A Unique Entity

Abstract Introduction - Sclerosing mucoepidermoid thyroid cancer is a rare entity with approximately 60 cases reported in the literature. Initially described by Chan. Et al in 1991,1 it was included as a separate entity by WHO in 2004.2 Previously considered to have indolent nature, recent evidence has reported aggressive nature ranging from local invasion to metastasis. Case - 66-year-old female with complaints of difficulty in swallowing, breathing, and sensation of a lump in her throat for last 6 months, was noted to have left thyroid mass on ultrasound. Thyroid ultrasound showed solid hypoechoic nodule, 8.2×5.3×5.9 cm replacing left thyroid lobe with solid hypoechoic nodule 2.2×1.1x 1.6 cm at the right end of the isthmus. The neck ultrasound was negative for lymph nodes. Past medical history was significant for long-standing hypothyroidism, and recently diagnosed invasive ductal carcinoma of the breast. CT chest showed an enlarged thyroid gland with substernal extension and mass effect on the trachea. FNA thyroid showed Bethesda category 5, suspicious for papillary thyroid cancer. The patient underwent a total thyroidectomy. Pathology for left nodule showed sclerosing mucoepidermoid carcinoma with eosinophils, 8.6×6.9×5.8 cm, p T4a N×Mx, with positive margins for tumor, no angiolymphatic invasion with co-existing right-sided papillary microcarcinoma (follicular variant) with chronic lymphocytic thyroiditis. Levothyroxine was dosed to aim goal TSH &amp;lt;0.1, considering the high risk of recurrence. Post-op Thyroglobulin was 1 ng/ml (&amp;lt; 2 ng/ml) with elevated Thyroglobulin antibodies 6.4 U/ml (&amp;lt;0.4). The patient further had radioiodine ablation with 150 mCi I-131, 3 months later. Post therapy whole-body scan showed multiple foci of increased uptake in thyroid bed consistent with thyroid tissue/ residual disease. No distant metastasis was noted. Discussion – Sclerosing mucoepidermoid cancer is thought to be derived from the ultimobranchial body.1 It is more common in females in age groups 3rd - 8th decade.3 Most common presentation is unilateral painless thyroid mass. Coexistent chronic lymphocytic thyroiditis and papillary thyroid cancer are usually found. On literature review of 56 cases, the gross extrathyroidal extension was seen in 26% of cases with distant metastasis was most commonly seen in lungs.3 No established treatment strategy exists due to a small number of reported cases, however, treatment ranges from only Thyroid surgery to Thyroid surgery with radiation +/- chemotherapy and radioactive iodine. References Shah AA, La Fortune K et al. Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity. Mod Pathol. 2017;30: 329–339. Pantola C, Kala S, Athar M, et al. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a cytological dilemma. J Cytol 2016; 33: 37. Chambers M, Nosé V et al. Salivary-Like Tumors of the Thyroid: A Comprehensive Review of Three Rare Carcinomas. Head Neck Pathol. 2021 Mar;15(1): 212-224. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT341 Hashimoto's Thyroiditis After Allogenic Bone Marrow Transplantation

Abstract Introduction Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is a common autoimmune-mediated thyroid disease triggered by an inappropriate T and B cells response. We present a case of a female without personal or family history of autoimmune disease, who developed Hashimoto's thyroiditis with severe hypothyroidism after undergoing bone marrow transplant (BMT). Clinical Case A 57-year-old woman with hypoplastic myelodysplastic syndrome (MDS) was initially started on immunosuppressive therapy, complicated by autoimmune hemolytic anemia and thrombocytopenia. Three years after diagnosis, she underwent allogenic BMT from a matched unrelated donor. A year later, she presented with weight gain, fatigue, cold intolerance, insomnia, eye puffiness and lower extremity weakness, developed over a month. Exam was notable for periorbital edema and delayed DTRs. Laboratory workup revealed an elevated TSH at 302 µIU/mL (0.27-4.2) with undetectable free T4 and total T4 levels and elevated anti-thyroglobulin antibodies of 2698 IU/mL (0-40) and antiTPO antibodies of 90 IU/mL (0-35). Cortisol was normal at 14 µg/dL. TSH was normal prior to the BMT. Thyroid ultrasound revealed a normal-sized thyroid with a slightly heterogeneous echotexture, suggestive of thyroiditis without distinct nodules. Myxedema coma was ruled out at the time of diagnosis. The patient was started on levothyroxine and noticed a significant improvement of her symptoms within few weeks. Our patient does not have a personal or family history of thyroid disease or other autoimmune disorders. She did not receive radiation treatment or steroid treatment prior to her hypothyroidism diagnosis. She had an RSV upper respiratory infection two months prior to the diagnosis of hypothyroidism without associated neck pain. The clinical and biochemical picture suggest that her hypothyroidism could be related to her allogenic BMT. The presumed mechanism for the autoimmune thyroid dysfunction noted in this patient is the transfer of autoantibodies and donor lymphocytes during BMT. Conclusion Adoptive autoimmune hypothyroidism can occur post-BMT, especially if the donor has genetic susceptibility. It is now accepted that autoimmune thyroiditis can be transferred from donors to recipients during BMT. Reference Buxbaum NP, Pavletic SZ. Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2020 Aug 25;11: 2017. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV.

Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host's burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2- γδ T-cells-populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden.

An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary

Dr Khemani and colleagues have presented a diagnostically challenging case of a sporadic, adult onset ataxia (SAOA) syndrome resembling Multiple System Atrophy cerebellar type (MSA-C), with an atypical presentation of focal amyotrophy, eventually diagnosed as spinocerebellar ataxia type 3 (SCA3) [ [1] Khemani P. Elliott M. Levine T. An Atypical Clinical Course of a 71-Year-Old Man with Right Arm Weakness and Ataxia. Parkinsonism Relat Disord, 2022 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. The patient had presented elsewhere three years prior, with a Miller Fisher syndrome (MFS) associated with an elevated antiGQ1b antibody titer. However, as the patient had become wheelchair bound over the subsequent three years, the initial diagnosis of MFS is perhaps questionable. When evaluating ataxic disorders, it is important to establish the disease onset and course accurately. As the patient had a progressive cerebellar syndrome, the possible causes could be categorized broadly as: primary autoimmune (paraneoplastic or non-paraneoplastic); or neurodegenerative (sporadic or genetic). Primary autoimmune cerebellar ataxia encompassing paraneoplastic ataxia syndromes, and immune-mediated ataxias (gluten ataxia and anti-GAD65 ataxia) may present insidiously, with accumulating disability especially if timely and appropriate immunosuppressive therapies are not instituted [ [2] Hadjivassiliou M. Graus F. Honnorat J. Jarius S. Titulaer M. Manto M. Hoggard N. Sarrigiannis P. Mitoma H. Diagnostic criteria for primary autoimmune cerebellar ataxia-guidelines from an international task force on immune-mediated cerebellar ataxias. Cerebellum. 2020; 19: 605-610 Crossref PubMed Scopus (35) Google Scholar ].

A CASE OF MICROSCOPIC POLYANGIITIS (MPA) FOLLOWING SARS-COV-2 INFECTION

A CASE OF MICROSCOPIC POLYANGIITIS (MPA) FOLLOWING SARS-COV-2 INFECTION

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME: A VICIOUS CIRCLE OF CLOTTING AND BLEEDING

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME: A VICIOUS CIRCLE OF CLOTTING AND BLEEDING

EP(ILEPT)IC COMPLICATIONS

EP(ILEPT)IC COMPLICATIONS

S2907 COVID-19 Vaccine-Induced Liver Injury: A Case Series

Introduction: The coronavirus 2019 (COVID-19) pandemic has caused over 248 million cases and over 5 million deaths worldwide. Given its high morbidity and mortality, there was a rapid effort to develop a vaccine within a year of the commencement of the pandemic. Although these vaccines have excellent safety profiles, there is a risk of adverse effects such as fever, fatigue, arthralgias, injection site pain, and, less commonly, anaphylactic reaction. Drug-induced hepatotoxicity (DIH) is a rare side effect of vaccines that has rarely been reported. We report a cohort of four patients who presented with DIH following COVID-19 vaccination. Case Description/Methods: Our cohort includes four patients, aged 39-70, who presented between 12 to 82 days after their second dose of Pfizer COVID-19 vaccine. Only one patient had a history of COVID-19 infection. One patient had a history of hepatic steatosis. All four patients had normal alanine transaminase [ALT] and aspartate transaminase [AST] within one year before the current presentation. All patients demonstrated a hepatocellular pattern of liver injury (peak ALT range of 57 to 904 U/L and AST range of 51 to 828 U/L). Tests for acute viral hepatitis were negative. One patient was found to have positive antinuclear antibodies and anti-smooth muscle antibodies. One patient was found to have an elevated antimitochondrial antibody. Liver stiffness measurement in three patients showed no evidence of fibrosis. Three patients underwent liver biopsy of which two suggested evidence of toxic/drug induced liver injury while the other demonstrated nonspecific inflammation. (Figure) Discussion: DIH leads to 10% of all cases of acute hepatitis and up to 50% of all cases of liver failure, making it one of the common reasons for withdrawal of medications from the market. We observed that our patients developed hepatic injury after Pfizer COVID-19 vaccination. Vaccine-induced immune-mediated hepatitis is a known phenomenon thought to be secondary to the COVID-19 spike protein triggering an auto-immune-like hepatic condition. This could explain the findings seen in our patients, raising the question of inflammatory response in patients with underlying autoimmune conditions. It is important that these patients receive pre and post vaccination laboratory monitoring, especially given the emergence of booster vaccinations. There is a need to follow these patients in the long-term to monitor for changes in clinical and laboratory studies in order to assess the risk of complications and outcomes.Figure 1.: Patient demographics and characteristics

Decreasing Tryptophan and Increasing Neopterin Plasma Levels During Pregnancy are Associated with High First Trimester Porphyromonas gingivalis K-Serotype IgG Serointensity in a Cohort of Hispanic Women.

Immune activation or high levels of stress may lead to increased metabolism of tryptophan during pregnancy. Porphyromonas gingivalis (Pg), the "keystone" periodontal pathogen, induces immune and indoleamine 2,3-dioxygenase (IDO) activation. Thus, we hypothesized that larger gestational decreases in tryptophan and elevations in neopterin and kynurenine would occur in pregnant women with elevated IgG antibodies to Pg capsular (K) serotypes. Venous blood of 52 Hispanic pregnant women with a mean age (SD) of 31.8 (5.9) years was sampled once per trimester of pregnancy (V1, V2, V3), and plasma was obtained and stored. ELISAs were used to measure Pg capsular (K) serotype IgG serointensity (V1 only) and neopterin levels (V1-V3). Tryptophan and kynurenine (V1-V3) were measured with high-performance liquid chromatography. The participants having IgG serointensity for any of the seven Pg K serotypes in the highest quartile were defined as the "High PgK_IgG" group and those having IgG serointensity for all K serotypes in the lowest three quartiles were defined as the "Low PgK_IgG" group. Statistics included multivariable linear and nonparametric methods. Significant decreases in plasma tryptophan levels and increases in neopterin during gestation were found in "High PgK_IgG" women but not in "Low PgK_IgG" women. Kynurenine changes were not significantly different between the two groups. If replicated in larger studies and further characterized clinically, radiologically, and microbiologically, our results may potentially lead to novel interventional targets, as well as the development of more complete prognostic and predictive interactive biomarkers for adverse obstetrical outcomes and peripartum depression, and their prevention.