A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

Introduction: Hyperthyroidism is known to increase catabolism of vitamin-K-dependent clotting factors (II, VII, IX, X) and increase the response of vitamin K antagonists, usually warfarin. Primary biliary cirrhosis (PBC) has been associated with thyroid dysfunction (TD), especially with autoimmune thyroid disease. In the below case, a patient with known PBC on warfarin is found to have severely elevated INR related to new-onset hyperthyroidism with clinical consequences of hemorrhage including upper GI bleed. Case Description/Methods: A 64-year-old female with PBC and antiphospholipid antibody syndrome on warfarin was admitted for hemorrhagic epiglottitis requiring emergency intubation and supratherapeutic INR. Her PBC was diagnosed as stage II on biopsy 23 years ago and has remained clinically stable on ursodiol therapy. On presentation, the patient was tachycardic, tachypneic, and had O2 saturations <90% on HFNC prior to intubation. Physical exam significant for larger goiter with diffuse upper airway swelling. She was admitted and found to have COVID-19 infection, INR .16.0 and PT>200.0 (limit of lab), WBC of 22.8, and lactate of 2.5. LFTs WNL aside from albumin of 2.0. TSH was <0.0017 (limit of lab) and free T4 of 3.4, free T3 of 5.3. TSH receptor antibody (TRAB) and thyroid stimulating immunoglobulin (TSI) levels were normal. Her last TSH was normal a year ago. CTA chest found a 5.7cm heterogeneous, partially calcified superior mediastinal mass consistent with multinodular thyroid goiter. Patient was initially given prothrombin complex concentrate and vitamin K with correction of INR over the following few days. She was extubated and started on methimazole. During the hospital course, she was found to have coffee ground emesis for which an EGD was done with findings of non-bleeding gastric ulcer (Forrest Class IIc) and LA Grade D esophagitis with adherent clot and bleeding for which hemostatic spray was applied. Patient was discharged a few days later following resumption of warfarin and on pantoprazole and methimazole. Discussion(s): The above case demonstrates a rare case of PBC and new-onset hyperthyroidism due to multinodular thyroid goiter causing significantly elevated INR in the setting of warfarin use with hospital course complicated by GI bleed. PBC is associated with TD - hyperthyroidism, hypothyroidism, and thyroid cancer. Hyperthyroidism is less commonly associated with PBC compared to other TDs but should be considered especially with a finding of elevated INR.

Silent Thyroiditis as a Complication of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine

Introduction: Silent autoimmune thyroiditis, a type of chronic autoimmune thyroiditis, as an adverse effect of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is infrequently reported in the literature. We hereby describe a case of silent thyroiditis followed by Grave's orbitopathy after vaccination against SARS-CoV2. Case Description: An 84-year-old male presented to clinic with a 10-pound weight loss with no other symptoms of hyperthyroidism, no personal history of thyroid illnesses, or recent viral infections. He had normal thyroid function 3 months prior to presentation. He had received 3 doses of SARS-CoV2 Pfizer-BioNTech vaccine with the last dose 5 months prior to presentation. Thyroid exam was normal. Laboratory testing revealed thyroid stimulating hormone (TSH) level of 0.005 IU/ml (0.45-4.5 IU/ml), total T4 14.4 g/dl (4.5-12.1 g/dl), and total T3 1.22 nmol/l (0.6-1.81 nmol/l). Thyroid Ultrasound revealed a heterogeneous atrophic thyroid gland with no nodules or hypervascularity. He was started on Methimazole by primary care provider. Four months later, he was seen in the Endocrinology clinic and reported no hyperthyroidism symptoms. His TSH level at that time was 65.9 IU/ml, free T4 0.47 ng/dl (normal: 0.82-1.77 ng/dl), total T3 level 75 ng/dl (normal: 71-180 ng/dl), thyroid stimulating immunoglobulin 2.05 IU/l (0-0.55 IU/L), thyrotropin receptor antibody level 2.8 (0-1.75). Methimazole was discontinued. At 6 months after initial presentation laboratory testing showed TSH 5.010 IU/ml, free T4 1.2 ng/dl, thyroid peroxidase antibody of 148 IU/ml (normal 0-34 IU/ml), thyroglobulin antibody 131.6 IU/ml (normal 0.0-0.9 IU/ml). He was diagnosed with silent autoimmune thyroiditis. A few weeks later, the patient presented to an ophthalmologist with bilateral eye bulging and impaired vision. He was diagnosed with acute Graves' orbitopathy and started on pulse-dose of intravenous Methylprednisolone 250 mg twice daily and urgently referred to a tertiary ophthalmology center for teprotumumab infusion. His thyroid function tests were normal at that time on no thyroid medications. Discussion(s): The underlying mechanisms of thyroid impairment following SARS-CoV2 vaccination are not completely understood. There is a role of molecular mimicry between SARS-CoV2 antigens and thyroid antigens that may help to hasten the emergence of autoimmunity in vulnerable individuals. Our patient developed multiple thyroid-related antibodies following vaccination. Silent painless thyroiditis is a self-limiting condition, characterized by temporary thyrotoxicosis, followed by a brief period of hypothyroidism and then a complete return to normal thyroid function. A radioactive iodine uptake scan can help differentiate between the different causes of thyrotoxicosis in the acute thyrotoxic phase. Development of severe Graves orbitopathy following silent autoimmune thyroiditis after SARS COV2 vaccination has not been previously reported.Copyright © 2023

New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves' Disease Post-Radioactive Iodine Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves' Disease (GD) even after treatment with radioactive iodine (RAI). Case Description: In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. Discussion(s): GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.Copyright © 2023

DISSEMINATED INVASIVE ASPERGILLUS MASQUERADING AS AMIODARONE-INDUCED THYROTOXICOSIS

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Aspergillus is a group of opportunistic endemic fungal species that causes pathology within the respiratory tract and sinuses of individuals with predisposing factors, such as immunosuppression. While less frequently discussed, aspergillosis thyroiditis represents the most common fungal thyroiditis. We present a case of this condition that was misdiagnosed as amiodarone induced thyrotoxicosis. CASE PRESENTATION: A 54-year-old male was evaluated in outpatient pulmonary clinic after a chest CT revealed new upper lobe mass-like pleural based infiltrates with accompanying symptoms of dyspnea on exertion and fevers. His medical history was significant for orthotopic heart transplant 6 months ago due to a combination of non-ischemic cardiomyopathy with further decompensation from COVID-19 infection. After transplant, he was diagnosed with thyrotoxicosis secondary to amiodarone that was being treated with prednisone and methimazole. Given the concern for infection on imaging, he was admitted to the hospital and underwent urgent bronchoscopic evaluation. During the procedure, he was noted to have severe extrinsic tracheal compression. His neck imaging was consistent with a nodular goiter. The BAL revealed Aspergillosis fumigatus and he was subsequently treated with isavuconazium. Given the compression on the trachea and persistent dyspnea, the decision was to pursue total thyroidectomy. Surgery occurred 2 months after treatment was initiated for the Aspergillosis and with improvement on serial chest CTs. Pathologic examination of the thyroid tissue revealed extensive invasive aspergillus with abscesses involving both lobes. DISCUSSION: Aspergillus infection leading to disseminated disease typically occurs in individuals that have a compromised immune system such as seen in malignancy, solid organ transplant, chronic steroid use, and poorly controlled diabetes mellitus. Recently, it has been cited that up to 15% of hospitalized COVID-19 patients requiring intensive care develop aspergillus infection. After initial aspergillosis infection has been established, the thyroid gland is a site for dissemination due to its rich vascular supply. In addition, due to the angioinvasive properties of the pathogen, the fungus can breakdown tissue planes and easily travel from its site of origin. Thereby a primary infection in the respiratory tract can lead to dissemination to the neck structures due to its proximity. When thyroid invasion occurs, the common complaints are neck pain and swelling. Thyroid laboratory findings encompass the full spectrum including hyperthyroidism, hypothyroidism, and euthyroid. Given these non-specific findings, clinicians need to be conscious of this disease entity. CONCLUSIONS: In patients with immunocompromising conditions, findings of neck pain, swelling, and abnormal thyroid laboratory values should broaden the differential for clinicians to include aspergillosis thyroiditis. Reference #1: Alvi, Madiha M et al. "Aspergillus thyroiditis: a complication of respiratory tract infection in an immunocompromised patient.” Case reports in endocrinology vol. 2013 (2013): 741041. doi:10.1155/2013/741041 Reference #2: Marui, Suemi, et al. "Suppurative thyroiditis due to aspergillosis: a case report.” Journal of Medical Case Reports 8.1 (2014): 1-3. Reference #3: Kuehn, Bridget M. "Aspergillosis Is Common Among COVID-19 Patients in the ICU.” JAMA 326.16 (2021): 1573-1573. DISCLOSURES: No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Honoraria Removed 04/03/2022 by A. Whitney Brown No relevant relationships by A. Whitney Brown, value=Consulting fee Removed 04/03/2022 by A. Whitney Brown No relevant relationships by Kristen Bussa Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2019-2021 Added 04/03/2022 by Christopher King, value=Consulting f e Advisory Committee Member relationship with Actelion Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: 2019-2022 Added 04/03/2022 by Christopher King, value=Consulting fee Speaker/Speaker's Bureau relationship with United Therapeutics Please note: 2020-22 Added 04/03/2022 by Christopher King, value=Consulting fee No relevant relationships by Haresh Mani No relevant relationships by Mary Beth Maydosz No relevant relationships by Alan Nyquist No relevant relationships by Anju Singhal No relevant relationships by Amy Thatcher

GLASSY LUNGS, DRUGS AND MELENIC RUNS, A CASE REPORT

CASE: A 73-year-old male with a history of prostate cancer, hypertension and hyperthyroidism presented with one week of worsening dyspnea, productive cough and pleurisy. He also endorsed new orthopnea and melena over the last three days. Home medications included abiraterone, prednisone, methimazole and amlodipine. On admission, vitals were notable for tachycardia, tachypnea and hypoxia (82% on room air and 90% on 3L by nasal canula (NC)). Initials labs showed WBC count 17.4, Hemoglobin 7.1, proBNP 256, two negative COVID-19 PCR tests, negative respiratory virus panel and normal TSH and PSA. CTPE was negative for pulmonary embolism but showed new diffuse ground glass opacities. The patient was started on broad spectrum antibiotics and IV diuretics for possible pneumonia and new heart failure. However, the patient's respiratory status continued to decline, now requiring 6L by NC. Hemoglobin also continued to drop precipitously. A broad rheumatologic and infectious workup was largely negative with findings notable for a positive ANA, CRP 74, LDH 359 and an undetectable haptoglobin. A urinalysis was positive for protein and blood. At this time, empiric treatment for pneumocystis pneumonia was initiated with a plan for bronchoscopy. The bronchoscopy with bronchoalveolar lavage (BAL) revealed diffuse alveolar hemorrhage (DAH) with studies negative for infection or malignancy. An upper endoscopy did not reveal any gastrointestinal source of bleeding but rather favored a pulmonary source due to some red blood in the esophagus and coffee ground material in the stomach. Given these findings, a diagnosis of “Methimazole induced vasculitis with DAH” was made, a diagnosis of exclusion. The patient was started on pulse steroids for three days and his methimazole was held. By day four, the patient reported improvement and his oxygen was decreased to 2L. He was subsequently discharged on a steroid taper. At his two-week follow-up, the patient had improving respiratory status and repeat labs showed an improved and stable hemoglobin, and normal haptoglobin. IMPACT/DISCUSSION: This case illustrates a rare but life-threatening complication of methimazole use. Common offenders of drug-induced DAH include propylthiouracil, carbimazole and hydralazine. This complication is reported in 15-37% of patients on propylthiouracil but only 0-3% of patients on methimazole. A third of patients with DAH do not present with hemoptysis making this diagnosis challenging. Lab findings can also be largely nonspecific making a thorough history, imaging and interdisciplinary collaboration key in identifying this adverse effect early on to prevent mortality. CONCLUSION: Include drug-induced DAH on the differential for patients presenting with respiratory failure in the setting of new anemia, melena or hemoptysis. Stopping the offending drug and initiating steroids is the treatment of choice. Consider empiric PCP treatment and BAL for patients with severe hypoxia, ground glass opacities and immunosuppression.

New diagnosis of Graves' disease during SARS-CoV-2 infection. A further trigger of hyperthyroidism?

Background: Graves' disease is an autoimmune disorder which represents the most common cause of hyperthyroidism. It is often triggered by an acute event, such as infections. SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2), expressed mostly in the lungs but also in several endocrine organs like thyroid. Description of the Case: We report a case of a 49-years-old woman admitted to our Unit due to fever, tachycardia and worsening dyspnea. Nasopharyngeal swab test resulted positive for SARS-CoV-2 (PCR). Blood sample test for D-dimer resulted increased (1272 ug/l, normal value <500), and bilateral subsegmental embolism was found on CTAngiography. She reported palpitations, insomnia and weight loss in the past days. Past medical history included euthyroid nodular thyroid disease, hypertension and obesity. Laboratory tests revealed hyperthyroidism with positive thyroid antibodies with TSH<0.05 mU/l, FT4 32 ng/l and FT3 5.9 ng/l (normal value 8-17 and 2-4, respectively), and elevated AbTPO 137 KU/l (<34) and AbTSH-r 2.4 U/l (<2). Thyroid ultrasound showed an enlarged gland with heterogeneous echotexture and hyperechoic nodules;an hypervascular pattern with elevated peak systolic velocity in inferior thyroid artery (50-69 cm/s) was found at colorDoppler. A diagnosis of Graves' disease was established and treatment with thiamazole was started, achieving normal heart rate control and recovery of symptoms. Conclusions: In the absence of a clear trigger for our patient's thyroid storm, we suggest SARS-CoV-2 infection, in addition to CT iodinate contrast medium, might precipitate or worsen a latent Graves' disease.

A case of Post-COVID-19 thyrotoxicosis and a cavalcade of complications

Thyroid dysfunction has been reported following COVID-19 infection in the recent past. A 50 year old hypertensive female with no previous thyroid illness, developed features of thyrotoxicosis two weeks after a COVID-19 infection. There was no thyromegaly, neck pain or fever and her ESR was 15 mm/hour. She was initiated on propranolol and methimazole in an outside hospital. Ten days later, she presented to our hospital with fever, sore throat, cough and breathing difficulty. On evaluation she was found to be in neutropenic sepsis (WBC -820 cells/mm3, ANC-6 cells/mm3). Evaluation of thyroid functions showed: TSH- <0.00025 IU/ml, free T3 - 4.17 pg/ml, free T4- 3.59 ng/ml and Thyroid Receptor Antibody Levels (TRAb)- 2.53 IU/L. Following treatment with colony stimulating factors and antibiotics she recovered. The patient was commenced on lithium bicarbonate and cholestyramine, along with propranolol. On follow up in the OPD she is euthyroid with free T4 1.43 ng/ml (normal) levels. Post COVID-19 thyrotoxicosis in this case is likely due to Graves' disease. Thyrotoxicosis following COVID-19 is now being recognised and is possibly due to infection induced molecular mimicry with activation of immune pathways causing autoimmune disorders.

Thyroid myopathy after receiving COVID-19 Vaccine

Introduction: There have been few reported cases of post-vaccination thyroiditis and Grave's disease. Here, we present a unique case of post vaccination thyroiditis associated with thyrotoxic myopathy after COVID-19 vaccination. Case Description: A 39-year-old man with no significant past medical history presented to the ED complaining of diffuse muscle pain, joint pain and stiffness for 2 days. He was unable to stand without support. On examination, he had normal deep tendon reflexes but decreased power on the right arm and leg. Admission labs revealed TSH of 0.008 (0.55- 4.7 uIU/mL), Free T4 2.49 (0.89 - 1.76 ng/dl) and FT3 7.4 (2.3-4.2 ng/dl), low potassium of 3.0 L (3.6 - 5.1 mmol/L) and normal CPK 135 (49 – 397 IU/L). MRI of the brain and cervical spine did not show any pathology. Muscle weakness was assessed to be from hypokalemia related to thyrotoxicosis. After potassium replacement, his symptoms improved but did not resolve completely. He was discharged home on methimazole and propranolol. During out-patient follow up 2 months later, his TFTs did not improve (FT4 2.90 ng/dl and TSH of 0.008 uIU/mL) with persistent muscle weakness and muscle aches despite normal potassium of 4.4 (3.6 - 5.1 mmol/L). TSI and TPO antibodies came back negative. Thyroid uptake and scan revealed decreased 4-hour (3.4%) and 24-hour (4%) uptake. Additional history revealed that he received his second dose of COVID-19 vaccine 6 days prior to onset of symptoms. At this point, a diagnosis of post COVID vaccination thyrotoxic myopathy was made. Methimazole was stopped and he was treated with a tapering dose of prednisone. His symptoms resolved completely with normalization of TFTs after a month (Free T4 1.28 ng/dl, TSH 2.993 uIU/mL). Discussion: Autoimmune thyroid disease including thyroiditis and Grave‘s disease have been reported after receiving COVID-19 vaccine. One of the mechanisms for this complication is thought to be autoimmune/inflammatory syndrome induced by vaccine adjuvants. This case illustrates the importance of keeping broad differentials in mind in patients who recently received COVID-19 vaccine especially as the pandemic persists and more people are being vaccinated.

Unilateral Massive Pleural Effusion as Manifestation of Severe Hyperthyroidism

Introduction: Non-cardiogenic pleural involvement in hyperthyroidism is rare, with unilateral involvement being rarer still. We present the case of a patient with Graves’ disease (GD) with thyroid storm criteria who presented right pleural effusion compatible with exudate. Case Description: A 40-year-old female patient, with a history of hyperthyroidism for 3 years without treatment for severe rash to thiamazole on two occasions. She was admitted to the emergency room of a private clinic due to dyspnea that progressed to respiratory failure, a massive right pleural effusion was found for which they performed evacuatory thoracentesis, prescribed lugol, bisoprolol and dexamethasone, and she was transferred to our hospital with a total of 45 points on the Burch-Wartofsky’s scale, had respiratory failure and jaundice. The analysis showed: Hemogram: Leukocytes 9700, Hemoglobin: 10.8 g/dl;CRP: 0.43 mg/dl;Glucose 157 mg/dl;Creatinine: 0.29 mg/dl, TSH: < 0.004 uIU/ml, Free T4: > 7.77 ng/ml;Free T3: > 16 pg/ml, Anti-thyroperoxidase: > 1000 IU/ml;Total bilirubins: 5.52 mg/dL;Direct bilirubin: 3.79 mg/dL. COVID infection was ruled out, the analysis of the pleural fluid was compatible with exudate, an echocardiogram showed LVEF: 60% and mild pulmonary hypertension. Thyroid ultrasound revealed diffuse hypervascularized goiter;thyroid scintigraphy showed diffuse hyper-uptake goiter. Dexamethasone with lithium carbonate was indicated with gradual improvement in thyroid function tests and cholestatic pattern. Once compensated she received 20mCi of 131I. She was discharged with an improvement in her symptoms. Her X-ray and her control chest ultrasound did not show the presence of pleural effusion. Discussion: GD is a pathology that presents with a variety of symptoms and signs due to its multisystemic involvement, which can become life-threatening, such as a thyroid storm, if it is not treated properly and in a timely manner. The fact of presenting unilateral massive pleural effusion is a rare presentation of hyperthyroidism reported in other cases.

GRAVE DANGER: RARE CASE OF COMPLETE HEART BLOCK SECONDARY TO GRAVES DISEASE

Background: Complete heart block (CHB) is a cardiac conduction disorder commonly due to age-related degeneration of the conduction system. Other etiologies include hypothyroidism, Lyme disease or COVID-19, infiltrative cardiomyopathy, myocarditis, and atrioventricular (AV) nodal blocking agents. Hyperthyroidism is an extremely rare cause of CHB. Case: We present the case of a 40-year-old previously healthy male who presented after two syncopal episodes. He denied any home medications, recreational drug use, or prior syncopal episodes. He did endorse worsening palpitations, heat intolerance, anxiety, insomnia and diarrhea for one month. Initial EKG was normal. Labs revealed an undetectable thyroid stimulating hormone (TSH), and high T4 of 3.26 ng/dL. Potassium was 3.1 mMol/L which was replaced to normal levels. In the emergency department, he had another syncopal episode. Telemetry showed a 20 second episode of CHB. Patient was admitted and started on methimazole. Decision-making: Labs showed positive TSH receptor antibodies and thyroid stimulating immunoglobulins, confirming a diagnosis of Graves’ disease. COVID-19 IgG antibodies were positive with negative COVID-19 PCR, indicative of remote COVID 19 infection. Cardiac MRI did not show any myocarditis or infiltrative disease, and otherwise revealed a structurally normal heart. Lyme disease antibodies were negative. Toxicology screen was negative. Thyroid ultrasound showed diffuse heterogeneity of the gland. 72 hour telemetry monitoring revealed no further conduction abnormalities. At this point, CHB wes attributed to hyperthyroidism. As this was reversible, and CHB resolved after initiation of methimazole, a permanent pacemaker was not placed. He was discharged with a 30-day event monitor which did not show any conduction abnormalities. Conclusion: This case highlights a rare sequela of hyperthyroidism induced CHB. Although the pathophysiology is not well understood, a proposed mechanism is the direct toxic effect of T3 leading to focal inflammation of the AV node. Further studies are needed to evaluate the pathophysiology and chronicity of this process, which will assist in the decision to implant a permanent pacemaker.