Subacute Thyroiditis Following Vaccination with COVID-19 mRNA Vaccine

Introduction: Subacute thyroiditis is a self-limiting post-viral inflammatory disorder occurring in 3 phases (hyper-, hypo-, and euthyroidism) Post-vaccine thyroiditis has also been reported, but is rare. Case Description: A 36-year-old Emirati female presented to our clinic with generalized fatigue, mild to moderate vague neck pain, intermittent palpitations, and loss of appetite 2 weeks after receiving her first dose of Pfizer-BioNTech mRNA vaccine against COVID-19. Clinical examination findings and laboratory test results were consistent with subacute thyroiditis. Patient is a mother of 5 healthy children, youngest is breast-fed infant (11 months old). There was no history suggestive of postpartum thyroiditis and no family history of thyroid dysfunction. Physical examination at initial visit showed mild tachycardia, and a normal blood pressure. She weighed 66 kg. Thyroid function tests revealed a suppressed TSH of 0.011 muIU/mL, high Free T4 of >100 pmol/l), and Free T3 FT3 of 29.6 pmol/L. Both TSH receptor antibodies, and Thyroid antibodies (TPO) were negative. Thyroid scintigraphy showed decreased uptake in both lobes. Thyroid ultrasound showed hypoechoic heterogeneous echotexture of the thyroid gland with vascular conglomerate and micro-calcification, along with normal sized reactive lymph nodes at sternal angle. Symptoms aggravated through the next week;patient dropped 3kg of her body weight and her palpitations increased, with a recorded resting heart rate between 120-130 beats/min. TSH decreased to 0.001muIU/mL while FT4 remained high, with an improvement to 90 pmol/L. Subsequently, the patient started to regain weight. Palpitations improved within a month. She developed a biochemically hypothyroid picture followed by clinical and biochemical euthyroidism after one more month. Second dose of the vaccine was uneventful. Last evaluation was 10 months later;TSH, FT3 and FT4 were all in normal range, acute-phase reactants were completely normal and in complete remission. Discussion(s): The exact mechanism for post-vaccination subacute thyroiditis remains unknown, vaccine adjuvants may induce diverse autoimmune and inflammatory reaction. Subacute thyroiditis has rarely been reported with other COVID-19 vaccines contains no Polyethylene glycol (PEG). A possible cross-reactivity between thyroid cell antigens and spike protein of the coronavirus produced by mRNA vaccines might be responsible. Further research is needed to investigate the incidence of subacute thyroiditis in COVID-19 pandemic days.Copyright © 2023

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

Relationship between thyroid function tests and mortality in severe Covid-19 pneumonia cases admitted to the intensive care unit Severe COVID-19 and thyroid function tests

Aim: In severe COVID-19 infection, most organs are affected, including the thyroid gland. A decrease in thyroid functions can be seen in relation to the severity of the disease. We aimed to retrospectively analyze the relationship between thyroid function tests and mortality in patients admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia. Material(s) and Method(s): The study was performed retrospectively on 46 adult patients admitted to the intensive care unit with severe COVID-19 pneumonia. Demographic, clinical, laboratory data were recorded. Patients were grouped into two according to mortality. Laboratory data were compared between groups. Additionally, the correlation of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) with infection parameters was investigated. Result(s): At the time of ICU admission, fT3 levels below the normal range were present in 91.3%, fT4 levels were below normal in 39.13%, and TSH levels were below normal in 52.17% of the study patients. There was a positive correlation between fT4 and CRP (r=0.315, p<0.05), while there were no significant correlations between other parameters. TSH, fT3, or fT4 did not differ between patients with and without mortality. Partial arterial oxygen pressure/fraction of inspired oxygen was lower in patients with mortality (p=0.015). Discussion(s): Low thyroid hormone levels and TSH are common occurrences in patients admitted to the ICU with severe COVID-19 pneumonia. No relationship could be shown between low thyroid function test levels and mortality in patients with severe COVID-19 pneumonia.Copyright © 2022, Derman Medical Publishing. All rights reserved.

More Than Meets the Eye: Orbital Swelling in an Adolescent with Sickle Cell Disease

Periorbital swelling is a clinical presentation with a broad differential and potentially deleterious consequence. Causes range from benign, including allergic reaction, to vision-and life-threatening, including orbital cellulitis and orbital infarction. The recent climate of SARS-CoV-2 has further complicated this differential, as the virus poses broad clinical presentations with new manifestations reported frequently. Rapid identification of the underlying etiology is crucial, as treatment approaches diverge greatly. Here, we report the case of an African American adolescent male with a history of homozygous sickle cell anemia presenting to an inner city hospital with bilateral periorbital swelling amid the coronavirus pandemic. Differentials including orbital cellulitis, COVID-MIS-C, orbital inflammatory syndrome, Hoagland sign, and orbital infarction secondary to sickle cell crisis are contrasted. We contrast our case with 12 case reports of orbital infarction in the setting of sickle cell crisis within the past 10 years, highlighting how these presentations, along with commonly reported findings of orbital infarction, compare with our patient. Copyright © 2022 Tehran University of Medical Sciences.

COVID-19-INDUCED POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is one of the most common autonomic disorders (1). POTS is diagnosed by increasing heart rate by 30 bpm on more, within the first 10 minutes of standing, without orthostatic hypotension (2). Associated debilitating symptoms are lightheadedness, fainting, tremor, orthostatic intolerance, and tachycardia (2). Viral infections such as HIV, hepatitis C, mumps, Epstein bar virus, and influenza have been commonly reported with POTS syndrome (3 ). We are presenting a rare case of COVID-19 induced POTS. CASE PRESENTATION: 38-year-old presented to the hospital with the chief complaint of shortness of breath chest tightness. Her past medical history was significant for COVID-19 infection two weeks before presentation. On arrival patient's vitals were within normal limits. Her physical examination was unremarkable. Laboratory investigations, including complete blood count, thyroid function test, and comprehensive metabolic profile, were unremarkable. Chest x-ray, CT angiogram, and echocardiogram were unremarkable for any consolidation, pulmonary embolism, and congestive heart failure. Orthostatic vitals were obtained, showing that the patient's heart rate increased from 90 beats/minute to 140 beats/minute, from supine to standing. This patient was diagnosed with COVID-19 induced POTS, given she was meeting the criteria of POTS and no other reason was found for postural orthostatic tachycardia. She was managed conservatively with hydration, and the patient was also instructed about yoga therapy. She was discharged home with a cardiology follow-up. DISCUSSION: COVID-19 induced POTS is a relatively new entity that most commonly affect female, and the estimated prevalence is around is 17 per 100,000 patients (3). It has been reported that 10% of the patient who tests positive for COVID-19 infection remains unwell beyond three weeks after recovery from the infection (2). For some of those patients, POTS may be the cause of their symptoms. The exact pathophysiology for COVID-19 induced POTS is poorly understood and may includes peripheral neuropathy, baroreceptor dysfunction, hypovolemia, and increased serum norepinephrine (2). Nonpharmacological treatment includes increasing fluid consumption of 2 to 3 L of water per day, lower limb compression stockings, and regular exercise (2). The commonly off-label pharmacological treatment include ivabradine, fludrocortisone, midodrine, and beta-blockers (2). CONCLUSIONS: POTS is a new and under-recognized entity. The clinician should have a high suspicion of POTS syndrome in a patient with a history of recent or remote COVID-19 infection presenting with orthostatic symptoms. Timely diagnosis is essential to prevent the morbidity associated with debilitating symptoms. Reference #1: Blitshteyn S & Whitelaw S. Postural Orthostatic Tachycardia Syndrome (POTS) and Other Autonomic Disorders After COVID-19 Infection: A Case Series of 20 Patients. Immunol Res. 2021;69(2):205-11. Reference #2: Jenna Stephanie O'Sullivan, Andrew Lyne, Carl J Vaughan. COVID-19-Induced Postural Orthostatic Tachycardia Syndrome Treated with Ivabradine. BMJ Case Reports CP. 2021;14(6):e243585. Reference #3: Sujana Reddy, Satvik Reddy, Manish Arora. A Case of Postural Orthostatic Tachycardia Syndrome Secondary to the Messenger RNA COVID-19 Vaccine. Cureus. 2021;13(5). DISCLOSURES: No relevant relationships by Arshan Khan

State of Pediatric Celiac Disease Practice in North America: A Naspghan 2021 Survey

Background and Aims: Substantial practice variation exists in both the diagnostic criteria for and the post-diagnosis monitoring of celiac disease (CeD). Differences include standards for serological diagnosis, endoscopic practices, models of care, and long-term clinical monitoring, all confounded by the COVID-19 pandemic. With the exponential rise of gluten-related disorders, revised ESPGHAN guidelines and new healthcare barriers, it is helpful to explore practice patterns to inform updates to clinical guidelines and future research endeavors. The purpose of this survey was to understand the expertise and practice parameters of pediatric gastroenterology (GI) clinicians across North America for the diagnosis and management of children with celiac disease. Method(s): A 23-item survey designed by a working committee of the NASPGHAN Celiac Disease Special Interest Group was distributed electronically to NASPGHAN members, including attending physicians, fellows, and advanced practice providers from September to December 2021. Four themes were explored: 1) screening and diagnosis;2) monitoring;3) impact of the COVID-19 pandemic;and 4) education and training. The implementaion of the ESPGHAN non-biopsy serologic diagnosis (based on the 2020 guidelines: tissue transglutaminase IgA (TTG-IgA) 10x upper limit of normal and a second sample with a positive endomysial antibody) by providers was explored. Descriptive statistics were tabulated by region, clinical role and those who identified as working at a celiac center. Result(s): A total of 284 surveys were completed with a response rate of 11.1% (264/2552). The majority of respondents were from the United States (89%, n=235) and Canada (8%, n=22) with 2% (n=5) from Mexico. Serology-based diagnosis as per ESPGHAN 2020 guidelines was accepted by 54.5% (n=12/22) of Canadian respondents and 39.6% (n=93/235) from the U.S (p=0.17). Since the COVID-19 pandemic, 36% of respondents have increased their application of non-biopsy diagnosis. Canadian respondents reported offering the ESPGHAN non-biopsy approach to diagnosis more often during the COVID-19 pandemic (Canada 74% vs US 33%, <0.0001). A higher precentage of patients who lived in Canada (52%) with positive celiac serologies waited >1 month to be evaluated by GI than the US (30%);p=0.03. There was also a significant difference between access to endoscopy within a month between patients who lived in Canada and the US patients (Canada 77% >1 month, US 20% >1 month;p=<0.001). Investigations at follow-up which were completed most frequently by those who identified as working at a celiac center (n=108) included complete blood count, thyroid function tests, liver enzymes, iron profile, Vitamin D and TTG-IgA (Figure 1). Among these respondents, 49.1% (n=53/108) repeat family screening ranging every 1-5 years. Specialty training in CeD remains limited as only 25.7% (n=61/237) staff pediatric gastroenterologists had celiac-focused didactic lectures, and 23.3% (n=55/237) participated in a CeD specialty clinic during their fellowship. Conclusion(s): This survey revealed heterogeneity in current practices for the diagnosis and management of CeD in North America and the influence of the COVID-19 pandemic in increasing the use of the ESPGHAN no-biopsy approach to diagnosis. An education gap was identified for CeD in pediatric GI fellowship training. Further studies are needed to understand the impact of these variable practices and future research priorities and clinical guidelines should take this variation into consideration. (Figure Presented).

Thyroid storm in pregnancy: A case study

Introduction: Inadequately treated maternal hyperthyroidism increases the risk of severe preeclampsia, heart failure, and thyroid storm. Thyroid storm is a life-threatening endocrine emergency characterized by multiple organ failure due to severe thyrotoxicosis. A storm can be triggered by precipitating events such as trauma, surgery, infection, delivery;even pregnancy itself. Case Description: A 35-year-old lady presented to the emergency department with complete miscarriage. She had underlying hyperthyroidism for six years but defaulted her follow-ups and medications since the beginning of the Covid-19 pandemic. She complained of palpitations despite minimal vaginal blood loss. ECG showed sinus tachycardia with a heart rate of 190 beats per minute. Her hemoglobin level was stable, but thyroid function test showed hyperthyroidism with raised free T4 (60 pmol/L) and low TSH (< 0.01 mIU/L). Her Burch-Wartofsky score was 35, implying an impending thyroid storm. IV Verapamil was given immediately and her heart rate improved to 140-150 bpm. She was transferred to a high dependency ward for close monitoring and started on oral Propylthiouracil and Propranolol. Regrettably, when she began to improve, she requested for discharge against medical advice. Discussion: The diagnosis of thyroid storm is clinical, with laboratory tests consistent with overt hyperthyroidism. Clinical scoring systems such as the Burch-Wartofsky Score helps to confirm diagnosis and triage disease severity. Treatment is multimodal using medications (thioamides, iodide, beta-blockers, corticosteroids, antipyretics), oxygen, volume resuscitation, and correction of electrolyte imbalance. A high index of suspicion, rapid recognition, prompt treatment and intensive monitoring are key elements of management.

SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARSCoV- 2) VACCINE-INDUCED THYROID DYSFUNCTION: A TALE OF TWO PATIENTS

Introduction SARS-CoV-2 vaccine has been the main pillar in battling the coronavirus disease 2019 (COVID-19) pandemic. However, the current vast scale of SARS-CoV-2 vaccination programme has led to inevitable reports of various adverse reactions, one of which include thyroid dysfunction. CASES We describe two patients who manifested hyperthyroidism following BNT162b2 mRNA-based COVID-19 vaccine boosters. Patient 1, a previously euthyroid 46-year-old female, has an eight-year history of type 1 diabetes mellitus. She developed palpitations of increasing severity about two weeks after her COVID-19 booster vaccine on 20th January 2022. She had weight loss of 4 kg and experienced menstrual irregularities in the subsequent three months. Examination revealed tachycardia (112 beats per minute, regular) and bilateral fine tremors of the hands. There was no goitre or neck tenderness. Blood investigations showed overt hyperthyroidism with positive thyroid autoantibodies, consistent with Graves' disease. Treatment with carbimazole led to marked symptomatic improvement. Patient 2, a 38-year-old female with a six-year history of Hashimoto thyroiditis, was clinically and biochemically euthyroid while taking levothyroxine 100 mcg daily prior to her COVID-19 booster vaccine on 5th January 2022. Five weeks following the vaccine, her thyroid function test during her endocrine clinic appointment showed overt hyperthyroidism, which was confirmed by a second blood sample ten days later. There was neither a change in levothyroxine dose nor any additional supplement intake. She was otherwise asymptomatic. Levothyroxine was then withheld. She regained her baseline hypothyroid state two weeks later, during which levothyroxine was resumed. Conclusion SARS-CoV-2 vaccine-induced thyroid dysfunction can affect both euthyroid and hypothyroid patients. A history of recent COVID-19 vaccination should be included in the clinical evaluation of a newly diagnosed hyperthyroid patient or unexplained hyperthyroidism in a long-standing hypothyroid patient.

THYROID FUNCTION TEST IN SEVERE COVID-19 PATIENTS IN HOSPITAL SUNGAI BULOH

Introduction COVID-19 may have widespread effects throughout the body, including the endocrine glands, which can be impaired by different mechanisms. Several recent reports have described the onset of thyroid dysfunction in previously healthy patients diagnosed with COVID-19. Thus, we aimed to describe the pattern of abnormal thyroid function tests (TFTs) in severe COVID-19 patients in Hospital Sungai Buloh. METHODOLOGY Thyroid stimulating hormone (TSH) and free thyroxine (fT4) were received from all critical care wards catering for severe COVID-19 adult patients (Clinically Stage 4 and 5) from December 2020 till June 2021. It was retrospectively reviewed in Laboratory Information System (LIS) with exclusion of thyroid disease, pregnancy or immunotherapy. SARS-CoV-2 infection was confirmed by RT-PCR of nasopharyngeal swab samples and severity classification was based on the Malaysia MOH guideline. Analysis of TFT was performed on Siemens Atellica using chemiluminescent immunoassay Results From 184 TFT results analysed, about 120 patients (65%) had abnormal thyroid function, of which 62.5% had low TSH level with normal fT4 and 15.8% had low TSH with high fT4. This indicated that abnormal TFT is common among COVID-19 patients, with low TSH being most common. However, we are unable to exclude steroid use as a cause of low TSH levels, as steroid are one of the main treatments prescribed in severe COVID-19 cases. Conclusion There was a high proportion of abnormal TFT in severe COVID-19 patients even in the absence of pre-existing thyroid conditions. Clinicians directly involved in treating these patients need to be vigilant in interpreting thyroid function abnormalities in COVID-19 infection.

NEW-ONSET THYROID EYE DISEASE AFTER COVID-19 VACCINATION: A CASE REPORT

Introduction The relationship between autoimmunity and SARS-CoV-2 vaccine has explained how thyroid dysfunction developed following vaccination but the onset of thyroid eye disease (TED) is scarcely described. We report a case of Graves' disease (GD) who developed TED after three weeks of BNT162B2 SARS-CoV-2 vaccine (Pfizer-BioNTech) injection. CASE A 54-year-old non-smoking male presented with newonset bilateral eyes redness, proptosis, and diplopia three weeks after receiving the second dose of mRNA BNT162B2 SARS-CoV-2 vaccine. He was diagnosed with GD without TED in 2003 and underwent radioactive iodine ablation in 2020. He subsequently developed hypothyroidism and was started on levothyroxine with stable thyroid function test throughout clinic visits. There were no recent stressful events including COVID-19 infection. On examination, he has bilateral exophthalmos, chemosis, conjunctival injection, swollen eyelids and caruncles, with intact vision. Blood tests revealed normal TSH, free T4, and T3, but elevated TSH-receptor antibodies of 3.60 IU/L (<1.75) and antithyroid peroxidase (TPO) antibodies of >600 IU/ml (0-34). MRI orbit showed bilateral extraocular muscle enlargement and proptosis. Intravenous methylprednisolone was given weekly for 12 weeks. There was significant improvement concerning congestive symptoms and diplopia after the third dose of methylprednisolone. Thyroid eye disease is the extrathyroidal manifestation of GD resulting from the autoimmune and inflammatory process. The temporal relationship of the onset of TED after mRNA SARS-CoV-2 vaccination in our case was suggestive, and there were no other inciting events identified. The postulated mechanisms include immune reactivation, molecular mimicry between the SARS-CoV-2 spike proteins and thyroid proteins, and the autoimmune/ inflammatory syndrome induced by adjuvants present in the mRNA vaccine. Conclusion Patients with autoimmune thyroiditis should be monitored closely after SARS-CoV-2 vaccine as they may develop TED and require treatment.

Post-COVID vaccination ASIA syndrome (autoimmune/inflammatory syndrome induced by adjuvants) and thyroid dysfunction

Background: ASIA syndrome is an entity that incorporates diverse autoimmune conditions after exposure to various adjuvants in vaccines. There is limited literature available regarding development of thyroid disorders after covid 19 vaccination. Aims and Objectives: Retrospective case series of patients diagnosed with thyroid disease within 2 months of covid-19 vaccination. History, examination, relationship with covid infection and vaccination, onset of symptoms, thyroid function tests, TRAb, Anti-TPO, ESR, CRP, Tc99-thyroid scan were recorded for each of the patient. Results: We observed 9 subjects (females 5, males 4;age range 22-63 yrs) with thyrotoxicosis. The onset of symptoms after vaccination ranged from 2 days to 60 days. Six subjects had Graves' disease (GD) while 3 had subacute thyroiditis (SAT). Two subjects had acute onset of thyroid associated opthalmopathy;one patient needed glucocorticoids (GC). All subjects with GD were treated with antithyroid drugs while subjects with SAT were treated with NSAIDS;none required GC. Conclusions: SAT and GD may develop as a manifestation of ASIA syndrome after covid 19 vaccine. Long-term multicentric observational studies are needed to establish the natural history of ASIA syndrome following covid vaccination.

Thyroid function abnormalities in hospitalized patients with COVID-19 infection - A cross-sectional study

Background: Thyroid gland expresses ACE-2 receptors. It is thus a potential target for involvement by the COVID virus. Also, the cytokine storm and various drugs used in the treatment for COVID-19 can affect the thyroid function tests. Aim: To study thyroid function abnormalities in hospitalized patients with COVID19 infection. Objective: To study the proportion of patients with thyroid function abnormalities in hospitalized patients with COVID-19 infection. Results: Total 271 Covid -19 patients were included in the study, of which 27 were asymptomatic, 158 mild, 39 moderate and 47 severe categories classified according to the MOHFW criteria. The mean age was 49 ±17 years, 64.9% were male. Abnormal thyroid function test was present in 37.2% (101/271) patients. Low fT3, low fT4 and low TSH were present in 21.03%, 15.9% and 4.5%, respectively. Mean fT3 and fT3/fT4 ratio decreased with increasing severity of COVID-19 illness (p=0.000). In multivariate analysis, low fT3 was associated with increased risk of mortality (OR 12.36, 95% CI: 1.23- 124.19;P=0.033). Conclusion: Low fT3 and fT3/fT4 ratio helps to predicts disease severity. Low fT3 is associated with increased risk of mortality.

Case of COVID-19 Related Thyroiditis

Introduction: The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA beta-coronavirus responsible for the Coronavirus disease-19 (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. The SARS-CoV-2 pandemic has spread rapidly worldwide. Few cases and case series have been published reporting COVID-19 related subacute thyroiditis. We report a case of COVID-19 related thyroiditis. Case Description: 73-year-old female presented to the hospital with complaint of shortness of breath, fever and weakness. She was diagnosed with COVID-19 pneumonia and treated with dexamethasone and convalescent plasma. Patient was discharged home after 10 days. Two days after discharge, she presented with complaint of generalized weakness. She was noted to have thyrotoxicosis. Patient was not taking lithium or amiodarone and she did not receive iodinated contrast. She had no sign or symptoms of thyrotoxicosis. She denied neck pain or difficulty swallowing. On laboratory evaluation, SARS Coronavirus 2 RNA was positive. RSV, Influenza A and Influenza B by PCR were negative. TSH was low at 0.182 uIU/mL (0.450-5.330 uIU/mL), free T4 elevated at 3.00 ng/dL (0.58-1.64 ng/dL), free T3 elevated at 5.24 pg/mL (2.20-4.10 pg/mL). Her TSH 3 weeks ago was normal at 0.723 uIU/mL. Thyroid stimulating immunoglobulin negative < 0.10 (< =0.54 IU/L). Thyroid ultrasound showed normal sized gland, few sub centimeter nodules bilaterally. NM thyroid uptake and scan showed low uptake and no focal hot or cold nodule. Her workup was consistent with thyroiditis. Correlating with the diagnosis of COVID-19, this could be most likely COVID-19 related thyroiditis. Repeat labs in a week showed normal TSH 1.138 uIU/mL, normal free T4 1.28 ng/dL and low free T3 1.93 pg/mL. The patient likely had thyroiditis during early course of COVID-19 infection and was caught during the late phase and hence, improvement of thyroid function within a week of biochemical diagnosis. Discussion: Subacute thyroiditis is a self-limited inflammatory disorder, characterized by neck pain, general symptoms and thyroid dysfunction. It has been linked to viral infection like mumps virus, coxsackievirus, adenovirus, Epstein-Barr virus, rubella and cytomegalovirus. In our patient, SARS-CoV-2 was the likely cause of thyroiditis. A single center retrospective study done in 287 patients hospitalized with COVID-19 in Milan, Italy reported 20% of patients with thyrotoxicosis, 5% with hypothyroidism and 74% with normal thyroid function test. We report this case to alert clinicians that thyroiditis and resultant thyrotoxicosis should always be considered as a differential diagnosis in patients with COVID-19.

A Case of Hashimoto's Encephalopathy Presenting with Cognitive Impairment and Visual Hallucinations

Introduction: Hashimoto's encephalopathy (HE) is a rare immune–mediated complication of Hashimoto thyroiditis. It is presented as subacute onset of altered mental status with confusion, seizures and myoclonus. It is a diagnosis of exclusion and requires that all other possible causes of cognitive impairment are excluded with a response to steroid therapy and evidence of thyroid autoimmunity in a patient. Here, we present a case of HE in a patient who presented with altered mental status and visual hallucinations despite no history or symptoms of thyroid disorder. Case Description: A 77 year old male with past medical history of hypertension presented with altered mental status, lethargy, and visual hallucinations. Per patient’s wife, patient started to get somnolent and was having memory problems six weeks prior to presentation. His mental status gradually deteriorated, and he started to have visual hallucinations. He was somnolent and noted to have myoclonus and twitching on admission. Magnetic resonance imaging (MRI) of the brain with gadolinium showed chronic microvascular changes with no acute intracranial pathology or masses. Electroencephalogram (EEG) showed no signs of epileptiform activity. Infectious disease work up, including complete blood count, urinalysis, sexually transmitted diseases, and cerebrospinal fluid (CSF) analysis, was negative. Blood glucose levels, serum electrolytes, liver function tests, blood urea nitrogen, and creatinine were normal. Coronavirus disease 2019 (COVID-19) was negative. CSF analysis for autoimmune encephalopathy and Creutzfeldt-Jakob disease was negative. Thyroid function tests were normal. Thyroid peroxidase antibody (TPOAb) was negative (8.6 IU/mL [reference range (RR): < 9.0 IU/mL]) and TgAb was positive (8.2 ng/ mL [RR: < 4 IU/ mL]). With suspicion of Hashimoto's encephalopathy, he was started on intravenous Solu-Medrol 1 g for five days. He was then switched to oral prednisone 60 mg daily, which he received for ten days. His mental status improved upon day 14 of admission. On day 17 of admission, he was discharged on oral prednisone 40 mg daily with taper for five weeks. He was evaluated in the clinic few months after discharge. His mental status had improved significantly, and he was back to his baseline in about two months after discharge as per his wife. Repeat thyroid function tests, TPOAb, and TgAb were negative. Discussion: The incidence of Hashimoto’s encephalopathy (HE) is 2.1 per 100,000 individuals in the general population, and is more common in women than men. This case highlights that HE should be considered in patients with subacute presentation of neurological problems, which cannot be explained with other possible diagnosis, despite no symptoms of thyroid disease such as the patient in this case study. Therefore, HE should be evaluated for in patients with cognitive impairment for prompt diagnosis and treatment with steroid therapy in order to improve the prognosis in these patients.

Transient Elastography of Liver and Serum Hyaluronic Acid Levels In Adult Transfusion Dependent Thalassemia Patients

Iron overload occurs as a result of multiple blood transfusions and increased iron absorption in thalassemia patients. Iron deposition in liver results in liver stiffness and fibrosis. Non invasive methods including imaging and serum biomarkers have been introduced for assessment of liver fibrosis. We aimed to study liver stiffness using transient elastography and serum hyaluronic acid levels and correlate them with serum ferritin levels in adult transfusion dependent beta thalassemia patients. MATERIAL: 70 transfusion dependent thalassemia patients of age ≥18 years, registered at Thalassemia Day Care Centre were subjected to investigations like CBC, Liver function tests, viral markers, serum ferritin, serum hyaluronic acid levels and transient elastography. Fibrosis indices like FIB-4, AAR and APRI were also calculated. 45 patients had T2*MRI reports with them;which were also included and analysed. Spearman coefficient r was used to test correlations between TE values and serum HA levels with other variables. OBSERVATION: 70 patients (41 male and 29 female) with mean age of 24.09±5.38 years and BMI 20.51 ±3.47 kg/m², were enrolled. Median values of hemoglobin, AST, ALT, TE, serum HA and serum ferritin were, 9.15 g/dl, 42 IU/L, 47.50 IU/L, 9.1 kPa, 284 ng/dl and 1841 ng/ml, respectively . TE values had significant positive correlation with serum ferritin (r=0.5, p < 0.001), ALT (r=0.59, p < 0.001), AST (r=0.58, p< 0.001), APRI (r=0.5, p<0.001) and FIB-4 (p=0.02), respectively and significant negative correlation with T2* MRI (ms) (r= -0.5, p<0.001). No significant correlation of HA was found with any variable. CONCLUSION: Transient elastography can be used as a non expensive, easily accessible and non invasive marker of liver iron overload. Further detailed studies are required to establish the role of serum Hyaluronic acid in thalassemia patients. © Journal of the Association of Physicians of India 2011.

Wide Spectrum of Thyroid Function Tests in COVID-19: From Nonthyroidal Illness to Isolated Hyperthyroxinemia.

Background: Changes in thyroid function test (TFT) in COVID-19 patients have been reported in several studies. However, some features such as thyrotoxicosis are inconsistent in these studies. In addition, some drugs such as heparin interfere with the free T4 assay. Objectives: This study was designed to examine TFT abnormalities in COVID-19, utilizing direct and indirect methods of free T4 assay. Methods: This prospective cross-sectional study was conducted on 131 hospitalized COVID-19 patients. Serum levels of total T3, TSH, T3RU, and total T4 were measured. The free T4 assay was performed using direct (free T4) and indirect (free thyroxin index or FT4I) methods. The patients were categorized into different TFT groups. The clinical characteristics, laboratory findings, and outcomes were compared between the groups. Results: The frequencies of nonthyroidal illness (NTI), subclinical/overt hypothyroidism and subclinical/overt thyrotoxicosis were 51.7, 6.9, and 6.9%, respectively. Besides, 6 and 8.1% of the patients had isolated high free T4 and isolated high FT4I without any other TFT abnormality, respectively. The lymphocyte percent was lower in the subclinical/overt group than in other TFT groups (P = 0.002). Atrial Fibrillation (AF) was found in 37.5% of subclinical/overt thyrotoxicosis patients versus 1.7% in the NTI and nil in the other three groups (P < 0.001). Conclusions: In addition to the reported TFT abnormalities in COVID-19 in previous studies, some new features like isolated hyperthyroxinemia were found in our study. We found a strong association between subclinical/overt thyrotoxicosis and AF. Regarding the high prevalence of AF in hospitalized COVID-19 patients, request for thyroid function test is rational in COVID-19 patients with this arrhythmia.

Subacute thyroiditis post COVID-9 vaccinations

Background: Subacute thyroiditis is being frequently seen after Covid infection as the cases of many other viral infections. Patients classically complain of symptoms of thyrotoxicosis mainly palpitations and sweating but with associated tenderness in neck with or without fever. Subacute thyroiditis has seldom been seen after viral vaccinations. We present a case series of subacute thyroiditis which presented after administration of the COVID-19 vaccine. Material(s) and Method(s): Case 1: A 28-year-old female without previous medical problems, presented to the clinic for sore throat, palpitations and dizziness . No recent history of any upper respiratory tract infection or pregnancy. The patient received her second dose of Pfizer/BioNTech mRNA vaccine for COVID-19 2 weeks earlier. Thyroid function testing was done and revealed TSH 0.001, fT4 3.29, fT3 6.8. Her TPO antibody, thyroglobulin antibodies and Trab were negative. Technetium-99m pertechnetate scan revealed diffuse thyroiditis. The patient was prescribed prednisone 20 mg daily. She reports rapid improvement of her symptoms and prednisone treatment was given for 3 weeks then stopped. Repeated tests showed normal TSH 10 days after stopping steroids. Case 2: A 49-year-old female with the history of V Leiden mutation and repetitive abortions presented to the clinics on May 25, 2021 for the complaint of unintentional weight loss of 6 kg in 20 days and palpitations, preceded by fever and neck pain at the end of April. The patient noted that she was vaccinated with her second dose of Sinopharm vaccine on the 6th of April 2021. Thyroid function test revealed a thyrotoxic profile TSH 0.005, fT4: 42, fT3 9,02. With negative thyroglobulin antibody, TRAb. CRP 60 , . Thyroid Ultrasound showed a diffuse heterogenous echtexture of the thyroid. A fever work up was done to rule out other infectious causes including Salmonella and Brucella, all were negative. The patient was prescribed prednisone 40 mg daily and propranolol 10 three times daily, gradually tapered over one months. Her Symptoms resolved and her follow up tests showed normal tsh and CRP Result(s): Discussion: Subacute thyroiditis is usually associated with upper respiratory tract infections including Covid -19 infection. This can be explained by T cells cross reacting between the virus and the thyroid cells. Moreover, De Quervain thyroiditis following viral vaccines has been reported influenza vaccines. Thyroiditis has not been described until now as a frequent side effect of Covid vaccine. So we presented the cases of a 28 and 49- year-old females who has presented with cases of subacute thyroiditis after receiving respectively the Pfizer mRNA vaccine and Sinopharm vaccine for COVID-19. Conclusion(s): Conclusion: Subacute thyroiditis after Covid-19 vaccine is rare but may be underreported. Further investigations are required to evaluate predisposing factors to De Quervain thyroiditis following Covid-19 vaccine.

Clinical chemistry and immunoassay test results: Harmonisation and standardization of discordant notes

However, it is this very set of tests that have come Hin question. First, what is the normal and acceptable range (upper & lower limits) of different Clinical Chemistry and Immunoassay biomarkers in a particular population has been debated in different scientific fora. This is because the level of markers can change in relation to other biochemicals, biomolecules and hormones, which themselves vary considerably with race, gender, age, different physiological conditions (like pregnancy, new-born) and other illnesses & interfering substances. The variation can be to an extent that each individual can seem to have their own set-point of these parameters. A second problem which the diagnosticians have to grapple with is the variability of test-results in itself;even a broadly similar set of instruments and methods can provide variable results. It is then a real challenge to physicians, to decide whether the patient is suffering from a disease or not, since other factors can also cause changes in test levels. Standardization and harmonization of clinical chemistry and immunoassay testingis therefore still a formidable challenge, due to the lack of proper reference intervals and sometimes due to standardized measurement procedures. Laboratory medicine community the world over has realized that, variability in test results in different platforms can create a lot of confusion to clinicians and the general population;harmonization of procedures is therefore the need of the hour. In this talk, I will provide few examples and technical solutions to address laboratory challenges and to take it forward from both Clinical Chemistry as well as Immunoassay platforms. To begin with, harmonization and standardization of TSH and other thyroid function tests are still a formidable challenge, due to the lack of proper reference intervals and standardized measurement procedures. It has been documented that even a broadly similar set of instruments and methods can give up to 40% more or less values in TSH levels. Based on a particular population's demographic variations, reference interval can be different for immunoassay like TSH. Therefore, we have verified the reference interval for the Indian population for TSH in our laboratory. We have screened 800 subjects, of which 630 healthy subjects were chosen in the study group for reference interval verification. The reference interval (90% Confidence interval) for TSH by non-parametric procedure (bootstrap) was 0.48- 4.52, and by parametric one (after transformation of the data) was 0.45-4.27 for the adult population, which is little different from the manufacturer's guidelines. Similarly, we have conducted a study of 2797 female patients and 2805 male patients in a six month period and have observed that, women have a greater risk of being 14% under-diagnosed of acute coronary syndrome, if we donot use gender specific cut off (Male: 32.3 pg/ml and Female: 14.6pg/ml for the Indian population), with high th sensitive troponin I assay near the 99 percentile of a reference control population. Therefore, implementation of sex-specific hs-cTnI assay was able to identify 14% of under-diagnosed women with ACS in 6 months period. This in turn also decreased the number of men being diagnosed by 3%. On a similar note, there has been a continuous challenge in the health care system in U.S, Europe and other countries to standardize and harmonize the HbA1c reporting: the decision on what to report in NGSP (%) and/or IFCC (mmol/mol) units along with eAG (in either mmol/L or mg/dL). This globalization places a responsibility on laboratory medicine specialists to work together to reduce the current variability in patient results, which arises from differences between units, methods and laboratory practices in different countries. Due to the standardization efforts of IFCC, NGSP, and also due to ongoing efforts of manufacturers and laboratories, the quality of HbA1c reporting has increased dramatically. Consequently, there has been a paradigm shift: HbA1c is now considered the gold standard, not only for monitoring, but also for diagnosis of diabetes. We have performed verification studies of HbA1c by different methods: HPLC, Capillary Electrophoresis, Enzymatic, Immunoassays in 200 samples and compared 60 samples with hemoglobinopathies. Finally, we have also explored harmonizing the clinical protocol based on the use of inflammatory and routine laboratory biomarkers in 2,654 COVID-19 patients. To explain the role of harmonizing routine laboratory parameters in disease monitoring, two adult males, two adult females and one adolescent girl were selected. These are representative examples of different manifestations of COVID 19, with Adult Respiratory Distress Syndrome (ARDS), Cardiac Injury, Neurological manifestations and Pediatric Multi system inflammatory syndrome (PIMS), admitted in the Intensive care unit (ICU) of the hospital, which will be discussed. Therefore, the road map for laboratory medicine will involve strategies for harmonizing, communicating and integrating with all stakeholders, like, clinicians, diagnosticians and IVD industry, in order to formulate guidelines for assisting in correct measurement, diagnosis and management of diseases.

Seizure, abdominal pain, and urine pink in an adolescent female-what's the link?

Case Report A 17 year-old female with history of depression was transferred to the pediatric intensive care unit (PICU) from an emergency department (ED) for first time seizure and subsequent encephalopathy after five days of severe, diffuse abdominal pain and vomiting. The night prior to admission, she complained of lightheadedness and then had a witnessed generalized tonic-clonic seizure lasting 45 seconds. She initially returned to her baseline but then had three additional seizures requiring ED evaluation. She received intravenous doses of lorazepam and levetiracetam that aborted the clinical seizures. She remained encephalopathic and was orotracheally intubated for airway protection. Family denied known ingestions but reported she did vape nicotine. Urine drug screen was positive for benzodiazepines, consistent with seizure management. Cerebrospinal fluid analysis was unrevealing. Urinalysis showed moderate ketones and trace blood. Urine pregnancy test and nasopharyngeal SARS-CoV-2 polymerase chain reaction were negative. Head computerized tomography scan showed no intracranial pathology. On arrival to the PICU, the patient was afebrile, tachycardic, and hypertensive to 171/118 mmHg. She was somnolent on arrival but aroused to sternal rub without focal neurologic deficit. She presented with a Foley catheter that drained pinkorange urine. A nicardipine infusion was started given concern for the development of posterior reversible encephalopathy syndrome (PRES). Thyroid function tests were consistent with euthyroid sick syndrome. BioFire meningitis panel, plasma SARS-CoV-2 IgG, and toxicologic evaluation were all negative. Electrocardiogram showed sinus tachycardia. Magnetic resonance imaging of the brain revealed cortical and subcortical areas of diffusion restriction consistent with PRES. Ultimately, a random urine porphobilinogen and a 24-hour measurement of urine porphyrins collected on hospital day 1 were both markedly elevated. A diagnosis of Acute Intermittent Porphyria (AIP) was made. A gastrointestinal porphyria specialist was consulted and recommended monthly outpatient injections of givosiran upon hospital discharge. Discussion This case illustrates the importance of considering AIP in the differential diagnosis of new onset seizure or encephalopathy associated with hypertension, tachycardia, and abdominal pain in an adolescent. This case also adds to a small number of cases associating AIP with PRES. AIP is often viewed as an adult disease because it typically presents in the third or fourth decade of life. Timely recognition of AIP in the pediatric setting is critical to preventing delays in diagnosis, treatment, and patient education on triggers of acute attacks. AIP attacks are treated with dextrose and hemin infusions to reduce production of porphyrin precursors. Prophylactic treatment of AIP now includes givosiran, an interfering mRNA that reduces levels of intermediates in heme synthesis that are neurotoxic when elevated.

Delayed Onset of Central Hypocortisolism in a Patient Recovering From COVID-19.

OBJECTIVE: The objective of this report is to highlight the possible but little-known association between coronavirus disease 2019 (COVID-19) and delayed onset of central hypocortisolism, which may be of significant clinical importance. METHODS: We describe a patient who developed new-onset central hypocortisolism in the convalescent phase of mild COVID-19, which has not been previously reported. RESULTS: A 47-year-old man with recent COVID-19 upper respiratory tract infection developed new-onset persistent dyspepsia and eosinophilia for which multiple investigations were normal. He was eventually diagnosed with central hypocortisolism, as evidenced by 8 AM cortisol level of 19 nmol/L (normal, 133-537 nmol/L) and adrenocorticotropic hormone of 7.1 ng/mL (normal, 10.0-60.0 ng/mL). He was started on hydrocortisone, which led to resolution of both dyspepsia and eosinophilia. At the same time, an interesting thyroid function trend was observed-an initial increase in both free thyroxine and thyroid stimulating hormone was followed by temporary central hypothyroidism before subsequent spontaneous recovery. On follow-up 3 weeks later, the patient remained hypocortisolemic. CONCLUSION: COVID-19 may be associated with the delayed onset of central hypocortisolism in its convalescent phase. Although various mechanisms are possible, hypothalamic-pituitary activation during systemic illness, followed by a rebound decrease in activity after recovery, is consistent with the clinical course and thyroid function trend in this patient. It is essential that physicians consider endocrinopathies in the differential diagnosis of such cases, given the risk of life-threatening adrenal crises and their possible contribution to persistent symptoms following recovery from COVID-19.