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.

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

Thyroiditis Post COVID-19 mRNA Booster Dose Vaccination

Introduction: SARS-CoV-2 vaccines have been associated with thyroid dysfunction including thyroiditis and Graves' disease. We report a patient who developed thyrotoxicosis secondary to thyroiditis after COVID-19 mRNA booster dose vaccination. Case Description: A 74-year-old man with no known personal or family history of thyroid disorders went to his primary care physician with symptoms of palpitations. Of note, he had the first booster (third dose) of the Pfizer/BioNTech vaccine about 1 week before. He did not recall any similar symptoms after the first two doses of the same vaccine. There were no other symptoms of thyrotoxicosis such as hand tremors, weight loss or mood change. There was no family history of thyroid disorders. He was not on any medications such as amiodarone and was not taking any herbal supplements. He did not have any symptoms of upper respiratory tract infection. There was no neck pain. Physical examination was unremarkable with no goiter or thyroid eye manifestations. Thyroid function: free T4 elevated at 46.7 pmol/L (11.5-22.7) and TSH suppressed at 0.01 mIU/L (0.5-4.5). Thyroid stimulating immunoglobulin was positive at 200% (50-179). He was initially started on carbimazole 15mg daily. However, the patient became rapidly hypothyroid despite dose reduction and subsequent discontinuation of carbimazole with free T4 of 8 pmol/L and TSH of 36.4 mIU/L. An ultrasound of the thyroid gland showed vascularity with no discrete nodules. No thyroid uptake scan was done. The diagnosis was revised to thyroiditis post vaccination. Hypothyroidism persisted despite discontinuation of carbimazole before recovery 8 months later. Patient was well and did not require any thyroxine supplementation. Discussion(s): It is postulated that COVID-19 vaccines triggered thyroiditis via an autoimmune inflammatory syndrome caused by the vaccine adjuvants. A high index of suspicion is necessary and a thyroid uptake scan may be useful in making the diagnosis. Thyroiditis is a self-limiting condition and recognising it is important as no specific thyroid treatment is necessary in most patients. Patients should not be deterred from subsequent vaccination as COVID-19 infection has higher mortality risk than thyroiditis.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

Thyroid dysfunction reflects severity of COVID-19 pneumonia in hospitalized patients

Introduction: Coronavirus disease 2019 COVID-19 is clearly the pandemic of the new millennium. COVID-19 determines multi organ dysfunction including the inflammatory immune responses of thyroid gland. Objective(s): To determine whether the involvement of the thyroid gland by COVID-19 manifests as thyroid hormonal changes and development of thyroid disorders. Method(s): We studied prospectively 60 patients with COVID-19 pneumonia,without previous known history of thyroid disease nor pre-existing endocrine disorders, hospitalized between May and July 2021, and we performed serum thyroid hormonal analysis within the first 24 hours after admission, including TSH, Free T3, Free T4 and their antithyroglobulin antibodies (Anti-TG and Anti-TPO), and correlate them with clinical and laboratory data. Result(s): Samples were collected from 60 patients (31 males, 51.7%). 32 out of 60 (53.3%) showed significantly lower values of TSH (0,29 +- 0,07 mIU/mL) with decreased Free T3 serum levels (2,07 +- 0,131 pmol/L) and the thyroid autoantibodies (both Anti-TG and Anti-TPO) were positive. These 32 patients (27 males) demonstrated moderate to critical illness and they needed high oxygen flow. The other 28 patients with no evidence of thyroid abnormalities showed mild to moderate COVID-19 pneumonia and none needed high oxygen flows. Conclusion(s): In our study, 32/60 (53.3%) patients with moderate to severe COPVID-19 pneumonia were diagnosed with thyroid abnormalities. Thus, the development and the progression of respiratory failure due to SARS-COV-2 may affect the thyroid function.

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.

A case of subacute thyroiditis after influenza vaccination

A 40-year-old Japanese woman presented to the outpatient clinic with fever and palpitations 2 days after receiving the influenza vaccine (Influenza HA Vaccine 'KMB') following the second dose of coronavirus disease 2019 (COVID-19) vaccine (COVID-19 vaccine Moderna intramuscular injection). At the first visit, the patient presented with a swollen thyroid gland with mild tenderness, and she was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free T3: 5.42 pg/mL;free T4: 2.34 ng/dL;and thyroid-stimulating hormone (TSH): <0.01 muIU/mL), a high C-reactive protein level (5.77 mg/dL), a negative TSH receptor antibody, and characteristic ultrasound findings. The patient's human leukocyte antigen types were A2, A11, B35, B51, DR4, and DR1403. Prednisolone (15 mg/day) was given as an initial dose, after which the fever subsided, and the dose was tapered and discontinued after 6 weeks. The patient was thought to have developed SAT due to influenza vaccination. SAT after influenza vaccination may be overlooked. For patients with SAT, it is necessary to obtain information regarding their vaccination history.Copyright © 2023 The authors.

Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.

Objective: COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods: A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results: A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P < 0.001), and 0.22 (P < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions: Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.

Unusual case of Obesity and Hypoventilation in Childhood

Objectives Childhood obesity can be monogenic or polygenic in etiology and is associated with significant morbidities. Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation, and neural crest tumor (ROHHHAD[NET]) syndrome, is a rare autonomic and respiratory pediatric disorder presenting with rapid weight gain in early childhood, hypothalamic-pituitary dysfunction, central hypoventilation, and an association with neural crest tumors. Methods A 6-year-old Asian girl with abnormal weight gain since the age of 3 years, presented to the pediatrician's office due to pulse oximeter readings in the 60s at home. Parents were monitoring saturations at home as a way of screening for COVID-19 infection. The pediatrician confirmed hypoxemia and transferred the patient to the Children's Medical Center emergency department on oxygen via EMS. She had occasional snoring and nighttime cough, but no history of respiratory distress, or signs of infection. There was no hyperphagia, neonatal hypoglycemia, or developmental or behavioral concerns. On examination her body weight was 30 kg (+1.56 SD) and height was 113 cm (-1.46 SD) with a body mass index (BMI) of 23.4 kg/m2 (+2.33 SD). No acanthosis nigricans, cushingoid features, or respiratory distress were noted on examination. In the intensive care unit, she was diagnosed with central hypoventilation requiring mechanical ventilation. Her laboratory work-up revealed central hypothyroidism (low Free T4 of 0.64 ng/dl, TSH 1.553 microIU/L). Other anterior pituitary hormones were normal (adrenocorticotropic hormone, 16.3 pg/mL;cortisol, 10.7 mug/dL;prolactin, 9.95 ng/ml;Insulin-like growth factor-1, 83 ng/mL;and IGF binding protein 3, 3.02 mg/L). Genetic investigations revealed no known mutations in the PHOX2B gene, making a diagnosis of central hypoventilation syndrome unlikely. Results Rapid onset weight gain around 3 years of age, central hypoventilation, and anterior pituitary hormone deficiency in our patient with negative PHOX2B is consistent with a clinical diagnosis of ROHHHAD[NET]. Our patient was started on levothyroxine;received tracheostomy for mechanical ventilation;and gastrostomy for pharyngeal dysphagia. She is doing well, goes to school, and is tolerating trials off the ventilator during the day. Conclusions ROHHAD is an important differential to consider for any child with rapid and early obesity and hypoventilation as early diagnosis is critical in improving the clinical management and the prognosis.

Association of COVID-19 vaccination before conception with maternal thyroid function during early pregnancy: A single-center study in China.

Despite the high vaccination coverage, potential COVID-19 vaccine-induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID-19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID-19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (ß = -0.27, 95% confidence interval [CI], -0.42, -0.12), and the mean TSH levels were higher by 0.08 mIU/L (ß = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID-19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID-19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels.

New Graves Disease Diagnoses in Youth Before and During the COVID-19 Pandemic

Objectives The relationship between Coronavirus disease 2019 (CV-19) and thyroid disease remains undefined. Given reports of increasing incidence of autoimmune disease and observed trends in new Graves Disease (GD) diagnoses since the start of the CV-19 pandemic, we sought to assess the incidence and characteristics of new GD diagnoses in youth prior to and during the CV-19 pandemic. We hypothesized that there was an increased incidence in new onset GD in youth during the pandemic, and that patients with new onset GD were more symptomatic during the pandemic compared to those diagnosed prior to the pandemic. Methods We performed a retrospective chart review of all patients ages 0-18 years old with new onset GD diagnosed at a tertiary care pediatric hospital between 1/1/2018-8/31/21. March 1, 2020 was considered the start of the pandemic period. We ran two tailed t-tests and Pearson's chi-square tests using Microsoft Excel to compare findings between the pre-pandemic and pandemic groups and set significance to a p-value of 0.05. Results Over a 44-month period, 44 patients were diagnosed with GD at an average age of 13.5 years (SD 4.3). Most (81.8%) were female. There were gradually increasing numbers of new GD diagnoses over time: 8 in 2018 (average rate of 0.667 new diagnoses/month), 9 in 2019 (0.75 new diagnoses/month), 14 in 2020 (1.167 new diagnoses/month), and 13 in the first 8 months of 2021 (1.625 new diagnoses/month). Age, gender frequency, TSH levels, and free T4 levels did not differ before and during the pandemic (Table 1). A greater proportion of patients required beta blockade at time of diagnosis in the pandemic period (65.4%) compared to the prepandemic period (22.2%) (p = 0.0048) (Figure 1). Methimazole doses (mg/kg) did not differ by year. None were treated with radioactive iodine or surgery at diagnosis. Conclusions We observed a rise in the annual number of youth diagnosed with GD during the CV-19 pandemic. Youth with GD required treatment with beta blockers more during the CV-19 pandemic compared to prior, suggesting more symptomatic and/or later presentations. Further work is needed to understand the relationship between CV-19, the CV-19 pandemic, and GD in youth.

Complications of COVID-19 on the thyroid gland functioning

Annotation: Pandemics of coronoviral infection continues affecting the wold community, and with the comprehension of its pathological physiology an interest in endocrine effects of SARSCoV- 2 grows too. It was determined, that the main target organs affected by SARS-CoV-2 were lungs and immune system, while it is still not clear if SARS-CoV-2 has any impact on the thyroid function. In patients infected with SARS-CoV, coronovirus relevant to SARS-CoV-2, damage of parafollicular and follicular cells in thyroid glands was seen at autopsy. The Objective: To assess the consequent effect of Covid- 19viral infection on thyroid functions prior to operation period. Materials and Research Methods: While performing retrospective analysis we checked 110 case histories of patients receiving in-patient therapy in Vitamed clinic and Turakulov RSSPMC of Endocrinology from May 2020 to January 2021.We revealed 53 patients who recovered from Covid-19. We checked thyroid hormones (TTH, free T4, total T3), performed ultra sound imaging and histological test of thyroid gland, CBA, and biochemical tests. Result(s): Among 53 patients, who recovered from COVID-19, there were 40 (75%) women and 13 (25%) men. The age of the patients varied from 30 to 78 years old (average 52.6 years old). Eleven patients out of 53 complained discomfort at the frontal side of neck, dry skin, feeling of a lump in throat, loss of hair, weakness, and shortbreathing. Ultra sound imaging revealed presence of nodes. Histological tests showed, that 7 patients had thyroid cancer. Ultra sound showed, that six patients out of 11 had TI-RADS 4, four had TI-RADS 3, and one had TI-RADS 5.Histological tests revealed, that six patients out of 11 hadBETHESDA 4, two had BETHESDA 5, and two patients had histologically revealed BETHESDA 2.

Increasing incidence of Pediatric Graves' Disease

Introduction: Graves' diseases is a rare autoimmune disease in children. Viral infections are considered as a trigger for autoimmune thyroid disorders. A temporal association between SARSCoV- 2 and a novel pediatric hyperinflammatory condition called Paediatric inflammatory multisystem syndrome has been reported in 2020, raising questions about the link between SARS-CoV-2 and autoimmune and autoinflammatory diseases. Over the last year (2021), we noticed an increase in the number of children presenting to our department with Graves' disease. Our primary aim is to document the incidence of Graves' disease in our department since 2005, comparing our data with national data regarding thiamazol delivery. Our secondary aim is to compare the characteristics of the patients diagnosed before and during the SARS-CoV-2 outbreak. Material(s) and Method(s): A retrospective study including all the pediatric patients diagnosed with Graves' disease seen in our department since 2005 was performed. Hyperthyroid newborns were excluded. Data collected were the date and the age at diagnosis, the thyroid hormone levels, TSI at diagnosis, data from the national health insurance regarding the number of delivered thyroid hormone synthesis inhibitor drugs, thiamazol, in children (<18 years)/year. Result(s): A total of 48 patients with Graves' disease were diagnosed since 2005 in our department. Fifteen patients (1/3) were diagnosed since the SARS-CoV-2 outbreak, with the highest incidence in 2021 (11 patients). At the national level, an increase of thiamazol delivery is observed in 2020 and 2021 compared to the preceding years. Similar results regarding the age of diagnosis, free T4 and T3 levels or the presence of auto-immune diseases in the personal or family history were observed between the patients diagnosed before and those diagnosed during the SARS-CoV-2 outbreak. Conclusion(s): We observed a temporal association between SARS-CoV-2 outbreak and an increase in pediatric Graves' disease. The age and severity of the disease seems not to be influenced by the SARS-CoV-2 outbreak. SARS-CoV-2 could thus constitute a trigger for pediatric Graves' disease. Further studies are needed to confirm our findings.

Thyroid Function and COVID-19 Susceptibility and Its Severity: A Two-Sample Mendelian Randomization Study.

Several observational studies have confirmed the relationship between thyroid hormones and coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian randomization (MR) analysis based on the largest publicly available summary datasets. Summary statistics with 49 269 individuals for free thyroxine (FT4) and 54 288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [OR] = 0.818; 95% CI, 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95% CI, 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.

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.

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.

ENDOCRINE VIRTUAL CLINIC PATIENT SATISFACTION: A SINGLE-CENTRE EXPERIENCE IN PAHANG, MALAYSIA DURING THE CORONAVIRUS-19 (COVID-19) PANDEMIC

Introduction The COVID-19 pandemic had placed significant strain on the health care system across the world. The implementation of virtual clinics was suggested as an option to reduce faceto- face outpatient appointments and clinic congestion. This study highlights the challenges and patient satisfaction regarding the implementation of a Hyperthyroidism and Hypothyroidism Virtual Clinic in Hospital Sultan Haji Ahmad Shah, Temerloh, Pahang, Malaysia. Methodology This is a cross-sectional study that included all patients who received virtual clinic appointments between October 2020 and May 2021. Patients' satisfaction with their virtual clinic appointments was assessed by nurses through phone interviews. Patients' demographic data and responses to treatment were obtained through electronic medical data. Results Ninety-five patients were included in the study. The patients involved had a mean age of 38.9 (SD 13.6) years, 73.7% were female, and 87.4% were of Malay ethnicity. 65.3% of virtual clinic patients had hyperthyroidism. The mean free T4 for hypothyroid and hyperthyroid virtual clinic patients were 20.9 (SD 9.3) pmol/L and 21.7 (SD 11.9) pmol/L, respectively. The mean TSH for hypothyroid virtual clinic patients was 7.3 (SD10.5) mU/L. Nearly 50% of patients had no medication dose changes during their follow-up, while 26.3% required incremental adjustment of medication doses. 88.4% of patients were satisfied with their virtual clinic sessions. 66.3% of the patients interviewed preferred virtual clinics due to reduced waiting time for consultation, while 48.4% mentioned the decreased need for multiple and long hospital visits for clinical consultation. The main negative views cited regarding the virtual clinics were patients' poor internet connection and medication collection issues. Conclusion This study demonstrated that patients were receptive to the virtual clinic concept. Patient consultations were focused and waiting time was greatly reduced. Adjustments to patient medications also could be done effectively in a virtual clinic setting.

NEW ONSET GRAVES' DISEASE AFTER SARS-CoV-2 VACCINATION

Introduction There is an increasing number of reports of thyroid dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We would like to report a case of new onset Graves' disease following vaccination with the adenovirus-vectored Vaxzevria (Oxford-AstraZeneca). METHODOLOGY A 29-year-old female with no prior history of endocrine or autoimmune diseases, presented with a week of palpitations, heat intolerance and excessive sweating three days after her second dose of Vaxzevria. She did not experience these symptoms after her first dose which she received two months earlier. Her father and sister have Graves' disease. She had a diffuse goiter with no orbitopathy. Thyroid Stimulating Hormone (TSH) was <0.01 mIU/L (normal range: 0.27-4.2) with a markedly elevated free T4 of >100 pmol/L (normal range: 12-22). TSH receptor antibody was positive at >40.00 IU/L (Normal range: <1.75). Ultrasonography revealed a hypervascular, diffusely enlarged goiter. She was started on oral carbimazole and propranolol. Five months later, her free T4 had normalized at 18 pmol/L though her TSH was still undetectable. To date, she remains hesitant for her booster dose. Results SARS-CoV-2 infection and vaccination have been associated with subacute thyroiditis and autoimmune thyroid disease. While there are reports of new onset Graves' disease after mRNA and adenovirus-vectored vaccines, it has not been associated with inactivated virus vaccines. The current prevailing theory is that the adjuvants in the vaccines can trigger an autoimmune event, also called 'autoimmune/ inflammatory syndrome induced by adjuvants' (ASIA). Conclusion Physicians need to be aware of thyroid dysfunction after SARS-CoV-2 vaccination, especially in those with a strong family history of autoimmune disease. Nevertheless, it is also important to note that the benefit of vaccination far outweighs this uncommon potential risk. More studies are required to establish a causal relationship.

Small Fiber Neuropathy Associated with SARCoV-2 Infection

Objective: The development and persistence of neurological symptoms following SARS-CoV-2 infection is referred to as “long-haul” syndrome. Here, we aim to study the role of small fiber neuropathy (SFN) underlying neuropathic symptoms associated with COVID-19 infection. Background: Post COVID-19 “long-haul” syndrome include chronic fatigue, brain fog, sleep disturbance and paraesthesias. These symptoms can overlap with those seen in SFN, which have not been investigated given the recent wave of pandemic and patients who developed new onset of symptoms following infection. Design/Methods: Using retrospective study between May 2020 - May 2021, we screened the skin biopsy database of patients who were referred from the Center of Post-COVID Care at the Mount Sinai Hospital. Thirteen patients were identified and undergone routine nerve conduction studies and electromyography which ruled out evidence of a large fiber neuropathy. Patients were then clinically evaluated and consented for skin punch biopsy. All specimens were processed using PGP9.5 immunostaining for evaluating intraepidermal nerve fiber density (IENFD) to confirm SFN. Results: We identified 13 patients, 8 women and 5 men (age 38-67 years) with follow-up duration between 8-12 months. All had negative neuropathy blood profile including HbA1c, ANA, B12, TSH, free T4, and serum immunofixation. Three patients had pre-existing but controlled neuropathy risk factors. None had neurological symptoms prior to the SARS-CoV-2 infection. All patients developed new-onset paresthesias within 2 months following infection, with an acute onset in 7 and co-existing autonomic symptoms in 7. Six patients had biopsyconfirmed SFN, all of whom showed both neuropathy symptoms and signs, with 2 showing autonomic dysfunction. Of the remaining 7 patients with negative skin biopsies, 6 showed no clinical neuropathy signs, and 1 exhibited signs with abnormal autonomic function testing. Conclusions: Our findings support that symptoms of SFN may develop during or shortly after COVID-19 illness. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.

Are Thyroid Functions Affected in Multisystem Inflammatory Syndrome in Children?

Objective: Multisystem inflammatory syndrome in children (MIS-C), associated with Coronavirus disease-2019, is defined as the presence of documented fever, inflammation, and at least two signs of multisystem involvement and lack of an alternative microbial diagnosis in children who have recent or current Severe acute respiratory syndrome-Coronavirus-2 infection or exposure. In this study, we evaluated thyroid function tests in pediatric cases with MIS-C in order to understand how the hypothalamus-pituitary-thyroid axis was affected and to examine the relationship between disease severity and thyroid function. Methods: This case-control study was conducted between January 2021 and September 2021. The patient group consisted of 36 MIS-C cases, the control group included 72 healthy children. Demographic features, clinical findings, inflammatory markers, thyroid function tests, and thyroid antibody levels in cases of MIS-C were recorded. Thyroid function tests were recorded in the healthy control group. Results: When MIS-C and healthy control groups were compared, free triiodothyronine (fT3) level was lower in MIS-C cases, while free thyroxine (fT4) level was found to be lower in the healthy group (p<0.001, p=0.001, respectively). Although the fT4 level was significantly lower in controls, no significant difference was found compared with the age-appropriate reference intervals (p=0.318). When MIS-C cases were stratified by intensive care requirement, fT3 levels were also lower in those admitted to intensive care and also in those who received steroid treatment (p=0.043, p<0.001, respectively). Conclusion: Since the endocrine system critically coordinates and regulates important metabolic and biochemical pathways, investigation of endocrine function in MIS-C may be beneficial. These results show an association between low fT3 levels and both diagnosis of MIS-C and requirement for intensive care. Further studies are needed to predict the prognosis and develop a long-term follow-up management plan.