Sex: F
Vaccine: COVID19
Symptoms: Cardiac function test, Chest X-ray, Electrocardiogram, Haemoglobin, Heart rate
Clinical narrative: Graves' disease; This is a literature report  A 71-year-old woman with a history of stage 4 breast cancer in remission, struma ovarii at age 35 years and clinically stable multinodular goitre was admitted from the emergency department at a local hospital, for new onset heart palpitations. She first noticed tachycardia 10 days prior to presentation due to her wearable fitness tracker. She reported feeling feverish in addition to new onset sweating, shortness of breath, leg swelling and dizziness and subsequently developed nausea, diarrhoea, abdominal pain and hand tremors. There was no documented upper respiratory tract infection prior to the onset of symptoms. Pertinent initial findings were a resting pulse rate 111 beats per minute, blood pressure 125/74, temperature 37.8 C, respiratory rate 15 and O2 saturation 97% on room air. She was noted to be diaphoretic and mildly distressed but without observed ophthalmopathy initially. Her thyroid gland was diffusely enlarged to palpation. Cardiac examination was normal except for tachycardia. There was bilateral lower extremity oedema, extending halfway up the calves, with some tenderness in the left shin. She had a fine tremor on both hands. Investigations: Initial laboratory testing showed relatively low white cell count 2.8x109/L, Absolute Neutrophil Count 1.4x109/L haemoglobin 87 g/L, platelet count 146x109/L, glucose 140 mg/dL and urea nitrogen 35 mg/dL. Haematological findings were long standing due to continued therapy for in-remission stage 4 breast cancer. Thyroid function test revealed an undetectable Thyroid Stimulating Hormone (<0.01 u(IU)/mL) and elevation in both free T4 to 7.2 ng/dL and total T3 to 5.3 ng/mL. The thyroid stimulating immunoglobulin (TSI) test was also high at 349%. Both thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies were negative. Erythrocyte Sedimentation Rate was elevated to 126, from her previous baseline of 49. C-Reactive Protein was elevated to 6.9. Electrocardiogram indicated sinus tachycardia. The patient had a negative nasal swab COVID-19 rapid RNA antigen test. Chest X-ray was normal. Thyroid ultrasound showed a stable multinodular disease. The patient has had multiple thyroid biopsies in the past all of which were negative for malignancy. Subsequently, she was transferred to an inpatient endocrine service in a another hospital with a tentative diagnosis of thyroid storm. The temporal sequence of events 2 weeks after the second dose of the Pfizer-BioNTech SARS-CoV-2 vaccine is highly indicative of a vaccine-induced Graves' disease. The patient progressed from biochemically normal thyroid function and histologically normal multinodular at baseline to clinical thyroid storm after vaccination. Thyroid storm was associated with undetectable TSH, high free T4, high total T3, negative TPO and Tg antibodies and a rapid rise in TSI. DIFFERENTIAL DIAGNOSIS: The development of both clinical and biochemical hyperthyroidism with elevated acute inflammatory markers in a patient with a history of euthyroid multinodular goitre 2 weeks after administration of the vaccine makes vaccine-induced autoimmune syndrome the most likely explanation of our patient's presentation and symptoms. The patient's clinical manifestations suggest vaccine-induced Graves' disease, especially in the context of diffusely enlarged thyroid glands and an associated elevated TSI. Viral-induced subacute thyroiditis is another potential cause of the patient's hyperthyroid state, but the patient did not have a preceding viral infection. In addition, the patient responded appropriately to the antithyroid drug methimazole and did not become rapidly and profoundly hypothyroid as would be expected in viral subacute thyroiditis. Furthermore, hashitoxicosis is also an unlikely diagnosis in someone with the above presentation and negative TPO and Tg antibodies at baseline. In light of the clinical and biochemical findings and the temporal sequence of events following the vaccine, the most likely explanation of our patient's presentation is a vaccine-induced Graves' disease. TREATMENT: The patient was successfully treated with methimazole 20 mg two times per day and atenolol 25 mg daily with continued cardiac monitoring while in the hospital. With this regimen, her symptoms and biochemical profile began to improve significantly. At hospital discharge, her free T4 had fallen to 3.8 ug/dL and total T3 had fallen to 4.1 ng/mL. She reported no side effects of either medication and was discharged from the hospital on this treatment regimen and was recommended to follow-up with both endocrinology and ophthalmology. She continued to have appropriate medication dose adjustments at follow-up visits and is being monitored clinically and biochemically for resolution of her symptoms and normalisation of thyroid function. OUTCOME AND FOLLOW-UP: The patient has experienced a significant improvement in her symptoms. She is now clinically stable. She is being carefully monitored by an endocrinologist for management of probable Graves' disease. She is also being followed by an ophthalmologist for Graves' ophthalmopathy, which was classified as moderate to severe 10 weeks following her hospitalisation. The patient has reported resolved tachycardia and her FT4 and total T3 levels have returned to baseline. Thyroid Stimulating Hormone normalisation is lagging behind and thus remains undetectable. It is important to note that the patient has not experienced any hypothyroid symptoms since her hospitalisation, making a retrospective diagnosis of subacute thyroiditis unlikely.  Patient's baseline, presentation and 1-month follow-up labs Red cell count (Normal range: 4.0-5.2 x1012/L): 3.37 (baseline), 2.66 (Presentation), 3.22 (1-month follow-up);  White cell count (Normal range: 4.5-11.0x109/L): 2.46 (baseline), 2.77 (Presentation), 2.80 (1-month follow-up); Haemoglobin (Normal range: 120-150 g/L): 110 (baseline), 87 (Presentation), 97 (1-month follow-up); Platelets (Normal range: 150.0-350.0x109/L): 131 (baseline), 146 (Presentation), 290 (1-month follow-up); Absolute Neutrophil Count (Normal range: 1.5-7.80x109/L): 1.24 (baseline), 1.44 (Presentation), 1.97 (1-month follow-up); Mean Corpuscular Volume (Normal range: 80.0-100.0 fL): 100.3 (baseline), 96.6 (Presentation), 95.0 (1-month follow-up); Na (Normal range: 135-143 mmol/L): 142 (baseline), 140 (Presentation), 141 (1-month follow-up); K (Normal range: 3.6-5.0 mmol/L): 4.6 (baseline), 4.1 (Presentation), 4.6 (1-month follow-up); Cl (Normal range: 98-107 mmol/L): 107 (baseline), 105 (Presentation), 104 (1-month follow-up); HCO3 (Normal range: 23-27 mmol/L): 30 (baseline), 24 (Presentation), 26 (1-month follow-up); BUN (Normal range: 7-20 mg/dL): 34 (baseline), 35 (Presentation), 28 (1-month follow-up); Cr (Normal range: 0.5-1.6 mg/dL): 1.0 (baseline), 0.8 (Presentation), 0.9 (1-month follow-up); Alb (Normal range: 3.5-5.5 g/dL): 4.3 (baseline), 3.1 (Presentation), 3.8 (1-month follow-up); Bili (Normal range: <1.2 mg/dL): < 0.2 (baseline), <0.2 (Presentation), 0.4 (1-month follow-up); Alk phos (Normal range: 33-147 u(IU)/L): 79 (baseline), 64 (Presentation), 80 (1-month follow-up); Aspartate Aminotransferase (Normal range: 8-33 U/L): 15 (baseline), 18 (Presentation), 14 (1-month follow-up); Alanine Transaminase (Normal range: 7-55 U/L): 11 (baseline), 20 (Presentation), 25 (1-month follow-up); Glucose (Normal range: 71-99 mg/dL): 91 (baseline), 149(Presentation), 112 (1-month follow-up); Brain Natriuretic Peptide (Normal range: 20-127 pg/mL): 194 (baseline), 356 (Presentation), 248 (1-month follow-up); Erythrocyte Sedimentation Rate (Normal range: 0-30 mm/hour): 49 (baseline), 126 (Presentation), 108 (1-month follow-up); C-Reactive Protein (Normal range: 0.15-5.0 mg/L): 2.4 (baseline), 6.9 (Presentation), 2.3(1-month follow-up); Thyroid Stimulating Hormone (Normal range: 0.35-2.00 u(IU)/mL): 1.18 (baseline), <0.02 (Presentation), <0.02 (1-month follow-up); Free T4 (Normal range: 0.9-1.7 ng/dL): 1.4 (baseline), 7.2 (Presentation), 1.3 (1-month follow-up); Total T3 (Normal range: 0.8-2.8 ng/mL): 1.1 (baseline), 5.3 (Presentation), 1.3 (1-month follow-up); Thyroid stimulating immunoglobulin (Normal range: <140% baseline): 347 (Presentation), 438 (1-month follow-up); Thyroid peroxidase (Normal range: 0-9.0 IU/mL): 8.9 (Presentation), 8.6 (1-month follow-up).  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the available reported information, the causal association between the event Graves' disease, and the suspect drug BNT162B2 cannot be excluded considering drug-event temporal association. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate. ,Linked Report(s) : MX-PFIZER INC-202101291159 same drug/event, different patient;MX-PFIZER INC-202101291751 same drug/event, different patient;AT-PFIZER INC-202200146690 same drug/event, different patient