Two further cases of Graves’ disease following SARS-Cov-2 vaccination
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Abstract:
Recently, two cases of Graves' disease after SARS-Cov2 RNA vaccination with tozinameran have been reported [1].Here, we report two further cases: a late recurrence after 17 years and an initial manifestation.A 71-year-old lady had subtotal resection of the left lobe.Soon thereafter, Graves' disease occurred, treated by thyreostatic drugs until 2004.She has been in care of our Thyroid Center since 2008.She was euthyroid with normal TSH-receptor-antibody (TRAB) levels at yearly checkups.Sonography also did not show any dynamics: an enlarged 20 ml right lobe and a small 4 ml left lobe after partial resection.The parenchyma was slightly hypoechogenic.She was vaccinated with tozinameran on 21.March and 11.April.From Mid-May on, she noticed palpitations and sweating.On 26th May, she was seen in our Thyroid Center with a free T4 of 3.56 ng/dl (normal 0.70-1.70),a free T3 of 11.10 pg/ ml (normal 2.15-4.12),and a TRAB level of 4.2 IU/l (normal < 1.5).A marked change in sonography with multiple confluent anechogenic areas and increased vascularization was observed.Scintigraphy revealed the small (partly resected) left lobe and the enlarged right lobe with a patchy inhomogenous tracer distribution.Uptake was only mildly increased.Thyreostatic treatment led to a rapid normalization of thyroid function.Keywords:
Trab
Lobe
Palpitations
Parenchyma
Objective To investigate the significance of changes of serum TPOAb and TRAb levels in patients with Graves' disease(GD). Methods Serum TPOAb(with RIA) and TRAb(with RRA) levels were determined in 27 patients with Graves' disease,before treatment 10 patients with Graves' disease clinically cured and 35 controls.Results The serum levels and positive rates of TPOAb and TRAb in patients with Graves' disease before treatment were significantly higher than those in the patients with Graves' disease clinically cured and controls(P0.01).Conclusion TPOAb and TRAb were involved in the pathogenesis of Graves' disease and could be used as diagnostic and treatment indicators.
Trab
Pathogenesis
Clinical Significance
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Objective:To study the value of measurement of serum TRAb levels in diagnosis and treatment of patients with thyroid disease.Methods:The levels of serum TRAb(by RRA),FT 3?FT 4 and titrations of TGAb,TPOAb(by RIA) were measured in 308 patients with thyroid disease as well as in 50 normal people.Results:The average levels and positive rates of serum TRAb were significantly higher in patients with Graves' disease (including hypertyroid group and remission group) and Hashimoto's disease than those in normal group,and the hypertyroid group were significant higher than the remission group in level and positive rate of TRAb.There were no correlations between serum TRAb levels and FT3,FT4 levels in patients with Graves' disease,and titrations of TGAb,TPOAb in patients with Hashimoto's disease.Conclusion:Serum TRAb level can not reflect the severity of Graves' disease,and TRAb is another auto-antibody different from TGAb,TPOAb,but there is important value in determing the serum TRAb level in diagnosis and treatment of auto-immune thyoid disease,especially to Graves' disease.
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Euthyroid pregnant women with a previous history of Graves' disease treated with radioiodine or surgery may have persistently elevated TSH receptor antibody (TRAb) levels, putting their offspring at risk for fetal hyperthyroidism (FH) and/or neonatal hyperthyroidism (NH).We performed a literature review using a MEDLINE search to determine if and how anti-thyroid drugs (ATD) were utilized in euthyroid pregnant women with previous Graves' disease to prevent FH/NH.There are 11 published reports involving 13 pregnancies where ATDs were utilized to prevent FH in euthyroid mothers with a previous history of Graves' disease. Subjects were treated if high titres of TRAb (> 5-fold above normal) were noted on either radioreceptor assay or various bioassays. Such intervention appeared beneficial. Thirteen live births were observed when previously these mothers collectively experienced six miscarriages, stillborn or infant deaths attributed to FH or NH. Developmental consequences such as craniosynostosis or dysmorphic features were not observed in the infants described. Both propylthiouracil and methimazole were used effectively. When utilized, cordocentesis (or periumbilical blood sampling) to determine fetal thyroid status and TRAb levels proved to be of value in establishing the diagnosis and guiding therapy.Maternal ATD prevent the serious consequences of FH/NH and should be considered for euthyroid Graves' mothers with high TRAb titres.
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Propylthiouracil
Antithyroid agent
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Objective:To investigate the changes in serum thyrotropin receptor antibody(TRAb) in patients with Graves disease.Methods:One hundred and twenty seven patients with Graves disease were tested for TRAb by radioimmunoassay.Results:The study showed that the level of TRAb in the disremisson group was higher than that in the remission group( P 0.001).Compared with normal,the level of TRAb was increased in non iodine salt treated patients with Graves disease( P 0.001).Conclusions:It suggests that TRAb measurement is of value in initiating non iodine therapy for patients with Graves disease,evaluating the effect of the anti thyroid gland drugs,deciding the time to stop therapy and predicting the relapse.
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Thyrotropin receptor
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Objective To investigate the significance of detecting serum thyrotropin receptor antibodies(TRAb) in patients with Graves disease or Graves ophthalmopathy.Methods Serum TRAb was measured using radioimmunoassay in 83 patients with Graves disease(group A),73 patients with Graves ophthalmopathy(group B).Patients with Graves ophthalmopathy were assessed using clinical activity score(CAS) and the severity of Graves ophthalmopathy was evaluated using NOSPECS Grade.Results Serum concentration of TRAb was positively correlated with the activity and severity of Graves ophthalmopathy,which was higher in patients with middle and serious Graves ophthalmopathy than that in those with slight Graves ophthalmopathy(P0.05).ConclusionSignificant increase of serum TRAb may be taken as one of the markers to predict the development and guide the treatment in the patients with Graves ophthalmopathy.
Trab
Graves' ophthalmopathy
Clinical Significance
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Background : Graves’ disease is the leading cause of hyperthyroidism in children. The increase of hormones thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) in Graves' disease is caused by the presence of thyroid stimulating antibodies (TSHR-Ab) or Thyrotopin receptor antibodies (TRAb). Methimazole (MMI) is often use as anti thyroid medication in children. Methimazole therapy may give a good response to patients with new-onset Graves’ disease, high levels of thyroxine, high TRAb), and no or small goiters. Objective : The purpose of this study was to determine the differences in TRAb before and after Methimazole Therapy for 6 months in children with Graves’ disease. Method : Retrospective study on 28 children below 18 year old with Graves’ disease at H. Adam Malik General Hospital Medan with TRAb, fT4, TSH data collection before and after Methimazole therapy for 6 months taken from medical records. Result : Median age 11.85 ± 3.73 with the number of women 85.7% compared to men 14.3%. The median value before Methimazole therapy was TRAb 32,11 IU/L, fT4 3.56 ng/dl and TSH 0.01 mU/l. Median values after 6 months of Methimazolee therapy were TRAb 17.15 IU/L, fT4 1.51 ng/dl and TSH 0.51 mU/l with P values <0.001, P = 0.006, P <0.001 respectively. Conclusion: There was significant differences in TRAb, fT4, and TSH median values before and after 6 months of Methimazole therapy in children with Graves’ disease.
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Methimazole
Thyrotropin receptor
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Objective To explore the mechanism of persistent thyrotropin suppression in euthyroid patients with Graves′ disease after antithyroid drugs (ATD) treatment. Methods A prospective clinical study was performed in 122 patients with newly diagnosed Graves′ disease. All the patients were treated with 30 mg methimazole or 300 mg propylthiouracil daily, to whom L-T4was added, aiming at normalizing FT3 and FT4 but avoiding elevated TSH level. When the patients were clinically and biochemically euthyroid for at least 3 months, their blood levels of thyroid hormones, TSH, TSH receptor antibody(TRAb) and thyroid peroxidase antibody(TPOAb) were detected again and the cases were divided into two groups according to negative or positive TRAb. Results After treatment as long as (7.1±1.1) months, stable euthyroid status was restored for 3 months. When the patients reached the euthyroid state, 64 of them still had detectable TRAb levels, and 58 became negative TRAb. The two groups had similar levels of FT3 and FT4, but patients with positive TRAb had lower TSH level than patients with negative TRAb[0.044 mIU/L(0.001-4.163 mIU/L) vs 1.749 mIU/L(0.079-4.646 mIU/L),P＜0.01]. In addition, the TSH level was negatively correlated with TRAb level (r=-0.539, P＜0.01), and not with FT3, FT4 levels or other factors. Conclusion The present study showed that elevated TRAb level is associated with persistent suppression of TSH in patients with Graves′ disease after being rendered euthyroid. This finding may be due to the binding of TRAb to pituitary TSH receptor.
Key words:
Graves′ disease; Drug therapy; Thyrotropin; Antibodies; thyrotropin receptor
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Propylthiouracil
Thyroid peroxidase
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Background: Ophthalmopathy Graves’ is one of the serious complications of Graves’ diseases, that can decrease the quality of life of the patient. The pathogenesis is not well understood, resulting in less effective therapy and resulting in permanent eye function impairment. Objective: To determine the ratio of thyroid stimulating hormone receptor antibody (TRAb) between Graves’ disease patients with and without ophtalmopaty. Methods: This is a cross-sectional study involving 50 patients with Graves’ active disease, who underwent treatment at Endocrine and Metabolic Unit of Internal Disease, Outpatient Installation of Dr. Soetomo General Hospital Surabaya. Graves’ ophthalmopathy was determined when extracted eksoftalmus or eyelid retraction with thyroid dysfunction was found. Levels of thyroid-stimulating hormone (TSH) and FT4 were measured using the ELISA method. Meanwhile, TRAb level was measured using third generation thyroid binding inhibiting immunoglobulins (TBII) with ELISA method. Results: There were 25 (50%) patients in the active Graves’ patient group with and without ophthalmopathy, respectively, with age ranging from 20 to 65 years old. The median value of TRAb patients with Graves ‘disease with ophthalmopathy was 3.21 IU/l, which is higher and statistically significant (p = 0.001) than TRAb levels of patients with Graves’ disease without ophthalmopathy, with median value of 1.81 IU/l. Conclusion: Higher levels of TRAb were found and statistically significant in Graves ‘disease patients with ophthalmopathy than Graves’ patients without ophthalmopathy.
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Graves' ophthalmopathy
Outpatient clinic
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1345 Objectives: To evaluate longitudinal changes in serum TSH receptor antibodies (TRAb) following a single radioiodine therapy (RAI) for Graves’ hyperthyroidism (GH) and to correlate them with changes in thyroid weight and with therapeutic efficacy.
Methods: 56 patients (Male/Female 14/42. Age 20-73yrs.) with GH who were to undergo RAI were enrolled. 53 out of 56 patients were previously treated by anti-thyroid drugs. TRAb (normal range:>2,0 IU/L) was determines by ECLIA method and was positive in all but one patients. Thyroid weight (TW) was determined using either CT or US. Anti-thyroid drugs were discontinued 3 to 4 days prior to RAI. After instruction by dietitians, patients followed a low iodine diet ( 100g. As a rule, anti-thyroid drugs were resumed on 5 days after RAI. Serum FT3, FT4, TSH, TRAb, and thyroid weight was determined over 3 years at 6, 12, 18, 24, and 36 months after RAI. Success of RAI was defined as achievement of either of euthyroid, subclinical hypothyroid, or hypothyroid status. Relationship between changes in TRAb were correlated with those in thyroid weight and success rate of RAI.
Results: Pretreatment TRAb(IU/L) and TW ranged from 0,9-4.0 (Average 19.5) and17.9-127.0 (average 65.1), respectively. The average of TRAb at 6, 12, 18, 24 and 36 months was 128%(p<0.05),102%(ns), 89%(%ns), 73%(ns), and 53% (ns) of the pretreatment value, respectively. The disappearance of TRAb was seen only in 2%(1/56) of patients at 6 months after RAI. Although it significantly rose up to16% (9/56, p<0.05) at 18 months after RAI, it did not further increase at 24 and 36 months after RAI. The average of TW at 6, 12, 18, 24 and 36 months was 49% (p<0.01), 31% (p<0.01), 22% (p<0.005),18% (p<0.001), and 11% (p<0.001) of the pretreatment value, respectively. Longitudinal changes in TRAb after RAI paralleled those in TW. Overall success rate of RAI after 6, 12, 18, 24 and 36 months was 61%, 73%, 80%, 85% and 90%, respectively. There was a significant inverse correlation between longitudinal changes in TRAb and those in success rate of RAI (r=-0.99, p<0.01). Also, there was a significant inverse correlation between longitudinal changes in TW and those in success rate of RAI (r=-0.97, p<0.01). At 6 months after RAI, 55% of the patients (31/56) had TRAb values higher than 125% of the pretreatment values. However, successful rate at 6motnhs and 2 years after RAI among patients who showed elevated TRAb was comparable to that among their counterparts (65% vs. 56%, ns. and 78% vs. 81%, ns.).
Conclusions: More than 50% of patients underwent RAI showed higher TRAb compared with the pretreatment value at 6months after therapy. About 80% of the patients had positive TRAb at 36 months after RAI. However, the increase in TRAb was temporally that it gradually decreased over 3 years following RAI, paralleling the longitudinal decrease in the thyroid weight. In addition, temporally elevation in TRAb or persisting positivity of TRAb did not impair efficacy of RAI for GH.
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Subclinical infection
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Background: There are limited data about the factors affecting the response time to medical treatment in Graves’ disease (GD) although many studies examined the predictors of the relapse after drug withdrawal. The aim of the current study was to evaluate the time for becoming euthyroid under antithyroid drug (ATD) therapy and the parameters influencing this period in patients diagnosed as GD.Methods: Patients with newly-diagnosed GD and decided to treat with ATD initially between March 2017 and September 2018 were retrieved retrospectively. Sociodemographic features as well as laboratory parameters like thyroid function tests and thyroid-stimulating hormone-receptor antibody (TRab) at the time of diagnosis were recorded.Results: Out of 41 patients, 63.4% (n=26) were female. The mean age was 36.1±11.7 years and 43.9% (n=18) of them were smoking. The time between the initiation of treatment and the duration of becoming euthyroid was 2.4±1.8 months. No significant difference was noted between age, gender, and smoking status and the time to become euthyroid under ATD treatment. This period was significantly positively correlated with levels of free triiodothyronine, free thyroxine, and negatively correlated with thyroid-stimulating hormone. Response to ATD therapy was higher in patients with pre-treatment TRab levels <10 IU/l than TRab ≥10 IU/l (p=0.011).Conclusions: Pretreatment thyroid function tests and TRab levels may be taken into consideration before deciding treatment in patients with newly diagnosed GD. It would be useful to design more comprehensive studies so that this proposal can find a response in clinical practice.
Trab
Antithyroid drugs
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