Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

TRAbs at diagnosis may better predict disease severity and relapse in younger patients with Graves' disease / 中华内分泌代谢杂志

Thyrotropin receptor antibodies ( TRAbs) are pathognomonic for Graves' disease. Previous studies have linked serum titers of TRAbs to severity of Graves' disease and likelihood of Graves' disease relapse. However, we know little about factors that may be involved in the impact of TRAbs on Graves' disease patients. In December 2018,"The Journal of Clinical Endocrinology&Metabolism" online published an article [ Bano A, Gan E, Addison C, et al. Age may influence the impact of TRAbs on thyroid function and relapse-risk in patients with Graves' disease. J Clin Endocrinol Metab, 2019,104(5):1378-1385. DOI:10.1210/jc.2018-01738]. With the permission of the original journal, we translated the article into Chinese. This article aimed to investigate the association of TRAbs at diagnosis with thyroid hormones and risk of relapse, and to study the influencing factors on these associations. The results showed that TRAbs at diagnosis were positively associated with circulating thyroid hormone levels and risk of relapse, and these associations were influenced by age, but not by sex, race, smoking or thyroid peroxidase antibody levels. This study indicates TRAbs at diagnosis can better predict severity of elevated thyroid hormone levels and risk of relapse in younger patients with Graves' disease.

Clinical Implication of TSH Receptor Antibody Measurement

Autoantibodies directed against the thyrotropin receptor have been well known to be an important pathogenesis of Graves' disease. However, the diagnosis and management of Graves' disease are still mainly dependent on thyroid function itself and clinical manifestation of thyrotoxic patients. That is mainly due to the low sensitivity of early generation of thyrotropin receptor assay methods. The development of sensitive thyrotropin receptor measuring tools through third generation immunometric assay made the diagnosis of Graves' disease with mild hyperthyroidism accurate and convenient for patients. Bioassay to detect thyroid stimulating immunoglobulin is also commercially available nowadays, which theoretically discriminate thyroid stimulating antibodies from thyrotropin receptor-blocking antibodies. Although the use of these serologic markers plays an informative role in accurately diagnosing Graves' disease and predicting the prognosis of disease, consideration of the heterogeneous nature of autoimmunity of Graves' disease and the limitation of indirect antibody assay is also required for proper management of Graves' disease patients. In this review, the clinical usefulness of thyrotropin receptor antibody in various clinical situations of Graves' disease was overviewed.

The single nucleotide polymorphisms in the intron 1 of TSHR gene were associated with Graves' disease / 中华内分泌代谢杂志

Objective To investigate the association between single nucleotide polymorphisms in the intron 1 of thyroid stimnulating hormone receptor gene (TSHR) and Graves' disease (GD) in the Chinese Han population from Linyi city,Shandong Province.Methods A total of 1759 GD patients and 1740 control subjects were recruited for genotyping in TSHR intron 1 with genome-wide association study (GWAS) and Taqman probe technique.At the same time,serum thyroid hormone and TSH receptor antibody (TRAb) levels of patients were determined.Results Five SNPs were selected for further replication.The rs12101261 _T was significantly associated with GD risk ( OR=1.257,95％CI 1.137-1.390,P =8.23 × 10-6 ). Logistic regression identified that rs12101261 was an independent susceptibility locus of GD ( P=1.61 × 10-3 ).Furthermore,rs12101261 _T was strongly associated with GD ( OR =1.317,95％ CI 1.171-1.481,P=4.14× 10-4 ) in TRAb positive patients,but no association in TRAb negative patients ( OR=1.056,95％ CI 0.892-1.251,P=0.524 ).Serum TRAb concentration showed remarkable difference among three genotype groups of rs12101261.Conclusions Five SNPs in TSHR intron 1 are associated with GD.rs12101261 contributes to increased GD risk independently and is associated with serum TRAb level.

Immune effect of propylthiouracil and methimazole in the treatment of Graves' disease / 中华内分泌代谢杂志

ObjectiveTo observe the changes in TSH receptor antibody (TRAb) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) levels after treatment of propylthiouracil ( PTU ) and methimazole( MMI ) in patients with Graves' disease (GD). MethodsOne hundred and six cases of clinically diagnosed patients with GD were divided into PTU and MMI groups( each group, n =53 ). The patients in two groups were regularly followed for 36 months. TRAb and sICAM-1 were measured with ELISA method. Results( 1 ) The general data of two groups were not significantly different before treatment( all P＞0. 05 ). ( 2 ) There was no difference in TRAb positive rates between two groups before treatment. The clinical remission rates between PTU and MMI groups showed no difference (83.02％ vs88.68％ ). The cure rate was higher in MMI group than in PTU group( 58.49％ vs 37.74％, P＜ 0. 05 ). (3) There existed significant differences in TRAb levels determined before and 6, 12, 24,30, and 36 months after treatment( all P＜0. 01 ), being gradually decreased with time( F=275.48 ,P＜0.01 ). TRAb levels between two groups were significantly different( F=5.86, P＜0. 05 ). (4) sICAM-1 levels at 36 months after treatment compared with the baseline in both groups were statistically different (P＜0. 01 ), but no difference was found between two groups.ConclusionsBoth PTU and MMI improve the immune status of patients with GD,and the immunosuppressive effect of methimazole is more evident.

Analysis of factors affecting the prognosis of patients with Graves' disease treated with antithyroid drugs / 中华内分泌代谢杂志

A total of 96 patients with Graves'disease(GD)were followed for one and half years to observe the effect of antithyroid drugs(ATD)treatment.Serum TRAb,total iodine concentration and CD80 mRNA expression of peripheral blood monouclear ceils were measured.Logistics regression analysis was conducted with the combination of above parameters.Those GD patients with high level of TRAb,positive family history of GD, increased expression of CD80 and early age of onset were more inclined to relapse after ATD treatment.

Clinical Applications of TSH Receptor Antibodies in Thyroid Diseases

The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical impli-cations, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.

Clinical significance of classification of Graves' disease according to the characteristics of TSH receptor antibodies

BACKGROUND: It has been widely accepted that the epitope(s) and/or functional characteristics of thyrotropin receptor antibodies (TSHRAb) from Graves' patients are heterogenous among patients. However, the clinical significance of such heterogeneity has not been systematically evaluated yet. We were to elucidate and find the clinical significance of heterogeneity for TSH receptor antibodies in Graves' disease. METHODS: We measured stimulating TSHRAb (TSAb) activities using CHO-hTSHR cells, FRTL-5 cells and chimeric receptor expressing cells (Mc1 + 2 and Mc2), specific blocking TSHRAb (TSBAb) activities using Mc2 cells and TBII activities using porcine thyroid membrane in 136 patients with untreated hyperthyroid Graves' disease. RESULTS: Based on various TSHRAb activities from each patient, the patients could be categorized into 7 subgroups by cluster analysis; 1) Group 1 (n = 41) was characterized by moderate TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, typical TSAb epitope, rare blocking antibodies and high TBII activities. 2) Group 2 (n = 16) was characterized by the presence of blocking TSHRAb in most patients, albeit the other characteristics were the same as those in Group 1. 3) Group 3 (n = 19) patients had low TSAb activities both in CHO-hTSHR cells and in FRTL-5 cells, seldom had blocking TSHRAb, but they had high TBII activities. 4) Group 4 (n = 30) could be categorized as 'mild disease' group, as they had low activities in all kinds of TSHRAb assay and had low antimicrosomal antibody activities. 5) Group 5 (n = 14) was characterized by moderate TSAb activities with atypical epitope(s), rare blocking TSHRAb and moderate TBII activities. 6) Group 6 (n = 10) patients had very high TSAb activities with typical epitopes, seldom blocking TSHRAb and low TBII activities. 7) Group 7 (n = 6) was characterized by very high TSAb activities with atypical epitopes and high TBII activities. Pretreatment serum thyroid hormone level was low only in group 4 patients compared to the other 6 groups (p < 0.05). The size of goiter was significantly larger in those in group 1 and group 3 (p < 0.05) compared to the other 5 groups. The prevalence of clinically significant ophthalmopathy was higher in group 2 patients than the other 6 groups (50% vs. 27.5%, p = 0.06). Among 6 kinds of TSHRAb activities, only the blocking TSHRAb activity was significantly associated with the presence of ophthalmopathy in multivariate analysis. CONCLUSION: These results suggest that the differences in epitopes for TSAb or the presence of blocking TSHRAb is not a major factor in determining the degree of thyrotoxicosis in Graves' disease. Although the pathogenic mechanism is not clear yet, we suggest that patients with ophthalmopathy have different TSHRAb repertoire from those without ophthalmopathy in Graves' disease.

A Clinical Study of Subacute Thyoidits / 대한내과학회지

OBJECTIVES: Subacute thyroiditis is a nonsuppurative inflammation of thyroid gland and is probably caused by a cytopathic virus. Typical clinical symptoms and features of subacute thyroiditis vary widely during the course of illness. It has a clinical course, evolving from hyperthyroidism through a temporary hypothyroidism to recovery. However, the final outcome of this disease remains unpredictive in some patients. Permanet hypothyroidism occurs infrequently. METHODS: Thirty-three patients proven to have subacute thyroiditis at the Ewha Womans University Hospital from September 1993 to November 1995 were studied. We analyzed their clinical features, laboratory findings, and duration of recovery to cha- racterize the course of the disease. RESULTS: 1) Total 33 patients were studied: 31 patients were female and 2 patients were male. Their mean age was 42.6+/-8.3 years old. The peak months were August through October in this study. 2) Initial mean ESR was 73.0+/-35.2mm/hr, mean T3 was 217.3+/-73.9ng/dl, mean T4 was 15.2+/-8.5microgram/ dl, and TSH was 0.06+/-0.09microIU/ml. The positive rates of antithyroglobulin and anitmicrosomal antibodies were 31% and 6% respectively, and TSH receptor antibody was elevated in one patient. 3) In the thyroid scan, 91% showed both lobes nonvisualisation, and 9% showed one lobe nonvisualization. Radioactive iodine uptake(RAIU) at 24 hour was 2.4+/-3.3%. 4) With the predisolone therapy, 90% of patients completely recovered, 57% of these patients had no hypothyroid phase and remaining 33% of them had hypothyroid phase during course of the disease. Three of the patients had permanent hypothyroidim. 5) The average duration of recovery was 3.2+/-1.4 months and it has no correlation with initial thyroid hormone levels, antithyroid antibodies and duration of steroid administration. CONCLUSION: There was no historical, physical, laboratory findings that help us predict those patients likely to have an exacerbation of the disease.

A clinical study of Graves' disease in children

No abstract available.

THE RELATIONSHIP BETWEEN TRAb AND THYROID STATUS, REMISSION OR RELAPSE OF GRAVES' DISEASE / 中华内分泌代谢杂志

TSH receptor antibodies (TRAb) were measured using radioreceptor assay in 305 patients with Graves' disease. The results of this study showed that the positive rate (94.7%) and inhibition tate (47.1?2.2 %, sx) of TRAb in hyperthyroid group were much higher than those in euthyroid group. TRAb activity was detectable in 96.9% of 32 patients with relapsed Graves' disease and the inhibition value was 50.1? 26.2%. Both values were significantly higher than those in patients who were in remission. 38 euthyroid patients were followed-up for 8-30 months after stopping the antithyroid drug. The results showed that 12 out of 16 patients who were TRAb positive relapsed, while 22 patients who were negative for TRAb remained in remission except 5 patients. The TRAb activity was higher after relapse than before (P

The value of determination of serum TRAb levels in diagnosis and treatment of patients with thyroid disease / 重庆医科大学学报

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.

A RADIORECEPTOR ASSAY FOR HUMAN TSH RECEPTOR ANTIBODIES AND ITS CLINICAL APPLICATIONS / 中华内分泌代谢杂志

A radioreceptor assay for TRAb was described in which soluble TSH receptors obtained by solubilizing porcine thyroid membranes using 0.5% Triton X-100 and 125I-bTSH prepared by iodogen method and receptor-purification were used. The binding of 125I-bTSH to TSH receptors was inhibited by unlabeled bTSH and sera of patients with uncon-trolled Graves' disease (GD) in a dose-dependent manner. The assay was sensitive, specific, rapid and reproducible with interassay CV of 12.6% and 3.1% at mean inhibition values of 15.4% and 90.6% .respectively, being suitable for a clioical routine test. Of 133 patients with uncontrolled GD, TRAb was positive in 94.7%, while the absence of detectable TRAb was found in 6 patients with hyperthyroidism but not due to GD. This indicated TRAb measurement has important value in etiology and diagnosis of hyperthyroidism duc to GD.