促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.

Abstract：

It has been 50 years since the discovery of thyrotropin receptor autoantibody (TRAb). Advances in the knowledge of thyrotropin receptor ( TSHR) structure and function, combined with the elucidation of TSHR signaling and TSHR-autoantibody interaction have greatly facilitated our understanding of TRAb and their clinical applications. Measurement of TRAb activity plays an important role in the diagnosis of Graves' disease ( GD) and Graves' opthalmopathy. It has also been well recognized that TRAb is an effective predictor of GD relapse or remission after antithyroid drug and radioactive iodine treatment. TRAb test is of particular help in pregnant women and lactating mothers with recent iodine load, where radioactive iodine or technetium tests are contraindicated. In addition, it is useful in the diagnosis and differential diagnosis of fetal and neonatal hyperthyroidism as well as some rare forms of thyrotoxicosis in clinical practice. Accumulating evidence also indicates the possible correlation between thyroid cancer occurring in GD patients with positive TRAb and adverse outcomes. However, further innovation and standardization of TRAb tests are required to help pave the way for clinical applications.     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.     

甲状腺上动脉峰值血流速度在自身免疫性甲状腺毒症鉴别中的应用

目的探讨甲状腺上动脉峰值血流速度(STA-PSV)对自身免疫性甲状腺毒症病因鉴别诊断的临床应用价值。方法收集2015年1月至2018年10月北京大学人民医院内分泌科新诊断的未用抗甲状腺药物治疗的自身免疫性甲状腺毒症患者301例,其中Grave病(GD)患者241例,自身免疫性甲状腺炎(AIT)患者60例,比较两组患者STA-PSV、甲状腺功能、促甲状腺激素受体抗体(TRAb)等相关指标。通过多元线性回归分析影响STA-PSV的相关因素。通过受试者工作特征(ROC)曲线下面积(AUC)评价STA-PSV对GD的鉴别能力。结果GD组STA-PSV明显高于AIT组[61.00(41.00,86.50)cm/s比34.50(25.25,46.00)cm/s,P<0.001],ROC曲线分析,AUC为0.790(95%CI 0.734~0.845,P<0.001),当STA-PSV切点值≥49.5 cm/s时,诊断GD的敏感性为64.3%,特异性为83.3%。在所有甲状腺毒症患者中,以STA-PSV(对数转换后)为因变量,以游离甲状腺素(FT4)和TRAb为自变量进行多因素回归分析,结果显示STA-PSV与FT4(β=0.371,95%CI 0.005~0.010,P<0.001)和TRAb(β=0.138,95%CI 0.001~0.014,P=0.035)独立相关。结论STA-PSV对GD和AIT具有一定的鉴别诊断意义,且与甲状腺素水平和TRAb相关。     

Measuring TSH receptor antibody to influence treatment choices in Graves’ disease

TSH receptor antibody (TRAb) plays a key role in the pathogenesis of Graves’ disease (GD), and its levels correlate with the clinical course. The second‐ and third‐generation TRAb assays have >95% sensitivity and specificity for the diagnosis of GD and have improved the utility of TRAb to predict relapse. TRAb levels decline with antithyroid drug (ATD) therapy and after thyroidectomy. Its level increases for a year following radioactive iodine (RAI) therapy, with a gradual fall thereafter. TRAb level >12 IU/l at diagnosis of GD is associated with 60% risk of relapse at 2 years and 84% at 4 years. The prediction of risk of relapse improves further to >90% with TRAb >7·5 IU/l at 12 months or >3·85 IU/l at cessation of ATD therapy. TRAb tests are not expensive, and hence, TRAb measurements at presentation, after 12 months and/or 18 months (at cessation) of ATD therapy, could potentially guide treatment choices in GD. Elevated TRAb favours definitive treatment in the form of RAI or thyroidectomy, depending on the presence or absence of moderate‐to‐severe Graves’ ophthalmopathy (GO) and the ability to comply with radiation protection requirements. Use of ATDs in early pregnancy is associated with increased risk of congenital anomalies; early ablative treatment (RAI/surgery) should be considered in women of childbearing age at higher risk of relapse of GD. TRAb ≥5 IU/l in pregnant women with current or previously treated GD is associated with increased risk of foetal and neonatal thyrotoxicosis, and hence needs close monitoring. TRAb levels parallel the course of GO, and elevated TRAb is an indication for steroid prophylaxis to prevent progression of GO with RAI therapy.     

Subacute thyroiditis with highly positive thyrotropin receptor antibodies and high thyroidal radioactive iodine uptake

A 48-year-old woman with transient thyrotoxicosis, having a slightly high thyroidal 99mTc uptake (3.9% at 20 m) or radioactive iodine uptake (RAIU) (17.3% at 4 hour) and subacute thyroiditis (SAT)-like symptoms, signs and histological diagnosis (extensive cellular destruction and granulomatous inflammatory change), showed positive TRAb (59.9%) and TSAb (194%) activity. The high levels of TRAb and slightly high RAIU were still observed after one month of prednisolone treatment. Nine months later, the TRAb and TSAb levels finally normalized and her thyroid function has remained normal since then. We suspect that the slightly high RAIU were due to the presence of both the TRAb and the TSAb and the course of this case might mimic neonatal Graves' disease.     

Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period.

AIM AND METHODS: We performed a quantitative retrospective analysis of serum thyrotropin receptor antibody (TRAb) concentrations measured by a second-generation radioreceptor assay in 58 patients with Graves' disease (GD) at the onset of the disease, at the end of 18 month methimazole (MMI) treatment, and after MMI withdrawal in order to evaluate the correlation between the presence of these antibodies and the relapse of hyperthyroidism. Sixty healthy subjects were enrolled as a control group. RESULTS: Before MMI treatment the best cutoff TRAb value for identifying patients with GD was 1.45 UI/L (specificity, 100%; sensitivity, 98.3%). At the end of MMI treatment, serum TRAb concentrations were significantly lower (p < 0.001) than those measured at baseline, but they were still significantly higher (p < 0.001) than those found in the control subjects. At the end of MMI treatment, 44 patients (75.9%) had positive TRAb values (>1.45 UI/L). After MMI withdrawal (median, 15 months), 34 patients (58.6%) became hyperthyroid, 4 patients (6.9%) became hypothyroid, and 20 patients (34.5%) remained euthyroid. There was a significant correlation between serum TRAb concentrations at the end of MMI treatment and the percentage of patients who became hyperthyroid (r: 0.56; p < 0.001) and the time of appearance of hyperthyroidism (r: -0.38; p = 0.03). All 4 patients with TRAb values below 0.9 UI/L at the end of MMI treatment remained euthyroid throughout the follow-up period. Among the 27 patients who had serum TRAb values higher than 4.4 UI/L, 23 developed hyperthyroidism and 4 hypothyroidism. The TRAb values between 0.9 and 4.4 UI/L did not discriminate between the 27 patients (46.6%) who remained euthyroid from those who had relapse of hyperthyroidism. Thus a different TRAb end of treatment cutoff was calculated to identify patients who became again hyperthyroid. This TRAb cutoff value was 3.85 UI/L (sensitivity, 85.3%; specificity, 96.5%). All but 1 patient who had serum TRAb values above 3.85 UI/L became hyperthyroid after MMI was withdrawn (positive predictive value, 96.7%). In these patients, relapse of hyperthyroidism was independent of the changes in serum TRAb concentrations (r: 0.27; p = 0.15) and occurred after a median period of 8 weeks (range, 4-48). Hyperthyroidism also developed in 5 of 24 patients who had serum TRAb concentrations lower than 3.85 UI/L at the end of MMI treatment. In these 5 patients the relapse of hyperthyroidism occurred after a median period of 56 weeks (range, 24-120) and was always accompanied by an increase in serum TRAb concentrations. CONCLUSIONS: TRAb persist in the blood of most patients with GD after 18 months of MMI treatment. Both the frequency and the time of appearance of hyperthyroidism are closely correlated with serum TRAb concentrations at the end of MMI treatment. Our data would suggest that TRAb maintain stimulating activity after a full course of MMI treatment in the large majority of patients with GD. However, it is likely that the potency of these antibodies and/or the thyroid response to them change during treatment, as suggested by the different values measured in euthyroid control subjects and in euthyroid patients after MMI treatment.     

Toxic multinodular goiter with low radioactive iodine uptake

A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on (99m)Tc scintigraphy, (123)I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.     

Usefulness of the 2nd generation assay for anti-TSH receptor antibodies to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis after antithyroid drug treatment for Graves' disease

After antithyroid drug (ATD) treatment for Graves' disease, either a relapse of Graves' thyrotoxicosis or painless thyroiditis can develop. It is important to differentiate these two types of thyrotoxicosis because of the difference in required therapy. However, differentiation of thyrotoxicosis is usually difficult without radioactive iodine uptake (RAIU) which is not available in general practice. We investigated the clinical usefulness of the 2nd generation assay for anti-TSH receptor antibodies (TRAb) to differentiate these two types of thyrotoxicosis after ATD treatment for Graves' disease. We recruited 26 patients who developed thyrotoxicosis after ATD treatment for Graves' disease. These patients once became negative for TRAb and seemed to be in remission after ATD treatment. Upon development of thyrotoxicosis after ATD treatment, TSH, free T4, free T3 and TRAb were measured. TRAb were measured by the 2nd generation assay using recombinant human TSH receptors instead of porcine TSH receptors. Fourteen patients relapsed into Graves' thyrotoxicosis and 12 patients developed painless thyroiditis. Twelve (85.7%) of 14 patients with relapse of Graves' thyrotoxicosis were positive for TRAb. Eleven (91.7%) of 12 patients with development of painless thyroiditis after ATD treatment for Graves' disease were negative for TRAb. Levels of TRAb were significantly different between patients with relapse of Graves' thyrotoxicosis (4.86 +/- 6.45 IU/L) and those with painless thyroiditis (0.62 +/- 0.61 IU/L) (P<0.001). The 2nd generation assay for TRAb was useful to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis in patients who seemed to be in remission after ATD treatment for Graves' disease.     

Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?

OBJECTIVE A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with ‘burned-out’ disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. DESIGN Longitudinal prospective study of previously untreated patients with GD. PATIENTS Thirty-nine consecutive patients aged 10–72 years were treated with methimazole (MMI) for 12–24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. MEASUREMENTS Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. RESULTS Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1±1.1 vs 2±0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. CONCLUSIONS Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.     

Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves' disease

OBJECTIVE: Antithyroid drug treatment (ATD) is used world-wide in the treatment of thyrotoxicosis in patients with Graves' disease (GD). The main problem is a relapse rate of 30 to 50% within 2 years after the treatment has stopped. The measurement of thyrotropin receptor antibodies (TRAb) in serum has been used to confirm the diagnosis of GD in selected patients with a diagnostic specificity of 70 to 90%. However, in predicting the recurrence of thyrotoxicosis after discontinuing ATD it has been of little value. The aim of this study was to evaluate the ability of TRAb measured by the more sensitive recombinant human TSH receptor method to predict risk of recurrence of GD after discontinuing ATD. MATERIALS, PATIENTS AND METHODS: One hundred and twenty nine patients with newly diagnosed GD were included. Of these, 58 had relapse of hyperthyroidism in a follow-up of at least 11 months (median 18 months, range 11-49) after discontinuing ATD. In 122 Graves' patients TRAb were measured at the time of diagnosis and in all patients when discontinuing ATD by a competitive radioreceptor assay using recombinant human TSH receptors (TRAK human assay). RESULTS: We found an increased diagnostic specificity (99%) compared with the old TRAK porcine assay. The predictive values of a positive and negative test in relation to the prediction of a relapse of GD were found to be only 55% and 62% respectively when using a cut-off level of 1.5 IU/l, and the predictive value of a positive test decreased to 49% and of a negative test to 60% at a lower cut-off limit (1 IU/l). CONCLUSION: Our study confirms that the new TRAK human assay had a superior diagnostic sensitivity in comparison with the old TRAK porcine assay. Despite the higher diagnostic sensitivity of the TRAK human method, we could not find any improvement of predictive values for relapse of hyperthyroidism in the measurement of TRAb at the end of ATD.     

The perchlorate discharge test with and without supplement of potassium iodide

The purpose of the study was to compare the discharge of radioactive iodine from the thyroid after po administration of perchlorate with and without supplement of 2 mg potassium iodine (Kl) in 42 euthyroid controls, 26 patients with nontoxic goiter, 39 patients with thyrotoxicosis treated with radioactive iodine, and 39 patients with Pendred's syndrome. The discharge test was found to have a satisfactory specificity with supplement of 2 mg Kl, and was more sensitive to detect an organification defect than the standard perchlorate discharge test without Kl. In all groups of patients a significant discharge occurred after addition of Kl in contrast to healthy persons. Only in the group of patients with Pendred's syndrome a discharge of iodine was found in the perchlorate test without Kl.     

The effect of recombinant human tsh on the thyroid (123)i uptake in iodide treated normal subjects

Radioactive iodine therapy is often successful in the treatment of toxic or non-toxic multinodular goiter. However, when the patient has been exposed to iodine in the form of medication or radiocontrast agents prior to therapy, the thyroid radioactive iodine is often too low for successful ablation. Recently, administration of 0.9 mg of recombinant human TSH (rhTSH) has been shown to nearly double the 24-hour thyroid radioactive iodine uptake (RAIU) in euthyroid men living in the United States. In addition, 0.01 to 0.03 mg rhTSH administered 24 hours prior to (131)I in patients with a history of non-toxic multinodular goiter residing in an area of modestly low iodine intake, has also been shown to increase the 24-hour thyroid radioactive iodine uptake. We now have determined whether rhTSH administration prior to (123)I would increase the low thyroid RAIU in subjects treated with sodium iodide. Nine euthyroid men were given 15 mg iodide daily for 7 days. There was a marked increase in serum TSH values 8 and 24 hours after rhTSH administration, which induced elevated serum T4 and T3 concentrations. A 16 hour thyroid RAIU was measured at baseline, after 5 days of iodide administration, and either 8 or 32 hours after intramuscular administration of rhTSH. Administration of rhTSH 8 hours before (123)I to 4 subjects increased the 16 hour thyroid RAIU by 62% above the low post iodide thyroid RAIU. Administration of rhTSH 32 hours before (123)I administration to 5 subjects increased the 16 hour thyroid RAIU by 97% above the low iodide induced RAIU. Thus, the overall increase in the thyroid RAIU was 88% in the 9 subjects. Conclusion: Recombinant TSH moderately increased the thyroid RAIU in subjects with depressed thyroid RAIU's during iodide administration and thus may be useful in preparing patients with non-toxic or toxic goiters and low thyroid RAIU's due to excess iodine for radioactive iodine treatment. Further studies to determine the optimal protocol to enhance the effect of rhTSH will be carried out.     

Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves' disease (GD): an international multicentre trial

Background  Most recently, a new rapid and fully automated electrochemiluminescence immunoassay for the determination of TSH receptor autoantibodies (TRAb) based on the ability of TRAb to inhibit the binding of a human thyroid-stimulating monoclonal antibody (M22) has been established.
Objective  To evaluate this assay system in clinical routine based on an international multicentre trial and to compare the results with other established TRAb assays.
Patients and measurements  Totally 508 Graves' disease (GD), 142 autoimmune thyroiditis, 107 subacute thyroiditis, 109 nonautoimmune nodular goitre, 23 thyroid cancer patients and 446 normal controls were retrospectively evaluated.
Results  ROC plot analysis revealed an area under curve of 0·99 (95% CI: 0·99–1·0) indicating a high assay sensitivity and specificity. The highest sensitivity (99%) and specificity (99%) was seen at a cut-off level of 1·75 IU/l. Here, the calculated positive predictive value was 95%, whereas the negative predictive value was 100%. Applying the ROC plot-derived cut-off of 1·75 IU/l we found a sensitivity for TRAb positivity within the group of newly diagnosed GD patients of 97% which is in accordance to the sum of different nonautomated porcine TSH receptor-based assays with a sensitivity of 94% indicating an excellent analytical performance of the new assay format. Detailed comparison of the automated and the sum of manual assays revealed a near identical specificity.
Conclusion  Our results demonstrate that this new assay system has a high sensitivity for detecting GD and specificity for discriminating from other thyroid diseases. This assay may represent the future technology for rapid fully automated TRAb detection.     

Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease

OBJECTIVE: Differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis is important for selection of proper therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We investigated the possibility that assessment of thyroid blood flow would allow differentiation between the two entities. PATIENTS AND MEASUREMENTS: One hundred and fourteen untreated patients with thyrotoxicosis (56 Graves' disease, 28 painless thyroiditis, 30 subacute thyroiditis) and 25 normal controls were examined. Serum levels of freeT4 (FT4), freeT3 (FT3) and TSH were measured by chemiluminescent immunoassay, and anti-TSH receptor antibodies (TSH-binding inhibitory immunoglobulin, TBII) were measured by enzyme-linked immunosorbent assay. Thyroid volume and blood flow (TBF) were measured quantitatively by ultrasonography. RESULTS: TBF was significantly higher in Graves' disease (mean +/- 1SD: 14.9 +/- 6.4%, P < 0.0001) than in painless thyroiditis (0.8 +/- 0.5%), subacute thyroiditis (0.9 +/- 0.7%) and in normal controls (0.8 +/- 0.5%). All patients with Graves' disease had TBF values of more than 4% and all patients with painless thyroiditis and subacute thyroiditis had TBF values less than 4%. TBF values significantly correlated with values of radioactive iodine uptake (RAIU) either at 3 h (r = 0.492, P < 0.01) or 24 h (r = 0.762, P < 0.001) within the Graves' disease and painless thyroiditis groups. There was no relationship between TBF values and thyroid volumes or values of TBII in the Graves' disease group. All patients with Graves' disease had positive TBII of 15% or more. Three of 28 patients with painless thyroiditis and one of 30 patients with subacute thyroiditis had positive TBII. CONCLUSION: TBF was quantitatively measured by power Doppler ultrasonography and was more effective than TBII for differentiation between destruction-induced thyrotoxicosis (painless or subacute thyroiditis) and Graves' thyrotoxicosis. TBF values of less than 4% in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.     

TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays

OBJECTIVES: Graves' disease is characterized by stimulating autoantibodies to the TSH-receptor (TRAb). The aim of this study was to compare the performance of a new TRAb assay based on competitive binding to recombinant human TSH-receptors (H-TRAb) with an assay employing purified porcine TSH-receptors (P-TRAb). Furthermore, to evaluate the applicability of the H-TRAb assay to discriminate between patients with hyperthyroidism due to Graves' disease (GD) and multinodular toxic goitre (MNTG). DESIGN AND MEASUREMENTS: H-TRAb and P-TRAb were measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and MNTG (n = 94). For comparison, TRAb was measured in patients with primary autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by ultrasound, and healthy controls (n = 100 for each group). Patients were consecutively included from a population survey. RESULTS: If the cut-off values recommended by the manufacturer for TSH-receptor antibody positivity were used for evaluation, the sensitivity of the H-TRAb assay vs. the P-TRAb assay in diagnosing GD was: 95.3/67.9% (P < 0.001). Specificity was (H/P-TRAb): 99/99%. The sensitivity of P-TRAb was increased if the upper 97.5% limit of measurements in controls was used as cut-off (H-TRAb vs. P-TRAb: 95.3/80.2%, P < 0.001). Specificity (H/P-TRAb): 98/98%. The difference between assay performance may partly be due to a better technical performance of the H-TRAb assay with more reliable results in the low range of measurements. However, even in GD patients with clearly measurable TRAb, 25% had a P-TRAb < 50% of the value expected from the H-TRAb measurement. This suggests that a subgroup of patients produce TRAb with a higher affinity for the human than the porcine TSH receptor. A relatively high proportion of patients with MNTG were TRAb positive (H-TRAb/P-TRAb: 17/9%). Characteristics of H-TRAb positive and negative MNTG patients were compared. There was no difference between size of thyroid gland and number of nodules by ultrasonography. H-TRAb positive patients had significantly higher serum T4 and T3 and a greater number were TPO-Ab positive. CONCLUSIONS: H-TRAb diagnosed Graves' disease with a high sensitivity and specificity than P-TRAb. The high occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap between Graves' disease and multinodular toxic goitre in some patients.     

The significance of thyroid blood flow at the inferior thyroid artery as a predictor for early Graves' disease relapse

OBJECTIVE: We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse. MEASUREMENT: Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated. PATIENTS: ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17). RESULTS: In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF). CONCLUSION: ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.     

Iodine excess and hyperthyroidism.

150 microg iodine are daily required for thyroid hormone synthesis. The thyroid gland has intrinsic mechanisms that maintain normal thyroid function even in the presence of iodine excess. Large quantities of iodide are present in drugs, antiseptics, contrast media and food preservatives. Iodine induced hyperthyroidism is frequently observed in patients affected by euthyroid iodine deficient goiter when suddenly exposed to excess iodine. Possibly the presence of autonomous thyroid function permits the synthesis and release of excess quantities of thyroid hormones. The presence of thyroid autoimmunity in patients residing in iodine-insufficient areas who develop iodine-induced hyperthyroidism has not been unanimously observed. In iodine-sufficient areas, iodine-induced hyperthyroidism has been reported in euthyroid patients with previous thyroid diseases. Euthyroid patients previously treated with antithyroid drugs for Graves' disease are prone to develop iodine-induced hyperthyroidism. As well, excess iodine in hyperthyroid Graves' disease patients may reduce the effectiveness of the antithyroid drugs. Occasionally iodine-induced hyperthyroidism has been observed in euthyroid patients with a previous episode of post-partum thyroiditis, amiodarone destructive or type II thyrotoxicosis and recombinant interferon-alpha induced destructive thyrotoxicosis. Amiodarone administration may induce thyrotoxicosis. Two mechanisms are responsible for this condition. One is related to excess iodine released from the drug, approximately 9 mg of iodine following a daily dose of 300 mg amiodarone. This condition is an iodine-induced thyrotoxicosis or type I amiodarone-induced thyrotoxicosis. The other mechanism is due to the amiodarone molecule that induces a destruction of the thyroid follicles with a release of preformed hormones. This condition is called amiodarone-induced destructive thyrotoxicosis or type II thyrotoxicosis. Patients developing type I thyrotoxicosis in general have preexisting nodular goiter whereas those developing type II thyrotoxicosis have a normal thyroid gland. The latter group of patients, after recovering from the destructive process, may develop permanent hypothyroidism as the consequence of fibrosis of the gland.     

血清TRAb水平在Graves’病诊治中的意义

目的探讨促甲状腺激素受体抗体（TRAb）在Graves’病诊断、治疗及复发监测中的意义。方法电化学发光法测定Graves’病患者治疗前及治疗中TRAb的浓度,绘制ROC曲线,比较治疗前后和复发前后TRAb浓度的变化。结果 ROC曲线下面积为0.931、cut-off值为1.67 IU/L,此时对Graves’病诊断的敏感度为94%、特异性为85%。治疗前后及复发前后TRAb浓度的变化有统计学意义（P〈0.05）。结论电化学发光法测定TRAb是一种快速、敏感性和特异性较高的方法 ,有助于临床对Graves’病诊断、疗效观察和停药复发监测。     

Radioactive Iodine for Thyrotoxicosis in Childhood and Adolescence: Treatment and Outcomes

Objective: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence.Methods: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded.Results: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups.Conclusions: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment. . Conflict of interest:None declared.