Mechanism of persistent thyrotropin suppression in euthyroid patients with Graves′ disease after treatment
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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 receptorKeywords:
Trab
Propylthiouracil
Thyroid peroxidase
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Objective To investigate the change in levels of TRAb and TSH in patients with Graves disease,and to examine whether TRAb has inhibitive effect on TSH.Methods After Propylthiouracil(PTU) treatment,91 patients with Graves disease became euthyroid for at least 2 months.Among them,44 patients had low TSH level,while the other 47 had normal TSH level.The levels of TRAb between the two groups were compared.Results There were no significant differences in levels of FT3 and FT4 between the groups.The level of TRAb in low TSH level group was significantly higher than that in normal TSH group(P0.001),and TRAb levels were negatively correlated with TSH levels(r=-0.374,P0.001).Conclusion Thyrotropin suppression in treating euthyriod patients with Graves disease may be attributed to TSH receptor antibody activity.
Trab
Propylthiouracil
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TSH-receptor autoantibodies (TRAbs) are a valuable diagnostic tool for comfirming a diagnosis of Graves’ disease (GD). While there is evidence that high TRAb levels are associated with relapse of GD, whether a discrimination of TRAb into stimulating (TSAb) and blocking (TBAb) autoantibodies would benefit the clinician in terms of outcome prediction remains unclear. To address this issue, we have determined TRAb, TSAb and TBAb levels in serum samples of ninety-six euthyroid patients with GD taken four weeks after antithyroid drug withdrawal (ATDT). Forty-seven patients (49 %) underwent relapse of GD within two years. Amongst those, forty-one (87 %) had been positive for TRAb and thirty-five (74 %) for TSAb after treatment. All patients except one were negative for TBAb. The correlation between TRAb and TSAb in those treated GD patients was relatively weak (r = 0.268, p < 0.001). Based on a cut-off limit of 1.5 IU/l, the positive and negative predictive values with respect to prediction of relapse were too low for any clinical relevance (TRAb: 49 % and 54 %; TSAb: 51 % and 55 %). However, when a cut-off level above 10 IU/l was used, the positive and negative predictive values increased to 83 % and 62 %. The additional measurement of TSAb or TBAb in those samples after therapy did not add additional information, even at higher deciscion thresholds. In conclusion, differentiation of TRAb into TSAb and TBAb is of no help in the prediction of relapse of GD in euthyroid patients at the end of ATDT, and only high TRAb levels are associated with relapse.
Trab
Thyrotropin receptor
Blocking antibody
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Abstract Background Thyroid stimulating hormone receptor antibody (TRAb) is detected in the serum of patients with Graves’ disease (GD). This study aims to investigate the prevalence of euthyroid individuals showing positive results for TRAb and to clarify the clinical course of thyroid function and TRAb levels in these subjects. Objective Subjects were female patients who newly visited our hospital for a screening test prior to fertility treatment and showed normal thyroid function and volume without nodules between 2014 and 2017. After excluding subjects with a history of thyroid disease, 5,622 subjects were analyzed. Results Forty-seven of the 5,622 subjects showed positive results for TRAb (reference range, <2.0 IU/L) at the initial visit. Median initial TRAb was 2.9 IU/L (range, 2.0-14.7 IU/L) and median follow-up was 18.3 months (range, 0-66.5 months). Six of the 47 subjects (12.8%) developed GD and median duration until development was 6.6 months (range, 1.2-13.2 months). Median TRAb values initially and at diagnosis of GD for those 6 patients were 3.7 IU/L (range, 2.7-5.1 IU/L) and 7.2 IU/L (range 3.6-21.4 IU/L), respectively. TRAb results turned negative for 20 of the 47 subjects but remained positive despite normal thyroid function in 13 of the 47 subjects. Conclusion GD developed over time in 12.8% of euthyroid young female patients showing positive TRAb within a median of 6.6 months. A positive result for TRAb itself did not mean development of GD, so other factors must be essential for the pathogenesis of GD.
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We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positivefor anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.
Wolff–Chaikoff effect
Thyroid disease
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Trab
Anti-thyroid autoantibodies
Group B
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Summary Objective TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves’ disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow‐up could prove valuable to better understand treatment effectiveness. Study design TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow‐up length. Methods Sixty‐six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow‐up visit as well as bioassays of TSAb and TSBAb activity. Results Forty‐five per cent of all patients remained TRAb‐positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy per cent of TRAb‐positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well ( r = 0.83). In addition, 38/66 patients were TgAb‐positive, 47/66 were TPOAb‐positive and 6/66 were GADAb‐positive at follow‐up. Conclusions TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb‐positive at follow‐up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.
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Objective The clinical value of thyrotrophin receptor antibody(TRAb)in patients with Graves' hyperthyroidism was investigated during ~(131)I radiotherapy.Methods A total of 130 patients with Graves' hyperthyroidism and 50 normal controls were included in the study.Serum concentration of TRAb was measured by radioreceptor assay(RRA)before and at 3,6,12 and 24 months after ~(131)I radio- therapy.Results Abnormally higher TRAb level [(92.93±68.99)U/L] was noted in patients before treatment(P0.O1).The TRAb titer increased further to(139.04±77.19)U/L at 3 months after therapy (P0.01),before it dropped to(65.87±54.86)U/L and(14.16±12.35)U/L at 6 and 12 months re- spectively.At 24 months after ~(131)I radiotherapy,the TRAb [(12.99±5.52)U/L] was back to normal with no difference to that of controls(P0.05).Conclusion Serum concentration of TRAb was of clini- cal significance in the diagnosis of Graves' hyperthyroidism and in the monitoring of ~(131)I radiotherapy.
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One hundred and fifty-seven patients with Graves' disease treated with 131I from July 2001 to March 2003 were studied retrospectively. According to the thyroid function one year after 131I therapy, the patients were divided into 3 groups: remission group with normal FT3, FT4, partial remission group with above normal levels of FT3, FT4, and hypothyroid group with lowered levels of FT3, FT4. Prior to 131I treatment the thyroid-stimulating hormone receptor antibody (TRAb) was positive in 88.5% of the patients. After the therapy, TRAb levels rose transiently and reached the peak within 3-6 months and then dropped gradually thereafter. The weight of pretreatment thyroid, high levels of TRAb (≥405 U/L) and FT3, FT4 were predictors for the outcome of treatment.
Key words:
Graves' disease; Iodine radioisotopes; Thyrotropin receptor antibodies
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The outcome of 131I therapy for 109 patients with Graves' disease was analysed according to pretreatment laboratory data including thyrotropin receptor antibody (TRAb) activities. Forty-five percent of patients became euthyroid, and 13% of patients became hypothyroid within one year after 131I therapy. Forty-two percent of patients remained hyperthyroid one year after 131I therapy. Pretreatment values for serum T4, T3, and the estimated weight of the thyroid were significantly higher in the hyperthyroid group. The mean for the TRAb index of the hyperthyroid group was significantly higher than that of the euthyroid group. Life table analysis revealed a significant effect of the TRAb index on the rate of hyperthyroidism after 3 months or later. These results appear to suggest that the TRAb index is one of the factors which influence the outcome of 131I therapy for Graves' disease.
Radioiodine therapy
Thyrotropin receptor
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Objective
Changes of thyroid stimulating antibody(TSAb) and thyroid stimulating blocking antibody(TSBAb) in the treatment of anti-thyroid drugs(ATDs), and the effect of ATDs combining with levothyrocine(LT4) on TSAb and TSBAb were analyzed.
Methods
Using recombinant Trxfus. TSHRn protein and Trxfus. TSHRc protein as antigens, and TSH receptor antibody(TRAb)-N(TSAb binding hot spots), TRAb-C(TSBAb binding hot spots)in the serum of thyroid disease patients were measured with ELISA. The changes of TRAb-N, TRAb-C over 36 months in 117 TRAb-N positive Graves′ patients with hyperthyroidism were analyzed retrospectively. In the course of treatment, 41 cases as A group with ATDs and LT4 treatment, 76 cases as B group with only ATDs, The changes of TRAb-N and TRAb-C were observed in the two groups.
Results
(1)According to the change of TRAb-N, 117 TRAb-N positive Graves′ patients with hyperthyroidism were different. In group Ⅰ, 10 patients continued to have persistently positive TSAb and continued to have hyperthyroidism, remission rate 0%. In group Ⅱ, 17 patients showed complicated TRAb-N changes, 12 of 17 patients got relapse, 5 of 17 patients got remission, remission rate 29.4%. And in group Ⅲ, with TRAb-N dropping gradually, 15 of 89 patients got relapse, 74 of the 89 patients got remission, remission rate 83.1%. Three groups were significantly different with χ2 test(P 0.05).
Conclusion
TSAb and TSBAb can be used to document TRAb-function, which is significant for us to predict the changes of thyroid function. During ATDs treatment, the temporary early low-dose application of LT4 did not significantly affect TSAb and TSBAb. (Chin J Endocrinol Metab, 2017, 33: 662-667)
Key words:
Anti-thyroid drugs; Levothyrocine; Thyroid stimulating antibody; Thyroid stimulating blocking antibody
Trab
Blocking antibody
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