Ultrasonographic thyroid volume as a reliable prognostic index of radioiodine-131 treatment outcome in Graves' disease hyperthyroidism.

OBJECTIVE: We studied the relationship between thyroid volume, thyroid function and immunological markers of Graves' disease (GD) to determine prognostic factors of treatment response to low-dose radioiodine-131 (131I). MATERIAL AND METHODS: A prospective study of 40 patients with GD hyperthyroidism treated with 131I (141 +/- 85MBq) and 10 GD patients who went spontaneously into remission (controls). Free T4, total T3 and basal TSH levels, TSH-receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb) were studied. Thyroid volume was determined by ultrasonography. Logistic regression models were used to predict the probability of final thyroid status. Receiver-operating characteristics (ROC) curves and Hosmer Lemeshow tests were used to evaluate the final statistical models. RESULTS: Of 40 patients treated with 131I, 16 became euthyroid, 12 hyperthyroid and 12 hypothyroid at 12 months. Median thyroid volume was reduced from 24.8 ml before to 8.5 ml at 12 months (p<0.001). In 10 control patients, the median reduction was from 16.6 ml to 11.3 ml (p=0.029). Thyroid volume reduction was lower in the hyperthyroid than in the euthyroid group, but higher in the hypothyroid group. Thyroid volume at baseline and at 3 months predicted hyperthyroidism outcome with a cut-off of 45 ml and 24.4 ml, respectively (odds ratio 1.074, p=0.003, ROC curve 0.78 and odds ratio 1.182, p=0.012, ROC curve 0.86 respectively). Thyroid volume at 6 months differentiated the hyperthyroid group with a cut-off of 17 ml. Thyroid volume at 3 and 6 months with a cut-off of 8.5 ml and 9.3 ml respectively, predicts permanent hypothyroidism outcome (odds ratio 0.768 and 0.685, p=0.012 and p=0.008, ROC curve 0.89 and 0.88, respectively). Changes in thyroid echogenicity and TRAb and TPOAb levels did not show any predictive value in the follow-up after 131I therapeutic outcome. CONCLUSION: The study shows that the ultrasonographic thyroid volume at 3 and 6 months after low-dose 131I treatment for GD hyperthyroidism could be a reliable prognostic factor of thyroid function outcome in the first year after treatment, and also reveals that the changes in the thyroid echogenicity and in the immunological markers of GD have no prognostic value.     

Relationship among thyrotropin (TSH), thyroid stimulating immunoglobulins, and results of triiodothyronine (T3) suppression test in patients with Graves' disease

To investigate the relationship between TSH and abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease in whom normal thyroid hormone levels in the serum were maintained by antithyroid drug therapy and in patients with euthyroid Graves' disease, determinations were made of the TSH concentration, action of thyroid stimulating immunoglobulins (TSAb and TBII), and T3 suppression. Out of thirty-three patients with hyperthyroid Graves' disease, twelve patients with subnormal TSH levels were all non-suppressible according to the T3 suppression test results and the detectability of TSAb and/or TBII was as high as 75%. In three out of five patients with euthyroid Graves' disease, the serum TSH level was subnormal. All three showed non-suppressibility in the T3 suppression test and positive action of either TSAb or TBII. One of them became clinically thyrotoxic when the TSAb activity was further increased and TBII became positive, and was therefore diagnosed as having hyperthyroid Graves' disease. The present findings suggest that there are still abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease who have low TSH, even if their thyroid hormone concentrations remain normal. Moreover, it is likely that some of the patients with euthyroid Graves' disease are actually in a state of subclinical hyperthyroidism because of the presence of abnormal thyroid stimulator(s).     

Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.     

Obituaries

The outcome in 110 patients first treated with radioiodine (mean dose 6.56 mCi) for hyperthyroid Graves'' disease in 1980 was reviewed. In 23% of the patients the disease had not been controlled by the initial dose after 3 months, and 17% were given one or two more doses. Within 2 years 65% of the patients required replacement thyroxine therapy. Although about half of the patients were biochemically hypothyroid 3 months after the last dose of iodine 131, this condition was transient in a third of them; five of these patients even became hyperthyroid again. Patients with transient, as opposed to permanent, hypothyroidism at 3 months tended to be clinically euthyroid but to have residual palpable thyroid tissue and only a modest reduction in the serum thyroxine level. It is therefore recommended that patients not overtly hypothyroid 3 months after treatment with 131I be observed still longer before thyroxine replacement therapy is instituted.     

Radioiodine (131I) therapy of Graves' disease: use of the new high resolutional ultrasonic scanner for the determination of the accurate weight of the thyroid gland

In this series, eighteen patients with Graves' disease were treated with 8000 rads (80 Gy) of radioiodine (131I), using the new high resolutional ultrasonic scanner for the determination of the accurate weight of the thyroid gland. The mean dose of radioiodine administered orally was 4.6 +/- 3.0 mCi (170.2 +/- 110.0 MBq) and 133.7 +/- 44.6 microCi/g (4.95 +/- 1.65 MBq). At one year after treatment, twelve of eighteen patients (66.7%) became euthyroid, five (27.8%) remained hyperthyroid and one (5.6%) became hypothyroid. Analysis of various factors which may be related to the effect of radioiodine therapy revealed that the weight of the thyroid gland in the hyperthyroid and euthyroid groups was significantly different (61.7 +/- 33.5 g vs. 25.1 +/- 9.1 g, p less than 0.05). Furthermore, all patients with larger glands (more than sixty grams) remained hyperthyroid, while the incidence of euthyroidism was as high as 80% in patients with smaller glands (less than forty grams). Although the number of patients studied was small, these results indicate that a larger thyroid gland requires a larger radioiodine dose per gram of tissue than a smaller gland, suggesting that the therapeutic radiation dose should be graded according to the gland size even when the gland size is accurately estimated by ultrasound. Further study is required to determine the appropriate radiation dose graded according to the gland size.     

Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of Graves' disease and nodular goiter.

Cytokines might be involved in the immunological flare up, seen in some patients after 131I-treatment. Therefore, we measured serum levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interleukin-6 soluble receptor (IL-6sR) and Intercellular-adhesion-molecule-1 (ICAM-1) as well as tumor necrosis factor (TNF-alpha) after 131I-treatment of Graves' disease and nodular goiter. Seven patients with Graves' disease, eight with toxic nodular goiter and seven with non-toxic nodular goiter, were followed after 131I-treatment. The patients were treated in the euthyroid state. Blood samples were drawn at day 0, 4, 7, 21 and after 3 months. Significant increases were seen in free T4 index (FT4I), free T3 index (FT3I) and thyroglobulin (Tg) within the first weeks, and TSH simultaneously decreased. None of the cytokines demonstrated any change during follow-up, neither in the entire group nor in subgroups. FT4I and FT3I correlated significantly to ICAM-1. In conclusion, our data suggest that there does not seem to be prolonged cytokine activation after 131I-treatment for thyroid disorders.     

The influence of hyperthyroidism and glucocorticosteroid treatment on bone metabolism in patients with Graves' disease and ophthalmopathy

The aim of the study was to assess influence of hyperthyroidism and glucocorticosteroid treatment on changes of bone turnover markers in patients with Graves' disease and thyroid ophthalmopathy (TO). MATERIAL AND METHODS: Three groups of patients were included in the study. Group I was composed of 26 euthyroid Graves' disease patients with TO suitable for steroid treatment. Group II included 14 hyperthyroid Graves' patients without TO treated medically with anti-thyroid drugs. Group III (control group) included 20 healthy volunteers. Levels of the bone formation marker, i.e. bone-specific alkaline phosphatase (BALP) and the bone resorption marker, i.e. deoxypyridinoline (DPD) were measured in the group I before steroid treatment administration, after 3 methylprednisolone i.v. pulses and after completing the oral prednisone treatment. In the group II levels of BALP and DPD were assessed twice: before treatment of hyperthyroidism and after 6 months since euthyroid state had been achieved. In the group III levels of BALP and DPD were measured once in the basal conditions. RESULTS: Mean initial levels of BALP in groups I and II did not differ significantly and were increased when compared to healthy volunteers. In the group I a transient significant decrease in BALP levels after 3 i.v. pulses of methylprednisolone was observed, followed by a significant increase in BALP after completing the oral prednisone therapy. The achievement of euthyroid state in Graves' patients (II) did not influence significantly BALP values. In the group I initial DPD levels were significantly lower than those in group II and higher than those in the control group (III). During steroid treatment of TO (group I) no dynamic changes of DPD levels were observed. The achievement of euthyroid state in group II was accompanied by a significant decrease in DPD levels, which were however than those in the control group. CONCLUSIONS: 1. In hyperthyroid state is associated with the profound stimulation of bone resorption, and to a lesser extent of bone formation. 2. The achievement of euthyroid state causes a rapid inhibition of bone resorption and maintains a compensatory stimulation of bone formation. 3. Glucocorticosteroid treatment with methylprednisolone i.v. pulses and orally administered prednisone do not influence significantly the processes of bone formation and bone resorption.     

Variation of the thyrotropin-releasing-hormone (TRH) stimulated thyrotropin (TSH) response in comparison with the tyhroid-gland-suppression test and the triiodothyronine (T3) and thyroxine (T4) blood levels in the so-called euthyroid endocrine ophthalmopathy]

21 patients with active signs of euthyroid Graves' disease were given 400 mug thyrotropin-releasing hormone (TRH) i.v. All subjects with unresponsiveness to TRH had a nonsuppressible thyroidal 131I-uptake. On the basis of serum total T3 14 patients were hyperthyroid, 2 more had an elevated value of free T3. 4 patients with normal total T3 and nonsuppressible 131I-uptake were unresponsive to TRH, in 2 of them the free T3 fraction was elevated, however. 4 subjects with nonsuppressible 131I-uptake had a TRH stimulated TSH response. 2 of these subjects had hyperthyroid values of free and total T3 in serum and responded to TRH with an exaggerate TSH increment. The variations of TRH responsiveness may demonstrate a different threshold of the pituitary and the peripheral T3 receptors.     

Binding, stimulating and blocking TSH receptor antibodies to the thyrotropin receptor as predictors of relapse of Graves' disease after withdrawal of antithyroid treatment.

TSH-receptor autoantibodies (TRAbs) are a valuable diagnostic tool for confirming 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 decision 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.     

Second-generation thyrotropin receptor antibodies assay and quantitative thyroid scintigraphy in autoimmune hyperthyroidism.

Graves' disease (GD) is characterized by circulating TSH receptor antibodies (TRAb), and so-called hyperthyroid autoimmune thyroiditis (H-AIT) generally shows negative TRAb results with first-generation assays. However, a positive titer was observed in up to 13% of patients with euthyroid or hypothyroid autoimmune thyroiditis (AIT) by second-generation TRAb assays, and a larger increase is expected in hyperfunctioning forms. A thyroid 99mTc-pertechnetate uptake (TcTUs) cutoff of 2% previously was shown to accurately discriminate between GD and H-AIT. Here we evaluated the relationship between second-generation TRAb assays and TcTUs in 139 patients with untreated autoimmune hyperthyroidism. An increase in TRAb levels was found in 114 of 139 patients (82%). All patients with TcTUs >2% and 66% of those with lower values had positive TRAb measurements. When the cutoff was increased to 5.9 U/l, positive TRAb occurred in 92.6% of those having higher TcTUs and in 1.4% of those with lower TcTUs. TRAb levels significantly increased in patients with TcTUs higher than 2% as compared with those having lower values, while no differences occurred in patients with TcTUs ranging from 0 to 1%, from 1.1 to 1.5%, or from 1.6 to 2%. A significant relationship between TRAb and TcTUs (as well as fT3, fT4, and thyroid volume) was found. TcTUs, fT4, fT3, and thyroid volume significantly increased in patients with positive TRAb (cutoff 1.5 U/l) compared with those testing negative. Our data indicate that a large proportion of patients with hyperthyroidism and hypoechoic thyroid, including those previously diagnosed as having H-AIT, actually have circulating TRAb. TRAb levels predicate the degree of iodine uptake (as measured by TcTUs) and thyroid hyperfunction. The role of baseline TRAb measurement by second-generation assays to predict patients' outcome needs to be further evaluated and compared with TcTUs in prospective studies.     

TRAb在Graves病~(131)I治疗中的临床价值

目的:探讨促甲状腺激素受体抗体(TRAb)在Graves病131I治疗中的临床价值。方法:回顾性分析我院经131I治疗的186例Graves病患者,与70例健康对照组分别于131I治疗前及治疗后3、6、12和18月采用电化学发光免疫分析法(ECLA)动态检测血清TRAb、FT3、FT4、TSH浓度变化,进行统计分析,并计算TRAb的阳性率。结果:70例健康对照组TRAb水平1.09±0.45 IU/L,186例Graves病131I治疗前血清TRAb水平9.95±7.18 IU/L,明显高于健康对照组,两组比较有显著的统计学意义(t=-10.306,P0.001)。131I治疗3月后TRAb水平14.81±10.37 IU/L,明显高于治疗前(t=-5.26,P0.001);131I治疗6月后TRAb水平12.33±8.73 IU/L开始下降,治疗12月后TRAb水平3.14±0.87 IU/L明显降低;治疗18月后TRAb水平1.19±0.45 IU/L与健康对照组比较差异无统计学意义(t=-1.588,P=0.113)。Graves病131I治疗前TRAb阳性率为93.5%,治疗后3、6、12、18个月TRAb阳性率分别为93.5%、79.6%、27.4%和8.6%。结论:Graves病131I治疗中检测TRAb水平具有指导治疗、判断疗效、预测复发等重要的临床价值。     

Elevated serum IL-16 and RANTES levels in patients with autoimmune thyroid diseases and modulation by methimazole therapy

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.     

Sodium ipodate in the preparation of Graves' hyperthyroid patients for thyroidectomy

Sodium ipodate (SI) is an oral cholecystographic agent that also affects thyroid hormone metabolism. It inhibits the peripheral T4 to T3 conversion and the thyroidal hormone release. We investigated the safety and efficacy of SI (500 mg daily during 5 days) in the preparation for subtotal thyroidectomy of 7 Graves' hyperthyroid patients in whom treatment with thionamides was unsuccessful due to allergy or noncompliance. Plasma T3 levels (mean +/- SD) decreased from 4.90 +/- 1.80 nmol/l on day 0 to 1.70 +/- 0.30 nmol/l on day 4 of treatment. Thyroidectomy performed on day 5 of treatment was uneventful. In comparison with 14 Graves' hyperthyroid patients who underwent thyroidectomy during the same period after conventional preparation with thionamides and potassium iodide, the therapeutic outcome 1 year postoperatively was similar in both groups. However, in the mildly hypothyroid patients prepared with SI, the plasma thyroid-stimulating hormone level was transiently higher 3 and 6 months postoperatively. It is concluded (1) that SI is a safe and efficacious drug in the preparation of Graves' hyperthyroid patients for thyroidectomy; (2) the therapeutic outcome 12 months postoperatively is similar in SI and in conventionally prepared Graves' hyperthyroid patients, and (3) postoperative mild or subclinical hypothyroidism is more pronounced in SI than in conventionally prepared patients.     

Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid improvement of thyroid function by using glucocorticoid indicated for the preoperative preparation of subtotal thyroidectomy in Graves' disease

Glucocorticoid therapy is not considered as an authentic method for obtaining euthyroid in Graves' disease. We tried the administration of prednisolone as a preoperative preparation for subtotal thyroidectomy in 4 hyperthyroid patients with Graves' disease who had suffered adverse effects of thionamide antithyroid drugs, including agranulocytosis, liver damage and skin eruptions. Following oral administration of a 30 mg daily dose of prednisolone, with or without other antithyroid reagents, both serum T4 and T3 concentrations decreased rapidly and reached the normal range within 2 weeks. The clinical signs and symptoms of hyperthyroidism also improved rapidly and subtotal thyroidectomies were performed uneventfully in all cases. These results suggest that 1) glucocorticoid medication can normalize the circulating hormone levels rapidly in Graves' disease, 2) it is a useful method as preoperative preparation for subtotal thyroidectomy, especially when other conventional methods are not available or effective in obtaining euthyroid, and 3) mechanisms other than thyroid stimulation by circulating immunoglobulin seem to play an important role in causing hyperfunction of the gland.     

Na-K-dependent ATPase in red cells and thyroid status

The Relationship between ouabain-sensitive ATPase (Na-K ATPase) activity in erythrocytes and the thyroid status was studied in 36 patients with Graves' disease and 58 patients receiving L-thyroxine (T4) replacement therapy. Forty normal children served as control. Total ATPase activity in 4 untreated hypothyroid patients was significantly reduced (11.0 +/- 4.6 vs 17.3 +/- 4.1 micrograms-P/h/mg-protein, P less than 0.01), and Na-K ATPase was undetectable, both of which were normalized after 4 weeks of L-T4 therapy. Na-K ATPase in hyperthyroid patients was also decreased (0.9 +/- 0.8 vs. 4.0 +/- 2.7, P less than 0.01), but was gradually normalized after 3 months of euthyroid state. Clinically euthyroid children treated with L-T4 were divided into 2 groups with regard to Na-K ATPase activity, normal and low. Analysis of the possible factors producing this difference revealed that, in primary hypothyroidism, the factor appeared to be the endogenous T4 level, while in patients with dwarfism, the secretory capacity of TSH or TSH-releasing hormone (TRH) was contributory. Thus Na-K ATPase activity in red cells remains within the normal range after L-T4 replacement in the presence of a severe degree of primary hypothyroidism or in association with secondary or tertiary hypothyroidism. Other factors such as the L-T4 dose, duration of the therapy, serum T4 and T3 concentrations, were not significantly different in the two groups. These results indicate that (1) Na-K ATPase in red cells is decreased in hyper- or hypothyroid state, (2) restoration of normal activity requires 1-3 months of euthyroid period, and (3) it is a sensitive index of peripheral thyroid status over the preceding few months.     

促甲状腺素受体抗体及白细胞介素-2、白细胞介素-6在Graves病131I治疗中的变化及临床意义

目的:研究促甲状腺素受体抗体(TRAb)及白细胞介素-2(IL-2)、白细胞介素-6(IL-6)在Graves病~(131)I治疗中的变化并分析其临床意义。方法:选取2015年8月-2016年8月于我院接受~(131)I治疗的Graves病患者112例为研究对象,按照第6个月的甲状腺功能检查结果的不同分为治愈组(n=54),缓解组(n=21)和甲减组(n=37)。分别比较治疗前、治疗3个月、6个月后三组患者的甲状腺功能指标以及TRAb、IL-2、IL-6水平。结果:治疗前三组患者游离T3(FT3)、游离T4(FT4)、促甲状腺激素(TSH)水平比较差异无统计学意义(P0.05),治疗3个月、6个月后三组患者FT3、FT4水平均明显低于治疗前,而TSH水平明显高于治疗前(P0.05)。治疗3个月、6个月后甲减组FT3、FT4水平均明显低于治愈组、缓解组,治愈组又明显低于缓解组,TSH水平明显高于治愈组、缓解组,治愈组又明显高于缓解组(P0.05)。治疗前三组患者TRAb、IL-2、IL-6水平比较差异无统计学意义(P0.05)。治疗3个月后三组患者TRAb水平均明显高于治疗前(P0.05),治疗6个月后治愈组与甲减组患者TRAb水平与治疗前比较无统计学差异(P0.05),但缓解组患者TRAb水平高于甲减组,差异有统计学意义(P0.05)。治疗3个月、6个月后,治愈组与甲减组患者IL-2、IL-6水平均低于治疗前,而缓解组高于甲减组,差异均有统计学意义(P0.05)。结论:TRAb、IL-2、IL-6可作为评估Graves病~(131)I治疗后的指标,通过检测三项指标治疗前后水平变化情况,从而为临床预后评估提供指导作用。     

Immunological abnormality of peripheral blood B cells in patients with autoimmune thyroid disease

We investigated the response to immunoglobulin G-secreting cells (ISC) by peripheral blood mononuclear cells (PB-MNC) and purified B cells following stimulation with Staphylococcus aureus Cowan 1 (SAC) or with B cell stimulatory factor 2 (interleukin 6: IL-6), using the reverse hemolytic plaque assay in an attempt to clarify the immunological functions of peripheral blood B cells in patients with autoimmune thyroid disease (AITD). ISC response by PB-MNC following stimulation with SAC was significantly decreased in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis as compared with that of normal controls. The difference in SAC-response was not significant between patients with euthyroid state of Graves' disease and normal controls. ISC response by PB-MNC following stimulation with SAC exhibited a reciprocal relationship to TRAb in patients with Graves' disease. Using purified B cells, some spontaneous ISC response without SAC stimulation was observed in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis. This spontaneous ISC response was further enhanced by IL-6. These results suggest that in organ-specific autoimmune diseases such as AITD, immunological abnormalities exist in B cells and some B cells are nonspecifically activated in the immunologically active state.     

Similarity and dissimilarity between clinical and laboratory findings, especially anti-thyrotropin receptor antibody in ophthalmic Graves' disease without persistent hyperthyroidism and hyperthyroid Graves' disease

The aim of this study was to investigate thyroid states, significance of anti-TSH receptor antibodies and the clinical courses of patients with euthyroid Graves' ophthalmopathy. The clinical and laboratory finding of 30 patients with euthyroid Graves' ophthalmopathy were briefly as follows: 1) normal sized thyroid or small goiter; 2) negative or weakly positive thyrotropin binding inhibitor immunoglobulin (TBII); 3) normal thyroid [99 m-Tc] pertechnetate uptake; and 4) frequent observations of low serum TSH values. Besides TBII, thyroid stimulating antibody (TSAb) was measured under low salt and isotonic conditions using FRTL-5 rat thyroid cells. Both TBII and TSAb titers were lower in euthyroid Graves' ophthalmopathy than in hyperthyroid Graves' disease. Serum TSH levels frequently became low in patients considered as euthyroid upon the first examination as well as in Graves' patients in remission, reflecting preceding or mild hyperthyroidism. In follow-up studies, these patients with mildly elevated thyroid hormone levels and low TSH levels seldom reached a state of persistent hyperthyroidism, when TBII was negative or only weakly positive.     

Serum T3 level in the patients with hyperthyroidism after therapy.

Serum T3 level in various thyroid diseases was determined in unextracted serum with the Dainabot kit for T3 RIA. The serum T3 level in 33 normal subjects was 0.8-1.6 ng/ml. It was 5.7 +/- 3.5 ng/ml (mean +/- S.D.) in 36 hyperthyroid patients, and undetectable to 0.8 ng/ml in 21 hypothyroid patients. Generally the serum T4 and serum T3 decreased in parallel after radioiodine therapy for hyperthyroidism. However, in some cases the serum T3 level remained high in spite of normalized serum T4 after radioiodine therapy. This state indicated "T3-toxicosis", and hyperthyroidism was apt to recur. When thyroid function was observed for 2 years following radioiodine treatment, the ratio of serum T3 (T3 level before treatment/T3 level after treatment) decreased more significantly as compared with the ratio of serum T4 in euthyroid cases. Serum T3 provides a more sensitive index of thyroid function than serum T4 in euthyroid states after radioiodine or anti-thyroid drug therapy. The present data indicate that the serum T3 level and the T4/T3 ratio are valuable aids in the estimation of prognosis of hyperthyroid patients after various treatments.