Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves' disease

Studies on thyrotropin receptor autoantibodies (TRAb) by measurement of both thyroid-stimulating antibodies (TSAb) and thyrotropin-binding inhibitory immunoglobulins (TBII) in serum from children with Graves' disease are limited in number of studies. The aim of this study was to investigate the levels of serum TSAb and TBII in children with Graves' disease, and to evaluate the clinical significance of these antibodies. We measured the serum TSAb and TBII at diagnosis and during management in 65 children with Graves' disease. Patients were divided into four groups according to their metabolic state: those with untreated active Graves' disease, those receiving treatment with antithyroid drugs, those in remission, and those in relapse. At diagnosis, both TSAb and TBII assays had high sensitivities and high specificities. In follow-up, the levels of both TSAb and TBII paralleled the course of the disease. There was a strong positive correlation between TSAb and TBII. TBII levels were significantly higher in the patients with ophthalmopathy than those without ophthalmopathy in untreated Graves' children. It was concluded that TSAb and TBII measurements are valuable in the diagnosis and management of children with Graves' disease.     

Paired determination of thyroid-stimulating and TSH-binding inhibitory activities in patients with Graves' disease during antithyroid drug treatment

Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P less than 0.02). In 9 patients who became euthyroid as early as after 1-4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months-2 years). One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.     

Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment.

It is important to know whether a patient with Graves' disease will get into remission or not during antithyroid drug (ATD) treatment. Thyrotropin (TSH) receptor antibodies (TRAb) cause Graves' disease. Thyroid-stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) have been measured as TRAb to diagnose Graves' disease and to follow Graves' patients. Smooth decreases of TSAb and TBII during ATD treatment predict the remission of Graves' hyperthyroidism. We followed serial changes of TSAb and TBII in 58 Graves' patients before, during, and after ATD treatment; TSAb was measured as a stimulator assay, using porcine thyroid cells, and TBII as a receptor assay. Patterns of TSAb and TBII changes during ATD treatment differ from one patient to another. TSAb and TBII activities decreased and disappeared in 52 (group A) but continued to be high in the other 6 (group B); 39 of the 52 group A patients achieved remission, but all of the 6 group B patients with persistently positive TSAb and TBII continued to have hyperthyroidism. No differences in the initial TSAb and TBII activities were noted between the 52 group A patients and the 6 group B patients. Of the 52 group A patients in whom TSAb and TBII had disappeared, 44 had smooth decreases of TSAb and TBII (group A1), and 8 had complex changes of TSAb and/or TBII (group A2); 36 of the 44 group A1 patients (82%) but only 3 of the 8 group A2 patients (37%) continued to be in remission more than 1 year after ATD discontinuation. The number of remission in group A1 was significantly larger than that in group A2. No differences in the initial TSAb and TBII activities were noted between group A1 and group A2. More than 80% of group A1 patients, who had smooth decreases of TSAb and TBII, continued to be in remission longer than 1 year. We demonstrated that smooth decreases of TSAb and TBII during ATD treatment predicted the remission of Graves' hyperthyroidism. The Graves' patients can be classified into A1, A2, and B groups according to the patterns of TSAb and TBII changes during ATD treatment. Group A1 patients, who had smooth decreases of TSAb and TBII, had higher rate of remission than the others. Smooth decreases of TSAb and TBII during the early phase of ATD treatment are a reliable predictor of the remission.     

Triiodothyronine autoantibodies in Graves' disease: their changes after antithyroid therapy and relationship with the thyroglobulin antibodies.

Sera of 63 patients with Graves' disease, and 49 control subjects were assayed for T3 autoantibodies by a sensitive radioimmunoassay after being stripped of the endogenous thyroid hormone. T3 autoantibodies were demonstrated in 27% of patients with Graves' disease. After antithyroid treatment, T3 autoantibodies in 75% of the patients with positive antibody before therapy changed to negative titre during a follow-up period of 1 to 12 months. Also, a significant decrease of T3 autoantibodies was observed at 1 month after therapy in all patients who received antithyroid treatment. A further study of T3 autoantibodies and anti-thyroglobulin antibodies showed that the latter were demonstrated in 100% of patients with positive T3 autoantibodies and that T3 autoantibodies existed in about one third of patients with positive anti-thyroglobulin antibodies. The results suggested that T3 autoantibodies could be a subpopulation of the heterogenous anti-thyroglobulin antibodies. Although the fall of T3 autoantibodies in some patients was correlated to that of anti-thyroglobulin antibodies, the overall correlation between T3 autoantibodies and anti-thyroglobulin antibodies was poor. In conclusion: 1. T3 autoantibodies may be suppressed by antithyroid drugs. 2. Being a subpopulation of anti-thyroglobulin antibodies, T3 autoantibodies may be caused by an antigenic site within the big thyroglobulin molecule, whereas their titre was not correlated with that of the overall heterogenous anti-thyroglobulin antibodies.     

Blocking-type anti-TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves' disease

OBJECTIVE: Antithyroid drugs are effective in some patients with Graves' disease but not in others. The factors responsible for this difference are still unknown. We examined the relationship between the nature of anti-TSH receptor (TSH-R) antibodies and responsiveness to drugs in Graves' disease. PATIENTS: Twenty-eight untreated patients with Graves' disease were treated with thiamazole and followed for up to 13 years. MEASUREMENT: Antithyroid microsomal antibodies (MCHAs) and antithyroglobulin antibodies (TGHAs) were measured by the passive haemagglutination method. Anti-TSH-R antibodies were measured by a radioreceptor assay (TBII), and thyroid-stimulating antibodies (TSAbs) and TSH-stimulation blocking antibodies (TSBAbs) were measured by bioassays using FRTL-5 cells. Blocking antibodies were also measured by the conversion assay. In order to confirm the usefulness of the conversion assay, in vitro experiments using mixtures of TSAb serum and TSBAb serum were performed. RESULTS: In in vitro conversion experiments, the conversion assay sensitively detected coexisting blocking antibodies. TSBAb was found in seven patients and a positive conversion ratio was found in four patients, and, of these, three patients had both antibodies. Finally, eight patients (28.6%) had blocking antibodies and 25 of 28 patients (89.3%) had stimulating antibodies. These patients with blocking antibodies (Group A) responded well initially to antithyroid drugs and showed earlier normalization of the serum T4 level (3.0 +/- 1.2 weeks) than patients without blocking antibodies (Group B, 10.7 +/- 8.5, P < 0.001). Unexpectedly, remission of Graves' thyrotoxicosis was earlier in Group B (5.1 +/- 4.4 years) than in Group A (8.0 +/- 4.3 years, P < 0.05). Other parameters, including serum T4, goitre size, ophthalmopathy, TBII, TSAb, TGHA and MCHA, were not different between the two groups. CONCLUSIONS: Graves' patients with coexisting blocking antibodies initially respond well to thiamazole but are relatively slow to achieve remission. Measurement of blocking antibodies may be useful for selection of treatment options in Graves' disease.     

Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease.

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.     

Serum thyroglobulin changes in patients with Graves' disease treated with long term antithyroid drug therapy

In 29 patients with thyrotoxic Graves' disease treated with conventional long term antithyroid drug therapy, serum thyroglobulin (Tg) was serially determined by RIA and compared with clinical course, goiter shrinkage, and 131I uptake suppression. Those subjects with Tg autoantibody-negative sera comprised 46% of the patients with Graves' disease. They were divided into a remission group (G I) and an exacerbation group (G II). G I was subdivided into G Ia, who were in remission for 7-40 months, and G Ib, who relapsed more than 15 months after therapy. G II was still on therapy 27-62 months after its initiation, because these subjects exacerbated on reduction of the drugs. Goiter shrinkage occurred in 60% and 0%, and 131I uptakes were suppressed by T3 in 50% and 0% in G I and G II, respectively. Serum Tg in G I declined progressively and reached 48 +/- 5 (+/-SE) ng/ml on discontinuation of therapy, in sharp contrast with serum Tg in G II which remained high throughout (154 +/- 29 ng/ml at the last examination; P less than 0.001). Results of goiter shrinkage, 131I uptake suppressibility, and serum Tg levels were similar in G Ia and G Ib on cessation of therapy. Serum Tg levels less than 68 or more than 140 ng/ml on discontinuation of therapy were helpful in predicting the outcome of therapy. On the other hand, Tg levels were low and goiters were small in size in euthyroid Graves' disease. Tg levels were not clearly correlated with goiter weight or serum T4 and T3 levels before treatment. In conclusion, serial determinations of serum Tg reflect thyroid activity and provide information useful in the decision to discontinue therapy and observation after that.     

Pituitary-thyroid feedback regulation in patients with Graves' disease during antithyroid drug therapy

In an attempt to study the mode of normalization of thyroid function in patients with Graves' disease, a study was made on 140 patients with Graves' disease who were eumetabolic after appropriate therapy with antithyroid drugs for more than 9 months. T3 administration failed to suppress thyroidal radioiodine uptake and serum T4 in patients with TRH-unresponsive TSH secretion. In addition, exogenous TSH failed to elevate serum levels of T4 and T3. In patients with TRH-responsive pituitaries, T3 administration uniformly made serum TSH undetectable but produced various effects (unsuppressible, partially suppressible, and suppressible) on radioiodine uptake and serum T4. The magnitude of suppression of radioiodine uptake paralleled that of serum T4. In patients with unsuppressible or partially suppressible thyroids, exogenous and endogenous TSH were less effective in elevating serum T4 and T3. In patients with suppressible thyroids, T3 administration depressed radioiodine uptake and serum T4; the magnitudes of depression were comparable to those found in normal subjects. Exogenous and endogenous TSH elevated serum T4 and T3 in patients with suppressible thyroids. Here again, the magnitudes of elevation were comparable to those found in the normal subjects. The serum T3 to T4 ratio was high before treatment, but decreased significantly during antithyroid drug therapy. The magnitude of decrease was roughly proportional to the degree of T3 suppressibility.     

The prevalence of transient thyrotoxicosis after antithyroid drug therapy in patients with Graves' disease.

BACKGROUND: Although transient thyrotoxicosis occurring after antithyroid drug (ATD) withdrawal in patients with Graves' hyperthyroidism has been reported, the prevalence of transient thyrotoxicosis after ATD therapy is as yet unknown. When patients with transient hyperthyroidism are mistakenly regarded as recurrences, they receive unnecessary therapy. The aim of this study was to investigate the prevalence of transient thyrotoxicosis after ATD withdrawal. METHODS: We selected 110 consecutive patients with Graves' disease whose ATD therapy was stopped from December 2002 to September 2004 prospectively. Patients were observed for more than 1 year after ATD withdrawal, and 12 patients dropped out. Serum levels of free thyroxine (FT(4)), thyrotropin, and thyrotropin-binding inhibitor immunoglobulin were measured at ATD withdrawal, and 3, 6, and 12 months after withdrawal. When the patients showed mild thyrotoxicosis (serum FT(4) level of less than 3.00 ng/dL), we followed them up for 1 month without medication. RESULTS: The remission rate of the study group was 61.8% (68/110). Twenty-eight patients became euthyroid after transient thyrotoxicosis, equivalent to 41.2% of the remission patients. Eight of 28 patients showed overt thyrotoxicosis, and the rest subclinical thyrotoxicosis. Transient thyrotoxicosis occurred mostly 3-6 months after ATD withdrawal. CONCLUSIONS: Transient thyrotoxicosis after ATD withdrawal in patients with Graves' disease is not a rare phenomenon. Clinicians should be aware that the recurrence of Graves' disease after the withdrawal of ATD may be transient.     

Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term outcome in Graves' patients treated with antithyroid drugs

Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from patients with untreated Graves' disease were compared with long-term response to antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras, wherein TSHR residues 9-165 or 90-165 had been substituted with comparable residues of the LH/chorionic gonadotropin receptor. Of 159 patients studied, 52 (32.7%) exhibited positive TSAb activity with one or both chimera lines (heterogeneous group), and 107 (67.3%) had no activity with either (homogeneous group). Independent of all other parameters, patients with heterogeneous epitopes responded more favorably to oral antithyroid drugs than patients with homogeneous epitopes (65.4% vs. 41.9%, P = 0.011: estimated odds ratio by logistic regression, 2.17). Although most clinical parameters were not different at presentation, significant differences in the size of goiters, total T(3) concentrations, and titers of TSH-binding inhibitory Igs were evident in the successfully treated group (n = 80) by comparison to the group of patients whose treatment failed (n = 79). Alone, these three parameters did not predict outcome; however, when either of these parameters were considered together with epitope heterogeneity, predictability of a positive therapeutic response was increased to nearly 80%. Thus, the presence of TSAbs with a heterogeneous epitope in a patient with Graves' disease is not only associated with a favorable response to antithyroid drug treatment, it may help predict the response to treatment when the patient is initially seen.     

彩色多普勒超声检查在抗甲状腺药物治疗Graves病预后判断中的价值

毒性弥漫性甲状腺肿,即Graves病（GD）是甲状腺机能亢进的最常见的致病因素,抗甲状腺药物（ATD）是治疗GD选择较多的手段,但撤药后复发率高,部分患者预后不尽人意。预测ATD治疗GD预后的指标很多,但都不够完善。彩色多普勒超声在预测GD患者经ATD治疗后复发方面有一定价值。如诊断GD时彩色多普勒超声显示甲状腺体积明显增大,平均收缩期峰血流值和体积流量值分别高于139cm／s和195ml／min的患者治疗后复发可能性大。撤药后甲状腺低回声的程度越低,则GD缓解的可能性越大。这些指标均有利于临床医师更好地选择治疗方案并调整治疗周期,使GD患者的药物治疗达到更高的长期缓解率。     

Changes in thyroid volume during antithyroid drug therapy for Graves' disease and its relationship to TSH receptor antibodies, TSH and thyroglobulin

Changes in thyroid volume during antithyroid drug therapy for Graves' disease compared with circulating thyroid parameters were evaluated. One hundred and forty-four patients with Graves' disease were treated with methimazole. Thyroid volume was measured by ultrasonography (thyroid volume = pi abc/6, where a is length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins, thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and antithyroglobulin antibodies were also measured. In the whole group of patients, thyroid volume correlated significantly with thyroglobulin (p less than 0.01) and TSH-binding inhibitory immunoglobulins (p less than 0.01), but not with TSH, antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a positive correlation was found between thyroglobulin and TSH-binding inhibitory immunoglobulins (p less than 0.01). In 11 patients the mean thyroid volume decreased significantly after one year of therapy (p less than 0.01), associated with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten patients experienced transient hypothyroidism with an overdose of methimazole, and the mean thyroid volume increased significantly (p less than 0.01) with increasing serum TSH levels. In conclusion, it is suggested that TSH receptor antibodies may have a thyroid growth-stimulating effect. In addition, circulating thyroglobulin levels reflect thyroid volume in Graves' disease.     

A polymorphism of interferon-gamma gene associated with changes of anti-thyrotropin receptor antibodies induced by antithyroid drug treatment for Graves' disease in Japanese patients.

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. Interferon-gamma (IFN-gamma) is an important mediator of inflammatory and immune responses. The aim of the present study was to investigate whether the polymorphism of IFN-gamma gene is associated with the development of GD or with clinical course during the antithyroid drug therapy. We have studied the CA repeat polymorphisms in the first intron of IFN gamma gene in Japanese patients with GD (n = 162) and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n = 133). There was no difference in allele frequency of IFN-gamma gene polymorphism between patients with GD and control subjects. However, the allele 4 (15 CA repeats) frequency was significantly greater in patients whose antithyrotropin receptor antibody (TRAb) became negative within 3 years by antithyroid drug treatment than those with consistently positive TRAb for more than 3 years (34.1% vs. 15.7%, chi2 = 8.545, p = 0.0035, pc = 0.049). The in vitro production of IFN-gamma by concanavalin A-stimulated peripheral blood mononuclear cells was significantly smaller in control subjects with the allele 4 compared to those with the other alleles. In conclusions, the CA repeat polymorphism of the IFN-gamma gene might be associated with the outcome of anti-thyroid drug treatment.     

Prediction of relapse after antithyroid drug therapy of Graves' disease: value of color Doppler sonography.

Opinions differ regarding the indications for antithyroid drugs, radioiodine and surgery in patients with Graves' disease because the likelihood of long-term remission after medical treatment cannot be predicted. The aim of this study was to assess the value of quantifying thyroid blood flow in an attempt to predict outcome following withdrawal of antithyroid drug therapy. Spectral Doppler recordings were obtained from the thyroid arteries in 24 patients with Graves' disease at the time of diagnosis. Thyroid blood flow levels measured at the time of diagnosis of Graves' disease were correlated with outcome following withdrawal of medical treatment (mean duration of treatment: 14 months). Clinical follow-up for at least 18 months (range: 18 - 39 months) after antithyroid drug withdrawal was possible in 13 patients (12 women). Mean peak systolic velocity and volume flow rate values as well as thyroid volume measured at the time of diagnosis were significantly higher (139 cm/s, SD 46; 195 ml/min, SD 170; 52 ml, SD 18) in patients who relapsed after drug treatment compared with patients in remission (71 cm/s, SD 27; 67 ml/min, SD 61; 25 ml, SD 13). The correlation between thyroid blood flow measurements and thyroid volume was high (r = 0.79 - 0.96). Recurrence of disease could be predicted with a sensitivity of 71 % and a specificity of 100 % based on thyroid blood flow measurements. This preliminary data suggest that quantification of thyroid blood flow by means of Doppler sonography might be a useful tool to predict the outcome of Graves' disease following withdrawal of medical treatment and could be helpful in finding the adequate kind of therapy.     

Impact of smoking on the course of Graves' disease after withdrawal of antithyroid drugs.

Cigarette smoking has been reported to alter relapse rate in patients with Graves' disease (GD). However, the predictive effect of smoking in GD patients after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A prospective multicenter trial has previously identified smoking as an independent risk factor for relapse. Based on this study, the present paper gives a more detailed analysis of the impact of smoking on the long-term course of GD after ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later (visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs. 6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis showed a significantly higher relapse rate in smokers than non-smokers. A subset of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse during follow-up. Among them, smokers more often relapsed than non-smokers irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10 IU/L the predictive values of a positive and negative test for relapse was 68% and 73%, respectively (specificity 95%). In conclusion, we identified two effects by which smoking alters the course of GD. First, smoking is implicated to elevate TRAb levels and therefore increase the risk for relapse during follow-up. Second, smoking is an independent risk factor to worsen the clinical course of both, GD patients with low and high immunological risk to experience relapse after a successful outcome of ATDT. Thus, our data suggest that smoking has modifying immunological consequences and an adverse impact on the course of GD after withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.     

Postpartum recurrence of hyperthyroidism and changes of thyroid-stimulating immunoglobulins in Graves' disease

The changes of circulating thyroid-stimulating antibody (TSAb) in three patients with Graves' disease with relapsed hyperthyroidism after delivery were examined. All three patients were in clinical remission before and during pregnancy, but hyperthyroidism, with high radioactive iodine uptake, recurred 3--5 months post partum. TSAb activity, measured serially, was not detected at the time of the postpartum relapse, although it was detectable during pregnancy and in the euthyroid state after therapy. In two cases, the titer of antithyroid microsomal antibody increased concomitantly with an increase in the free T4 index. These data suggest that TSAb may not be a pathological thyroid stimulator in patients with recurrent hyperthyroidism after delivery in Graves' disease.     

Thyroid glands in patients with Graves' disease are sources of thyrotropin-binding inhibitory (TBI) activity

In order to investigate the main sources of production of Graves' immunoglobulins, 4 women with Graves' hyperthyroidism, which relapsed after withdrawal of methimazole (MMI) therapy, were selected for this study. The patients underwent subtotal thyroidectomy after pre-operative treatment with MMI and Lugol's solution. Seven blood samples were obtained in each patient during surgery from: a peripheral vein, immediately before neck incision; the carotid artery; and the left and right inferior thyroid veins, respectively, before manipulation of the thyroid; and the left and right inferior thyroid veins, respectively, after surgical handling of the gland; a peripheral vein at the end of operation. Thyrotropin-binding inhibitory (TBI) activity was measured in all samples by a radioligand method. Serum TSH was also measured in those samples. There was a substantial increment of TBI in the thyroid veins compared with the activity in the carotid artery. The mean TBI was significantly higher after surgical handling of the thyroid lobes. The two lobes from each gland secreted differing levels of TBI, whereas the TSH concentrations were similar in all samples from each individual patients. We conclude that at least part of the TBI activity in patients with Graves' disease comes from the lymphocytic infiltration of the glands, and that differences in antibody production between the thyroid lobes may explain the difference in TBI activity in their respective thyroid veins.     

Studies of sex-steroid-binding plasma protein (SBP) in Graves' disease before and under antithyroid drug therapy

The serum concentration of sex-steroid-binding plasma protein (SBP) was measured with radioimmunoassay for 92 patients with Graves' disease, 36 males and 56 females, as well as 92 age- and sex-matched controls. In 24 male patients with hyperthyroidism, the mean SBP concentration was 6.4 +/- 0.2 (mean +/- SD) microgram/ml, whereas it was 2.3 +/- 0.2 micrograms/ml for the controls. The mean SBP concentration in 28 female patients with hyperthyroidism was 7.4 +/- 0.6 micrograms/ml, whereas it was 3.2 +/- 0.6 micrograms/ml for the controls. In Graves patients who were euthyroid following treatment, SBP levels were decreased near normal in both sexes. There was a significant correlation between T4 and SBP concentrations as well as between T3 and SBP concentrations in patients with Graves' disease in both sexes, with a better correlation in females. Increased SBP in untreated Graves' disease initiated to decline within a month following administration of antithyroid drugs, taking over 3 months to decline to the normal range.