THE ACUTE CHANGES IN THYROID STIMULATING IMMUNOGLOBULINS,THYROGLOBULIN AND THYROGLOBULIN ANTIBODIES FOLLOWING SUBTOTAL THYROIDECTOMY*

The acute changes in thyroid adenylate cyclase stimulating immunoglobulins (TACSI), TSH binding inhibiting immunoglobulins (TBII), thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) in serum after subtotal thyroidectomy were studied in thirteen patients with Graves' disease (GD) and thirteen patients with non-toxic goitre (NG). Prior to operation eight patients with GD were TACSI positive (mean ± SEM: 135·18%) and within 8 h following surgery TACSI increased and became positive in all thirteen patients (mean 172 ± 20%). There was a parallel increase in Tg and a decline in TgAb. A secondary rise in TACSI was observed 3–4 days after operation followed by a gradual fall which was associated with an increase in TgAb reaching a maximum 10 days after surgery. TACSI were still detectable 1 month postoperatively, but had disappeared by 3 months. In four of nine patients with GD TBII were present prior to operation. Immediately after surgery TBII decreased significantly (P < 0·05) and two of the four patients who were TBII positive became permanently negative, while the other two patients remained positive. A transient increase of the mean TBII levels was observed 5 days after surgery. Two of thirteen patients with NG were TACSI positive before operation and no significant changes were observed after surgery. The mean levels were significantly lower than in GD. Tg was measurable in eleven patients and showed a lower increase than in GD following surgery. TgAb were present in two patients prior to operation but disappeared in one and in the other one the changes following surgery were similar to the changes in GD.     

A novel mutation causing complete deficiency of thyroxine binding globulin

OBJECTIVE Recovery of thyroid function in patients following hypothyroidism induced by ¹³¹I therapy for Graves' disease has been described, but only a few detailed clinical and biochemical studies of this phenomenon (transient hypothyroidism) have been published. The prevalence, mechanism, and final outcome of transient hypothyroidism in 260 patients with Graves’ disease treated with ¹³¹I was studied. DESIGN A retrospective study. PATIENTS Two hundred sixty patients with Graves' disease, treated with ¹³¹I between 1 and 15 years previously, were categorized into 4 groups according to their thyroid function during and 1 year after therapy (Group 1: permanent hypothyroidism, 28 patients; Group 2: transient hypothyroidism, 39 patients; Group 3: euthyroidism without transient hypothyroidism, 83 patients; Group 4: hyperthyroidism, 110 patients). MEASUREMENTS We compared total T4, total T3, TSH, anti-thyroglobulin (TGHA) and anti-microsomal (MCHA) antibodies, the TSH-binding inhibitory immunoglobulin (TBII) index, thyroid weight, dose of ¹³¹I, and 24-hour ¹³¹I uptake as pretreatment variables. The mean time for permanent hypothyroidism to develop was estimated by the Kaplan–Meier product limit method. The TBII index and thyroid stimulating antibody (TSAb) activity were measured in seven patients from Group 1 and in nine patients from Group 2 at the time that they became hypothyroid. RESULTS Hypothyroidism developing within 12 months of therapy was transient in 58% (39/67) of patients. No pretreatment variables were found to differ between patients with and without transient hypothyroidism. The mean estimated time between therapy and the development of permanent hypothyroidism was 96 months in Group 2; this time interval was significantly shorter than 126 months in Group 3 and 129 months in Group 4 (P<0.05, P<0.01, respectively). TSAb activity was > 500% in 78% (7/9) of patients from Group 2, which was significantly higher than that found (14%, 1/7) in Group 1. CONCLUSIONS These results indicate that (1) more than half the patients who developed hypothyroidism within 6 months after ¹³¹I treatment for Graves' disease recovered spontaneously, (2) TSAb activity might play some role in the recovery of transient hypothyroidism, and (3) the development of transient hypothyroidism may influence long-term thyroid function.     

The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly

OBJECTIVE Graves' disease is recognized as an organ-specific autoimmune disorder caused by the presence of TSH receptor antibodies. The long-term effects of ¹³¹I treatment for Graves' disease on TSH receptor antibodies have not previously been studied. We have measured the TSH-binding Inhibitory immunoglobulin (TBII) Index and thyroid stimulating antibody (TSAb) activity in patients with Graves' disease following treatment with ¹³¹I. DESIGN A retrospective study. PATIENTS Two hundred and twenty-five patients with Graves' disease who were treated with ¹³¹I 1–13 years earlier were studied (1 year: 27 patients; 2–5 years: 42 patients; 6–9 years: 79 patients; 10–13 years: 77 patients). MEASUREMENTS The TBII index was measured as the percentage ¹²⁵I-TSH bound to pig thyroid membranes and TSAb activity as the amount of cAMP produced by cultured FRTL-5 cells. RESULTS TBII was detected in 78% of patients prior to ¹³¹I administration. Following ¹³¹I administration, the Incidence of positive TBII was 85% at the end of the first year decreasing to 40,19 and 17% at 2–5,6–9 and 10–13 years, respectively. The frequency of a positive TSAb was 74% at the end of the first year, and also decreased to 49, 27 and 29% at 2–5, 6–9 and 10–13 years, respectively. At more than 2 years after ¹³¹I therapy, the frequencies of hyperthyroidism In TBII and TSAb positive patients were 42% (19/45) and 30% (19/63), respectively, which were significantly higher than those In TBII and TSAb negative patients (8%: 12/153 and 8%:11/131, respectively). The frequency of hyperthyroidism after ¹³¹I treatment in patients with negative TBII before treatment (7%: 2/29) was significantly lower than that (29%: 30/102) In patients with positive TBII before treatment. CONCLUSIONS These results indicate that (1) the TBII Index and TSAb activity decreased over a period of more than 2 years after ¹³¹I therapy for Graves' disease, and (2) the TBII index before treatment may influence the long-term outcome of ¹³¹I therapy.     

Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre

A patient with toxic nodular goitre is described in whom radioiodine (¹³¹I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse ¹³¹I uptake by the gland. A second administration of ¹³¹I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH-receptor antibody and thyroid stimulating antibody were undetectable before ¹³¹I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of ¹³¹I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH-receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH-receptor, thus turning a toxic nodular goitre into Graves' disease.     

Metastatic thyroid cancer presenting as thyrotoxicosis: report of three cases

Three patients with metastatic thyroid follicular carcinoma developed thyrotoxicosis. Two had mild T3 toxicosis without detectable TSH binding inhibitor immunoglobulins (TBII) or thyroid stimulating antibodies (TSAb). Considerable concentration of ¹³¹***I by tumours occurred, although serum TSH was undetectable. The third patient developed thyrotoxicosis several months after treatment with ¹³¹I had commenced and this was associated with concurrent increase in both TBII (90%; normal, less than 11%) and TSAb (2100%). We conclude that thyrotoxicosis in patients with metastatic thyroid carcinoma may result from a large bulk of tumour functioning either autonomously or after stimulation by TSH receptor antibodies.     

The prognostic value of parallel measurements of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb) in Graves' disease after longterm antithyroid treatment

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves' disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBII or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves' disease, though this evaluation was only possible in part of the patients.     

Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves' disease

Abstract. Objectives . To investigate the long-term effect of radioactive iodine (¹³¹I) on thyroid function and size in patients with Graves' disease. Setting . Out-patient clinic in Herlev Hospital. Subjects . One hundred and seventeen consecutive patients (104 women) with Graves' disease selected for ¹³¹I treatment and followed for a minimum of 12 months (range 1–10 years, median 5 years). Interventions . ¹³¹I dose was calculated based on thyroid volume and 24-h ¹³¹I uptake. Main outcome measures . Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. Results . Seventy-eight patients were cured by one ¹³¹I dose and 30 by two doses, while the remaining nine patients received additional doses (range one to five doses, median one dose). Within one year, 25% developed hypothyroidism, and hereafter, hypothyroidism developed at a constant rate of 3% per year independent of antithyroid pretreatment. The cumulative 10-year risk of hypothyroidism was 60%. Initial median thyroid volume was 33 mL (range 9–106 mL). At 12 months after the last ¹³¹I dose, median thyroid volume was reduced to 14 mL (range 6–36 mL) (P < 0.00001). The median reduction being 58% (range 0–80%,), hereafter no further reduction occurred. A significant reduction in thyroid volume was also noted in patients needing subsequent ¹³¹I doses and in those developing hypothyroidism within the first year. Conclusions . ¹³¹I normalizes thyroid volume in patients with Graves' disease. Hypothyroidism seems an inevitable end result of this treatment. The present study suggests that it will be impossible to modify ¹³¹I therapy in a way to achieve both early control of hyperthyroidism and a low incidence of hypothyroidism.     

Hyperthyroidism following hypothyroidism

Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves' disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.     

Standardized radioiodine therapy in Graves' disease: the persistent effect of thyroid weight and radioiodine uptake on outcome

Abstract. Objective. To assess the incidence of hypothyroidism, euthyroidism, and recurrent hyperthyroidism following a standard dose of Na¹³¹I (3.7 MBq or 100 μCi) per g thyroid tissue, adjusted for radioiodine tracer uptake. Design. A single-centre prospective follow-up study from January 1990 to December 1992. Setting. Academic Hospital in Utrecht, the Netherlands. Subjects. Newly diagnosed patients with Graves' disease (n = 148). Interventions. Radioiodine treatment at a standard dose of 3.7 MBq or 100 μCi per g thyroid tissue. Main outcome measures. Confidence interval testing of resulting thyroid status, defined by biochemical criteria. Results. The overall cure rate was 70% (103 of 148 subjects), confidence interval (CI) 62–77%. A 90% incidence of hypothyroidism was found in patients with a small thyroid (less than 20 g). Recurrent hyperthyroidism was found significantly more often in subjects with a thyroid weight exceeding 60 g compared to those who had a thyroid of 9–59 g. More recurrences were found in subjects in the highest tertile of a 24-h radioiodine uptake test (> 80% uptake) compared to those in the lowest tertile (< 60% uptake). Conclusions. No uniform treatment results expressed per thyroid weight category were obtained, in spite of standardizing the treatment Na¹³¹I dose (3.7 MBq per g thyroid). Graves' patients with a thyroid smaller than 20 g and those with less than 60% 24-h radioiodine uptake have a 50–90% chance of hypothyroidism at the 12-month follow-up.     

EFFECT OF RADIOIODINE ON STIMULATORY ACTIVITY OF GRAVES'IMMUNOGLOBULINS

The effects of ¹³¹I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves’disease have been studied. Prior to ¹³¹I administration TSAb was detected in 84%, and TBII in 68% of patients. Following ¹³¹I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pre treatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after ¹³¹I therapy for Graves’hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement.     

Studies on the radioreceptor assay of TSH: the properties of TSH-binding inhibitor immunoglobulins (TBII) in patients with Hashimoto's thyroiditis (author's transl)]

TSH-binding inhibitor immunoglobulins (TBII) have been detected not only in patients with Graves' disease but also in those with Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In the present study, the properties of TBII in patients with Hashimoto's thyroiditis are discussed. Two (7%) of 29 patients with Hashimoto's thyroiditis had detectable levels of TBII in their gamma-globulin fractions. Both patients were untreated and clinically hypothyroid. One of them had no goiter, and her thyroidal 99mTc uptake was 0% (normal range: 0.4 approximately 3.0%). Despite having potent TSH-binding inhibitor activity in the TSH radioreceptor assay, her serum or its IgG fraction (H-IgG) did not contain any significant anti-TSH antibody, LATS, LATS-protector or human thyroid adenylate cyclase (AC) stimulating activity. This H-IgG inhibited both human thyroid AC stimulation and c-AMP increase in mice thyroid glands induced by TSH or LATS. Furthermore, her serum caused significant inhibition of 131I-release by LATS in a McKenzie mouse bioassay. The present study demonstrates that the serum of one patient with Hashimoto's thyroiditis contained antibodies which 1) blocked the binding of lablled TSH to the receptor, 2) had no thyroid-stimulating activity by themselves, and 3) inhibited AC stimulation by TSH. Such antibodies may cause unresponsiveness to TSH stimulation, hypothyroidism, and, if this state persists for a long time, eventually may result in atrophy of the thyroid tissue. Further, these data indicate that TBII detected by the TSH radioreceptor assay did not always show thyroid stimulating activities.     

Follow-up study of thyroid stimulating-blocking antibodies in hypothyroid patients

It has been shown that hypothyroidism of some patients may be associated with increased activity of thyroid stimulating-blocking antibodies (TSBAb). The present study was undertaken to follow the course of thyroid blocking, stimulating immunoglobulins and TSH-binding inhibitor immunoglobulins (TBII) in six hypothyroid patients who had elevated TSBAb and were treated with T4. Four of the six had Graves' disease previously treated with antithyroidal drugs, one had Graves' disease treated with 131I and one had subacute thyroiditis and subsequently became hypothyroid. The patients were followed for 1-5 years. Blocking activity and TBII normalized in four of the six during T4 therapy, so T4 was discontinued and they remained euthyroid. These data indicate that it is important to monitor carefully thyroid function in hypothyroid patients treated with a fixed amount of T4 to avoid subclinical hyperthyroidism and its consequence, e.g. osteoporosis.     

Immunological findings and thyroid function of untreated Graves' disease patients with undetectable TSH-binding inhibitor immunoglobulin

OBJECTIVE TSH-binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease. PATIENTS We examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age ± SEM 35 ± 2 years, group A). MEASUREMENTS We compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age ±SEM 40 ±2 years, group B). T4, TSH, FT4, FT3, 1231 thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit. RESULTS Serum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P<0 001). The values of TSAb in group A were significantly lower than those in group B (593±67 (mean±SE) vs 2143±280%, respectively, P < 0001). The 1231 thyroid uptake in group A was significantly lower than that in group B (53 1 ±11 vs 61 -4±14%, respectively, P<0.01).The thyroid volume in group A was significantly smaller than that in group B (391 ±3 0 vs 51 3±3 3 ml, respectively, P<0 01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit. CONCLUSION In the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated ¹²³l uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was also confirmed.     

Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis.

TSH-binding inhibitor immunoglobulins (TBII) have been detected in patients with Graves' disease and Hashimoto's thyroiditis by using the radioreceptor assay of TSH. In untreated Graves' patients, TBII levels correlated well with thyroidal 99mTc uptake at 30 min and the grade of epithelial hyperplasia of thyroid follicles. There were many Graves' patients whose sera contained high TBII levels but no detectable bioassayable thyroid-stimulating activity (LATS), and in these patients, close correlation was observed between serum levels of TBII and bioassayable LATS-protector activity. TBII were detectable in 2 (10%) of 20 patients with Hashimoto's thyroiditis, both of whom were clinically hypothyroid. The serum or IgG fraction from one of them, however, did not contain any significant LATS, LATS-protector, or human thyroid adenylate cyclase-stimulating activity and caused inhibition of adenylate cyclase stimulation by TSH. In that patient, TBII may be acting to block TSH binding to TSH receptors, thus causing TSH unresponsiveness and hypothyroidism.     

Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles

The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.     

Blocking type antithyrotropin receptor antibody in patients with nongoitrous hypothyroidism: its incidence and characteristics of action

The incidence, characteristics of action, and pathogenetic importance of blocking type anti-TSH receptor antibody were examined in patients with autoimmune thyroiditis. Serum immunoglobulin G (IgG) from 8 of 20 patients with nongoitrous hypothyroidism contained substantial amounts of TSH binding inhibitor immunoglobulin (TBII) activity. Newborn infants of a patient with the greatest TBII activity had neonatal transient hypothyroidism. In sera of patients with goitrous hypothyroidism and euthryoid chronic thyroiditis, only weakly positive or negative TBII activity was found. IgGs of these patients and those of nongoitrous hypothyroid patients without strongly positive TBII activity did not inhibit TSH stimulation of thyroid adenylate cyclase activity. Seven of 8 IgGs which had strongly positive TBII activity significantly inhibited cAMP generation induced by 9.1 mU/ml TSH, and the eighth IgG inhibited stimulation with 0.5 mU/ml TSH. Although the modes of TSH binding inhibition were variable, markedly close correlation was found between TSH binding- and TSH stimulation-inhibiting activities of these 8 IgGs (r = 0.90; P less than 0.01). These IgGs may exert their inhibitory effects on adenylate cyclase activity by inhibiting TSH binding to its receptor.     

Prediction of the Course of Graves' Disease after Medical Antithyroid Treatment

ABSTRACT The course of thyrotoxicosis in 33 patients with Graves' disease was evaluated clinically and biochemically (free thyroxine index, serum triiodothyronine, thyroid stimulating antibodies, (TSAb), thyroid stimulating hormone binding inhibiting immunoglobulins (TBII)). Relapse of the disease was found to be correlated to anamnestic information of thyrotoxicosis among first degree relatives (predictive value 90%) and to concomitantly raised levels of TSAb and TBII at the start of treatment (predictive value 71%). Mean duration of treatment of patients with long-lasting remission was 16.8 months. When comparing various information used to predict relapse of Graves' disease, anamnestic information of familial predisposition to thyrotoxicosis carries the highest predictive value.     

Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves' disease

A 54-year-old woman was treated with an oral dose of S55MBq of ¹³¹I radioiodine for thyrotoxicosis. She had no clinically detectable extrathyroidal manifestations of Graves' disease at the time, but within two months developed moderately severe ophthalmopathy and very extensive thyroid dermopathy affecting her face, arms, hands and feet, in addition to the classic pre-tlblal area. Although she developed mild post radioiodine hypothyroidism, this was detected at an early stage and its treatment had no effect on the extrathyroldal signs. Thyrotrophin receptor antibodies (TRAb) were positive before treatment (22% Inhibition of T S H binding in neat serum), rose to very high levels following radioiodine (97.6% Inhibition), and fell progressively over the following year during treatment with prednisolone. Thyroglobulln autoantibodies became detectable following radioiodine but thyroid peroxidase antibodies were undetectable throughout. Serum and purified IgG from blood samples obtained prior to steroid therapy and over the subsequent year were tested on a dermal fibroblast cell line in vitro for the stimulation of synthesis of glycosamlnoglycans, protein and DNA, but no increase in radiolabel incorporation was apparent for any sample when compared to controls. The temporal relation between the radioiodine and the acute onset of dermopathy and ophthalmopathy, together with the abrupt rise in TRAbs, indicates a probable causal association. However, the absence of In-vitro fibroblast stimulation would suggest that the pathogenesis of Graves' dermopathy is not dependent solely on any simple humoral factor.     

EFFECTS OF RADIOIODINE ON THYROTROPHIN BINDING INHIBITING IMMUNOGLOBULINS IN GRAVES''DISEASE

We have studied the effects of 131I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) in fifty-five patients with Graves' disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves' disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131I there was a marked increase in the serum TBII activity during the 3 months following therapy, whereas drug-treated patient showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131I treatment or during drug treatment provide insight into the basic defects responsible for the development of hyperthyroid Graves' disease and suggest that both the thyroid and immune system are involved.     

Methimazole, but not betamethasone, prevents 131I treatment-induced rises in thyrotropin receptor autoantibodies in hyperthyroid Graves' disease

The effects of methimazole or betamethasone therapy on the TSH receptor antibody response to radioiodine therapy were compared in a prospective randomized study of 60 patients with hyperthyroidism due to Graves' disease. The patients were followed for 1 yr after treatment with 131I. Twenty-three patients received 131I alone, 17 were treated with methimazole for 2 months before and 3 months after 131I therapy, and 20 patients were treated with betamethasone for 3 weeks before and 4 weeks after 131I therapy. 131I induced a transient rise in the mean serum level of TSH receptor autoantibodies, measured as TSH binding inhibitory immunoglobulin (TBII), but in patients receiving methimazole treatment, no such rise occurred. In the betamethasone-treated patients, TBII increased similarly to that in patients treated with 131I alone. In addition, in patients given betamethasone, there was an early decrease in total serum immunoglobulin G, which persisted throughout the follow-up period. In the other 2 groups, no changes in total immunoglobulin G were found. The results demonstrate that in hyperthyroid Graves' disease, TBII production is influenced by therapy. Methimazole abolished the 131I-induced increase in TBII, whereas betamethasone did not have such an inhibitory effect.