Thyroid Stimulation Blocking Antibody Research Articles

Development of chicken antibodies toward the human thyrotropin receptor peptides and their bioactivities

We have synthesized four peptides (P2, P4, E3 and P1) corresponding to different segments of human thyrotropin (TSH) receptor. We have obtained antibodies by immunizing them to chickens, and antibodies are evaluated for their thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and TSH-binding inhibitor immunoglobulin (TBII) activities. None of the antibodies had TSAb activity. Antibodies against human TSH receptor specific region such as P2 and P4 (P2: No. 372–397, P4: No. 341–358) had TSBAb and TBII activities. Anti-E3 antibody (E3: the third putative extracellular loop, No. 649–661) had only TSBAb activity. Anti-P1 antibody (P1: high homology with pig LH CG receptor, No. 398–417), however, had none. These results suggest that anti-TSH receptor antibodies to different antigenic epitopes show heterogeneity in their biological activities.

Graves' Disease Following Hypothyroidism Due To Hashimoto's Disease: Studies Of Eight Cases

Hashimoto's and Graves' diseases represent the main two types of autoimmune thyroid disease. The combination of these two is well known. However, occurrence of Graves' disease after primary hypothyroidism is rare. We report seven patients with hypothyroidism due to Hashimoto's disease, who developed Graves' disease with hyperthyroidism. We also report one patient with hypothyroidism due to Hashimoto's disease, who continued to be hypothyroid even in the presence of TSAb (thyroid stimulating antibody). These patients were divided into three groups according to the changes in thyroid function and clinical course: (1) transient hyperthyroidism due to Graves' disease following hypothyroidism; (2) persistent hyperthyroidism due to Graves' disease following hypothyroidism; and (3) persistent hypothyroidism with positive TSAb. Such changes in thyroid function and clinical course seem to be decided by three factors: (1) TSAb and (2) TSBAb (thyroid stimulation blocking antibody) activities in the blood and (3) the responsiveness of the thyroid gland to TSAb. Seven patients had hyperthyroidism, when they had TSAb, which stimulated the thyroid gland; one of these seven patients had TSBAb during the hypothyroid state and TSAb during the hyperthyroid state, indicating that the alterations in the thyroid state related to the balance between the activities of TSAB and TSBAb. Another patient continued to be hypothyroid despite the presence of TSAb; his thyroid gland was not palpable and could not respond to TSAb.

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.

Low Prevalence of Thyrotropin Receptor Antibody in Primary Hypothyroidism in Japan

The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH-binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients with goitrous Hashimoto's disease (group A) and 51 with primary atrophic hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%), TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in 7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity was low or moderate in group A, but strongly positive in group B. No relationship was apparent in either group between TBII or TSBAb activity and any clinical or laboratory parameter examined. Moreover, no clinical or laboratory findings distinguished patients with TRAb from those without. The low prevalence of TRAb in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive mechanisms may be more important in the pathogenesis of hypothyroidism in autoimmune thyroiditis.

Goitrous Hypothyroidism with Blocking or Stimulating Thyrotropin Binding Inhibitor Immunoglobulins

The significance of thyrotropin-binding inhibitor immunoglobulin (TBII) was evaluated in goitrous hypothyroidism associated with chronic thyroiditis (serum TSH greater than 10 mU/L, n = 148). TBII was measured by a RRA, and thyroid-stimulating antibody (TSab) and thyroid-stimulation-blocking antibody (TSBab) were determined using porcine thyroid cells. The prevalence of patients having TBII was 11% or 7.4% of 148 patients, which was not significantly different from that of 5% or 9.6% of 52 patients with atrophic thyroiditis. Although TBII was shown to be TSBab in 6, TSab was found in the other 5 patients despite hypothyroidism. There was little correlation between severity of hypothyroidism and TBII or TSBab activity. One patient continued to be latently hypothyroid despite apparently positive TSBab. Five other patients with TSBab and 2 patients with TSab suffered from overt, irreversible hypothyroidism, and 2 of the patients with TSBab continued to be hypothyroid even after the disappearance of TSBab. Biopsy of the thyroid gland performed in 4 patients revealed severely damaged thyroid follicles with mononuclear cell infiltration with or without fibrosis. Three of the patients with TSab had been taking excess iodine, and recovery of thyroid function was observed after iodine restriction. A perchlorate discharge test performed in two of these patients was positive, suggesting an iodide organification defect. These results indicate that, although TBII is not infrequently found in goitrous hypothyroidism, cellular or chemical damage of the thyroid gland plays an important role in the pathogenesis of thyroid hypofunction and TSBab may only have a precipitating role.

Thyroid Response, Especially to Thyrotropin-Binding Inhibitory Immunoglobulins, in Euthyroid Relatives of Patients with Graves' Disease: A Clinical Follow-Up

Three hundred and fifty-three euthyroid relatives of Graves' disease patients were tested for TSH binding inhibitory immunoglobulins (TBII). Eighteen had elevated levels of TBII, and 232 who had negative TBII levels also agreed to be followed for a period of 6-30 months. TBII was chosen as the critical screening measurement for this study, rather than thyroid-stimulating antibodies (TSAb) and thyroid-stimulating blocking antibodies (TSBAb), because of the availability and ease of use of TBII RIA kits. Eleven of the 18 subjects with elevated TBII were T3 nonsuppressible (group I), and 10 of the 11 were TRH unresponsive. Nine of these 10 subjects showed TSH levels below 0.05 mU/L. The remaining 7 subjects were T3 suppressible and TRH responsive (group II). Alterations in thyroid status occurred in 8 of the 11 subjects in group I during follow-up. One developed hypothyroidism, and 7 became hyperthyroid. The hypothyroid subject had initial titers of TBII, TSAb, and TSBAb that were markedly elevated, and TSAb disappeared when she became hypothyroid. Six of the 7 subjects who developed hyperthyroidism had elevated TSAb and negative TSBAb titers while they were euthyroid. All 7 subjects in group II remained euthyroid during the follow-up period. Only 2 of the 232 relatives who initially had negative TBII titers became hyperthyroid during the follow-up period. The results indicate that euthyroid relatives with a family history of Graves' disease who have elevated TBII levels and suppressed basal serum TSH concentrations have a much higher potential to develop hyperthyroidism than those who have normal or negative TBII levels.

Three Patients Who Spontaneously Developed Persistent Hypothyroidism During or Following Treatment With Antithyroid Drugs for Graves' Hyperthyroidism

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.

Disappearance of thyroid-stimulation blocking antibody by glucocorticoid therapy in a patient with primary myxedema who developed aortitis syndrome during L-thyroxine supplementation

A 39-year-old woman with primary myxedema, who had the potent activities of thyrotropin-binding inhibitory immunoglobulins (TBII) and thyroid-stimulation blocking antibodies (TSBAb), developed aortitis syndrome about 6 months after the initiation of L-thyroxine (L-T4) supplementation. A 35 mg daily dose of prednisolone for aortitis syndrome was initiated, and the dose was gradually reduced. TBII and TSBAb activities were gradually decreased, and both reached normal levels (7.7% and 10.1%, respectively) 3 months after the initiation of prednisolone. Therefore, dose of L-T4 was gradually reduced, and L-T4 supplementation was stopped. Subsequently, however, recurrence of hypothyroidism was not observed. These observations indicate the possibility that hypothyroidism remits with disappearance of TBII and TSBAb activities in not only neonatal cases but also adult cases.

Comparison of atrophic and goitrous auto-immune thyroiditis in children: Clinical, laboratory and TSH-receptor antibody studies

We studied the clinical features, laboratory and thyroid functions and thyrotropin (TSH)-receptor and thyroid-stimulation antibodies in 21 patients with atrophic auto-immune thyroiditis (AAT) and 48 patients with goitrous auto-immune thyroiditis (GAT) of childhood onset. The clinical features of patient with AAT were cessation of growth and obesity, while asymptomatic enlargement of the thyroid gland was the sole symptom in most patients with GAT. Although the ages at diagnosis were comparable in both groups, the estimated ages at onset were much lower in patients with AAT than in those with GAT. Patients with AAT exhibited more severe hypothyroidism when evaluated by serum thyroxine (T4), tri-iodothyronine (T3), TSH, cholesterol levels and basal metabolic rates. The 24 h 123I-thyroidal uptake was significantly lower in patients with AAT than in those with GAT. None of the 19 patients with AAT possessed TSH-binding inhibitor immunoglobulins (TBII). On the other hand, 3 of the 32 GAT patients tested, possessed weak to potent TBII activities. Three TBII-positive patients with GAT also possessed thyroid-stimulation blocking antibodies. These findings suggest that: 1. Pathogenesis of AAT in children whose onset of hypothyroidism was before puberty is not due to TSH-receptor blocking antibodies, which are often found in patients with AAT of postpubertal onset. 2. AAT in children is considered not to be due to the later stage of GAT. 3. Some patients with GAT possessed TSH-receptor blocking antibodies. The aetiology and pathogenesis of AAT in children have yet to be elucidated.

Thyroid-stimulating antibody and thyrotropin-binding inhibitory immunoglobulin activity in hypothyroid patients who subsequently developed thyrotoxicosis

Although abnormal thyroid-stimulating and -blocking antibodies have been demonstrated in hyperthyroid and hypothyroid patients with autoimmune thyroid disorders, a direct correlation is not always observed. Thyroid-stimulating antibody, thyrotropin-binding inhibitory immunoglobulin, and thyroid-stimulating blocking antibody levels were determined in three hypothyroid patients who subsequently developed hyperthyroidism. Thyroid-stimulating antibodies levels were normal in one, elevated in another, and unmeasured in the third hypothyroid patient, but became elevated in all patients with the onset of hyperthyroidism. There was discordance, however, in one patient who had markedly elevated thyroid-stimulating antibodies and TSH-binding inhibitory immunoglobulin levels when she was hypothyroid. The data indicate that thyroidal responses to the abnormal stimulating antibodies may differ among patients with autoimmune thyroid disease.

Chronic Thyroiditis with Painful Tender Thyroid Enlargement and Transient Thyrotoxicosis

Clinical and laboratory findings and long term outcome (1.5-9 yr) in 7 women and 1 man with chronic thyroiditis (CT) who had painful tender thyroid enlargement were evaluated and compared with those in 11 women with subacute thyroiditis (SAT). Histological features consistent with SAT were not demonstrable, and various forms of CT (fibrous variant, diffuse, or focal lymphocytic thyroiditis) were observed. There were no differences in mean age, duration of symptoms, erythrocyte sedimentation rate, and C-reactive protein values in the 2 diseases. Seven patients had a history of goiter, and none had a history of a preceding upper respiratory tract infection. The mean white blood cell count was significantly lower in CT than in SAT patients. Six CT patients had transient thyrotoxicosis with a marked depression of radioactive iodine uptake. Mean serum T4 and T3 levels and T3 to T4 ratio in these 6 patients did not differ from those in the SAT patients. Five (all with high antimicrosomal antibody titers) of 8 CT patients developed persistent hypothyroidism. In contrast, none of the SAT patients became permanently hypothyroid. TSH binding inhibitory immunoglobulins and thyroid stimulation-blocking antibody at recent examination were negative in these 5 patients. Patients with this disorder present with transient thyrotoxicosis, with a marked depression of the thyroid radioactive iodine uptake, and often develop goitrous or atropic persistent hypothyroidism. This disorder may represent acute exacerbation of an underlying immunological process during the course of CT. To differentiate this syndrome from SAT, thyroid biopsy is necessary.

PRESENCE OF BOTH STIMULATING AND BLOCKING TYPES OF TSH‐RECEPTOR ANTIBODIES IN SERA FROM THREE PATIENTS WITH PRIMARY HYPOTHYROIDISM

A case report of three patients with primary hypothyroidism who had potent TSH-binding inhibitor immunoglobulins (TBII) and both thyroid stimulating (TSAb) and thyroid stimulation-blocking antibodies (TSBAb) has been described. Two patients displayed symptoms and signs indistinguishable from those in primary myxoedema (cases 1 and 2), and another patient had a history of Graves' disease (case 3). TBII, TSAb and TSBAb activities were 90.0, 1084.2 and 94.5% in case 1, 91.5, 826.6 and 95.8% in case 2, 76.0, 230.0 and 95.0% in case 3, respectively (normal range, less than 11.0%, less than 145.0 and less than 22.0%, respectively. The results indicate that both stimulating and blocking types of TSH-receptor antibodies exist in these patients. The possible mechanism whereby hypothyroidism developed has been discussed.

Changes in the Properties of the Thyrotropin Receptor Antibody in Patients with Graves` Disease after Radioiodine Treatment

We investigated the effect of a single dose of 131I upon thyrotropin receptor antibodies (TRAb) in 21 patients with Graves’ disease. The thyrotropin receptor antibodies were assessed by parallel measurements of thyrotropin binding inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation in FRTL-5 cells, respectively. Prior to radioiodine treatment, TBII was detected in all 21 patients and TSAb in 19 patients. After radioiodine treatment, TBII activities did not change during the 12-months observation period, but in eight patients TSAb activities gradually decreased and were undetectable at the end of the 12-month observation period. Persistence of TSAb was not associated with the clinical outcome. Eight patients developed hypothyroidism within one year after radioiodine treatment. Three of the hypothyroid patients developed TSBAb, and the appearance of TSBAb coincided with the development of hypothyroidism. These results suggest that TSBAb might develop after radioiodine treatment in a minority of patients with Graves’ disease and that the appearance of TSBAb, in addition to radiation-induced thyroid destruction, might be involved in the development of hypothyroidism following radioiodine treatment.

Transient Hypothyroidism in Infants Born to Mothers with Chronic Thyroiditis-A Nationwide Study of Twenty-three Cases.

To define the difference in prognosis and the clinical features of transient neonatal hypothyroidism in infants born to mothers with chronic thyroiditis, we conducted a nationwide study of this condition. Sixteen mothers with chronic thyroiditis and twenty-three of their offspring with transient hypothyroidism were registered and reported in this paper. Five (group A) of twenty-two live infants showed physical, mental and/or psychomotor developmental delay (IQ below 80). No significant difference between TSH-binding inhibitor immunoglobulin (TBII) or thyroid-stimulation blocking antibody (TSBAb) activities in groups A and B (normal development) were noted. Moreover, there was no significant difference in thyroid function in the newborn period, ages at the start of thyroid medication or the dose and duration of treatment in the two groups. A striking difference observed between the two groups was the thyroid function of their mothers during pregnancy. In group A, four mothers were hypothyroid during pregnancy, and another mother discontinued thyroid medication in the last trimester and her baby was most delayed at the start thyroid medication. On the other hand, the mothers of only two of seventeen live cases in group B had mild hypothyroidism during pregnancy. There were two sets of siblings whose mother received inadequate treatment during the first pregnancy and adequate treatment during the second pregnancy. The psychomotor, physical and mental developmental delay were observed in their first babies. These findings suggested that maternal thyroid function during pregnancy might be an important factor in the prognosis of infants born to mothers with chronic thyroiditis.

Silent thyroiditis with thyroid-stimulation-blocking antibodies(TSBAb).

A 24-year-old man showed thyrotoxic symptoms with hypokalemic periodic paralysis. Serum thyroid hormone levels were high and thyrotropin (TSH) was undetectable. 123I-thyroidal uptake was suppressed. TSH-binding inhibitor immunoglobulin (TBII) was positive. After a month without any treatment, he became hypothyroid. Thyroid hormone level was decreased and TSH was increased to above the normal range. 123I-thyroidal uptake was increased. TBII activity was still positive. From the clinical findings, a diagnosis of silent thyroiditis was made. Sera obtained in the hypothyroid state revealed the presence of thyroid-stimulation-blocking antibodies (TSBAb), but there were no thyroid-stimulating antibodies (TSAb). These results suggest that the hypothyroidism in this patient was due to the presence of TSBAb with TBII activity.

Pathogenetic role of thyrotropin receptor antibody in the development of hyperthyroidism following primary hypothyroidism.

The authors measured thyrotropin binding inhibitory immunoglobulin (TBII), thyroid stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) sequentially in patients who developed hyperthyroidism following primary hypothyroidism, and compared changes in these various funcional parameters of thyrotropin receptor antibody (TRAb) with clinical manifestations, in order to investigate the role of TRAb in the development of hyperthyroidism following primary hypothyroidism.In a patient with goitrous chronic thyroiditis, TBII, TSAb and TSBAb were not detected at the initial hypothyroid phase. But with appearance of TBII and TSAb, the patient developed hyperthyroidism. In a patient with primary nongoitrous myxedema, initially high TBII and TSBAb were detected without TSAb activity. His TSBAb disappeared and TSAb appeared with development of goiter growth and hyperthyroidism.These two mechanisms, that is, appearance of previously absent TSAb and conversion of TSBAb to TSAb, might play a causative role in the development of hyperthyroidism following primary hypothyroidism. These phenomena might be evidence that Graves’ disease, chronic thyroiditis, and primary nongoitrous myxedema are on a continuing spectrum of a common syndrome sharing similar pathophysiology, at least with respect to TRAb.

Role of blocking TSH receptor antibodies on the development of hypothyroidism and thyroid atrophy in primary myxedema.

We studied blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto’s thyroiditis by measuring the ability of their IgG to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto’s thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These antibodies inhibited the receptor binding of 125I-bTSH dose-dependently, and also inhibited dose-dependently not only TSH-stimulated but also Graves’ IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary myxedema were significantly correlated with both their TSBAb (r=0.665; p<0.01) and TGBAb (r=0.618; p<0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong TSBAb (75.1–100%) and TGBAb (57.4–100%) activities. Transient neonatal hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby’s IgG inhibited TSH-stimulated cAMP increase and 3H-thymidine incorporation.These data suggest that a significant proportion of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibition of TSH-stimulated cAMP generation.

Significance of circulating anti-thyroid stimulating hormone (TSH) receptor antibodies in patients with autoimmune thyroid diseases--thyroid stimulation blocking antibody in patients with Graves' disease

It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease.

Activity of Thyroid Stimulating Antibody and Thyroid Stimulation Blocking Antibody Determined by Radioiodine Uptake into FRTL-5 Cells.

To investigate the pathophysiology of patients with autoimmune thyroid diseases, we measured serum thyroid stimulating antibody (TSAb) activity and thyroid stimulation blocking antibody (TSBAb) activity by determining the radioiodine (125I) uptake into FRTL-5 cells. FRTL-5 cells were pre-incubated for seven days with 5H medium and then incubated for 48 hours with patients' crude IgG prepared by polyethylene glycol precipitation. In order to measure TSBAb, 10 microU/ml TSH was also added. 125I was added one hour before the end of the 48 hour incubation period. After the incubation, the medium was aspirated, and the radioactivity in the cells was counted. In patients with untreated hyperthyroid Graves' disease, TSAb was detectable in 18 of 20 patients, the detectability being 90%, and activity showed a statistically significant positive correlation with TSAb activity determined by c-AMP accumulation. Out of 41 patients with hypothyroidism, TSBAb determined by 125I uptake was positive in six cases, the detectability being 14.6%. The inhibition of 125I uptake by one of these six IgGs was suggested to be at the TSH receptor level because it inhibited TSH induced c-AMP accumulation and showed positive thyrotropin binding inhibitor immunoglobulin (TBI I) activity, but did not inhibit the forskolin- and (Bu)2cAMP-induced 125I uptake. Inhibition of another IgG was suggested at the post-receptor level because it did not inhibit TSH induced cAMP accumulation and showed negative TBI I activity, but inhibited forskolin- and (Bu)2cAMP-induced 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Coexistence of thyroid-stimulating and thyroid-blocking antibodies in a patient with graves' disease who had transient hypothyroidism

T hyrotropin (TSH)-binding inhibitor immunoglobulins (TBIIs), detected by the ability of patients’ immunoglobulins to inhibit the binding of radiolabeled TSH to its receptor, were first demonstrated in patients with Graves’ disease [l-3] and later in some patients with primary myxoedema of Hashimoto’s disease [4]. The TBIIs include antibodies against the TSH receptor, which stimulate thyroid function or block TSH-induced thyroid stimulation. Thyroid-stimulating antibodies (TSAb), measured as biologic activities to stimulate the thyroid, are considered to be the major cause of hyperthyroidism in Graves’ disease [5-81. Thyroid-stimulation-blocking antibodies (TSBAb), measured by inhibition of TSHinduced CAMP increase, may play a pathogenic role in some patients with primary myxoedema [9]. Herein we report the coexistence of TSAb and TSBAb in a patient with Graves’ disease in whom hypothyroidism developed shortly after antithyroid drug treatment and who experienced a relapse during L-thyroxine replacement therapy.