Long-term effects of radioiodine on thyrotrophin receptor antibodies in Graves' disease.

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.

Inhibition of placental thyroxine 5-deiodinase activity decreases amniotic fluid concentration of 3,3',5'-triiodothyronine in rat.

We investigated whether the inhibition of placental T4 5-deiodinase (5-D) activity would decrease the amniotic fluid (AF) concentration of rT3. Iopanoic acid (IOP) was used to inhibit placental T4 5-D activity. From gestation days 14 to 17, a group of rats received IOP (10 mg/100 g bw/day, sc) once daily in experiment (exp) 1, and received it (40 mg/100 g bw/day) four times daily in exp 2. In exp 2, control dams received propylthiouracil (PTU; 2 mg/100 g bw/day) instead of IOP. Methimazole and T4 were also given to all dams in exp 1 and 2. On day 17 of gestation, we collected the liver, placenta, blood, and AF of each animal. In the IOP-treated group in both experiments, the serum T4 concentration was significantly increased. Hepatic T4 5'-deiodinase activity was significantly decreased by either PTU or IOP administration. In both experiments placental T4 5-D activity was significantly decreased in the IOP-treated group. The concentration of rT3 in AF was significantly decreased in the IOP-treated group in exp 2 (1.71 vs. 0.75 nmol/l, P < 0.01) despite a higher serum T4 concentration. There was a significant positive correlation between placental T4 5-D activity and the concentration of rT3 in AF in exp 2 (r = 0.62, P < 0.05). These observations indicate that the inhibition of placental T4 5-D activity decreases the concentration of rT3 in rat AF, and that placental T4 5-D and the T4 concentration in maternal serum plays important roles in maintaining the concentration of rT3 in rat AF.

Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment.

Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of atrial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T4 and T3 decreased to hypothyroid levels in 3.2 +/- 1.3 months, and one month later all patients had their sinus rhythm restored while T4 and T3 remained below normal (2.6 +/- 1.1 micrograms/dl and 77.9 +/- 34.4 ng/dl, respectively). Although T4 and T3 also decreased within 3.5 +/- 1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T4 and T3 (10.4 +/- 5.3 micrograms/dl and 157.7 +/- 67.5 ng/dl, respectively) rose significantly compared to those in group I (P less than 0.001 and P less than 0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month.

Clinical utility of red blood cell carbonic anhydrase I and zinc concentrations in patients with thyroid diseases.

We have recently reported that, in patients with hyperthyroidism, the red blood cell (RBC) carbonic anhydrase I (CAI) and zinc (Zn) concentrations both reflect the patient's integrated thyroid hormone level over the preceding few months. In this study, we evaluated the clinical usefulness of determining the RBC CAI and Zn concentrations in patients with various types of thyroid disease. Six patients with painless thyroiditis (PT) had normal RBC CAI concentrations and the two patients tested had normal RBC Zn levels. In four patients with syndromes of inappropriate thyrotropin (TSH) secretion (SITSH) two euthyroid patients had normal RBC CAI and two hyperthyroid patients had subnormal RBC CAI and Zn. In a patient with Graves' disease whose plasma thyroxine (T4) and triiodothyronine (T3) concentrations changed remarkably because of poor compliance with the regimen, the change in plasma thyroid hormone levels preceded the change in the RBC CAI and Zn concentrations by 2 to 3 months. These observations suggest that the measurement of RBC CAI and Zn concentrations may be useful clinically as follows: (1) in differentiating hyperthyroid Graves' disease from transient hyperthyroidism due to destructive thyroiditis; and (2) in obtaining an accurate estimate of the extent of elevated thyroid hormone levels in hyperthyroid patients over time.

Thyrotropin receptor antibody activities significantly correlate with the outcome of radioiodine (131I) therapy for hyperthyroid Graves' disease.

The outcome of 131I therapy for 109 patients with Graves' disease was analysed according to pretreatment laboratory data including thyrotropin receptor antibody (TRAb) activities. Forty-five percent of patients became euthyroid, and 13% of patients became hypothyroid within one year after 131I therapy. Forty-two percent of patients remained hyperthyroid one year after 131I therapy. Pretreatment values for serum T4, T3, and the estimated weight of the thyroid were significantly higher in the hyperthyroid group. The mean for the TRAb index of the hyperthyroid group was significantly higher than that of the euthyroid group. Life table analysis revealed a significant effect of the TRAb index on the rate of hyperthyroidism after 3 months or later. These results appear to suggest that the TRAb index is one of the factors which influence the outcome of 131I therapy for Graves' disease.

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.

Erythrocyte carbonic anhydrase-I concentrations in patients with Graves' disease and subacute thyroiditis reflect integrated thyroid hormone levels over the previous few months.

We have recently reported that in patients with hyperthyroidism, red blood cell (RBC) zinc (Zn), most of which is present as the metal of carbonic anhydrase-I isozyme (CAI), reflects a patient's integrated thyroid hormone level over the previous few months. In the present report the RBC CAI concentration was measured by RIA in 26 healthy controls, 25 patients with hyperthyroid Graves' disease, 5 patients with primary hypothyroidism, and 10 subjects with subacute thyroiditis with elevated thyroid hormone levels. The mean (+/- SD) RBC CAI concentration in euthyroid controls was 380 +/- 70 nmol/g hemoglobin (Hb), and the normal range defined as the mean +/- 2 SD, was 240-520 nmol/g Hb. The mean RBC CAI in Graves' disease was decreased (180 +/- 53 nmol/g Hb), and 22 patients (88%) had subnormal values. The mean RBC CAI concentrations in hypothyroidism and subacute thyroiditis were not different from the control values. After treatment with antithyroid drugs, both mean the plasma T4 and T3 levels in 11 Graves' patients became normal within 4 weeks, but the normalization of RBC CAI lagged behind by about 2 months. Furthermore, the highest correlation was observed between the RBC CAI and plasma T4 and T3 levels measured 8 weeks earlier. During prednisolone therapy the RBC CAI in patients with subacute thyroiditis remained at a normal level. These results suggest that 1) not only RBC Zn but also the RBC CAI concentration in patients with Graves' disease reflect the patient's mean thyroid hormone level over the preceding several months; and 2) in patients with subacute thyroiditis, elevation of plasma thyroid hormone concentrations is transient and causes little change in the RBC CAI concentration.

Thyroxine 5'-deiodinase in human anterior pituitary tumors.

The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

A case of thyrotropin (TSH)-secreting tumor complicated by periodic paralysis.

A 27-year-old man had symptoms of hyperthyroidism and periodic paralysis. While hyperthyroid, his serum thyrotropin (TSH) level was inappropriately elevated at 6.4 microU/ml. The serum alpha subunit level was also elevated. MR imaging revealed a pituitary tumor and transsphenoidal adenomectomy was performed. Immunocytochemistry with an antibody directed against the beta-subunit of TSH revealed a TSH-secreting tumor. This is the first case of hyperthyroidism due to a TSH-secreting pituitary tumor complicated by periodic paralysis. This association indicates that thyrotoxicosis may induce paralysis in susceptible persons by a mechanism which is not autoimmune.

The influence of immunosuppressive acidic protein on the activity of peripheral K-lymphocytes in subacute thyroiditis.

We previously reported that immunosuppressive acidic protein (IAP), an alpha 1-acid glycoprotein, is increased during the acute phase of subacute thyroiditis (SAT). In this study we measured the percentage and absolute number of peripheral K-cells using a plaque-forming cell technique to investigate immunological abnormalities associated with SAT. Additionally, we investigated the relationship between IAP and peripheral K-cell activity. In normal controls, a sex-related difference in the percentage of K-cells among total lymphocytes was present; the percentage was significantly lower in women (mean +/- SD, 5.0 +/- 2.0%; n = 12; P less than 0.01) than in men (8.4 +/- 2.9%; n = 13). However, there was no difference (0.153 +/- 0.073 x 10(9)/L in five females; 0.173 +/- 0.054 x 10(9)/L in seven males) in the absolute number of peripheral K-cells. During the acute phase of SAT, the percentage (2.4 +/- 1.9% in 16 females; 2.7 +/- 1.0% in 3 males) and absolute number (0.058 +/- 0.048 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls. These values returned to normal during the recovery phase, although their mean values were still lower than those in normal controls. In female patients with Graves' disease, the percentage (2.2 +/- 1.8% in 11 females) and absolute number (0.038 +/- 0.033 x 10(9)/L in 11 females) of K-cells were significantly lower than those in normal controls; in male patients, the percentage (4.2 +/- 2.7% in 5 males) was lower than that in normal controls, but the absolute number (0.136 +/- 0.114 x 10(9)/L) of K-cells was not significantly different. Serum IAP values during the acute phase of SAT showed a significant negative correlation with the percentage of K-cells (r = -0.66; P less than 0.01). The number of K-cells from a normal subject decreased significantly when these lymphocytes were incubated with sera from patients with SAT, and the mean inhibition rate of K-cells by serum samples from 13 SAT patients during the acute phase was higher than that during the recovery phase (68.0 +/- 21.0 vs. 38.0 +/- 23.0%; P less than 0.01). Purified IAP inhibited the activity of K-cells from normal subjects dose dependently. These results suggest that 1) there may be inhibitory factors for the antibody-dependent cell-mediated cytotoxicity of peripheral K-cells in the serum of patients with SAT, and 2) IAP may be one of these inhibitory factors.

Thyroid function in patients with myotonic dystrophy.

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean +/- SD) of T4 (114.7 +/- 26.8 vs 129.9 +/- 28.3 nmol/l), FT4 (16.6 +/- 4.5 vs 18.4 +/- 3.8 pmol/l), T3 (1.61 +/- 0.29 vs 1.86 +/- 0.33 pmol/l), TSH (2.7 +/- 1.3 vs 2.4 +/- 1.4 mU/l), TBG (26.7 +/- 5.5 vs 27.6 +/- 4.9 mg/l), T4/T3 (84.3 +/- 18.4 vs 82.1 +/- 15.3), and FT4/FT3 (0.28 +/- 0.05 vs 0.33 +/- 0.08). Serum FT3 (4.3 +/- 1.4 pmol/l) in patients were significantly lower than those (5.3 +/- 0.9 pmol/l) in normal controls (P less than 0.02). Thyroidal 131I-uptakes (8.7 +/- 4.3%) in patients were significantly lower than those (25.8 +/- 7.4%) in controls (P less than 0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4 +/- 4.5 vs 17.0 +/- 6.2 mU/l; P less than 0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.

Erythrocyte zinc concentration in patients with subacute thyroiditis.

We have recently reported that red blood cell (RBC) zinc (Zn) in patients with hyperthyroidism reflects a patient's integrated thyroid hormone level over the previous few months. In the present paper RBC Zn concentrations were measured in 10 patients with subacute thyroiditis whose total plasma T4 and T3 levels were elevated. The values were compared with those obtained in 10 patients with untreated Graves' disease, whose plasma T4 concentrations were elevated to the same level as in the former group. The RBC Zn concentration was normal in 9 of 10 patients with subacute thyroiditis, but was depressed in all patients with Graves' disease. The mean (+/- SE) RBC Zn in patients with subacute thyroiditis was 162 +/- 9 mumol/L, significantly (P less than 0.001) higher than that in Graves' disease (87 +/- 5 mumol/L). During prednisolone treatment the RBC Zn in patients with subacute thyroiditis remained at the normal level and did not change significantly, although it was slightly decreased at 2 and 4 weeks of treatment. On the other hand, the RBC Zn in patients with Graves' disease was significantly increased at 8 weeks of treatment and reached the normal range in 12 weeks. These results suggest that elevation of plasma thyroid hormone concentrations in patients with subacute thyroiditis is transient and does not cause any significant change in the RBC Zn concentration.

Erythrocyte zinc in hyperthyroidism: reflection of integrated thyroid hormone levels over the previous few months.

Red blood cell (RBC) zinc (Zn) concentration was measured by atomic absorption spectrophotometry in 28 healthy volunteers, in 46 patients with hyperthyroidism, and in 6 patients with hypothyroidism. The mean (+/- SD) RBC Zn concentration in euthyroid controls was 11.4 +/- 1.5 mg/L RBC, and the normal range defined as the mean +/- 2 SD was 8.5 to 14.3 mg/L RBC. The mean RBC Zn in patients with hyperthyroidism was decreased to 6.4 +/- 1.6 mg/L RBC, and 43 (93%) had low values. The mean RBC Zn in patients with hypothyroidism was not different from that in the controls. There was a significant negative correlation between the concentrations of RBC Zn and those of both plasma thyroxine (T4; r = -0.73) and plasma 3,5,3'-triiodothyronine (T3; r = -0.70). After the treatment of 17 hyperthyroid patients with antithyroid drugs, both mean plasma T4 and T3 levels became normal within 4 weeks, but the normalization of RBC Zn lagged about 2 months behind them. The RBC Zn levels significantly correlated with both the plasma T4 and T3 levels obtained 0, 4, 8, and 12 weeks prior to the RBC sampling, and the highest correlation was observed between the RBC Zn levels and plasma T4 and T3 levels measured 8 weeks previously. These data suggest that RBC Zn concentration in hyperthyroid patients reflects a patient's mean thyroid hormone level over the preceding several months as glycosylated hemoglobin level does in diabetic patients.

Relationship between serum free thyroid hormone concentrations and target organ responsiveness in thyroid disease patients before and after treatment.

Relationship between serum free thyroid hormone concentrations and several markers of peripheral tissue response to thyroid status was studied in 24 patients with hyperthyroidism, 17 with euthyroidism with goiter and 10 with primary hypothyroidism before and after the initiation of standard forms of treatment. Before treatment, serum free T4 correlated significantly, either positively or negatively, with the basal metabolic rate (BMR), duration of the achilles tendon reflex (ATR), resting pulse rate (RPR), serum total cholesterol (T-cholesterol), ratio of the pre-ejection period to the left ventricular ejection time (PEP/LVET), serum high density lipoprotein (HDL) and creatine phosphokinase (CPK) in the descending order. Serum free T3 also correlated significantly all the these parameters. After treatment, changes in both serum free T4 and free T3 correlated well with those of the BMR and ATR in the patients with hyperthyroidism, and with those of the ATR, serum CPK and T-cholesterol in the patients with hypothyroidism. These results indicate that these peripheral parameters correlated well with serum free thyroid hormone concentrations in thyroid disease patients. Therefore, these parameters can be used to assess thyroid functions in patients with thyroid hormone resistance.

A case of refetoff syndrome: selective venous sampling for TSH is useful in differentiating thyroid hormone resistance from TSH secreting tumor.

A 22-year old man with a goiter and clinical manifestations of mild thyrotoxicosis (finger tremor, palpitation, tachycardia) was diagnosed as a syndrome of inappropriate secretion of TSH. Serum concentrations of T4, free T4, T3 and TSH were 24.1 micrograms/100 ml, 4.07 ng/100 ml, 261 ng/100 ml and 1.72 microU/ml, respectively. Thyroidal 131I uptake at 24 hr was 80%. The BMR was within the normal range. He had a normal TSH response to TRH (500 micrograms) with a peak level of 23.8 microU/ml. The basal level of alpha-subunit of TSH was not elevated (0.35 ng/ml). Oral 1-T3 administration (75 and 150 micrograms daily) raised serum T3 concentration, reduced basal TSH and blunted TSH response to TRH. The diurnal variation of TSH was maintained. There was no evidence of abnormalities in the secretion of other pituitary hormones. These findings were compatible with thyroid hormone resistance. However, the presence of a microadenoma in the pituitary gland was suspected with CT scan. Bilateral and simultaneous venous sampling for TSH from inferior petrosal sinus showed no gradient in TSH concentration indicating that a TSH secreting pituitary tumor was unlikely. These data suggest that inappropriate TSH secretion in the present patient is resulted from resistance to thyroid hormone. In the present study selective venous sampling is useful to differentiate the thyroid hormone resistance from a TSH secreting tumor.

Recurrence of subacute thyroiditis over 10 years after the first attack in three cases.

We saw a total of 4 episodes of the recurrence of subacute thyroiditis in 3 patients out of 222. The recurrent episodes were similar to the first episodes of subacute thyroiditis. The titers of various viral antibodies were not increased significantly during the clinical course of the recurrence. Regarding the HLA typing, A26, B35 and C3 were positive in all 3 patients. The association between the occurrence of subacute thyroiditis and the presence of HLA-B35 and C3 has hitherto been reported, although the association of HLA-A26 with recurrent type of subacute thyroiditis was observed and described for the first time in this report. It is suggested that HLA-A26 may somehow be related to the predisposition to the recurrence of subacute thyroiditis which developed after more than 10 years.

Measurement of thyroid stimulating hormone (TSH) in human urine.

Using a highly sensitive and specific immunoradiometric assay kit for human TSH, we measured TSH concentrations in unprocessed urines in normal subjects, in patients with primary hypothyroidism, and patients with renal disease. In five of ten normal subjects TSH was detectable in urine samples (less than 20-69 microU/day). In five patients with hypothyroidism, the urinary TSH excretion was increased. In seven out of ten patients with nephrotic syndrome, eight out of nine patients with chronic renal failure and two patients with tubular dysfunction, the urinary TSH excretion was increased. The urinary TSH excretion correlated significantly with both urinary protein excretion and urinary beta 2-microglobulin excretion. These results suggest that the renal handling of TSH involves both glomerular filtration and tubular re-absorption, and that urinary TSH excretion is increased when serum TSH is increased and either glomerular or tubular function is impaired.

Properties of thyrotropin (TSH) binding to plasma membranes prepared from rat fat tissues.

Rat fat membranes were prepared from male Sprague-Dawley rats. At 37 degrees C, TSH binding to rat fat membranes was rapid and unstable, although the binding reached a steady state after 2 hr and unchanged up to 24 hr at 4 degrees C. The binding to rat fat membranes was significantly inhibited by 50 mM NaCl and almost completely inhibited by 150 mM NaCl. TSH binding to rat fat membranes was not affected by 10 mM dithiothreitol (DTT) or 1 mM diamide although the binding to human thyroid membranes was inhibited by 10 mM DTT significantly. Conventional Scatchard analysis revealed a single class of binding site which had lower Ka value (2.6 X 10(8) M-1) than that of high affinity binding site of human thyroid membranes (9.3 X 10(8) M-1). Immunoglobulin G (IgG) from patients with Graves' disease inhibited the binding of TSH to rat fat membranes. A significant correlation was observed between the inhibiting activity of Graves' IgG measured with rat fat and human thyroid membranes (r = 0.82, p less than 0.01). In conclusion, TSH receptors on rat fat membranes were not identical to those on human thyroid membranes, but TSH receptor antibodies crossreacted with TSH receptors in rat fat tissue.

Effect of prednisolone and salicylate on serum thyroglobulin level in patients with subacute thyroiditis.

Twelve patients with subacute thyroiditis were divided into two groups and treated with prednisolone or salicylate. The initially elevated T4, T3, free T4 (FT4), free T3 (FT3) and erythrocyte sedimentation rate (ESR) were reduced during the early phase within about 4 weeks in both groups. The serum levels of thyroglobulin (Tg) were elevated in both groups treated with salicylate and prednisolone (252 +/- SD 117 ng/ml and 233 +/- SD 157 ng/ml, respectively) at initial examination. The serum level of Tg declined during the early phase with prednisolone treatment, and it reached normal values at the end of the early phase (17 +/- SD 15 ng/ml). With salicylate treatment, the decline of levels of Tg was delayed and it was elevated (80 +/- SD 34 ng/ml) despite normal levels of thyroid hormones and ESR at the end of early phase. The serum level of Tg at the end of the early phase of prednisolone treated was significantly lower than that of salicylate treatment (P less than 0.01). It is suggested that the effect of prednisolone on rapid decrease of Tg may be related to its inhibitory action of intrathyroid hydrolysis.

Characteristics of anti-TSH receptor antibodies in two patients who developed spontaneous hypothyroidism after antithyroid drug therapy for hyperthyroid Graves' disease.

Spontaneous hypothyroidism was developed in two patients with Graves' hyperthyroidism 1.8 or 1 years after antithyroid drug therapy. In these patients anti-thyrotropin (TSH) receptor antibodies were detected. Thyrotropin receptor antibody (TRAb) index measured with TSH radioreceptor assay was 61.0% in case 1 and 68.0% in case 2 (normal value: -10 to 10%), and human thyroid adenylate cyclase stimulating activities (HTACS) were 154% in case 1 and 190% in case 2 (normal value: 70 to 130%). IgG from case 1 suppressed the stimulating activity of bovine TSH (bTSH) on thyroid adenylate cyclase in low concentrations in vitro. These results indicate that a blocking type of anti-TSH receptor antibodies as well as concomitant chronic thyroiditis might be a causative factor in patients who developed spontaneous hypothyroidism shortly after the cessation of antithyroid drugs.