Nobuko Kaise

Role of thyroid-stimulating blocking antibody in patients who developed hypothyroidism within one year after 131I treatment for Graves' disease.

We recently reported that thyroid‐stimulating blocking antibody (TSBAb) may not contribute to the development of hypothyroidism more than six years after 131I treatment. In the present study, we attempted to determine whether hypothyroidism that develops within a shorter period of time following 131I therapy is associated with TSBAb.

Relationship between thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins years after administration of radioiodine for Graves’ disease: retrospective clinical survey

Thyroid-stimulating antibody (TSAb) activity and the TSH-binding inhibitory immunoglobulin (TBII) index were assessed in 158 patients with Graves’ disease who had been treated with 131I 6–14 years earlier. Twenty-one patients (13%) were still hyperthyroid, 45 (28%) were euthyroid, 44 (28%) were subclinically hypothyroid, and 48 (30%) were overtly hypothyroid. Positive results were obtained in 10 (48%) of the 21 patients with hyperthyroidism for both TSAb and TBII assays, and in 3 patients (14%) in one of the assays. In contrast, only two (5%) patients with subclinical hypothyroidism and 1 (2%) patient with overt hypothyroidism tested positive in both assays, and 11 (25%) subclinically hypothyroid patients and 15 (31%) overtly hypothyroid patients tested positive in one of the assays. The correlation coefficients between TSAb and TBII were 0.88 (p<0.01) in hyperthyroid patients, 0.49 (p<0.01) in euthyroid patients, 0.34 (p<0.05) in subclinically hypothyroid patients, and 0.12 (p>0.05) in patients with overt hypothyroidism. Findings indicate the presence of long-term changes in the population of TSH receptor antibodies years after 131I treatment, which may influence thyroid function.

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<0.02). Thyroidal131 I‐uptakes (8.7±4.3%) in patients were significantly lower than those (25.8±7.4%) in controls (P<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<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.

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<001). It is suggested that the effect of prednisolone on rapid decrease of Tg may be related to its inhibitory action of intrathyroid hydrolysis.

Artifactually Elevated Serum-Free Thyroxine Levels Measured by Equilibrium Dialysis in a Pregnant Woman with Familial Dysalbuminemic Hyperthyroxinemia

Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including equilibrium dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T4 binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT4 determined by equilibrium dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.

Thyroid peroxidase activity in euthyroid and mild hypothyroid patients with Hashimoto's thyroiditis

Thyroid peroxidase (TPO) activity was measured spectrophotometrically according to Hosoyas guaiacol method. The mean TPO activity in ten patients with Hashimotos thyroiditis was 19.8 +/- 7.6 (mean +/- SE) in an arbitrary unit, which was not significantly different from the normal value in seven normal thyroid tissues (33.7 +/- 5.4). The ten patients were divided into two groups, euthyroid and mild hypothyroid, on the basis of their basal serum TSH. In the euthyroid group, TPO activity (8.17 +/- 1.3) was significantly less than the normal tissue (p less than 0.01). In the hypothyroid group, TPO activity (27.64 +/- 13.8) was almost similar to the normal tissue. A positive correlation was obtained between TPO activity and serum TSH in ten patients with Hashimotos thyroiditis (r = 0.85, p less than 0.01). It was concluded that TPO activity is significantly decreased in Hashimotos thyroiditis even when the thyroid function was still within normal range, but the activity might be restored to normal in hypothyroid patients by the stimulation of elevated TSH.

The Monodeiodination of Thyroxine to 3, 3^|^prime;, 5^|^prime;-Triiodothyronine in the Human Placenta

We investigated the characteristics of the monodeiodination of thyroxine to T3 and rT3 in human placentas which were obtained at normal delivery. The placentas were homogenized in a cold sucrose Tris-HCl buffer, pH 7.5. The microsomal fraction was incubated at 37 degrees C in air for 1 hr with 2 micrograms of T4 in the presence of 50mM DTT. The T3 and rT3 generated in the reaction mixture were extracted into cold ethanol and measured by RIA. Among the usal subcellular fractions of the placental homogenate, microsomes were the most potent in deiodinating T4 to rT3. In microsomes, production of rT3 increased with protein concentration, incubation temperature up to 37 degrees C, incubation time up to 120 min and T4 concentration up to 16 micrograms/tube. The production of rT3 from T4 was lost by prior heating of the microsomal fraction to 56 degrees C for 30 min. The net production rate of T4 to rT3 in the microsomal fraction was 17.9 ng/mg protein/micrograms T4/60 min at pH 7.5. RT3 production from T4 was maximal at pH 7.0. The production of T3 from T4 was negligible in the present system. Degradation of T3 in the placentas was rapid. Although the addition of anti-T3 antibody to the reaction mixture suppressed the degradation of T3, it had no effect on the net production of T3, suggesting that the obtained net T3 production rate had not been influenced by its degradation. Degradation of rT3 was negligible. These results indicate that the human placenta actively deiodinates T4 to rT3 enzymatically. This enzyme system might have some influence on the transplacental passage of the thyroid hormone from the mother to the fetus.

Complement Activities and Circulating Immune Complexes in Sera of Patients With Graves′ Disease and Hashimotofs Thyroiditis

In autoimmune thyroid diseases various immunological abnormalities were observed. Circulating immune complexes (CIC) have been detected in sera from patients with Graves′ disease(GD) and Hashimoto’s thyroiditis (HT). Intrathyroidal deposition of immune complexes was reported in these diseases. But the role of CIC in these diseases is not clear. Deposition of immune complexes induces activation of complement system and leads cells to lysis. In these process serum complements are consumed and its activities are reduced in some autoimmune diseases such as systemic lupus erythematodes and serum sickness. In such diseases serum complement activities were reported to correlate with the activity of the disease. In this report we studied about CIC and serum complement activities in patients with GD and HT to clarify the role of CIC and complement in these diseases.

[Two cases of hypothyroidism due to chronic thyroiditis preceding thyrotoxic Graves' disease].

慢性甲状腺炎による甲状腺機能低下症の治療中にBasedow病を発症した2症例を報告した.症例1は39才,症例2は46才の女性で,両者の血清T4, T3および症例1の131I摂取率は正常であつたが,血清TSHが高値であり,抗サイログロブリン抗体,および抗マイクロゾーム抗体が陽性のため,慢性甲状腺炎に伴うsubclinical hypothyroidismとしてl-thyroxineを投与していた.それぞれ2年半および1年後に, T4およびT3が高値となり, l-thyroxineを中止後も高値を持続した. 131I摂取率も高値となり, T3の投与にても抑制されず,ともにBasedow病を発症したものと思われた.症例2では眼症状も認められた.またこれらの例ではTSHリセプター抗体が陽性であつた.

The relationship between serum IAP and peripheral K cells in patients with subacute thyroiditis

In a previous study, we showed that the percentage of peripheral K cells of patients with subacute thyroiditis (SAT), determined by a plaque-forming cell technique, was significantly lower than that of normal controls, and that ther sera from SAT significantly inhibited the activity of K cells in normal lymphocytes, suggesting that in the sera of SAT there is some factor which inhibits K cell activity. In this study, we investigated the relationship between K cells and the serum immunosuppressive acidic protein (IAP), the sex difference in percentage of K cells, and the absolute count of K cells in patients with SAT. In normal controls, there was a sex difference in the percentage of K cells in total lymphocytes; the percentage was significantly lower in women (mean +/- S.D., 5.0 +/- 2.0%; n = 12; p less than 0.01) than in men (8.4 +/- 2.9%; n = 20). However, there was no sex difference in the absolute count of peripheral K cells. In the acute phase of SAT, the percentages of K cells wee 2.4 +/- 1.8%; 2.4 +/- 1.9% and 2.7 +/- 1.0% in 19 patients, 16 females and 3 males, respectively, which were significantly lower than 6.8 +/- 3.0%, 5.0 +/- 2.0% and 8.4 +/- 2.9% in 25 controls, 12 females and 13 males, respectively. The absolute counts of K cells in the acute phase of SAT were 56 +/- 45/mm3 and 58 +/- 48/mm3 in 13 patients including 11 females, respectively, which were significantly lower than 165 +/- 63/mm3 and 153 +/- 73/mm3 in 12 patients including 5 female controls, respectively. It was observed that serum IAP values in SAT were correlated negatively with the percentage of K cells and positively with the inhibition rate of SAT sera on K cells from normal subjects. Moreover, purified IAP showed a dose-related inhibition on the K cells from the control subjects. These results suggest that IAP in the sera of SAT seems to be one of the factors which inhibits the activity of K cells.