Makiko Yamamoto

Postpartum recurrence of Graves’ hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy

objective Previous studies recommend the discontinuation of antithyroid drug (ATD) therapy during pregnancy in women with well‐controlled Graves’ hyperthyroidism (GH). In this study, we investigated whether this termination of ATD therapy during pregnancy is beneficial in terms of postpartum GH recurrence.

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.

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.

Purified Protein Derivative Reaction and Urinary Immunosuppressive Acidic Protein in Patients With Subacute Thyroiditis

Recently we reported1-2 that in acute phase of subacute thyroiditis (SAT) serum immunosuppressive acidic protein (IAP), a type of α1-acid glycoprotein measured by single radial immunodiffusion method is increased, and peripheral K cell activity measured by the modified plaquemethod of Biberfeld et al. was decreased and negatively correlated with serum IAP. Inhibition rate of K cells from a normal subject by sera of patients with SAT in acute phase was higher than that in recovery phase and those of normal control. Purified IAP inhibited K cell activity of normal subject in a dose-dependent manner. Circulating immune-complex measured by modified solid phase Clq-binding assay was almost normal and had no correlation with serum IAP in SAT. Trypsynization of K cells resulted in no change of K cells in both normal subjects and patients with SAT. From these results, it is conceivable that the K cell function is activated to destroy the affected cells probably by virus in the very early phase of SAT and that the K cell activity in SAT might be suppressed by IAP produced from macrophages as defense mechanism against the endless destruction of affected cells by K cells.

[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.

[Free thyroxine estimation for screening of hyper- and hypothyroidism in an adult population].

Serum free thyroxine (FT4) was determined in 1,114 adults (male 239, female 875) in a periodic health evaluation in 1980 to detect unsuspected thyroid dysfunction, especially hyper- and hypothyroidism. The participants were dwelling in two towns of Miyagi prefecture. Beside FT4, serum T4 and T3 were also determined by radioimmunoassay. If thyroid dysfunction was suspected, further detailed examinations such as TRH-test (500 micrograms i.v.), radioimmunologic determinations of serum TSH and TBG, resin-sponge T3-uptake, 24-hr thyroid radioiodine 131I-uptake, radioiodine thyroid scan and anti-thyroid antibodies were performed. There were 3 patients with hyperthyroidism (0.27%), 4 with hypothyroidism (0.36%), 3 taking thyroid medication (2; Hashimotos disease, 1; goiter), 3 on estrogen administration, 4 with Hashimotos disease and 1 with goiter. Excluding these 18 patients, FT4, T4 and T3 values in 1,096 euthyroid subjects, 236 males and 860 females, were 1.1 +/- 0.3 (mean +/- S.D.), 1.1 +/- 0.3 and 1.0 +/- 0.3 ng/100 ml, 8.9 +/- 1.5, 8.8 +/- 1.6 and 9.0 +/- 1.5 micrograms/100 ml, and 122 +/- 33, 125 +/- 26 and 122 +/- 35 ng/100 ml, respectively. Serum FT4, T4 and T3 showed the distribution of logarithmic normal probability. The 95% normal range for free T4 was 0.60 to 1.80 ng/100 ml, total T4 6.0 to 11.8 micrograms/100 ml, and T3 84 to 176 ng/100 ml, respectively. Out of 1,114 subjects examined, the cases to be reexamined for the higher serum concentration than normal were 26 in FT4, 35 in T4 and 27 in T3, respectively. And the cases for lower values were 28 in FT4, 31 in T4 and 24 in T3, respectively. Serum FT4 values in the subjects during the administration of estrogens were within the normal range. FT4 and T4 were low in four patients with hypothyroidism, but two of them showed normal T3 values. Determinations of serum FT4, total T4 and total T3 were all useful for the screening of hyperthyroidism. But serum FT4 was the most reliable of the three. Determination of either serum FT4 or total T4 was suitable for the screening of hypothyroidism, but serum total T3 measurement did not cover all patients with hypothyroidism.

Changes of serum TSH, T3 and T4 in the patients with breast cancer by TRH-test

Twenty-six patients with breast cancer were intravenously injected with 500 pg of synthetic TRH. With one exception, none had received any treatment for breast canser. Blood samples were taken at intervals of 10, 20, 30, 40, 60, 90 and 120 min after the TRH-injection. Basal serum TSH values of those patients were significantly higher than those of normal subjects. Their serum TSH responses to TRH-injection were moderately delayed and higher when compared to those of normal subjects. Serum T4 values of the patients with breast cancer determined 120 min after the TRH-injection were significantly lower than those of normal subjects. However, serum T3 values of the same patients obtained 60min after the TRH-injection were signicantly higher than those of normal subjects. Serum T4/T3 ratios of breast cancer measured 60 min after the TRH-injection were significantly lower than those of normal subjects. These data suggest that thyroid function in patients with breast cancer may be suppressed. One patient with breast cancer also had adenomatous goiter. Two other patients with breast cancer were hypothyroid. One patient with breast cancer who received chemotherapy for 4 days before the TRH-injection showed a high basal serum TSH value, delayed and high TSH-response and lack of serum T4 response to the TRHinjection. Tests for anti-TG and anti-MC antibodies were positive in one patient with breast cancer, for anti-TG antibody in two patients and for anti-MC antibody in two other patients.