Although chronic thyroiditis has been recently noticed as an autoimmune disease, the histological classification based on clinico-pathological correlation is still vague at present.
The specimens subjected to this study were taken by exploratory excision from 63 patients who were clinically diagnosed as chronic thyroiditis. Histological observation was done regarding the progress of pathologic changes in the thyroid gland.
Lymphoid type (14 cases) : lymph-follicle formation with scattered infiltration of lymphocytes was the predominant feature in this group. No definite alteration of the thyroid epithelium was observed. Some of the so-called focal thyroiditis may be included in the early stage of this group. Some of them may develop into tremendous proliferation of lymphoid tissue in its late stage.
Oxyphilic cell type (34 cases) : oxyphilic alteration of the epithelium was predominant, but lymphocytic infiltrations observed in varying degrees was not an essential feature of this group. Fibrosis may possibly become more prominent with destruction of thyroid follicles in the late stage.
Hyperplastic type (9 cases) : most follicles were lined by cuboidal or tall epithelium with papillary infolding and contained thin colloid and some cell aggregates. This type of thyroiditis also may result in a proliferation of interlobular fibrous tissue in its more advanced stage.
Fibrous type (6 cases) : this type of thyroiditis is believed to be a late stage of the other three types. The original type of thyroiditis, however, was not clear because of advanced fibrosis.
Evidences of the progress of the histological changes were observed in 12 out of 40 patients in whom the specimens were taken from both lobes and in two others whose specimens were taken twice at different stages.
Clinical correlation of this classification was studied. The lymphoid type was found in 14 out of 53 female patients, but in none of 10 males. In age distribution the hyperplastic type was observed to be more common than the other types among younger people. The clinical signs of hypothyroidism were recognized most frequently in the oxyphilic cell type but not in the hyperplastic type. Thyroid function test, however, demonstrated no definite differences among the four types.
Relationships were discussed in this paper between this author's classification and that of Woolner-also relationships to Hashimoto's thyroiditis and Riedel's struma.

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This study was undertaken to try to determine the incidence of rheumatiod factor in patients with diabetes mellitus by the Hyland RA slide test and the RAHA test (the sensitized sheep red cell agglutination test).
Sera from 507 patients with diabetes mellitus and 2073 controls were investigated for the presence of rheumatiod factors.
RA test was positive in 8. 7 per cent and RAHA test in 6. 1 per cent in sera from patients with diabetes mellitus compared to 4. 1 percent and 3. 6 per cent respectively in healthy subjects.

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A fundamental study of testosterone-estradiol binding globulin (TeBG) activity for estradiol-17β was investigated by equilibrium dialysis. In addition, the interaction of TeBG activity for estradiol and estradiol metabolism during a menstrual cycle and in hyperthyroidism was attempted to elucidate. Estradiol in plasma and 24 hrs urine was measured by radioimmunoassay. TeBG binding capacity (TBC) was measured by ammonium sulfate method and associate constant (K_a) of TeBG for estradiol was estimated by equilibrium dialysis.
1. In several pooled plasmas, the mean K_a of TeBG for estradiol was 1.25×10⁸ L/M at 4°C and 0.78×10⁸ L/M at room temperature. The K_a decreased with increasing temperature and could not be determined with a sufficient accuracy at 37°C. The mean TBC was 4.4×10^-8 M/L.
2. TBC and K_a of TeBG for estradiol during the normal menstrual cycle of a woman were fairly unchanged. The unconjugated estradiol value in urine showed the same biphasic pattern with a midcycle peak as that of the unconjugated estradiol value in urine.
3. A normal man was induced hyperthyroidism with a administration of triiodothyronine. The treatment of triiodothyronine caused a remarkable increase of TBC, but no changes of K_a of TeBG for estradiol and unconjugated estradiol values in plasma and urine. From these results it was suggested that the rate of metabolism of estradiol increased in hyperthyroidism.

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In an attempt to investigate the effect of ovulating hormone on the steroidogenesis of mature follicles in the course of ovulation, transitory changes of steroidogenesis in isolated rabbit follicles have been studied at several intervals after injection of an ovulatory dose of human chorionic gonadotropin (hCG)
Five to ten follicles of approximately 1-2 mm in diameter were isolated from ovaries of a mature rabbit (2. 5-3. 0 kg) under streomicroscope, before and at the 3 rd, 6 th, 9 th and 12 th hours after intravenous injection of of 100 IU/kg of hCG. Follicles were incubated with 100 μCi of acetate-1-¹⁴C in 2 ml of Krebs-Ringer bicarbonate buffer (pH 7. 4) at 37°C for 3 hours under 95 % oxygen plus 5 % carbon dioxide. Each incubation was terminated by quick freezing and stored forzen at -20°C until eighty follicles had been collected for each time period before commencement of analysis.
Incorporation of radioactive acetate into pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone., 20α-dihydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol-17β were analysed by the reverse dilution technique and identified in radiochemically pure form by recrystallization to constant specific activities.
The steroidogenic activity of the follicles was evaluated by overall as well as fractionated incorporations.
A peak in the overall incorporation of ¹⁴C- acetate into the ten steroids at the 3 rd hour after hCG injection, followed by gradual decrease up to the 9 th hour was observed. The incorporation decreased markedly to a minimum level at the 12th hour after hCG injection, which was below the level of preinjection control.
Comparable quantitative fluctuations were found with the fractionated incorporation of ¹⁴C-acetate into the C₂₁ and C₁₈ steroids in the time sequence following hCG injection. However, the fractionated incorporation into C₁₉ steroids reached to a maximumat the 6 th hour after hCG injection.
Distribution patterns of incorporation among the individual steroids were varied at each interval of time. In the non-injected control, mature follicles synthesized predominantly estradiol-17β, testosterone and androstenedione. Divergent steroids were formed from radioactive acetate at the 3 rd hour after hCG injection. These included porgestogen, androgen and estrogen, but pregnenolone and 17hydroxyprogesterone were the two principal steroids produced.
There was no essential difference in the steroidogenic patterns between the 6 th and 9 th hour, the major products being C₂₁ and C₁₉ steroids such as pregnenolone, 17hydroxyprogesterone, dehydroepiandrosterone and testosterone. The three androgens were the major steroids formed at the 12th hour after hCG injection. Thus the chages in the steroidogenic profile of the follicle was obvious in the course of ovulation.
The basis of the qualitative changes in follicular steroidogenesis during the process of ovulation have been discussed in connection with an accompanying effect of an ovulatory dose of hCG.

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The purpose of our study was to determine the incidence of thyroid antibodies in diabetes mellitus in childhood and to discuss the correlation between thyroid antibodies and insulin antibodies.
The sera of 50 children with diabetes mellitus and 437 children as disease controls were tested by thyroglobulin and microsome coated tanned red cell hemagglutination test (Fuji Zoki Co. Tokyo).
One of the 50 children with diabetes mellitus (2%) was positive with antithyroglobulin antibodies and eleven (22%) were positive with antimicrosomal antibodies compared to 0. 4% and 1. 1% respectively in 437 disease controls.
To clarify the association of insulin antibodies and thyroid antibodies in diabetes mellitus in childhood, insulin antibodies were demonstrated by using a modified method described by Wright.
One of the 33 children with negative insulin antibody (2. 8 %) was positive with antithyroglobulin antibodies and eight (24%) were positive antimicrosomal antibodies. None of the 17 children with positive insulin antibodies were positive with antithyroglobulin antibodies and three (18%) were positive with antimicrosomal antibodies.
No evident correlation was observed between antithyroid antibodies and insulin antibodies.

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The direct inhibitory action of somatostatin (cyclized SRIF) on the pancreatic endocrine function was investigated by a technique using pancreaticoduodenal arteriovenous system in vivo.
Somatostatin was infused for 20 minutes at a speed of 2.5 μg/minute into the superior pancreaticoduodenal artery with an infusion pump. Plasma levels of glucose, insulin (IRI) and glucagon (IRG) in the pancreaticoduodenal vein and femoral artery were measured before and every 5 minutes throughout the experiment for 30 minutes. The results were compared with those obtained from the control experiment which was carried out in the same time schedule under infusion of physiologic saline solution instead of somatostatin. Next, the effect of somatostatin on the glucose-induced insulin release from the pancreas was also evaluated.
The following findings were obtained. (1) Somatostatin infused at a speed of 2. 5μg /minute into the superior pancreaticoduodenal artery caused a statistically significant inhibition of plasma levels of IRI and IRG and also pancreatic output of these hormones. With the sessation of somatostatin infusion an abrupt rise of the hormones were seen. This “rebound” phenomenon was more pronounced in insulin secretion than in glucagon. No significant changes in the plasma glucose levels in either the pancreaticoduodenal vein or the femoral artery throughout the experiment were found. (2) During infusion of somatostatin at a speed of 1. 25 μg/minute, insulin response to glucose injected into the pancreaticoduodenal artery in a small dose, as well as having no effect on the plasma glucose level in systemic circulation, was also significantlyinhibited.
From these findings obtained by direct experiment using the pancreaticoduodenal arterio-venous system, it was confirmed that somatostatin exhibits a direct inhibitory action on pancreas endocrine in a very low concentration in vivo, and it was suggested that this action might be partly due to a reduction in pancreatic circulation.

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The author previously reported that the serum calcium (Ca) and inorganic phosphorus (P) levels were gradually decreased with advance in age in regularly menstruating women, but that they were rapidly increased soon after the menopause. In this experiment the changes of the serum Ca and P levels in postmenopausal women were studied more precisely in 410 peri- or post-menopausal subjects and 534 controls with regular menses. They were classified into 12 groups according to age or period since last menses. The clavicular cortical thickness was also measured as an index of bone resorption.
Blood samples were taken between 9-11 A. M. after an overnight fast and the separated sera were applied to a Technicon Autoanalyzer SMA 12/60 and analyzed. The mean levels of Ca and P in serum were both increased following the menopause and reached a plateau in Groups F-3 (12-24 months since last menses) and G (2-5 years since last menses). In Group H (5-10 years since last menses) both the levels were slightly declined. Then a dissociation was observed in Groups I-1 and 1-2. This was a successive decrease of Ca and a re -increase of P. This dissociation might be explained partly by the physiologic fall of parathyroid function. Furthermore the clavicular cortical thickness was measured with a micrometer in the middle of the clavicle on the chest X-ray film of the same subjects and the clavicular score was computed as Cortical width X 100/ Whole width. The score was gradually but steadily reduced with the lapse of time after the menopause and in Group I-2 it was lowered to approximately 45% of that in the premenopausal groups. From these results it is certain that the decline of estrogen secretion led to the elevation of the serum Ca and P levels and subsequently to the reduction in the clavicular score.

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TRH and T₃ suppression tests were performed on patients (124 cases) with Graves' disease who underwent radiation therapy.
TRH test was performed at 4-6 months (Group I), 6-12 months (Group II), 12-24 months (Group III) and 24-50 months (Group IV) after final radiation therapy, and T₃ suppression test was performed just after each TRH test.
The response to TRH test was defined as positive when the basal TSH value was less than 2.0 μU/ml and the peak value was more than 6.2 μU/ml, or the difference between basal and peak TSH value was over 5 μU/ml following TRH (500 μg) injection.
T₃ suppression test was performed by measuring the 24-hr thyroidal uptake of radioiodine after daily administration of 75 μg of T₃ for 8 days. The response was defined as positive when the value for 24-hr uptake after T₃ administration was less than half of the control value.
The results were as follows ;
1) Among 124 patients in Group I to IV who were clinically euthyroid and whose T₃-RU and T₄ values were normal, compared with other groups, Group IV (2-4. 2Y) showed a significantly higher percentage of positive responses to both TRH and T₃ suppression tests.
However, among 49 of 124 patients whose T₃ was also normal, there were no significant differences between the groups.
2) The value of triiodothyronine was above the normal range in many cases up to 2 years after radiation therapy (in Group I, II, III).
3) There were no significant differences in the percentage of hyperresponses between any of the four groups. Half of the patients who showed positive responses to TRH test showed exaggerated responses.
4) In all cases when the responses to TRH and T₃ suppression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodo-thyronine.
5) As in more than 30% of cases TRH and T₃ suppression tests remained negative even though their T₃-RU, T₄, T₃, values became normal after radiation therapy, the regulation of hypothalamo-hypophyseal thyroid axis do not always return to normal even though circulating thyroidal hormone level return to an euthyroid state.

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Blood TSH (Thyroid Stimulating Hormone) was successfully measured by radioimmunoassay in a dried blood spot on filter paper which is obtained in newborn screening for metabolic disorders. By this method, the minimal detectable level of blood TSH was about 10 μU/ml, which is the approximate upper limit of normal values of blood TSH. Good correlation was found between the TSH values obtained from this specimen and from liquid serum samples from the same subjects. The duplication of assay of a single sample was not necessary. A screening program using the method described here was initiated and a 4 year old infant was found to have primary hypothyroidism, later verified by other testing methods. Since the technique is simple and adequately sensitive for the detection of hypothyroidism, it could be a valuable method for use in mass-screening of newborns for congenital hypothyroidism.

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