After the administration of a new diuretic agent, furosemide, in non-diabetic & diabetic hypertensive patients, we have observed far less influences on glucose tolerance, serum potassium and serum urea nitrogen levels than those caused by previous thiazides. As a few cases showed abnormal carbohydrate metabolism similar to that produced by thiazide, further observation should be performed in long term treatment.

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The exact experimental evaluation of adrenocortical function in vivo by determining steroids in urine must be carried out with cases who have not steroidproductive organs except the adrenal. Since the steroid metabolites in urine will fluctuate following the change of shifts of the metabolic pathway according to cases and to the states of the cases, it is obviously better to determine the main several metabolites in urine than to determine the single steroid.
On this viewpoint, 17-OHCS, 17-KS, pregnandiol and pregnantriol in urine of 22 castrated females were determined to examine the effects of medication on the adrenal. ACTH, pantothenic acid, vitamin C, gonadotropin and dexamethasone were used as the drugs which have been thought to have influence on the adrenal and used widely in clinics.
As the results, after ACTH administration, all steroids increased, especially pregnandiol and pregantriol showed high increasing rates. The results suggest that pregnandiol and pregnantriol values are useful as the index of adrenocortical function, and when we evaluate pregnandiol and pregnantriol as an index of progestational function, the influence of the adrenal function must be cosnidered. The administration of pantothenic acid, aspirin, vitamin C did not affect the excretion values of the steroids, in spite of the fact that they are being used widely in clinics. By gonadotropin administration, a slight but insignificant increase of steroids was shown.

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The changes of the activities of serine dehydratase (SDH) and glucokinase were examined in order to evaluate dietary and hormonal effects on the metabolism of amino acids and carbohydrate.
1) In the livers of alloxan-diabetic rats, about a sixfold increase of SDH was observed, and this increase was diminished to the normal level by the injection of protamine zinc insulin. The increase was inhibited approximately 75% by an administration of actinomycin S. Adrenalectomized rats showed no increase of SDH for 48 hours after the injection of alloxan monohydrate, although a gradual increase was observed 3 to 4 days later.
On the basis of these facts, adrenalectomized rats treated with alloxan monohydrate at zero time, were given three injections of 5 mg of hydrocortisone acetate at 15, 24 and 40 hours and then sacrificed at 45 hours. SDH was enhanced about fivefold, whereas no increase was found without the alloxan treatment. In normal rats, daily administration of 15mg of hydrocortisone acetate for 3 days produced only a 1.7 fold increase. No increase of SDH was observed in rats which were hypophysectomized either before or after the injection of alloxan monohydrate. An injection of somatotrophic hormone proved to be ineffective on SDH in the hypophysectomized alloxan-diabetic rats.
2) The activity of glucokinase decreased to one seventh of normal level in the liver of alloxan-diabetic rats. The activity returned to normal level by the injection of protamine zinc insulin. Adrenalectomy showed no inhibitory effect on the decrease of glucokinase in the alloxan-diabetic rats. Hydrocortisone acetate could not affect the activity of glucokinase in the liver of adrenalectomized alloxan-diabetic rats.
3) No increase of SDH was observed after starvation for 3 days. In the rats fed with high protein diet, SDH increased to the same level as in the alloxan-diabetic rats.
4) As indicated by the activity of SDH, the conversion of serine to pyruvate increases in the liver of alloxan-diabetic rats, and pyruvate is synthesized to glucose through the pathway of the activated gluconeogenesis. The utilization of glucose is inhibited in the diabetic rats as shown by the decreased activity of glucokinase.
5) The response of SDH to hydrocortisone as evidenced by the elevation of SDH activity in adrenalectomized alloxan-diabetic rats supports the view that insulin counteracts the effect of hydrocortisone on SDH. Of special interest in this connection, there are similar reciprocal changes between the activites of SDH and glucokinase in the livers of alloxan-diabetic and high protein-fed rats compared with normal rats.
It is a problem to be solved whether a dietary stress might regulate the flow rate of metabolites via hormonal control.

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Clinical and microscopical studies were made on 61 cases of thyroiditis and 161 cases of other thyroid diseases.
The following findings were obtained :
Most of the usual thyroiditis could be classified either as Hashimoto's disease or as de Quervain's subacute thyroiditis. Hashimoto's disease occurs mainly in women of 20 to 50 years of age demonstrating only a firmly diffuse goiter with no complaints. In Hashimoto's disease, the thyroid showed microscopically atrophic acini and localized or diffuse lymphocytic infiltration, or often, an appearance of lymphofollicle ; occasionally a marked fibrosis was dominant with the disappearance of thyroid acini.
In this disease, antithyroid antibody by Oudin's agar gel diffusion technique was demonstrated with high incidence and high titer. General condition of this disease did not change entirely during an observation period of 5 to 6 years. Treatment is seldom necessary for this disease.
De Quervain's subacute thyroiditis also occurs mainly in women of 20 to 50 yeasrs of age. High fever, headache, pain in the neck and shoulder, and localized firm swelling of thyroid are usually seen in acute stage, disappearing slowly in 1 to 3 weeks after an onset. Red cell sedimentation rate is highly accelerated, and ¹³¹I uptake ratio is remark-ably reduced. ¹³¹I scintigram showed either no silouette or thinly mottled silouette. Microscopical findings of the thyroid showed destruction of acini, appearace of characteristic giant cells, and fibrosis. Then regenerated acini appeared.
Follow-up study for 5 to 6 years revealed that all the patients complained of nothing, except one with myxedema following thyroidectomy. Therefore, their recovery can be considered complete.
There was no case of Riedel's thyroiditis which lacked resemblance to Hashimoto's disease or subacute thyroiditis. Microscopically, some cases of Grave's disease, thyrotoxicosis and spontaneous myxedema resembled Hashimoto's disease so much that a close relation was thought to exist between them.
Some experiments were performed in order to produce experimental thyroiditis.
(1) Experimental Hashimoto's disease by immunizing a rabbit with the tissue extracts of other rabbit's thyroid.
(2) Experimental suppurative thyroiditis by infecting a rabbit with staphylococcus after having immunized it with the tissue extract of other rabbit's thyroid.
(3) Experimental subacute thyroiditis by infecting a mouse with influenza virus after having immunized it with the tissue extract of other mouse's thyroid.
By these experiments, the author obtained the result of a few pathological findings of experimental thyroiditis.

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Adrenocortical atrophy of the male Wistar rat, induced by daily injetions of hydrocortisone 10 mg/kg, paramethasone 0.5 mg/kg and dexamethasone 0.25 mg/kg, respectively, for 5 days and 1, 2, 3 and 5 weeks, was studied by histologic, histometric and enzyme histochemical procedures.
Significant reduction in weight of the adrenal gland and in width of the cortex which was, in particular, involved in the diminshing in length of the fascicular and reticular layers, were detected in the dexamethasone groups. These atrophic changes were less evident in the paramethasone groups and very slight in the hydrocortisone groups.
In the dexamethasone groups, the conspicuous atrophy of the fascicular and reticular layers appeared within 5 days to 1 week. Degeneration atrophy in the adrenal cortex was accelerated by the prolongation of the daily injections. In 2 and 3 weeks, necrosis and necrobiosis were particularly profound in the reticular layer, which was followed by zonal fibrosis in 5 weeks. In the paramethasone groups, there were no severe cortical lesions resulting in fibrosis. The atrophic changes continued to be slight in the hydrocortisone groups.
In the dexamethasone groups, the activity of glucose-6-phosphate dehydrogenase was suppressed moderately in the fascicular and reticular layers within 5 days to 1 week, and the change was evident in the animals of 2 to 5 weeks. The loss of glucose-6phosphate dehydrogenase activity was less severe in the paramethasone groups and very slight in the hydrocortisone groups.
In the dexamethasone groups, accumulation of intracellular coarse lipid globules appeared in the fascicular and reticular layers within 5 days to 1 week. In the paramethasone groups, the same change was demonstrable within 1 to 2 weeks, and in the hydrocortisone groups within 5 days to 1 week. Intracellular lipid globules were gradually decreased in size and in density by the prolongation of daily injections. The animals with in 5 weeks of dexamethasone injection had only a small amount of faint lipid droplets within the cortical cells. The decrease of cortical lipids was less severe in the paramethasone groups and very slight in the hydrocortisone groups.
The activity of alkaline phosphatase in the capillary wall in the fascicular and reticular layers was reduced markedly in 1 week in the dexamethasone group and moderately in 2 weeks in the paramethasone and hydrocortisone groups. In these animals, the reduction of the activity was considered to be in reliable relation to the density of coarse lipid globules in the cortical cells. The reduction of the alkaline phosphatase activity was gradually mended by the prolongation of the daily injection in all experimental groups, and in 5 weeks the activity was the same as that in normal control animals. It was suggested that the mending of the reduction of the alkaline phosphatase activity was induced by the release of the intracellular lipid material and of cortical cell debris into the blood stream through the capillary wall.
The activity of triphosphopyridine nucleotide diaphorase was slight but had a similar pattern to that of glucose-6-phosphate dehydrogenase. There were no reliable changes in the activities of acid phosphatase, adenosine triphosphatase, nonspecific esterase, succinic dehydrogenase, and 9 other dehydrogenases and diaphorases in all experimental groups.

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1. Preliminary experiments on the determination of urinary 17-KGS fractions.
The procedure employed was Few's method partially modified by Kanbegawa. The urine was treated with sodium borohydride, sodium periodate, then extracted with ethylether and fractionated into 2 parts of 11-deoxy-17-KGS and 11-oxy-17-KGS by means of column chromatography on alumina, and finally determined with Zimmermann's reaction. Satisfactory results were obtained in the separation of both fractions, the recovery ratio and the reproduction with 7 kinds of pure reference C-21-steroids (Fig. 2, Table 1, 2). After studying Zimmermann's reaction, it was found that method B is suitable for the determination of both fractions (Table 3).
2. Determination of the 24-hour urinary excretion of the 17-KGS fractions was carried out in 55 normal children (27 males and 28 females) whose ages ranged from 3 to 15 years and in 10 normal adults. A gradual increase according to the age was observed on both fractions. The value per body surface unit was calculated. An approximately constant value was obtained in the group of children under 12 years old and over 13 years old, respectively. Similar tendencies were observed on the basis of body weight. As the value per body weight ranged more widely than those per body surface unit, the latter is more suitable as a normal standard. No sex differences were noted in the group of children between 3 to 12 years of age while sex differences were noted in the group over 13 years old (Fig. 4, 6, 7, Table 4a). 11-deoxy-17-KGS/11-oxy-17-KGS ratio was 0.22±0.14 (5% rejection limit) with no differences in relation to age and sex (Fig. 5, Table 5).
3. Determination of the 24-hour urinary excretion of the total 17-KS was also carried out in the same subjects. Similar tendency of the gradual increase with age noted in 17-KGS was also observed in 17-KS. However, the values per body suface were approximately constant in the group of children under 12 years old, but not in the group over 13 years old. Age and sex differences were observed in the latter group (Fig. 9, Table 4a).
4. Urinary pregnanetriol was determined in 19 cases of normal children by the method of Bongiovanni-Eberlein and the values were compared with those of 11-deoxy17-KGS. Pregnanetrol/11-deoxy-17-KGS ratio was 0.44 (mean) ±0.23 (standard deviation), which seemed to increase according to the age over 13 years old (Fig. 8. Table 4b).
5. Positive correlation was observed between 17-KGS and 17-KS. However the KS values were relatively larger in the group over 13 years old than in children under 12 years old (Fig. 10).

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