It has been clincically known that thyroid diseases are seen more frequently in the female than in the male. However, the sexual differences are not as yet fully explained. For this purpose, effects of castration on the thyroid function and effects of gonadal steroid hormones on the thyroid function of the castrate mature rats of both sexes were investigated. For determination of the thyroid function, radioactive iodine I¹³¹ was used and remarkable findings were obtained.
The results are summarized as follows :
1) Effects of castration on the thyroid function were manifested by hypofunction, usually, 14 days in the female and 42 days in the male, after castration, and greater changes were found in females than in males, and the effects were persisted even 2 months after the castration. It may be concluded that those greater changes in females without distinction to post-operative period had apparently indicated the fact that there are substantial differences of the thyroid function between male and females.
2) It is the matter of course that sexual differences should be looked for in the gonads. But, for the explanation of this mechanism, 3 kinds of steroid hormones ; estradiol benzoate, progesterone, and testosterone propionate were administered to the castrated mature rats and these effects on the thyroid function were examined. Marked differences have been found to exist between two sexes.
(1) Estrogen has an accelerating effects on the thyroid uptake of I¹³¹ for the female, and on the release of thyroid hormone in the blood of male rats. This diverse response against estrogen is considered to be attributable to the difference in the affinity of the thyroid to estrogen.
(2) When progesterone is injected to the castrated female rats, no changes were found, and in the male, decreased thyroid uptake of I¹³¹ was found 14 days, and no obvious changes occurred 2 months after castration.
(3) Androgen has no constant effects on the thyroid of the castrated both sexes.
(4) By the fact that estrogen has coherent effects on the thyroid while androgen causes no change, it can be assumed that the sexual differences are chiefly attributable to estrogen.
(5) The results of steroid hormones injection indicated that in the female thyroid is closely related with the gonad, while the thyroid in the male is not under this control.
(6) Estrogen has an accelerating effects on the female thyroid uptake of I¹³² irrespective of post-operative periods, suggests the reason for the more frequent occurrence of thyroid diseases in the female.
3) In order to explain the mechanism in which estrogen is the primary fractor on the sexual differences of the thyroid, estrogen was administered to the hypophysectomized female rats and its effect was investigated. Thyroid uptake of I¹³¹ showed remarkable increase in comparison with the control groups. By this fact, it can be noted that the estrogen has a direct effects on the thyroid.

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In a 32 year-old married women, complaining of headach, general tiredness, and left backache, typical Cushing's syndrome developed in the course of a year, with amenorrhoea, hypertension, characteristic face and somatic conformation. The urinary 17-ketosteroids were 2.5 to 9.5mg per twenty-four hours, and the 17-β-ketosterois and 11-hydroxy-17-ketosteroids patterns were increased by the columnchromatography. The urinary 17-hydroxycorticorticoids were 8.4 to 19.2mg per twenty-four hours, and the serum 17-hydroxycorticoids concentrations were 27.7 to 45.0μg per 100ml. The 17-ketosteroids excretion was not significantly depressed by administering large dose of cortisone, 100mg daily for five days, and both urinary 17-hydroxycorticoids and serum 17-hydrocorticoids levels were slightly elevated by administration of corticotropin, 25 units daily for two days. Adrenalradiography by presacral air insufflation showed a tumor of the left adrenal gland.
The labolatory findings suggested that the cause of this condition seemed to be left adrenal adenoma, and then left total adrenalectomy was performed. At operation, tumor measured 2.9 × 2.4 × 2.0cm and weight 14.8g was found and it's histologic structure revealed adenoma. Postoperative course was excedingly smooth, and the patient. returned to be the physical status prior to the disease and was completely free of symptoms four months after operation.
The patient has been observed for about one and a half year postoperatively and did not require any adrenocortical preparations except replacement therapy at and immediately after operation.

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An electron microscopic observation of the ultra fine structure of the adrenal cortex of the normal Wistar strain rat was studied. The following essential observation were made :
1. The capsullar tissue is composed of fibrocytes and no other specialized cells could be seen.
2. The cells of the zona glomerulosa contained numerous small rod like mitochondrias and found fine smooth surfaced endoplasmic reticulums. The inner structure of mitochondria presented fence like appearance, and were either tubular or honeycombed.
3. The mitochondria of the cells of zona fasiculta is round in shape and its inner structure is honeycombed. The smooth surfaced endoplasmic reticulum is lesser as it closer to the inner zone from the outer zone ; and besides, there are numerous dark cells which contained of large number of mitochondrias intermingled with clear cells.
4. The cells of zona reticularis seemed closely resembled with those of the zona fasiculata and hardly no essential differene could be observed.
5. The electron dense granules found in the cortical cells can be classified into four types by their morphological characteristics.
(a) Type I. : Small compact.
(b) Type II : Small empty.
(c) Type III : Small multilobular empty.
(d) Type IV : Large compact.
6. The subendothelial space between the hemoangio-endothelial cell and the villous projection of the surface of cortical cell which is contiguous with intercellular space was formed with the cells of adjacent cortical cells.
The endothelial projection presents small window like opening and they connect with vascular space and the subendothelial space.
An electron microscopic observation was undertaken to observe on the influence of adrenocortical cell by the stress induced by formalin, cold and upon a prolonged administration of formalian or A.C.T.H.
1. Immediately after the application of stress on the cells of the zona fasiculata, there developed giant vacuoles which were formed as the result of disappearing organelles, and which were found to drain into either subendothelial space or vascular space were also observed. The intercellular structure resumed the normal condition after six hours.
2. With a single administration of A.C.T.H. 10mg., the smooth surfaced endoplasmic reticulum seemed to be increased after six hours, but after 12 hours, along with the increase of smooth surfaced endoplasmic reticulum and mitochondria, there were observed of increased Type I small compact granules of high electron denseness, Type II small empty, Type III small multilobular empty and Type IV large compact, respectively.
3. With a prolonged administration of formalin or A.C.T.H., the findings were almost identical with what have been observed with the above. In the outer zone of the zona glomerulosa and zona fasiculata, there were definite increase noted of the smooth surfaced endoplasmic reticulum and the high electron dense granules of Type I, II & III which were presumably of the lipid granules had appeared in a large number. The only difference between prolonged formalin injected group and A.C.T.H. administered group was that the former exhibited the large degenerated granules in their cells. There were also noted of the presence of disintegrated cells.
The various organelles and its morphological changes of the normal and experimental groups with their significance were summarized.
1. Mitochondrial changes :
(a) Vacuolization.
(b) Deposit of the substance in the space.
(c) Vacuole formation by tne projection of outer mitochondrial membrane.
2. It has been deduced that there were three processes of forming the lipid granules which were presumed to be high electron dense granules.
(a) Due to deposit of substance within the mitochondrial space.
(b) Due to deposit of substance in the vacuole which have shifted from mitochondria.
(c) Due to shift from the low electron dense granules, Type D.

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As to the patients suffering from the essential hypertension whose systolic pressure more than 150mmHg, I measured the urinary total 17OHCS, 17KS and 17KS fraction, and administered ACTH Gel (14Units × 2) to all of the cases, and with its variation examined the adreno-cortical reserve concretely and synthetically. And also investigated the connection of the adreno-cortical reserve with eosinophil response and other clinical observations.
There was no difference in particular between the hypertension patients and normal persons on the excretion quantities per day of urinary total 17OHCS, 17KS and the rate of increase on a day when ACTH administered. But observing the variation process of each of them during three days including ones just before and after the administration day, I recognized more so-called 'the type of abnormal responsiveness' showing the delay of increase or non-response among the hypertension patients. On the measurment of urinary 17KS fraction there was a tendency to increase IV V fraction among male patients of hypertension, and when administered ACTH the variations divided into three types ; one showing III VI VII fraction increase, showing IV V fraction increase, and fraction unvarying. As these variations have some constant connection with varied quantities of total 17OHCS and 17KS on the day of ACTH administration, the adreno-cortical function can be divided into three main types ; sufficiency, comparative-insufficiency, and insufficiency. The types of insufficiency and comparative-insufficiency have their causes in lowering of adreno-cortical responsiveness or impediment in cortical metabolism, and there have been occupied 70% of all the essential hypertension cases, which showed the lowering of cortical function. Among the 70% there are many cases in which hypertension has been continued during long term and also arteriosclerosis has particularly been in advanced stage. Their eosinophil responses, too, were much worse than others.

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