For the past 3 years, 1649 patients with thyroid diseases have been examined in our thyroid clinic. Among them, 685 patients have hyperthyroidism, and 315 patients have chronic thyroiditis. Since a number of laboratory tests are available at present, diagnosis of hyperthyroidism is not difficult. However, hyperthyroid patients without goiter are sometimes misdiagnosed as having heart disease. Four hundred seventy one hyperthyroid patients were treated with propylthiouracil or methimazole for at least 12 months. About 60% of hyperthyroid patients showed a decrease of thyroid size after propylthiouracil treatment, whereas only 30% of hyperthyroid patients showed a decrease of thyroid size after methimazole therapy. In contrast, re-enlargement of the thyroid has often been found after methimazole therapy. This enlarged thyroid can be reduced by the administration of desiccated thyroid or triiodothyronine without affecting thyroidal radioiodine uptake, suggesting that partial re-establishment of pituitary-thyroid feedback mechanism is achieved shortly after starting goitrogen. A combined use of thiocyanate and propylthiouracil is advisable for an acute control of hyperthyroidism, since such therapy produced a rapid fall of PBI, BMR, thyroidal radioiodine uptake and resin sponge T₃ test (RSU), without producing any side effects. Two hundred twelve patients were treated with radioiodine. Eleven patients were actually hypothyroid states as evidenced by laboratory tests. Fourteen patients have suggestive signs of hypothyroidism but the data of laboratory tests were all within normal range. If overt and such subclinical cases were combined, incidence of hypothyroidism 10 years after radioiodine was about 12%, making a sharp contrast with the data of foreign country in which 30 to 75% of the treated patients were hypothyroid.
Among 315 patients with chronic thyroiditis, 117 patients received needle biopsy for histological examination. Analysis of the data obtained in those patients indicated that a) incidence is high at older age, b) size of the goiter is more in chronic thyroiditis than in simple goiter, c) hardness of the thyroid is increased particularly at upper half of the thyroid, d) a decrease of thyroid size hardly occurs after thyroid hormone but occurs in most cases after steroid therapy, e) thyroid autoantibody was found in most patients. Analysis of these findings makes us possible to do diagnosis of chronic thyroiditis without doing further histological examination.
Since the terms myxedema and hypothyroidism were used in the same manner, an analysis of overt and subclinical hypothyroidism was performed using thiocyanate and iodide loading tests. Through these particular tests, 3 types (A, B, C) of subclinical hypothyroidism have been classified and were designed as masked hypothyroidism. Type A does not have goiter and showed discharge of thyroidal iodide before and/or after iodide loading. BMR, thyroidal radioiodine uptake and RSU also decreased after iodide loading. Type B has goiter and does not show iodide discharge before iodide loading, but otherwise similar to Type A. Type C has goiter and does not show any abnormality before and after iodide loading except that thyroidal radioiodine uptake decreased markedly after iodide administration. Myxedematous patients without any detectable abnormality either in laboratory tests or in special tests should not be regarded as subclinical hypothyroidism, although the patients responded well to thyroid therapy.

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Mechanism through which homeostatic adaptation to severe iodine deficiency is produced have been studied in the rat. Within 24 hours after institution of a Remington low-iodine diet (LID) containing 30 μg I/kg there is a 50% increase in the 131-I uptake by the thyroid. The 4-hr uptake increases linearly from approximately 5% in Purinafed rats to 70% after 30 days LID. Thereafter the increase is very gradual, the 4-hr uptake averaging 80-90% between 4 and 15 months. Within one week of starting LID there is a statistically significant increase in thyroid size. The increase in relative thyroid weight is linear up to 5 months, going from 6.5 mg/100 g B.W. to approximately 60; there is a slow further increase up to at least 15 months. Total iodine content of the thyroid remains relatively constant for the first 1-2 weeks, then rapidly falls to 5% of the initial value by one month. This is associated with a rapid fall in serum PBI from 4 to 0.5 ug/100 ml between 2 and 4 weeks. In spite of maintenance of this extremely low PBI for more than one year on LID, the rats continue to grow, remain healthy, and are not “clinically” hypothyroid, as occurs after thyroidectomy or propylthiouracil administration. The thyroid MIT/DIT ratio begins to rise as soon as the rats are given LID, but the T3/T4 ratio does not begin to rise until about 2 weeks after institution of LID, coincident with fall in serum PBI and depletion of thyroid iodine stores. The T3/T4 ratio of iodothyronines secreted by the thyroid rises even faster in the gland, going from 0.2 in rats fed a high iodine diet to 3 after several month of LID. The preferential secretion of T₃ in iodine deficiency accounts for the maintenance of a relatively euthyroid state in spite of a very low PBI. T₃ is four times as potent as T₄ but contains only 75% as much iodine per mol molecule. It is thus teleologically sound for this qualitative adaptation of thyroid secretion to occur during periods of grossly inadequate availability of dietary iodine. All adaptive changes are dependent on increased TSH secretion and are abolished by hypophysectomy. However, they are not reproduced by administration of TSH unless the thyroid is simultaneously depleted of iodine. Thus the adaptation is synergically produced by autonomous and TSH-induced intrathyroidal mechanisms. The changes in thyroid iodine metabolism produced by iodine deficiency in the rat are consistent with observations in humans with endemic, iodine-deficiency goiter and provide a valuable experimental model.

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Radioimmunoassay techniques for gonadotropin are very sensitive methods but time consuming. By using immunoadsorbent which was prepared by polymerizing rabbit anti-HCG serum, we succeeded in assaying HCG radioimmunologically in only 60 minutes. Four ml of rabbit anti-HCG serum which was completely absorbed with child urine protein and lyophilized human plasma protein, were mixed with 6.0 ml. of normal rabbit serum. The pH of this mixture was adjusted to 4.5 with IN NaOH and 1N HC1 and then 0.4 ml of ethyl chloroformate was added drop by drop to the mixture with gentle stirring. The precipitate (gel) formed was stood for 60 minutes at room temperature. The precipitate was centrifuged at 3,000 rpm for 30 minutes and then suspended in 30 ml of phosphate buffered saline and homogenized with Potter-Elvehjem glass homogenizer. The suspension was centrifuged at 3,000 rpm for 30 minutes and the precipitate was washed twice. The precipitate was washed successively twice with 0.1 % sodium carbonate, twice with phosphate buffered saline and then repeatedly with glycinie-HCl buffer (pH 2.2, 0.2 M) until optical density of the supernatant was 0 at OD₂₈₀. After complete washing of the precipitate, it was suspended in phosphate buffered saline and homogenized again and then diluted to 400 ml with phosphate buffered saline. This suspension was kept at 4°C. The proper concentration of the immunoadsorbent was determined to a certain amount of ¹²⁵I-HCG. The slight antigen excess region was used for this experiment. The factors of time and temperature for binding _I-HCG to immunoadsorbent, were determined. The binding reached the maximum from 120 to 240 minutes at 37°C but about 8 hrs. at 4°C. The binding of ¹²⁵I-HCG to immunoadsorbent was inhibited by the presence of various amounts of cold HCG. From the standard inhibition curve of HCG for binding ¹²⁵I-HCG, the small amount of HCG could be assayed in 60 minutes accurately the same as other radioimmunoassays. When the sensitivity of this method is increased, human leutenizing hormone (LH) also could be assayed in the same way.

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Since over 100 years ago, it has been assumed that the excessive thyroid hormone potentiates the action of catecholamines. The mechanism of this interrelationship has been studied by many investigators, but the results have been divergent and have not led to any generally accepted explanation.
In the previous experiment, we confirmed that reserpine-treated hyperthyroid patients showed a definite clinical improvement. For example, in palpitation and sweating, while no change was observed in the basal metabolic rate and the uptake of radioactive iodine. Furthermore, no potentiation was found in the effects of catecholamines on the carbohydrate metabolism in the hyperthyroid rat muscle using a hindquarter preparation technique. It was, therefore, considered desirable to study this interrelationship between the catecholamine and thyroid hormone in two parts, firstly the relationship in the metabolic system, secondly the relationship in the cardiovascular system.
This investigation was undertaken to determine the effects of adrenaline on the cardiac phosphorylase activity and the heart rate in the normal and hyperthyroid rats.

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It has been well established that plasma cortisol levels vary with diurnal rhythm; its maximum level usually occurs in the early morning and its minimum at midnight. This basic periodicity of cortisol secretion, however, could be modified by some clinical states which affect the servomechanism of ACTH secretion or have influence directly on the steroid-biosynthesis in adrenal.
Using the fluorometric technique for the determination of cortisol, described by De Moor, the author evaluated the diurnal variation of plasma cortisol concentrations in hypertension and some endocrine disorders, and then investigated the distortion in diurnal variation of plasma cortisol concentrations in patients with diseases of the central nervous system with concurrent assessment of the negative feedback mechanism of cortisol secretion by the Metopirone test.
Blood samples for the determination of diurnal variation of plasma cortisol levels were obtained by antecubital venipuncture at 8 : 00 A. M., 12 : 00 N., 5 : 00 P.M., and 2 : 00 A.M. The Metopirone test was performed by evaluating the responses of urinary total 17-0HCS, plasma cortisol and 11-desoxycortisol to the oral administration of Metopirone, given in a dose of 250 mg. every 2 hours for 24 hours. Urinary total 17-0HCS were determined on the days before, during and after Metopirone administration according to a modified method of Glenn-Nelson. In the Metopirone test blood samples for the determination of plasma cortisol and 11-desoxycortisol were obtained before, at the end and 4 hours after the end of Metopirone administration. Plasma cortisol and 11-desoxycortisol were separated by silica gel microcolumn chromatography. Then plasma cortisol was estimated according to a modified method of De Moor and 11-desoxycortisol was quantified with Porter-Silber reagent.
The results are summarized as follows :
1) The diurnal variation of plasma cortisol levels in normal adults was usually characterized by highest levels at 8 : 00 A.M., with a valley at 2 : 00 A.M. The means and standard deviations for 12 normal control subjects were 12.8±3.5μg/dl at 8 : 00 A.M., 9.5±2.8μg/dl at 12 : 00 N., 6.9±2.2μg/dl at 5 : 00 P.M., and 5.2±1.3μg/dl at 2 : 00 A.M.
2) The diurnal variation of plasma cortisol levels in diabetic patients was normal. The means and standard deviations for 12 diabetic patients were 14.9±3.6μ/dl at 8 : 00 A.M., 10.1±2.9μg/dl at 12. : 00 N, 7.5±1.6μg/dl at 5 : 00 P.M., and 5.9±2.5μg/dl at 2 : 00 A.M.
3) In 25 hypertensive patients the mean plasma cortisol levels were 14.4±4.8μg/dl at 8 : 00 A.M., 10.6±3.2μg/dl at 12 : 00 N., 9.2±3.9μg/dl at 5 : 00 P.M., and 9.8±3.4μg/dl at 2 : 00 A.M. In most hypertensive patients, the morning levels of plasma cortisol were somewhat higher than those of normotensive subjects and the cortisol levels in the midnight period declined much less than in normal subjects. The difference in midnight levels between normotensive and hypertensive subjects was significant (p<0.001). This was observed in patients with essential hypertension and renovascular hypertension, and also in some cases of primary aldosteronism. In hyperthyroidism plasma cortisol was increased to a significantly high level in the morning and showed striking fluctuations in the daytime but fell to a normal level at midnight. In Cushing's syndrome high levels of plasma cortisol were observed throughout the day and the rhythm was lost. In patients with various meningitises the diurnal variation of plasma cortisol levels was lost and linear.
4) The abnormal diurnal variation of plasma cortisol levels was frequently observed within a week after the onset in patients with cerebrovascular diseases but they showed a normal response to Metopirone. Patients with intracranial tumor also showed an ab-normally high level of plasma cortisol at midnight.

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The antigenicity of purified human growth hormone (HGH) and the development of immunochemical technique have produced a new method of radioimmunoassay, which has made possible the measurement of plasma HGH concentration in normal subjects. Using sensitive radioimmunoassay, several investigators have shown that HGH secretion is stimulated by insulin-induced hypoglycemia, arginine infusion and others. The purpose of this paper is to evaluate the radioimmunoassay and investigate serum HGH responses to various stimuli in normal subjects.

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Radioimmunoassay for human growth hormone (HGH) has made it possible to detect serum HGH levels of normal subjects and its clinical application has provided a wide availability in diagnosis of hypothalamo-pituitary diseases. The present study was designed to investigate serum HGH values in patients with hypothalamo-pituitary and thyroid disorders.

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Testosterone, androstenedione, dehydroepiandrosterone, and androstenediol were isolated and identified in canine spermatic venous blood by several chromatographic procedures and by infrared spectroanalysis. These C₁₉ steroids were established as secretory products of canine testis on the basis of arterio-venous differences in the content of steroids. The secretory rate of these C₁₉ steroids into canine spermatic venous blood after LH (NIH-LH-B3, 0.2 mg/kg) administration was studied by means of gas-liquid chromatography. A significant increase in content of androstenediol, as well as testosterone, androstenedione and dehydroepiandrosterone was noted.
In vivo perfusion study revealed the conversion of dehydroepiandrosterone-4-¹⁴C into androstenediol-¹⁴C and testosterone-¹⁴C, and that of androstenediol-³H into testosterone-³H by the canine testis. When equal amounts of dehydroepiandrosterone-7α-³H and 17α-hydroxyprogesterone-4-¹⁴C were infused simultaneously, both isotopes were found in testosterone and androstenedione, and only tritium incorporation in androstenediol. The ³H/¹⁴C ratio in testosterone was persistently higher than in androstenedione, indicating that part of dehydroepiandrosterone was metabolized to testosterone through the pathway not involving androstenedione. Perfusion of androstenedione-4-¹⁴C or testosterone-4-¹⁴C via the spermatic artery produced no demonstrable androstenediol-¹⁴C in canine spermatic venous blood.
These findings strongly support the view that androstenediol is one of the important intermediates in testosterone biosynthesis by canine testis.

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Electron microscopic observations were made on the regenerative changes of the rabbit parathyroid gland after long-term administration of calcium and vitamin D₂ had destroyed most of the gland cells.
Twelve hours after the last administration of calcium and vitamin D₂ the cells of the gland were considerably reduced in size and number. Nuclei were small, with coarse clumping of chromatin, and nucleoli were either decreased in number or consisted of a small mass of increased electron density with small vacuoles. Mitochondria were swollen and contained short, broken cristae. The Golgi apparatus was greatly shrunken and many lysosomes appeared in or near the Golgi area. The amount of the rough-surfaced endoplasmic reticulum was diminished and most of them were degenerated. The secretory granules were not seen.
Four days after the last administration of calcium and vitamin D₂, many features of regeneration were seen. The chief cell with regularly round nuclei increased in number, most of which were regarded as regenerating cells. The amount of nucleoli and RNP particles were increased as compared with the amount of those of the cells 12 hours after the last administration. Some of the endoplastic reticulum showed the whorl-like appearance. The Golgi apparatuses were fairly well developed and occasionally contained numerous small sacs and vesicles which seemed to be prosecretory granules.
Seven days after the last administration of calcium and vitamin D₂ the regenerative changes were more prominent. Most of the cells, which were round or oval, seemed to be approximately normal. They contained a large nucleus with one or two relatively large nucleoli. The well-developed Golgi apparatuses containing numerous small sacs, vesicles and vacuoles partially filled with electron dense material were seen. Occasionally, fully developed secretory granules were present, usually in the Golgi area. There was no difference in the amount of the rough- surfaced endoplasmic reticulum and RNP particles between in the chief cell at this time and in the chief cell of the normal parathyroid gland. Sometimes swollen mitochondria and the whorl-like appearance of the rough surfaced endoplasmic reticulum were seen.
Fourteen days after the last administration, the morphologic outline of the parathyroid gland at this time was like the normal pattern. The chief cells had large, round nuclei containing prominent nucleoli. The Golgi apparatus was very extensive and large, and often more than one were present. In or near the Golgi area there were numerous small vesicles and vacuoles containing varying amount of electron-dense material. The rough- surfaced endoplasmic reticulum were present in approximately the same amount, and morphologically the same as the chief cell of the normal parathyroid gland. Numerous RNP particles were present. Many secretory granules were present near the Golgi apparatus. Lysosomes and lipid droplets were seldom seen.

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