The renin-angiotensin-aldosterone system has hitherto been investigated extensively in adults, but little information has been reported with regards to children, partly because large quantities of blood were needed for measuring the system's components and sampling difficulties were encountered in young children.
Recently, some simple radioimmunoassays were developed and it became easier to measure plasma aldosterone concentrations (PA) and plasma renin activity (PRA) in children. In this study, PA and PRA were determined by using radioimmunoassay, and electrolytes of plasma and erythrocyte were measured by flame photometer and an atomic absorption photospectrometer. In addition, in order to clarify the causes of high PA and PRA levels in neonates, the relationships between oral sodium intake on one hand and PA and PRA on the other were also examined.
The subjects were 418 children, aged from the first day of little to fifteen years, and 8 adults, who were in convalescence from acute infectious diseases without evidence of circulatory or renal diseases. They were on free diets and kept at rest in a supine position as a rule. Venous blood samples were taken during the one-hour period from 8 A.M. to 9 A.M. PA was measured by ALDOK-Kit (CIS), and PRA was measured by Renin-Riakit (Dinabot).
The child subjects were divided into 10 groups according to age difference, and the eleventh group of adults served as a control :
I) 0-6 days, II) 7-27 days, III) 1-2 months, IV) 3-5 months, V) 6-11 months, VI) 1-2 years, VII) 3-5 years, VIII) 6-8 years, IX) 9-11 years, X) 12-45 years, XI) adults.
The results were as follows :
A. The mean values of PA and PRA for each group :
1) PA (ng/dl) : I) 62.66 ± 48.54, II) 52.19 ± 23.49, III) 38.16 ± 20.95, IV) 29.91 ± 19.01, V) 17.37 ± 9.63, VI) 14.20 ± 7.56, VII) 11.43 ± 6.51, VIII) 9.72 ± 4.46, IX) 9.62 ± 4.59, X) 7.44 ± 2.23, XI) 8.47 ± 1.37.
2) PRA (ng/ml/hr) : I) 8.83 ± 8.67, II) 7.40 ± 3.74, III) 5.70 ± 2.97, IV) 3.54 ± 1.96, V) 2.58 ± 1.41, VI) 2.11 ± 1.14, VII) 1.76 ± 0.99, VIII) 1.37 ± 0.61, IX) 1.28 ± 0.55, X) 0.91 ± 0.42, XI) 1.01 ± 0.14.
B. 1) PA and PRA had similar patterns; in group I, the values were about 7-8 times as high as those of group XI and ranged widely. Then, they rapidly decreased with increasing age, the rate growing mild in group VI and after, and group X showed no significant difference from group XI.
2) A significant positive correlation was found between PA and PRA (r=0.5374, P<0.001, N=357).
3) No significant correlation was noted between PA and plasma sodium in any group.
4) A significant positive correlation was found between PA and plasma potassium in all groups except the neonatal period.
5) A significant negative correlation between PA and plasma magnesium was found in all groups, especially in the neonatal period.
6) There was no significant correlation between either of PA and PRA and the ratio of plasma electrolyte to erythrocyte electrolyte.
7) In children under six months, there was a significant negative correlation between both PA (r=-0.4601, P<0.001, N=77) and PRA (r=-0.3043, P<0.01, N=81) and oral sodium intake (mEq/M² /day).
8) A significant negative correlation was found between oral sodium intake and the ratio of PA to PRA (r=-0.4601, P<0.001, N=52) in the neonatal period.
These findings suggest that oral sodium intake is one of the causes of high PA and PRA levels in newborns and infants, and that in the neonatal period, markedly low sodium intake increases the sensitivity of angiotensin II receptor in the adrenal cortex to the renin substance.

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The changes with time in the concentrations of serum triiodothyronine (T₃), thyroxine (T₄) and thyrotropin (TSH) levels after the oral administration of various thyroid hormones were investigated in order to find an adequate way for the administration of these hormones in hypothyroid patients.
The subjects employed were 3 cases of untreated hypothyroidism, 138 cases of treated hypothyroidism, 72 cases of postoperative adenomatous goiter and 56 cases of postoperative thyroid cancer.
The blood was drawn at 0, 1, 3, 8 and 24 hours in untreated hypothyroid patients and at three to five or 18 to 24 hours in the long-term treated patients after the administration of various thyroid hormones. Then serum T₃, T₄ and TSH levels were determined.
The peak levels of serum T₃ were observed at one and three hours after the administration of a single dose of 10-20μg and 30-40μg of synthetic T3, respectively, and then the levels of serum T₃ decreased gradually and returned to pretreatment levels by 24 hours. The mean peak levels of serum T3 were 120,217,352 and 472ng per 100ml after the administration of a single oral dose of 10, 20, 30 and 40pg of synthetic T₃, respectively. In the patients given a long-term treatment with synthetic T₃, the levels of serum T₃ were observed to be 180-480ng per 100ml at three to five hours after the administration of the last doses of 30-70μg and to become within normal values at 18 to 24 hours.
After the administration of synthetic T₄ in untreated hypothyroid patients, the levels of serum T₃ and T₄ were found to show a nonspecific diurnal variation, the basal T₃ and T₄ levels increased slowly, and the levels of serum TSH decreased very slowly day by day. After three weeks of treatment with 100μg per day of T₄, serum T₃ and T₄ levels reached normal values of 5.4μg and 100ng per 100ml, respectively, while the serum TSH level decreased to 20μU per ml. And then, after another three weeks of treatment with 150/μg per day of T₄, serum T₄ and T₃ levels increased to 10.0μg and 140ng per 100ml, respectively, and the serum TSH level decreased to the normal range.
In the patients given a long-term treatment of from 50 to 250μg daily of synthetic T₄, the levels of serum T₃ and T₄ remained within normal ranges at any time observed.
After the single daily doses of 50 and 100mg of desiccated thyroid in untreated hypothyroidism, the levels of serum T₃ were observed to increase to peak values of 320 and 460ng per 100ml at the end of three hours, respectively, and then, the levels of serum T₃ decreased gradually and returned to basal values by 24 hours, whereas the levels of serum T₄ were found to increase gradually.
In the patients given a long-term treatment with 50mg (o.m.), 75mg (t.i.d.) and 100mg (b.i.d.) per day of desiccated thyroid, the serum T₃ levels were observed to be 320,292 and 326ng per 100ml, respectively, at three to five hours and within the normal range at 18 to 24 hours after the last dose, whereas the levels of serum T₄ were within the normal range at either point observed. A significant correlation was observed between the dose of desiccated thyroid per kilogram of body weight and serum T₃ levels at three to five hours after the administration of the drug.
From these data, it was thought that the reason why the severe side effect was observed after T₃ but not after T₄ administration was that serum T₃ reached an unphysiological high level 1-3 hours after the administration of certain amounts of T₃,

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The lymphocyte transformation response to the allogeneic lymphocytes (mixed lymphocyte culture, MLC) was determined in nineteen well-controlled insulin-dependent diabetics (IDD) and nineteen matched normal subjects. All possible combinations between lymphocytes from the patients and controls were mixed in both one-way and two-way MLC. From the results of one-way MLC, the stimulatory capacity (SC) and responding capacity (RC) of IDD lymphocytes were compared with those of normal lymphocytes as follows :
(1) Nm→N : 10,538 ± 3,937 N; normal lymphocytes
(2) Nm→D : 8,466 ± 5,387 D; IDD lymphocytes
(3) Dm→N : 7,562 ± 3,088 m; mitomycin-treated stimulating lymphocytes
(4) Dm→D : 7,102 ± 4,873 (→ ; stimulatory direction, results; M ± SD cpm)
IDD lymphocytes showed a marked depressive function as stimulators (SC, (1) - (3)), but the RC of IDD lymphocytes was unchanged ((1) - (2)).
Phytomitogen-response was studied simultaneously for the same responding lymphocytes (N, D) of MLC. IDD lymphocytes exhibited significantly decreased responses to phytohemagglutinin P, pokeweed mitogen and concanavalin A.

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In order to elucidate a predisposition for so-called autoimmune thyroid disorders such as Graves' disease, chronic thyroiditis and myxedema, the incidence of thyroid antibodies was studied in relatives of patients with thyroid disorders. The relatives studied were all limited within a two degree relationship of the patients.
Serum antibodies to thyroglobulin and thyroid microsome were determined by susing the method of a hemagglutination test.
The following results were obtained;
1) Thirty six of 103 relatives (35%) were found to have such antibodies, and sixteen (7.0%) of 230 hospital controls were positive. This difference was significant (P<0.001).
2) There was no difference in the incidence among relatives of patients with Graves' disease and those chronic thyroiditis.
3) With regard to age, the incidence in the more than 20 years old group was significantly greater than that in the under 19 years old group.
4) There was no difference in the incidence between male and female.
These results suggested that the relatives of patients with so-called autoimmune thyroid disorders may have a predisposition for thyroid disorders.

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In order to investigate the vasopressor role of ADH in the regulation of blood pressure, passive immunization experiments with an antibody to AVP were carried out in experimentally hypertensive rats.
In hypertensive rats treated with deoxycorticosterone acetate (DOCA), spontaneously hypertensive rats (SHR) and spontaneously hypertensive stroke-prone rats (SHR-sp), the intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood pressure of 11-25mmHg, while in rats with two-kidney Goldblatt hypertension and normal rats, the blood pressure was not affected.
This strongly suggests that ADH contributed to systemic vaso-constriction in DOCA hypertension and spontaneous hypertension in rats.

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A sensitive bioassay (Radio receptor assay : RRA) for urinary hCG which is independent of plasma half life and metabolism has been developed by utilizing the specific binding of ¹²⁵I-hCG to 150-2000g fraction of homogenates of the rat testis.
The receptor and immunological activity (RRA/RIA) ratio of urinary hCG in pregnant and trophoblastic diseased women was examined.
In addition, the urine of women with normal pregnancies was studied for quantitative and qualitative differences among hCG molecules, by gel filtration on a Sephadex G-100, and each fraction was measured by RRA and radioimmunoassay (RIA).
1) The sensitivity of RRA was 4 ng/ml with a precision (lambda) of 0.03. The intraassay coefficient of variation and that for inter assay were 2-10% and 12.1% respectively. There was a complete lack of cross reaction with PRL, hCGa, hCGβ, and FSH; this indicated a high specificity of the RRA.
2) Receptor reactive hCG in urine throughout pregnancy showed a major peak in the 10th week and declined, but remained fairly constant until the 31th week of pregnancy. The RRA/RIA ratio in urinary hCG of normal pregnancies was highest in the first trimester and lower in the second and third trimester. The average value throughout gestation was 2.04 ± 0.18 (SE), which was about 2 times greater than that (1.08 ± 0.11 (SE)) of trophoblastic diseases (p<0.01).
3) The RRA/RIA ratio in the patients with trophoblastic tumors was highest in the hydatidiform mole and lowest in the chorioepithelioma.
4) When the urine of normal pregnancies was gel filtrated on a Sephadex G-100, it was found that receptor active molecules of hCG were present in urine of the first and second trimester.
These results indicated that the RRA/RIA ratio in urinary hCG was distinct in normal pregnancies from trophoblastic tumors and would contribute sufficiently to an early diagnosis and the treatment of successive trophoblastic disease in follow-ups of patients with hydatidiform mole.

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Constant iv infusion of TRH tartrate for 2 hours was administered to normal men in a dosage of 0.5 (n=4), 1.0 (n=2) and 2 (n=4) mg/120 minutes. Measurements at every 15 minutes were performed for plasma levels of TRH, TSH, Thyroxine (T₄) and Triiodothyronine (T₃) by radioimmunoassay.
Plasma levels of TRH increased promptly and stayed at the same levels until the end of the infusion. The Mean Clearance Rate (MCR), Half-life and Volume of Distribution of TRH were respectively, 4.62 ± 0.53 L/min. (M ± SE), 17.8 ± 3.8 minutes and 112 ± 15 L in the 0.5 mg administered group and 6.38 ± 2.50 L/min., 9.0 ± 1.4 minutes and 82 ± 30 L in the 2 mg administered group. Plasma levels of TRH increased in two phases, and increments of plasma TSH were dose dependable to the dosage of TRH. Plasma levels of T₄ increased gradually in the course of TRH infusion and stayed at high levels even in the withdrawal phase of TRH. Plasma levels of T₃ increased markedly during and after the TRH infusion in the 0.5 mg administered group, while increments of plasma T₃ were minute in the 2 mg administered group.
From the above data, it is suggested that the amount of TRH production in man, which is much more than has previously been reported, may indicate the existence of an extrahypothalamic synthesis of TRH in man.

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