Many investigators have found that the degree of iodination of thyroglobulin (Tgb) is directly correlated with its resistance to a variety of agents, such as alkali, heat, sodium dodecyl sulfate and freezing. It is also known that GSH enhanced the release of iodo-amino acids from Tgb during endogenous proteolysis.
No detailed information is available on the effect of GSH on proteolytic digestion of Tgb with different degrees of iodination. The present study was undertaken to determine the effect of GSH disruption of disulfide bonds of Tgb molecules on the susceptibility to in vitro enzymatic attack. The thyroids of rats fed on a high iodine or low iodine diet were labeled with 'I in vivo. With the preincubation of GSH, the following results were obtained.
1) Poorly-iodinated thyroid was more sensitive to autolysis than was highly-iodinated thyroid.
2) Increased sensitivity to autolysis in poorly-iodinated thyroid was considered not to be due to stimulation of thyroid protease activity mediated by TSH.
3) Poorly-iodinated protein was more readily degraded than highly-iodinated protein by thyroid protease, pepsin and pancreatin under the various pH ranges.
Since GSH is known to disrupt disulfide bonds and permit dissociation of Tgb molecules more readily, these observations support the concept that the exposure of the disulfide bonds to attack is greater in poorly-iodinated than in highly-iodinated Tgb. It is also suggested that reduction of disulfide bonds may be of considerable importance in the normal intrathyroidal proteolysis of Tgb.

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Coor and Randle reported on inhibition by epinephrine of the stimulant effect on insulin output from the rabbit's pancreas. This observation has been confirmed by in vivo and in vitro experiments. We have reported on the patients with pheochromocytoma that insulin release to various stimuli was markedly reduced and that α-adrenergic receptor blocker phentolamine prevented this catecholamine inhibition of insulin release. On the contrary a similar treatment with β-blocker propranolol potentiated catecholamine inhibitory effect. These observations indicate that adrenergic receptor mechanism has influence on the insulin secretion. In an attempt to elucidate these mechanisms, the effect of adrenergic receptor agents on blood sugar and plasma insulin levels in normal subjects were investigated. Various adrenergic receptor agents dissolved in 500 ml of saline solution were infused into the autecubital vein over a period of two hours after overnight fasting.
In normal subjects, 50 gm of glucose, 1.0 mg of tolbutamide and 30 gm of arginine were administered with the start of infusion of various adrenergic receptor agents. Blood was withdrawn into a heparinized syringe every 15 or 30 minutes before, during and after infusion.
Blood sugar was measured by an Auto Analyzer and plasma insulin was measured by the double antibody radioimmunoassay technique of Hales and Randle.
Infusion of 8-stimulator isoproterenol 0.36 mg in 6 normal subjects resulted in prompt elevation of plasma IRI levels without any change in blood sugar.
Infusion of α-stimulator phenirephrine 1-3 mg in 6 normal subjects had no effect on blood sugar and plasma IRI levels.
Infusion of β-blocker propranolol 10 mg in 9 normal subjects had no effect on blood sugar and plasm IRI levels.
Infusion of β-blocker propranolol 10 mg in 4 normal subjects completely prevented the 8-stimulator isoproterenol 0.36 mg stimulant effect of insulin release.
Infusion of α-blocker phentolamine 10-20 mg in 6 normal subjects resulted in slight elevation of plasma IRI without any change in blood sugar.
Infusion of another a-blocker phenoxybenzamine 100 mg in 5 normal subjects showed a more marked rise in plasma insulin levels.
Infusion of α-stimulator methoxamine 25 mg in 4 normal subjects completely prevented the α-blocker phentolamine 20 mg stimulant effect of insulin release.
50 gm of glucose was administered orally with the start of epinephrine infusion in 3 normal subjects. In spite of marked hyperglycemia during infusion, the plasma IRI response was relatively low. And 15 minutes after infusion, there was a prompt rise in IRI levels.
50 gm of glucose was administered orally with the start of α and β blockers infusion in 6 normal subjects respectively. The glucose tolerance curve and plasma IRI responses were not changed as compared to those found in glucose administration alone.
30 gm of arginine was infused with the start of α-blocker phentolamine 20 mg in 6 normal subjects. Blood sugar showed no change but plasma IRI response was slightly elevated as compared to those found in arginine infusion alone.
1.0 gm of tolbutamide was injected with the start of α-blocker phentolamine 30 mg infusion in 3 normal subjects. Plasma IRI responses elevated markedly and the decline of blood sugar was prompt and profound as compared to tolbutamide injection alone.
These observations indicate that adrenergic receptor mechanism has influence on the insulin secretion and it is concluded that α-receptor has an inhibitory and β-receptor has a stimulatory effect on insulin secretion.

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Sixty minutes' intravenous glucose infusion tests were carried out in normal subjects, borderline cases, and diabetics which were diagnosed by 50 g oral glucose tolerance test. Infusion was performed at the rate of 5 mg/kg/min. or 15 mg/kg/min. using 5% or 10% glucose.
The difference in the insulin responses among these groups was rather marked in the case of 15 mg/kg/min. infusion of 10% glucose for 60 minutes.
In the diabetics the insulin response to continuous intravenous glucose infusion was low from the start of the test and remained low during the test.
Serum insulin response of normal subjects, diabetics and patients with chronic hepatitis or hyperthyroidism was increased for a little while after the end of a 30 minutes' glucose infusion against decreasing blood sugar level and then returned to the basal line.
Diabetics showed a low insulin response during the glucose infusion and a slight response after the end of infusion-delayed insulin response.
In patients with chronic hepatitis or hyperthyroidism insulin responses were higher than normal, during the infusion and especially after the end of glucose infusion, and the time to reach the peak value was later than normal subjects-excessive insulin response.
In the 60 minutes' glucose infusion test in the normal subjects total insulin response of the second half was higher than the first half. But, in the diabetics, total insulin response of the first half was almost the same as that of the second half.
We concluded that these two glucose infusion tests are excellent tests to differentiate normal subjects from diabetics and from patients with chronic hepatitis or hyperthyroidism.

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We studied on gonadotropic potency of the pituitary in cases with Turner's syndrome, premature thelarche, dwarfism and endocrine disorders with synthetic LH-RH. LH-RH were given 1 /μg/kg to children and 100/μg/body to adult patients subcutaneously. Plasma LH and FSH levels were measured by the double antibody method of radioimmunoassay. In prepuberal Turner's syndrome, who are younger than 11 years old, lower LH response was found but FSH was markedly increased. Adult patients with Turner's syndrome exhibited a higher response of both LH and FSH following the administration of LH-RH. The response of LH-RH did not differ significantly between normal children and premature thelarche. Most patients with dwarfism showed significantly lower response to LH-RH than other endocrine disorders of the same age but a markedly higher response of LH and FSH was obteined in a pituitary dwarfism who showed a well balanced body structure. Pituitary response to LH-RH in Laurence-Moon-Biedl syndrome, pituitary chromophobe adenoma, amenorrhea with galactorrhea and anorexia nervosa were lower than that in other patients with functional amenorrhea, but a case of pseudohypoparathyroidism showed a higher response as secondary amenorrhea.
From the results, it is postulated that in some cases with endocrine disorders and metabolic diseases the response to LH-RH differ between prepuberal and adult. Namely, there is an aging influence on the response of LH-RH even in those patients who have the important gonadal dysfunction.

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The kinetics of triiodothyronine (T₃) and thyroxine (T₄) were investigated in a case of thyroxine-binding globulin (TBG) deficiency with hypothyroidism.
A 35 year-old man was admitted to Tohoku University Hospital on June 8, 1972, with the complaints of edema of face, sensation of cold, slow speech, memory impairment, hoarseness, decreased sweating, weakness and lethargy.
His basal metabolic rate was-28%, 24 hr ¹³¹I-uptake of the thyroid was 7%, ¹³¹I-T₃ resin sponge uptake (Triosorb Kit, Abbott Lab.) was 52% and plasma TSH measured by radioimmunoassay were 84 μU/ml. Serum total and free T₄ values measured by radioimmunoassay were low : 0.6 μg/dl and 0.54 ng/dl, respectively. Serum total and free T, values measured by radioimmunoassay were low : 18 ng/dl and 74 pg/dl, respectively. T₄-binding capacity of TBG measured by the method of Tanaka and Starr was null. T₄-binding capacity of T₄-binding prealbumin measured by polyacrylamide gel electrophoresis (borate buffer, pH 8.2) and Sterling's method of reverse-flow paper electrophoresis (glycine acetate buffer, pH 8.6) were 223 and 240 pg/dl.
When T₄-kinetics was investigated by Ingbar's method and T₃-kinetics by McConnon's single injection method, half-times of both T₄ and T₄ were shortened, turnover rates, distribution spaces and clearance rates of both T₃ and T₄ increased, extrathyroidal organic iodine and T₃ pools decreased and degradation rates of both T₃ and T₄ decreased compared to normal values.
When 400 pg per day of l-T₄ was administered, clinical symptomes were improved and serum T₃ value remained considerably higher than the pre-administration value.
Decreased T₄-binding capacities of TBG were observed in mother and younger sister of the prorositus. And younger sister had rheumatoid arthritis and diffuse nontoxic goiter.

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Reports on 307 cases were collected from 31 Universities and 2 affiliated hospitals through the questionnaires sent to them. 219 cases (71 %) of adenoma, 68 cases (22.1 %) of hyperplasia and 5 cases (1.7%) of cancer were comprized in this series. Nodular hyperplasia was nearly twice that of diffuse hyperplasia. The majority of cases of adenoma and nodular hyperplasia were between the ages of 30 and 50 years and more commonly seen in female, but in marked contrast with them, nearly 60% of cases of diffuse hyperplasia were under 30 years of age and the ratio of female to male was equal.
Normokalemic aldosteronism was seen in 22 cases (7%) in this study. It is worthy of note that the incidence of normokalemia in cases of hyperplasia (13.6%) was much higher than that of adenoma (4.3%), and of particular interest is the highest incidence of normokalemia (18.2%) in cases of diffuse hyperplasia. This result could be predicted, because the biochemical features of hyperplasia is said to be milder than those of adenoma.
Over 90% of cases of adenoma were cured or improved by adrenal surgery, compatible with the reports of Conn and Torikai. However, as opposed to adenoma, surgical treatment of hyperplasia revealed much less favourable results. After subtotal adrenalectomy, only 50% of the cases of hyperplasia showed cure or improvement of hypertension and electrolyte abnormality and the ? effect of adrenal surgery on hypertension was seen onlyin 61.5%of the cases of hyperplasia. Besides it should be emphasized that subtotal adrenalectomy of diffuse hyperplasia was the least effective, e.g. cure or improvement in only 26% and treatment failure in up to 47% of cases of diffuse hyperplasia. Only 47% of the cases of diffuse hyperplasia showed hypotensive response to subtotal adrenalectomy.
Just as Conn analyzed a group with of patients with hyperaldosteronism due to hyperplasia under the age of 25 years and tentatively suggested “congenital aldosteronism because of possible genetic enzyme defect such as 17α hydroxylase defect, we collected and analyzed 10 cases of hyperplasia under 24 years of age (8 cases of diffuse and 2 cases of nodular hyperplasia, male 5 cases and female 5 cases, the youngest was 3 years old girl). 9 cases did not respond to glucocorticoid except one case, suggestive of glucocorticoid remedial aldosteronism or 17α hydroxylase defect. 2 cases of nodular hyperplasia were cured by subtotal adrenalectomy, but the remaining 7 cases of diffuse hyperplasia showed no improvement or slight improvement by subtotal adrenalectomy with or without spironolactone. These results suggest that in children or young adults, there exists adult type of hyperaldosteronism caused by hyperplasia, e.g. what is called “acquired aldosteronism” with a tendency to more common occurrence and less favourable response to adrenal surgery of diffuse hyperplasia than nodular hyperplasia.
We could obtain opinions about the future management and “the term” of hyperaldosteronism caused by hyperplasia from several endocrinologists abroad by personal communication.
There is a wide variety of the term of hyperaldosteronism caused by hyperplasia such as idiopathic (Conn), pseudo-primary (Laragh), secondary primary (Stanbury) or nontumorous primary (Laidlaw) aldosteronism. We believe that for the time being, idiopathic aldosteronism is the most appropriate term because of uncertainty of the pathogenesis of hyperaldosteronism due to hyperplasia.
In Japan, as a future management of hyperplasia, there is a strong trend to prefer bilateral total adrenalectomy to subtotal adrenalectomy performed most commonly in this series. However, medical treatment abroad of hyperplasia mainly by spironolactone seems to be preferred to adrenal surgery, because of good response to spironolactone and poor results by adrenal surgery.

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