Thyroxine analogues の代謝効果特に脂質代謝に対する効果
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Part 1. The metabolic effects of thyroxine analogues in the hypothyroid subjects ; A dissociation of various effects of analogues.<BR>L-thyroxine, L-triiodothyronine, D-triiodothyronine and four compounds of triiodothyroformic acid group were administrated in increasing doses to hypothyroid patients, and one gouty patient was administrated D-triiodothyronine or triiodothyropropionic acid.1. The administration of L-thyroxine and L-triiodothyronine to myxedematous patients did not result in a marked dissociation in the decrease in serum cholesterol level and the increase basal metabolic rate.<BR>2. In elevating the basal metabolic rate, D-triiodothyronine is approximately from 17 to 33 percent as active as L-thyroxine, acetyl triiodothyroformic acid is only from 0.1 to 0.4 percent as active as L-thyroxine, and each effect of triiodothyroformic acid, amide of triiodothyroformic acid and its methyl ester are less than from 0.1 to 0.2 percent, from 0.5 to 1.0 percent and from 0.1 to 0.2 percent of L-thyroxine.<BR>3. It seemed that D-triiodothyronine and triiodothyroformic acid group were more effective in reducing the serum cholesterol than in increasing the basal metabolic rate. It is interesting to note that this dissociation was marked in triiodothyroformic acid group.<BR>4. The administration of acetyl triiodothyroformic acid on hypothyroid subjects resulted in a decrease of serum uric acid and in an increase of urinary excretion of uric acid, and produced a negative phosphorus balance. In one gouty patient, a decrease of serum uric acid and an increase of urinary excretion of uric acid were observed over three months by the administration of D-triiodothyronine or triiodothyropropionic acid.<BR>5. The rate of disappearance of triiodothyroformic acid group from the blood of hypothyroid patients was observed as half time of protein bound iodine after the cessation of chronic administration. The half time of protein bound iodine were 2.9 days for triiodothyroformic acid, 2.0 and 2.4 days for acetyl triiodothyroformic acid, 8.8 days for its amide and 4.5 days for methyl ester.<BR>Part 2. The hypocholesterolemic effect of D-thyroxine and acetyl triiodothyroformic acid on euthyroid hypercholesterolemic patients.<BR>D-thyroxine or acetyl triiodothyroformic acid were administrated to the ten euthyroid hypercholesterolemic patients respectively.<BR>1. The administration of 4 mg. daily of D-thyroxine to ten euthyroid subjects produced a little elevation of basal metabolic rate. It seemed that the administration of less than 4 mg. daily of D-thyroxine failed to sustain the decreased serum cholesterol level in one or two weeks.<BR>2. In administering 4 mg. daily of D-thyroxine, the elevation of protein bound iodine level was slight but thyroidal radioiodine uptake was markedly inhibited.<BR>3. The administration ranging from 25 to 60 mg. daily of acetyl triiodothyroformic acid in ten euthyroid hypercholesterolemic patients produced rapid reduction of serum lipids without significant elevation of basal metabolic rate. In spite of the increase of doses, it seemed to return gradually to its pre-treatment value.<BR>4. The administration of relatively large doses, as much as 60 mg. daily of acetyl triiodothyroformic acid from the beginning was able to produce the reduction in serum cholesterol level without significant elevation of basal metabolic rate continuously for more than three months. At present, therefore, it seems that acetyl triiodothyroformic acid is the most potent hypocholesterolemic agents among thyroxine analogues.<BR>5. A high protein bound iodine and marked inhibition of thyroidal radioiodine uptake were observed by the administration of acetyl triiodothyroformic acid.
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