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Search for other papers by T. RUSSELL FRASER in
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1. Two in vitro tests are described for measuring the inhibitory potency of antithyroid drugs on enzymic and non-enzymic oxidative iodination of protein; one, a milk enzymic iodination test, and the other an enzyme-free peroxide iodination test.
2. Five recognized antithyroid drugs have been tested: 2-thiouracil, 2-carbethoxythio-methyl-glyoxaline, potassium thiocyanate, resorcinol and sulphathiazole. By means of the milk enzymic test they could be ranged in order of potency, as indicated by the molar concentrations required for 50 % inhibition. They could also be separated into different types by the speed with which they pass from minimal to maximal inhibition with rising molar concentration.
3. With the enzyme-free peroxide test, thiouracil, but not resorcinol, was found to be inert; with the enzymic test, both were nearly equivalent in potency.
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1. An anti-thyroxine compound, n-butyl-3:5-diiodo-4-hydroxy-benzoate (BDHB), did not exert any anti-thyroxine effect during the treatment of one myxoedematous patient with intravenous thyroxine.
2. This drug, when given for short periods to nine thyrotoxic patients, induced a partial remission, no greater than that obtained in two of these patients with iodides, and not well sustained beyond about three weeks' administration.
3. The results suggest that this drug cannot be employed clinically in dosages high enough to produce a definite anti-thyroxine effect.
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SUMMARY
(1) In a village in the endemic-goitre area in Thailand, studies of the iodine metabolism (127I as well as 131I, and including chromatographic analysis of thyroid biopsy digests) have been made on 35 subjects sampled particularly from the younger decades.
(2) The high 24-hr. uptake of 131I by the thyroid was correlated inversely with the urinary 127I-iodide excretion; the [131I]thyroid discharge rate was very rapid in the diffuse goitres of young subjects, less so in the older subjects with nodular goitres, and was not rendered normal by a previous iodide repletion.
(3) Thyroid biopsy studies on some of these subjects showed: (a) in the three diffuse endemic goitres of young subjects studied, low iodine concentrations, rapid formation of [131I]iodothyronines, a normal MIT:DIT ratio (< 1) and a normal distribution of 127I-iodoaminoacids; (b) in two nodular endemic goitres in older individuals total iodine concentration was similarly low, but the rate of formation of [131I]iodothyronines was very slow, the MIT:DIT ratio high (> 1), and the 127I-iodoaminoacids stored consisted preponderantly of iodotyrosines, as found also in twenty sporadic goitres in Londoners.
(4) These findings suggest that hormone synthesis was normal and rapid in the diffuse endemic goitres of the young subjects, but defective in the nodular endemic goitres of older subjects, as was also found in sporadic goitres.
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Search for other papers by T. RUSSELL FRASER in
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SUMMARY
As measured both by immunoassay and bioassay during a glucose tolerance test (50 g.) on ten subjects in the third trimester of pregnancy, the serum insulin levels fasting, 1 and 2 hr. after glucose were raised at least threefold compared with the levels in 23 non-pregnant women.
The renal clearance of immunoassayable insulin was lower than that in the non-pregnant state (the mean in the pregnant subjects was 0·18 ml./min. compared with 0·45 ml./min. in the normal non-pregnant subjects).
In the same subjects the mean serum non-suppressible insulin-like activity, which is unaltered by oral glucose, was 1·5 times higher than the non-pregnant mean level, but this difference was not significant.
Four pregnant latent diabetics, tested similarly in the latter part of pregnancy, showed even higher fasting serum insulin levels than the normal pregnant subjects, but a lessened response to the same glucose load.
Search for other papers by J. C. MARSHALL in
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Search for other papers by D. C. ANDERSON in
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Search for other papers by T. RUSSELL FRASER in
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SUMMARY
The effects of clomiphene citrate were studied in nine normal men, in three patients with partial panhypopituitarism, and in four patients with isolated gonadotrophin deficiency. The administration of this drug to the normal subjects in a dosage of 3 mg/kg/day for 10 days resulted in a mean rise in serum luteinizing hormone (LH) of 107%, in plasma 17β-hydroxyandrogens (17-OHA) of 114%, and in plasma total cortisol of 86%. The rise of testosterone concentration in normal subjects was associated with a doubling of the non-protein bound fraction, and also with increased binding of testosterone to sex hormone-binding globulin (SHBG). In contrast, plasma non-protein bound and urinary unconjugated cortisol remained unchanged. The percentage of plasma cortisol not bound to protein fell, indicating that the rise in total plasma cortisol was secondary to increased protein binding. This was confirmed by finding increased binding of both cortisol and testosterone to their specific binding globulins at 1 °C, due apparently to increased concentrations of SHBG and corticosteroid-binding globulin after clomiphene administration. All the responses to clomiphene were prevented by simultaneous administration of fluoxymesterone in two normal subjects.
All the hypopituitary patients showed no rise of LH, 17-OHA or cortisol. The hypogonadotrophic patients, however, showed a normal total cortisol rise.
It is suggested that clomiphene has two actions. First, it interferes with the hypothalamic feed-back mechanisms for testosterone, resulting in increased LH secretion, and secondly it has an oestrogen-like effect in stimulating production of steroid-binding globulins.
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Search for other papers by P. HARSOULIS in
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SUMMARY
Human luteinizing hormone (LH) was given by intravenous infusion to four normal male volunteers. The disappearance of immunoreactive LH from serum followed a single exponential decay, the mean half-life being 136 min. The effect on the testis of the infused LH was variable. Despite high serum LH levels being achieved, only one subject showed a clear increase in circulating 17β-hydroxyandrogen (17-OHA) levels, the other subjects showing little change in the immediate post-infusion period. All subjects had low 17-OHA levels in the period 24–36 h after the infusion. No consistent changes in serum follicle-stimulating hormone levels occurred during or after the infusion.
This suggests that other factors besides LH are necessary to produce maximal testosterone secretion by the testis, and may also be concerned in controlling the diurnal variation of testosterone.