The effects of canrenoate K on corticosteroid biosynthesis in nephrectomized dogs.

There is evidence from in vitro experiments that spironolactone not only antagonises the peripheral effects of aldosterone but also inhibits the production of corticosteroids by the adrenals. However relevant data from clinical studies are contradictory probably because spironolactone action on the kidneys also activates other mechanisms, such as renin secretion and potassium retention, which are potent stimulants of the adrenal cortex and thus tend to compensate for the inhibition. To determine the inhibitory effect of spironolactone on the adrenals in isolation, three groups of nephrectomized dogs were studied. Steroidogenesis was stimulated either by angiotensin II, potassium, or ACTH infusion. Potassium canrenoate was administered i.v. bolus at the beginning of the experiment. All the groups showed a similar marked decrease in plasma renin activity (PRA). Plasma aldosterone and cortisol were stimulated by the appropriate stimulus but their increase was blunted after the canrenoate K administration. The altered response between the subgroups was statistically significant (P less than 0.05). Plasma progesterone increased after the administration of canrenoate K. The response difference between the respective subgroups was again statistically significant (P less than 0.05). Canrenoate K was rapidly eliminated from the systemic circulation. These data indicate that canrenoate K causes a partial inhibition of aldosterone and cortisol stimulated secretion but augments the plasma levels of the precursor progesterone, as would be expected following inhibition of specific steps of corticosteroid biosynthesis.

The role of serum calcium on carbohydrate metabolism in severely uraemic patients.

In 25 severely uraemic patients, the relation of serum calcium levels and oral glucose tolerance test (GTT) was studied. Seventeen of the 25 patients, who had a creatinine clearance of 6.16 +/- 1.24 ml . l-1 and a low serum calcium (6.53 +/- 0.35 mg%), had abnormal oral GTT, while from the other 8 patients, who had a creatinine clearance of 6.73 +/- 1.05 ml . l-1 and a normal serum calcium (8.75 +/- 0.60 mg%), only 4 had abnormal oral GTT. In 6 out of 17 patients, the low serum calcium (6.50 +/- 0.34 mg%) was normalized (8.85 +/- 0.54 mg%) by giving calcium gluconate in normal saline intravenously for two days. Subsequently to the calcium treatment, in four of these six patients the oral GTT changed to normal. The insulinogenic index showed increased secretion of insulin in the four patients whose oral GTT was normalized. These findings led us to the conclusion that low serum calcium is one of the contributing factors in the development of abnormal GTT in severely uraemic patients.

Adrenal responsiveness during and after intermittent haemodialysis.

ACTH and cortisol were measured by radioimmunoassay in 15 patients undergoing long term haemodialysis. Also a basal ACTH stimulation test was done by administration of 250 micrograms of Synachten (Synthetic ACTH, CIBA foundation) and the results compared with those of normal controls and end-stage chronic renal failure patients (CRF). All 15 had been receiving intermittent haemodialysis three times weekly for 5 hours on a twin coil dialyser. The duration of dialysis was from 6 to 20 months and the mean value of pre - dialysis serum creatinine was 1093 +/- 182 mumol/l. Both hormones had significantly risen in the middle and at the end of dialysis (p less than 0.005), While they had fallen back to normal mean levels 24 hours after dialysis. The Synachten stimulation test showed that adrenal response was within normal limits in both groups of patients, but dialysis patients responded significantly better (p less than 0.05) than patients with end stage CRF. We concluded that the adrenal responsiveness is within normal limits during and after regular haemodialysis and our likely explanation is a fall in plasma volume produced by the extracorporeal circulation and the increased turnover of cortisol during haemodialysis.

Haemodialysis and hypothalamo-pituitary-testicular axis.

Disturbances in testicular function develop in uraemic patients, but the effect of haemodialysis on them has not been determined definitively. Because of this, 22 patients with chronic renal failure who were receiving regular dialysis treatment underwent studies of the hypothalamo-pituitary-testicular axis before, during and after a dialysis. On all these occasions, serum testosterone concentrations were lower than the values found in 26 normal men. In contrast, serum concentrations of FSH and LH were higher than normal. 13 of these patients showed a normal response of the hypothalamo-pituitary system to the clomiphene stimulation test and a diminished response of Leydig's cells to the human chorionic gonadotropin stimulation test. It is concluded that haemodialysis does not affect the impaired gonadal function of male uraemic patients.

Comparison of various treatment schedules for accelerating the elimination of radioiodine from the thyroid and the human body.

In 68 euthyroid patients undergoing 131I thyroid function tests the thyroidal, urinary and plasma protein-bound radioactivity has been serially measured for 14 days. The patients were subdivided in controls and 9 groups treated with potassium iodide, carbimazole, potassium perchlorate and TSH, singly or in combination. The aim was to devise a treatment scheme for accelerating the release of iodine from the thyroid and the elimination from the body in cases of accidental radioiodine poisoning if the patient is seen after the radioiodine has already been taken up by the gland. All treatment schedules were effective, but TSH injections gave the best results, especially if combined with carbimazole and potassium perchlorate. This combination is the treatment of choice under these circumstances.

Effect of frequency of administration on the accumulation and metabolism of (35S) propylthiouracil by the rat thyroid.

Repeated administration (every 8 h) of (35S) Propylthiouracil (PTU) resulted in gradual accumulation of unmetabolised PTU by the thyroid gland until the 9th dose was given. Subsequently a plateau-level was attained which was proportional to dose with the two dose levels used. During repeated administration once daily the intrathyroid concentration of free PTU varied markedly in the course of each 24-h period. Chromatographic analysis showed four compounds: PTU, sulphate and two unidentified compounds as well as origin material. The proportions of these compounds were different in the different dose studies. Thus, the ratio of compound Y/compound X was found to be inversely related to dose. The plasma 35S-radioactivity increased throughout the studies and was proportional to dose.