Abstract. Five normal young males on a low sodium diet received iv ACTH (1–24) infusions (10 IU/24 h) for 100 h in addition to diuretics. The aim of the study was to find out whether the biphasic effect of ACHT on aldosterone (initial stimulation followed by 'esacpe') could be prevented by keeping plasma renin activity (PRA) at a fairly constant high level. PRA was around 20 ng/kg/min before and towards the end of the ACTH infusion. Plasma aldosterone and aldosterone excretion rates were, nevertheless, only transiently stimulated, but the first was relatively more suppressed than the latter at the end of the ACTH infusion. Plasma 18-OH-corticosterone followed the same pattern. Even on the last infusion day, aldosterone and 18-OH-corticosterone levels were still higher than in normal ambulatory sodium-replete men. The fasciculata steroids cortisol, 11-deoxycorticosterone and corticosterone were continuously stimulated by ACTH. It is concluded that the biphasic response of zona glomerulosa steroids to ACTH is basically independent of renin and angiotensin II. However, the marked suppression of aldosterone secretion observed in sodium-replete individuals during prolonged ACTH treatment was not seen in this study. Angiotensin II or a different factor associated with sodium depletion may, therefore, partly protect the zona glomerulosa from adverse effects of ACTH observed in the sodium-repelete state.

Abstract. Mild Cushing's syndrome was diagnosed in a 35 year old woman. Elevated plasma and urinary cortisol levels were unsuppressible with up to 32 mg dexamethasone per day. Aldosterone, 18-OH-corticosterone and testosterone in plasma were normal and dehydroepiandrosterone-sulphate was low. No adrenal tumour was found by CT or adrenal venography, and bilateral cortisol secretion was demonstrated by steroid measurements in adrenal venous blood. A circadian rhythm of plasma cortisol was absent. Plasma ACTH was suppressed, even after injection of CRH, during insulininduced hypoglycaemia and after metyrapone administration, which led to a large fall in plasma cortisol but to a subnormal rise of plasma 11-deoxy-cortisol. The clinical diagnosis of primary micronodular adenomatosis of the adrenal gland was histologically confirmed, when the patient finally underwent bilateral adrenalectomy. In vitro, the adrenal cells did not produce more cortisol and aldosterone than adrenal cells from cadaver kidney donors. In vivo and in vitro, cortisol was slightly less than normally responsive to ACTH. Intermittent treatment of the patient with 800 mg/day of ketoconazole led to a rapid fall of cortisol secretion and clinical signs of adrenocortical insufficiency. Treatment for 7 weeks with 200–400 mg ketoconazole per day reduced plasma and urinary cortisol less dramatically into the normal range. This case unequivocally documents autonomous dysfunction of the adrenal cortex in this rare form of Cushing's syndrome and the efficacy of ketoconazole in the treatment of ACTH-independent hypercortisolism.

The transepithelial voltage (psi ms) of rat rectum in vivo increases for several hours in experiments under general anaesthesia. So far this was attributed by indirect evidence to increasing aldosterone plasma levels during the course of the experiment. We performed direct measurements of aldosterone and corticosterone plasma concentrations during intestinal perfusion experiments on barbiturate anaesthetized rats. Experiments were terminated for blood sampling at 10, 75, 300, 400, 800, or 1,800 min, respectively. (i) After 75 min of anaesthesia, surgical preparation was finished and plasma levels of aldosterone and of corticosterone were found increased by the factors 5 and 3, respectively, as compared to conscious controls. (ii) During the following 12 h, aldosterone further increased to levels 10 times as high as those of controls. In contrast, during the same period corticosterone slowly decreased but still remained elevated as compared to controls. (iii) The increase of both hormones was attenuated when abdominal surgery was omitted. (iv) The use of pentobarbital (Nembutal) instead of thiobarbital (Inactin) did not influence the adrenal response. (v) In adrenalectomized rats a continuous substitution with 65 ng X h-1 X kg-1 BWT aldosterone resulted in plasma levels as high as in conscious intact animals. (vi) Rectal psi ms started to move to higher lumen-negative values with a time delay of 1-1 1/2 h as compared with the increase of hormone levels. psi ms then stayed elevated until to the end of the experiments. We conclude that in vivo experiments of several hours duration in thio- or pentobarbital anaesthetized rats take place under conditions of aldosterone and corticosterone plasma levels which are high as compared to those of conscious unstressed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

A sensitive radioimmunoassay for estimating serum deoxycorticosterone is described which involves descending "overrunning" paper chromatography. An ethanolic paper eluate is used as a solvent for unlabelled deoxycorticosterone in the preparation of the standard curve. The values of the water blanks (7 ng/1) are similar to the sensitivity of the standard curve (5.8 ng/1). The normal mean serum concentration of deoxycorticosterone was found to be 84 ± 29 ng/1 (n = 30) in males and 55 ± 31 ng/1 (n = 35) in females. Serum deoxycorticosterone rose in healthy subjects upon injection of ACTH, after induction of insulin hypoglycemia and after administration of metyrapone, while the rise was absent or blunted in patients with Addison's disease and in patients with pituitary failure.

In a retrospective study on 59 patients (2 hypothalamic, 44 pituitary, 13 no confirmed disease) 69 pairs of insulin hypoglycemia tests (IHT) and short metyrapone tests (SMT) were evaluated. Cortisol and 11-desoxy-cortisol rsp. were compared as the endpoints. In 6 cases, the IHT was a technical failure because of insufficient hypoglycemia. In 25% of 63 pairs of tests, both tests were normal, (Group I), in 30% both abnormal (Gr. II). In 21%, IHT was normal, SMT abnormal (Gr. III) and in 24% IHT was abnormal and SMT normal (Gr. IV). The 2 patients with hypothalamic disease were in Group IV with completely normal SMT and severely pathological IHT. Other discrepancies could not be attributed to special pituitary disorders. In 9 patients of Group III and in 8 patients of Group IV (n = 17), the IHT alone was repeated 6-48 months after the original pair of tests which had been performed in most cases early after pituitary surgery. In 12 cases, the repeat IHT followed the trend of the SMT of the original test pair. In 5 cases, the IHT was unchanged. 14 of 19 patients of Group II, but only 5 of 28 patients of Group III and IV required permanent substitution with hydrocortisone.