Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys: metabolic and gas chromatography-mass spectrometry studies.

Infection-triggered, life-threatening salt-loss and hyperkalaemia developed in two male infants with wasting, inappropriately low plasma aldosterone concentrations and elevated plasma renin activity. The presumptive diagnosis of a defective terminal step in aldosterone biosynthesis was made by the presence of large amounts of 11-dehydrotetrahydrocorticosterone and its 18-hydroxylated metabolite (18-OH-THA), free 18-hydroxycorticosterone (18-OH-B) and 18-hydroxytetrahydrocorticosterone in the urine of both patients. The diagnosis of corticosterone methyl oxidase type II (CMO II) deficiency was confirmed by an elevated urinary 18-OH-THA to tetrahydroaldosterone ratio in one boy and by an elevated plasma 18-OH-B to aldosterone ratio in the other boy. Unknown steroids responsible for the salt-loss were not identified. Sodium supplementation but not short-term high dose oral 9 alpha-fluorcortisol (FF) normalized the hyponatraemia in one patient, in whom sodium (Na+)/potassium (K+) co-transport was decreased. Both patients eventually received long-term FF treatment to prevent impairment of longitudinal growth caused by chronic salt-loss. The diagnosis of CMO II deficiency should always be confirmed by elevated precursor-product ratios in urine or plasma, using radioimmunoassays with prior chromatographic separation. Metabolic studies as the short-term response of serum Na+ to high dose FF may not be helpful in differentiating aldosterone biosynthetic defects from end-organ resistance to mineralocorticoids.

[Treatment of radiogenic colitis with a rectal foam containing cortisol. Clinical and pharmacologic data]. / Die Therapie der radiogenen Kolitis mit einem cortisolhaltigen Rektalschaum. Klinische und pharmakologische Daten.

20 patients with highly dosed irradiation of the small pelvis had been treated with Colifoam (hydrocortisone) in order to prove the therapeutic effect of radiation-induced proctitis. Over a period of three to six weeks starting in the third week of irradiation all patients received one applicator filling of rectal foam after bowel movement daily. The findings were verified by proctoscopy, histology and subjective personal well being. In ten patients we determined the daily cortisol profiles. Six months post irradiation ten patients underwent barium enema of the colon. During therapy no major complaints were recorded. The proctoscopic findings showed little changes concerning the submucous vascular walls. In none of the patients any kind of late lesion could be observed. The daily cortisol profile did not show any aberration of the physiological patterns. In conclusion the local therapy of Colifoam can be considered an additional treatment of radiation-induced colitis (proctitis).

Effects of WY 47987 (atrial natriuretic factor 102-126) in patients with renal insufficiency: a placebo-controlled, randomised study.

We studied renal, hormonal and cardiovascular effects of ANF 102-126 (WY 47987) in seven patients with chronic renal failure (serum creatinine 25-68 mg/l) and in four normal volunteers. ANF or placebo bolus injections were given at 1, 2, and 3 micrograms/kg i.v. (each dose on separate days). As compared to placebo, ANF did not induce changes of renal excretory parameters, of plasma renin and aldosterone or of blood pressure and heart rate in patients. In healthy volunteers, however, the same dose of ANF increased urinary excretion of sodium, potassium, calcium, chloride and phosphorus as well as water, and creatinine clearances, and decreased plasma aldosterone. The data suggest blunted effectiveness of ANF bolus injections in patients with renal insufficiency.

Met-enkephalin inhibits mineralocorticoid production in isolated human aldosteronoma cells.

In vitro application of the morphinomimetic met-enkephalin resulted in inhibition of mineralocorticoid production by aldosterone-producing adenomas. Aldosterone, deoxycorticosterone, and corticosterone production by adrenocortical cells isolated from aldosteronomas has been studied under basal conditions and after stimulation with ACTH-(1-24). The blocking effect of met-enkephalin on the rate of aldosterone, deoxycorticosterone, and corticosterone release was significant at a concentration as low as 10(-11) M (P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Dose-dependent inhibition of steroid biosynthesis became more apparent with increasing amounts of met-enkephalin in the incubation medium (10(-11)-10(-5) M); at a concentration of 10(-5) M, met-enkephalin decreased the production of aldosterone by 45%, that of deoxycorticosterone by 51%, and that of corticosterone by 44%. Increased steroid biosynthesis stimulated by ACTH-(1-24) was also significantly blocked by met-enkephalin. In a concentration of 10(-5) M, met-enkephalin produced significant decreases in aldosterone (P less than 0.001), deoxycorticosterone (P less than 0.05), and corticosterone (P less than 0.001) production compared to the peak values obtained after stimulation with 0.85 X 10(-10) M ACTH-(1-24). These data allow us to conclude that the inhibitory effect of met-enkephalin on mineralocorticoid production exerted at the level of the adrenals might be complementary to the factor(s) thought to be involved in the regulation of adrenal steroid production, playing a role similar to that of the biogenic amines originating in the adrenal medulla and regulating the adrenal cortex by a peripheral neurohumoral paracrine mechanism.