Masaaki Yamazaki

原発性アルドステロン症に対するTrilostane (MWD-1822) の効果

Six patients with primary aldosteronism (PA), one with idiopathic hyperaldosteronism (IHA), one with glucocorticoid responsible hyperaldosteronism (GRHA) and eight with essential hypertension (EH) were treated with trilostane (MWD-1822) (4 alpha, 5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis, for 9-47 days with a daily dose of 30-960 mg. Blood pressure decreased slightly and gradually from 30 min. to 360 min, plasma aldosterone (PAC) and cortisol concentration (F) decreased, and plasma dehydroepiandrosterone concentration (DHEA) increased 120 min. after the administration of a single dose of 120 mg of trilostane. In the patients with PA, IHA and GRHA on long term therapy with trilostane, blood pressure decreased, PAC and F were depleted, serum improved within normal limits and DHEA increased, but plasma progesterone concentration (Prog.) changed variously and plasma renin activity (PRA) remained suppressed. In the patients with EH, systolic pressure decreased in 5 out of 8 (under - 20 mmHg), and diastolic pressure decreased in 3 out of 8 (under - 10 mmHg), DHEA increased in all, but the changes in serum potassium, PAC, F, Prog. and PRA were various. There was no remarkable reaction after the administration of trilostane. It is concluded that trilostane is an effective inhibitor of 3-hydroxysteroid dehydrogenase in vivo and that it is useful in the treatment of primary aldosteronism and other hypertension due to hyperproduction of aldosterone.

A Simple Method Measuring Aldosterone Secretion Rate Using 125I-aldosterone

: A simplified radioimmunoassay system for aldosterone secretion rate was developed by using radioiodine-labelled aldosterone and highly specific antiserum to aldosterone. An antibody was produced in rabbits by injecting aldosterone-oxime coupled with bovine gamma-globulin once a month. Aldosterone-oxime was labelled with 125I by using the chloramine T method described by Hunter and Greenwood. 3 ml of a twenty-four-hour urine specimen was used for the radioimmunoassay. Following CH2Cl2 extraction, pH 1 hydrolysis was carried out for twenty-four hours. Separation of the aldosterone extract was achieved by paper chromatography (hexane:benzene:methanol:water = 1:9:5:2.5). The minimum measurable concentration was under 1pg, and adequate intraassay and interassay precision were obtained. Aldosterone secretion rate was 89.6 +/- 25.8 (mean +/- SD)mug/day in normal subjects and was similar in low- and normal-renin essential hypertension. Significant high values (806.4 +/- 65.8mug/day) were obtained in primary aldosteronism and were slightly high in secondary aldosteronism and high-renin essential hypertension. The aldosterone secretion rate correlated positively with plasma aldosterone level (r = 0.731, p < 0.01). Aldosterone secretion rates were obviously higher than plasma levels in primary and idiopathic aldosteronism. From these results, it is concluded that this method is a very useful and reliable one for measuring aldosterone secretion rate and for discriminating primary aldosteronism from low-renin essential hypertension. it is superior in its simplicity, and there is no need to use a liquid scintillation counter.