Zusammenfassung
5 männliche Patienten mit primärem Hyperaldosteronismus (2 Adenomträger, 3 Fälle mit idiopathischer Hyperplasie), die unter einer Standarddiät mit 135 mval Natrium täglich standen, wurden stationär mit 3 × 100 mg Spironolakton täglich behandelt. Vor und 5 (7) Tage nach Einleitung der Therapie wurden die Serumspiegel der Spironolaktonmetabolite Canrenon und Canrenoat-K, von 8 Nebennieren-steroiden, von Natrium und Kalium, ferner Angiotensin II und die Plasmareninaktivität bestimmt sowie die Elektrolytausscheidung im Urin gemessen. Spironolakton hatte erwartungsgemäß eine Natriumausscheidung und Kaliumretention zur Folge. Während bei 4 Patienten die Plasmareninaktivität während des gesamten Versuchszeitraumes supprimiert blieb, stieg sie bei einem Patienten 3 Tage nach Behandlung stark an. Bei diesem Patienten kam es unter Spironolakton auch zu einem prompten und ausgeprägten Anstieg von 11-Desoxycortisol, 11-Desoxycorticosteron, Corticosteron und zu einem besonders terminal ausgeprägten Anstieg vom 18-OH-Desoxycorticosteron. Dies dürfte Ausdruck einer Hemmung der 11- und 18-Hydroxylasen durch Metabolite des Spironolaktons sein. Allerdings kam es nicht zu einem Abfall von Aldosteron. Dieses Hormon stieg vielmehr in den ersten 3 Behandlungstagen leicht, später in zeitlicher Übereinstimmung mit der Plasmareninaktivität stark an. Dagegen waren die Aldosteronkonzentrationen der übrigen Patienten 1 Tag nach Behandlungsbeginn leicht abgefallen, um im weiteren Verlauf um ihren Ausgangswert zu schwanken. Auch bei diesen Patienten sah man einen Anstieg von 11-Desoxycorticosteron und Corticosteron unter Spironolaktonbehandlung. Die beobachteten Veränderungen waren aber nicht so ausgeprägt, wie nach den Ergebnissen bei Versuchspersonen mit diätinduziertem Hyperaldosteronismus zunächst vermutet worden war. Obwohl Adenomträger unter Spironolakton zu einem leichten Abfall ihrer Serumaldosteronkonzentrationen tendierten, während die Patienten mit Hyperplasie im Mittel einen Anstieg zeigten, waren diese Unterschiede nicht ausgeprägt und trafen nicht in jedem Einzelfall zu. Offenbar ist Ausmaß und Dauer der Hemmung der Aldosteronbiosynthese durch Spironolakton individuell unterschiedlich, so daß sie bei der medikamentösen Therapie des Conn-Syndroms in ihrer Bedeutung hinter der Blockade der Aldosteronwirkung am Rezeptor zurücktritt.
Summary
5 male patients with primary hyperaldosteronism (2 due to adenomata, 3 due to idiopathic hyperplasia) were treated with 100 mg spironolactone t.i.d. while on a diet containing 135 meq sodium daily. Serum levels of drug metabolites, of 8 adrenal steroids, of sodium and potassium, plasma renin activity (PRA) and angiotensin II (AT II) in plasma as well as sodium excretion in urine were measured before and during 5 (7) days of treatment. Spironolactone caused sodium excretion and potassium retention as it was shown by the changes in electrolytes in the serum and urine. Whereas PRA remained suppressed in 4 patients during the period of observation, a significant increase of PRA occurred 3 days after starting the spironolactone medication in another patient. In this patient also, a prompt and considerable increase of 11-deoxycorticosol, 11-deoxycorticosterone, corticosterone and a terminal increase of 18-OH-deoxycorticosterone was seen, which points at an inhibition of adrenal 11- and 18-hydroxylases by metabolites of spironolactone. Serum aldosterone, however, did not fall, but rose slightly within the first 3 days and — in accordance with the kinetics of PRA — significantly during the following days under spironolactone. In the other 4 patients, the mean concentrations of aldosterone in serum decreased slightly within the first day of spironolactone medication and oscillated around the control levels on the following days. A moderate but significant increase of 11-deoxycorticosterone as well as of corticosterone was also observed under the influence of spironolactone in these patients. These alterations, which are also consistent with the hypothesis of an inhibition of 11- and especially 18-hydroxylases, were however, less pronounced than was expected from previous studies with diet-induced hyperaldosteronism. While patients suffering from adenoma tended to show a decrease in their serum aldosterone, those suffering from idiopathic hyperplasia tended to show an increase in response to spironolactone. There slight differences in the mean values, however, were neither significant nor consistent in the individual cases. It was concluded that the inhibitory action of spironolactone on aldosterone biosynthesis is variable and thus of less significance than its inhibition of the aldosterone effects at the receptor sites.
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Abshagen, U., Spörl, S. & Oelkers, W. Influence of spironolactone on serum corticosteroids in primary hyperaldosteronism. Klin Wochenschr 57, 173–180 (1979). https://doi.org/10.1007/BF01477405
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DOI: https://doi.org/10.1007/BF01477405