Urine electrolyte response to 18-hydroxy-11-deoxycorticosterone in normal man

Understanding how adrenal corticosteroids influence urine electrolyte balance is central to endocrinology and renal physiology. Prior research has shown that aldosterone significantly affects sodium and potassium excretion, but less is known about the effects of structurally related steroids. This gap motivated the investigation of 18-hydroxy-11-deoxycorticosterone (18-(OH)DOC), a less-characterized corticosteroid. No prior work had resolved whether 18-(OH)DOC alters sodium or potassium excretion in humans. Existing knowledge focused on aldosterone's role in electrolyte regulation, but the specific contribution of 18-(OH)DOC remained unclear. This uncertainty drove the need for controlled human studies. The study aimed to clarify whether 18-(OH)DOC could exert similar or distinct effects compared to aldosterone. By comparing 18-(OH)DOC with a known steroid, researchers sought to identify unique physiological responses. This approach provided a framework to explore novel corticosteroid actions in human subjects.

The aim of the study was to determine whether 18-hydroxy-11-deoxycorticosterone (18-(OH)DOC) influences urine electrolyte excretion in healthy male volunteers. Researchers wanted to compare the effects of 18-(OH)DOC with those of aldosterone, a well-established corticosteroid. The specific problem addressed was the lack of evidence regarding 18-(OH)DOC's renal effects in humans. This uncertainty prompted the investigation of its antinatriuretic and kaliuretic properties. The study also aimed to measure plasma concentrations and clearance rates of the corticosteroids. By administering controlled doses, the researchers could assess physiological responses in real time. The motivation stemmed from the need to expand the understanding of adrenal steroid actions. This work provided a direct comparison between two corticosteroids in a human model.

Seven male volunteers received intravenous infusions of 18-hydroxy-11-deoxycorticosterone (18-(OH)DOC) at a dose of 120 microgram (353 nmol) over 1 hour. The same subjects also received infusions of glucose (50 g/l) and aldosterone (80 microgram, 222 nmol) for comparative analysis. Urine samples were collected to measure electrolyte excretion rates. Plasma concentrations of both corticosteroids were monitored during the infusion periods. The study design included a control condition using glucose to isolate steroid effects. Researchers measured urine volume, pH, sodium, and potassium excretion rates. Blood samples were taken to assess metabolic clearance rates and plasma half-lives. This approach allowed direct comparisons of physiological responses to each compound.

The administration of 18-(OH)DOC produced a weak antinatriuretic effect, reducing sodium excretion slightly. Urine potassium excretion remained unchanged compared to baseline. Aldosterone increased potassium excretion while decreasing sodium output. Both corticosteroids lowered urine pH, with aldosterone having a stronger effect. Urine volume did not change significantly with 18-(OH)DOC administration. Plasma concentrations of 18-(OH)DOC rose tenfold during infusion. Similarly, aldosterone plasma levels increased tenfold. The metabolic clearance rate of 18-(OH)DOC was slower than that of aldosterone. These findings indicated a distinct pharmacokinetic profile for 18-(OH)DOC. The observed effects were consistent with a weak mineralocorticoid action.

The study demonstrated that 18-hydroxy-11-deoxycorticosterone (18-(OH)DOC) has a weak antinatriuretic effect in normal human subjects. The researchers observed no significant changes in urine potassium excretion. Aldosterone produced more pronounced effects on electrolyte balance. Both steroids lowered urine pH, with aldosterone showing a stronger impact. The slower clearance rate of 18-(OH)DOC compared to aldosterone was confirmed. Plasma concentrations of both corticosteroids increased tenfold during infusion. These findings suggest a distinct pharmacokinetic behavior for 18-(OH)DOC. The authors propose that further studies are needed to determine whether 18-(OH)DOC can elevate blood pressure in humans.