Abstract
Aldosterone is a homeostatic hormone, rising in volume depletion, sodium deficiency, and potassium loading, in response to angiotensin11 and elevation of plasma potassium. Pathophysiologically, in primary aldosteronism (PA) aldosterone levels are inappropriate for the patient’s sodium and potassium status, and thus outside the normal feedback loop. ACTH is equivalent with A11 and [K+] in elevating aldosterone: its effects differ from those of the other secretagogues in four ways. First, it is not sustained; second, it raises aldosterone and cortisol secretion with equal potency; third, it is outside the normal feedback loops, reflecting the epithelial action of aldosterone; and finally its possible role in driving inappropriate aldosterone secretion (aka PA) is not widely recognized. Thirty years ago, it was shown that on a fixed sodium intake of 175 meq/day 36 of 100 unselected hypertensives, in whom PA has been excluded on contemporary criteria, had 24 h urinary aldosterone levels above the upper limit of normotensive controls. More recently, the dexamethasone enhanced fludrocortisone suppression test (FDST) showed 29% of unselected hypertensives to have plasma aldosterone concentrations above the upper limit of normotensive controls. In subjects negative for PA on the FDST, 27% were extremely hyper-responsive to ultra-low dose ACTH infusion; the remaining 73% showed minimal aldosterone elevation, as did normotensive controls: all three groups had negligible cortisol responses. On treadmill testing, no differences were found between groups in (minimally altered) ACTH and cortisol levels: hyper-responders to ultra-low ACTH, however, showed a major elevation in PAC. The implications of these studies, when validated, are substantial for PA, in that approximately half of hypertensive patients appear to show inappropriate aldosterone levels for their sodium status. The physiological role(s) of ACTH as an acute aldosterone secretagogue, and the mechanisms whereby its continuous secretion is curtailed, remain to be established.
Highlights
For many years, most studies on aldosterone have focused on its action on renal salt and water transport, undeniably its major homeostatic role
primary aldosteronism (PA) clearly has a higher cardiovascular risk profile than age, sex, and blood pressure-matched essential hypertension (EH) [5, 6]: whether this is a primary effect of ACTH and Primary Aldosteronism aldosterone on the heart and/or blood vessels, or secondary to the increased total body sodium, is yet to be established [7]
It may be that they form part of the classical “fight or flight” response, by acutely activating mineralocorticoid receptors (MR) in the vasculature, a physiologic aldosterone target tissue expressing the specificity-conferring enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) [8]
Summary
ACTH is equivalent with A11 and [K+] in elevating aldosterone: its effects differ from those of the other secretagogues in four ways It is not sustained; second, it raises aldosterone and cortisol secretion with equal potency; third, it is outside the normal feedback loops, reflecting the epithelial action of aldosterone; and its possible role in driving inappropriate aldosterone secretion (aka PA) is not widely recognized. No differences were found between groups in (minimally altered) ACTH and cortisol levels: hyper-responders to ultra-low ACTH, showed a major elevation in PAC. The implications of these studies, when validated, are substantial for PA, in that approximately half of hypertensive patients appear to show inappropriate aldosterone levels for their sodium status.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
