Autonomous Aldosterone Secretion as a Subclinical Form of Primary Aldosteronism: Pathogenesis and Clinical Significance

Abstract

In recent years, a substantial prevalence of primary aldosteronism (PA) has been demonstrated in both normotensive and mildly hypertensive cohorts. Consequently, a classic presentation of the syndrome, i. e. moderate-to-severe and resistant hypertension with concomitant hypokalemia, should be considered a tip-of-the-iceberg phenotype of a wide PA spectrum. Its entire range encompasses the non-classic clinical forms of mild hypertension and prehypertension but also several biochemical presentations, including patients who meet PA screening and confirmation test criteria, as well as those with either of them and those with other parameters indicating mineralocorticoid excess. In the current review, research insights on the pathogenetic background and clinical significance of autonomous aldosterone secretion (AAS) are presented, which is defined as a constellation of either: 1) normotension, normokalemia, a positive PA screening (high aldosterone-to-renin ratio) and/or confirmation test, or 2) hypertension, normokalemia and a positive PA screening but negative confirmation test. For this purpose, a literature search of the PubMed database was conducted. Advances in immunohistochemistry and genetic sequencing of isolated adrenal cells are provided as probable morphologic basis of the wide range of aldosterone secretion autonomy. Also, the role of corticotropin as an aldosterone secretagogue is discussed. To date, clinical studies depict consequences of subclinical PA phenotypes, such as increased mortality and risk of developing hypertension, impaired arterial and kidney function, association with metabolic syndrome and age, as well as osteoporosis.

Autonomous Aldosterone Secretion in Patients with Adrenal Incidentaloma

“…Such research has been accumulating in the case of MACS [ 18 ]. In our view, in patients with adrenal adenomas, AAS should be considered on par with mild hypercortisolemia, since the clinical consequences of both endocrinopathies may prove equally severe [ 5 ].…”

“…The study protocol consisted of: recording patient history and physical examination, ECG, laboratory examinations, 24 h ambulatory blood pressure monitoring (ABPM), TTE, and measurement of common carotid arteries’ (CCAs) IMT. As previously reviewed, PA/AAS has been associated with HT, atherosclerosis, metabolic syndrome, and pathologic cardiac remodeling, which underlies the methodology of the study (respectively, ABPM, IMT, lipid profile, and TTE) [ 5 , 7 , 10 ].…”

“…In fact, accumulating evidence indicates the current approach toward PA does not encompass the whole spectrum of renin-independent excess aldosteronism [3,4]. Recently, we proposed the term 'autonomous aldosterone secretion' (AAS) to describe biochemical and clinical presentations of the disorder that do not meet current criteria of PA [5]. These presentations include: (1) patients with normotension (nT) and normokalemia but biochemically proven Ald excess, and (2) patients with HT and normokalemia who meet PA screening but not confirmatory test criteria, provided Ald is not suppressed (in both cases).…”

Progress on Genetic Basis of Primary Aldosteronism

“…[ 1 , 7 ]. It has been reported that autonomous aldosterone secretion as a subclinical form of PA accompanied by normotension increases the risk of cardiovascular disease, kidney disease, and osteoporosis [ 8 ].…”

Intrinsic Adrenal TWIK-Related Acid-Sensitive TASK Channel Dysfunction Produces Spontaneous Calcium Oscillations Sufficient to Drive AngII (Angiotensin II)-Unresponsive Hyperaldosteronism

“…Aldosterone production that is not fully suppressed by sodium loading, AngII (angiotensin II) receptor (AT 1 R) blockade, or mineralocorticoid receptor activation 1,2 is recognized as dysregulated and independent of the renin-angiotensin system (RAS). This RAS-independent (autonomous) component of aldosterone production occurs within a spectrum of disorders that range from subclinical disease to overt primary aldosteronism (PA).…”