Plasma Aldosterone ConcentrationEdit
Plasma aldosterone concentration (PAC) is the circulating level of the hormone aldosterone in blood plasma. Aldosterone is a mineralocorticoid produced by the adrenal cortex that acts on the distal nephron to promote sodium reabsorption, potassium excretion, and thereby influence extracellular fluid volume and blood pressure. Clinically, PAC is interpreted together with measures of the renin axis—most commonly plasma renin activity or direct renin concentration—as part of a screening algorithm for disorders of aldosterone production, particularly primary hyperaldosteronism. Measurements are typically reported in ng/dL or pmol/L, and values must be interpreted in the context of pre-analytic conditions, assay method, and concurrent therapies.
The physiology of PAC sits at the center of the body’s sodium and water balance. Aldosterone release is tightly regulated by the renin-angiotensin-aldosterone system (renin-angiotensin-aldosterone system), potassium levels, and adrenocorticotropic signals. When renal perfusion falls or potassium rises, the juxtaglomerular cells release renin, setting off a cascade that increases angiotensin II and ultimately stimulates aldosterone secretion. In the kidney, aldosterone binds to the mineralocorticoid receptor in principal cells of the distal tubule and collecting duct, increasing the transcription of sodium channels and the sodium-potassium ATPase, thereby promoting sodium reabsorption and potassium excretion. This process expands extracellular fluid and can raise blood pressure, while helping to maintain electrolyte homeostasis. In practice, PAC reflects both adrenal production and the broader activity of the RAAS, making interpretation sensitive to posture, hydration, salt intake, and medications that alter the renin axis.
Physiology and Regulation
The renin-angiotensin-aldosterone system
The RAAS links kidney perfusion and systemic blood pressure to aldosterone output. Low blood pressure or reduced effective circulating volume stimulates renin release, which converts angiotensinogen to angiotensin I and, via angiotensin-converting enzyme, to angiotensin II. Angiotensin II directly stimulates aldosterone synthesis and release, while also constricting efferent arterioles in the kidney and influencing thirst and sympathetic activity. The net effect is a coordinated attempt to restore blood pressure and volume. For this reason, PAC is interpreted with renin-related measures, and the ratio of aldosterone to renin (the aldosterone-to-renin ratio, or ARR) is a common screening tool for excess aldosterone production independent of renin activity. See Aldosterone-to-renin ratio for more on this composite metric.
Aldosterone physiology
Aldosterone’s primary target is the distal nephron, but it also exerts effects on other tissues, including the heart and vasculature, that may influence long-term cardiovascular risk. Aldosterone can promote sodium retention, potassium loss, and water reabsorption, contributing to volume expansion. While these actions are essential for responding to acute hypovolemia, chronic overproduction or inappropriate regulation can contribute to hypertension and electrolyte disturbances. See Aldosterone for a broader discussion of hormone biology and mineralocorticoid receptor for receptor signaling mechanisms.
Measurement and Interpretation
Methods and units
PAC is measured from blood samples drawn under standardized conditions. Common units are ng/dL or pmol/L; 1 ng/dL is approximately 27.1 pmol/L. Results are lab-dependent and must be interpreted using the reference ranges provided by the assay in use. Because aldosterone levels vary with posture, time of day, and salt balance, practice guidelines emphasize consistent sampling conditions when screening for disorders of aldosterone excess.
ARR and testing
Aldosterone-to-renin ratio (ARR) combines PAC with a renin measure—either plasma renin activity (PRA) or direct renin concentration—to identify cases in which aldosterone production is inappropriately high relative to renin activity. An elevated ARR suggests primary hyperaldosteronism and warrants confirmatory testing. See Aldosterone-to-renin ratio and plasma renin activity for related concepts. Clinicians may also use direct measures of renin to improve interpretability, depending on the laboratory and clinical context.
Pre-analytical considerations and common pitfalls
Several factors can bias PAC and ARR. Posture (upright versus recumbent), dietary salt intake, time of day, and hydration status influence PAC and renin. Medications have well-described effects: diuretics, ACE inhibitors, ARBs, certain beta-blockers, NSAIDs, and particularly potassium-sparing agents (e.g., spironolactone, eplerenone) can suppress or elevate the renin-angiotensin-aldosterone axis and lead to false positives or negatives in screening. For accurate interpretation, clinicians often require the patient to discontinue or substitute interfering drugs for an appropriate interval before testing, or to interpret results in light of current therapy. If testing is pursued, clinicians frequently measure both PAC and either PRA or direct renin concentration to calculate ARR and assess the likelihood of autonomous aldosterone production. See saline suppression test, salt loading test, and plasma renin activity for related confirmatory approaches.
Reference ranges and variability
Because assays differ and due to state-dependent variation, reference ranges are not universal. Laboratories provide assay-specific reference intervals, and clinicians interpret PAC and ARR within that framework, along with patient factors such as age, sex, body mass, and comorbidities. See Aldosterone for broader laboratory considerations in hormone testing.
Clinical Relevance
Primary hyperaldosteronism
Primary hyperaldosteronism is a disorder characterized by autonomous aldosterone production with relatively suppressed renin. It commonly presents with hypertension and may be accompanied by hypokalemia, though potassium levels can be normal in many cases. Common etiologies include aldosterone-producing adenoma (often termed Conn's syndrome) and bilateral adrenal hyperplasia. Early identification via PAC and ARR can guide management, including adrenal surgery for unilateral disease or mineralocorticoid receptor antagonists for bilateral disease. See primary hyperaldosteronism and Conn's syndrome for detailed discussions of presentation and management.
Secondary hyperaldosteronism
Secondary hyperaldosteronism results from elevated renin due to reduced renal perfusion, hypovolemia, heart failure, cirrhosis, or nephrotic syndrome. In these settings, high PAC reflects a compensatory response to systemic derangements rather than autonomous adrenal overproduction. Distinguishing primary from secondary forms is crucial for treatment decisions and prognosis and relies on ARR alongside clinical context and confirmatory testing. See secondary hyperaldosteronism for more.
Management implications
Treatment depends on the underlying cause and may involve lifestyle adjustments (such as sodium management) alongside pharmacologic therapy. Mineralocorticoid receptor antagonists like spironolactone and eplerenone are central in many cases of hyperaldosteronism and for resistant hypertension. In unilateral aldosterone excess, surgical removal of the abnormal adrenal tissue (adrenalectomy) may be curative. See spironolactone and eplerenone; adrenalectomy for related interventions.
Controversies and debates
Screening strategy: There is ongoing discussion about how broadly to screen hypertensive patients for primary hyperaldosteronism. A targeted approach focusing on resistant hypertension, hypokalemia, and early-onset hypertension is supported by many clinicians as cost-effective and clinically impactful, while some advocate broader screening in high-risk populations. The debate centers on balancing early detection with the resources required for testing and confirmatory procedures. See discussions around primary hyperaldosteronism and ARR-guided workflows.
Medication effects and testing timing: The accuracy of PAC and ARR is influenced by medications and recent dietary salt intake. Some clinicians argue for standardized pretreatment pauses for certain drugs, while others emphasize pragmatic patient management and risk-benefit considerations. This tension reflects a broader theme in laboratory medicine: achieving reliable biomarkers while respecting patient care realities.
Direct renin versus PRA: Different laboratories and guidelines prefer direct renin concentration (DRC) or plasma renin activity (PRA) in ARR calculations. Each approach has strengths and limitations, and units/methods can affect interpretation and thresholds. The choice often reflects local practice patterns and assay availability.
Role of imaging and genetics: As testing becomes more precise, debate persists about when imaging (like adrenal CT/MRI) is appropriate after a positive ARR and how genetic data (e.g., KCNJ5 mutations associated with some aldosterone-producing adenomas) should influence diagnosis and management. See KCNJ5 for a genetic angle on aldosterone-producing tumors.
Research and future directions
Advances in assay technology, standardization of ARR thresholds, and better understanding of how diet and comorbidities affect PAC promise to refine screening. Genetic and molecular studies are shedding light on the etiologies of aldosterone excess and may guide targeted therapies. Ongoing work also explores the long-term cardiovascular outcomes of early detection and treatment of primary hyperaldosteronism, as well as the potential for personalized medical management based on aldosterone signaling pathways. See KCNJ5 and mineralocorticoid receptor for related biological developments.