HyperaldosteronismEdit

Hyperaldosteronism is a disorder of the adrenal glands in which too much the hormone aldosterone is produced. Aldosterone acts on the kidneys to promote sodium retention and potassium excretion, which can raise blood pressure and disturb electrolyte balance. In many patients, the condition remains undetected until high blood pressure or low potassium levels prompt testing. The condition can be caused by a problem inside the adrenal glands (primary hyperaldosteronism) or by processes that stimulate the renin–angiotensin system (secondary hyperaldosteronism). Historically, the term Conn’s syndrome has been used for the classic adrenal adenoma–driven form, but today clinicians recognize a broader spectrum that includes bilateral adrenal hyperplasia and other etiologies Conn's syndrome aldosterone renin.

The recognition of hyperaldosteronism has grown as clinicians have linked it to a sizable portion of hypertension, especially cases that resist standard treatment. This has spurred discussions about screening in certain patient groups and about the most effective ways to diagnose and treat the condition in a way that balances patient outcomes with health-system costs. In practice, the key goals are to identify patients who would benefit from targeted therapy, reduce cardiovascular risk, and minimize treatment-related harms.

Overview

Hyperaldosteronism is defined by inappropriately high production of aldosterone relative to the body’s need, with consequences that include sodium retention, expanded blood volume, and suppressed plasma renin activity. The net effect is hypertension in many cases, and hypokalemia can occur, though potassium levels may be normal in a substantial share of patients, particularly with milder disease or ongoing medication adjustments. The condition is most often categorized as primary or secondary, depending on whether the adrenal glands themselves are the source of excess aldosterone or whether external signals drive the production.

Primary hyperaldosteronism occurs when aldosterone is produced autonomously by adrenal tissue, most commonly due to a unilateral adrenal adenoma (a hormone-producing tumor) or bilateral adrenal hyperplasia. In many populations this form accounts for a nontrivial fraction of hypertension and is especially common among patients with resistant hypertension or hypokalemia. Secondary hyperaldosteronism results from activation of the renin–angiotensin system outside the adrenals, such as from kidney disease, congestive heart failure, or certain medications that alter renal perfusion. The management implications differ markedly between unilateral disease (often surgical treatment) and bilateral disease (generally long-term medication therapy) adrenal adenoma adrenal gland hypertension.

Pathophysiology centers on the mineralocorticoid receptor in the distal nephron, through which aldosterone increases sodium reabsorption and potassium and hydrogen ion excretion. The resulting sodium retention expands extracellular volume and elevates blood pressure, while potassium loss can produce weakness, cramps, and metabolic alkalosis in more pronounced cases. The body’s renin level typically falls in primary disease due to negative feedback, whereas secondary forms reflect a compensatory rise in renin activity. Understanding this balance is crucial for diagnostic testing and for selecting the appropriate treatment strategy mineralocorticoid receptor renal physiology.

Types

Primary hyperaldosteronism (aldosterone-producing adenoma or bilateral adrenal hyperplasia): The classic picture is autonomous aldosterone secretion with suppressed renin. Unilateral disease is often treated with adrenalectomy, while bilateral disease is managed medically. The term Conn’s syndrome is still used in many circles to denote the adrenal adenoma–driven form, but the umbrella term covers a wider set of adrenal disorders Conn's syndrome adrenal adenoma.
Secondary hyperaldosteronism: This form arises when signals from outside the adrenal glands stimulate aldosterone production, most commonly via activation of the renin–angiotensin system. Causes include renal artery stenosis, certain heart and kidney conditions, and other systemic diseases. In these cases, addressing the underlying trigger or comorbidity is a central part of management, in addition to targeted aldosterone-related therapy renin–angiotensin system.

Signs and symptoms

Hypertension: The most consistent feature is high blood pressure, which can be difficult to control with standard antihypertensive regimens. In resistant hypertension, hyperaldosteronism is more often considered as a contributing factor.
Hypokalemia-related symptoms: Muscle weakness, cramps, fatigue, and in some cases paresthesias or cardiac rhythm disturbances may arise when potassium is depleted, though potassium may be normal in many patients.
Metabolic alkalosis and volume expansion: The body’s electrolyte and acid–base state can show alkalosis, and blood volume tends to be higher than normal in many individuals.

Because presentations vary, clinicians rely on targeted screening in people at higher risk (for example, those with resistant hypertension or unexplained hypokalemia) and on careful medication history to avoid confounding results. The goals of diagnosis are to confirm excess aldosterone activity, to distinguish unilateral from bilateral disease, and to guide treatment decisions that optimize cardiovascular risk reduction hypokalemia blood pressure.

Diagnosis

Screening tests: The primary screening approach uses the aldosterone-to-renin ratio (ARR), typically measured after participants have avoided interfering medications when feasible. A high ARR suggests autonomous aldosterone production and prompts further testing. Additional measurements of plasma aldosterone concentration (PAC) and plasma renin activity (PRA) or direct renin concentration help interpret results within the clinical context aldosterone renin.
Confirmatory testing: If screening is positive, confirmatory tests (such as saline infusion testing or other suppression tests) are used to establish biochemical evidence of hyperaldosteronism. These tests help reduce false positives and guide subsequent imaging and interventions saline infusion test.
Localization and imaging: Once biochemical hyperaldosteronism is established, imaging studies—usually computed tomography (computed tomography CT) or magnetic resonance imaging of the adrenals—are used to look for unilateral lesions or bilateral disease. Because imaging alone cannot reliably distinguish unilateral from bilateral sources, adrenal venous sampling (adrenal venous sampling) is sometimes employed to make this distinction, particularly when planning surgery. The goal is to identify candidates for adrenalectomy and to avoid unnecessary procedures in bilateral disease adrenal venous sampling.
Differential diagnosis and medication effects: Several drugs and conditions can affect ARR and aldosterone testing, including diuretics, ACE inhibitors, angiotensin II receptor blockers, and beta-blockers. Proper sequencing and timing of tests, as well as medication management, are essential for reliable results ACE inhibitors angiotensin II receptor blockers.

Management

Unilateral disease (adrenal adenoma or focal hyperplasia): The preferred therapy is usually surgical removal of the affected adrenal gland (adrenalectomy). This approach can cure or substantially reduce aldosterone excess and may lead to improved blood pressure control and corrected potassium balance. Postoperative monitoring is important to assess residual aldosterone activity and to adjust antihypertensive therapy adrenalectomy.
Bilateral disease (bilateral adrenal hyperplasia or diffuse aldosterone overproduction): Long-term medical therapy with mineralocorticoid receptor antagonists is standard. Spironolactone is effective but can cause antiandrogenic side effects (e.g., gynecomastia in men and hirsutism in women). Eplerenone is more selective for the mineralocorticoid receptor and tends to have fewer antiandrogenic effects, though it is typically more costly and sometimes less tolerated if kidney function is reduced. Dosing and monitoring focus on avoiding hyperkalemia while achieving blood pressure and potassium targets spironolactone eplerenone.
Additional management considerations: Beyond disease-specific therapy, clinicians pay attention to overall cardiovascular risk reduction, electrolyte monitoring, and interactions with other antihypertensive medications. Lifestyle measures and treatment of comorbid conditions remain important components of care. In cases of resistant hypertension, evaluating for hyperaldosteronism is part of a broader strategy to optimize outcomes hypertension.

Prognosis and outcomes

With appropriate treatment, many patients experience improvements in blood pressure control and potassium homeostasis, and the risk of certain cardiovascular complications tends to decline relative to untreated disease. The degree of reversal or stabilization of hypertension varies with the underlying pathology, duration of disease before treatment, and the presence of concurrent cardiovascular risk factors. Adrenalectomy can yield substantial gains for unilateral disease, while bilateral disease often requires ongoing medical management with MR antagonists. Long-term follow-up is essential to adjust therapies and monitor for recurrence or progression of electrolyte disturbances cardiovascular risk.

Epidemiology

Estimates of how commonly hyperaldosteronism contributes to hypertension vary by population and setting. It is recognized as a meaningful contributor to resistant hypertension and to cases of hypertension with low potassium, but precise prevalence depends on screening strategies and diagnostic criteria. Differences among populations may reflect biological factors, access to care, and the intensity of screening programs, rather than a simple racial or geographic pattern. In all groups, timely diagnosis and targeted treatment offer opportunities to reduce cardiovascular risk and improve quality of life resistant hypertension.

Controversies and debates

Screening in hypertensive patients: There is debate about who should be screened for hyperaldosteronism. Proponents of broader screening argue that identifying even a subset of patients with unilateral disease can drastically reduce cardiovascular risk and improve outcomes, while critics worry about the costs, potential false positives, and downstream imaging and procedures. In practice, many guidelines recommend targeted screening for resistant hypertension, persistent hypokalemia, or early onset hypertension, with testing adjustments based on medication use and patient factors hypertension.
Diagnostic testing and medication interference: Anti-hypertensives and diuretics can affect aldosterone and renin measurements, complicating interpretation. Some experts advocate delaying testing or temporarily adjusting medications under supervision to improve test accuracy, which can create practical challenges in busy primary care settings. This tension between ideal testing conditions and real-world practice is a focal point of ongoing debate among clinicians renin ACE inhibitors.
Surgical versus medical management: For unilateral disease, adrenalectomy offers the prospect of definitive treatment, but surgical risks and the potential need for lifelong glucocorticoid replacement in some cases require careful selection of patients. For bilateral disease, long-term MR antagonist therapy is effective but can introduce metabolic and endocrine side effects, adherence challenges, and expense considerations. Guidelines emphasize a patient-centered approach that weighs the expected benefits against risks and costs while considering individual preferences adrenalectomy spironolactone eplerenone.
Cost-effectiveness and health-system impact: Some critics highlight the balance between the costs of screening, confirmatory testing, imaging, and surgery versus the potential savings from reduced cardiovascular events. Supporters contend that targeted diagnosis yields outsized gains in cardiovascular outcomes, making it a prudent investment in high-risk groups. Debates continue about how aggressively to pursue screening in various health-care environments, reflecting broader policy questions about preventive medicine and resource allocation cost-effectiveness.