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Hyperaldosteronism

Author: Stephen W. Leslie Author: Vijayadershan Muppidi Editor: Sonu Gupta Updated: 6/24/2025 9:53:56 PM

Introduction

Aldosterone is a mineralocorticoid hormone that promotes sodium (salt) and water (fluid) retention, ultimately raising blood pressure. Aldosterone also increases urinary potassium excretion, which can sometimes lead to hypokalemia. Aldosterone is secreted by the zona glomerulosa, which is the outermost layer of the adrenal cortex. The production of this hormone is primarily regulated by angiotensin II, serum potassium, and adrenocorticotropic hormone (ACTH) levels.[1] Please see StatPearls' companion resources, "Physiology, Aldosterone" and "Primary Hyperaldosteronism," for more information.

Hyperaldosteronism refers to the excess production of aldosterone. Patients typically present with hypertension initially that ranges from mild to severe and often resists medical treatment. Underlying hyperaldosteronism, causing the hypertension, often goes undiagnosed.[2] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Hyperaldosteronism may be classified as either primary or secondary. Although both forms present with similar clinical features, they are distinguished through laboratory testing and other diagnostic studies. Primary hyperaldosteronism is characterized by inappropriate autonomous hypersecretion of aldosterone by the adrenal glands, resulting in low plasma renin concentrations (PRCs; typically <1 ng/mL/h) and elevated serum aldosterone levels (usually >20 ng/dL).[1] In contrast, secondary hyperaldosteronism arises from increased renin production and activity, often due to underlying conditions (see "Secondary Hyperaldosteronism" in the Etiology section below). Please see StatPearls' companion resources, "Physiology, Aldosterone" and "Primary Hyperaldosteronism," for more information.

The initial definitive laboratory tests for diagnosing hyperaldosteronism include serum aldosterone levels, PRC, plasma renin activity (PRA), and the aldosterone-to-renin ratio. Patients with hyperaldosteronism—particularly women—often face significant diagnostic delays, with more than one-third of patients waiting over 5 years to receive a correct diagnosis.[3] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Routine screening for hyperaldosteronism (defined by a serum aldosterone level >20 ng/dL or an aldosterone-to-renin ratio >20:1) is recommended for all patients newly diagnosed with hypertension. Screening is essential for individuals with an adrenal nodule, a family history of hyperaldosteronism, early-onset hypertension or stroke (before age 40), hypokalemia, the need for four or more antihypertensive medications, obstructive sleep apnea, atrial fibrillation, age younger than 35, or resistance to treatment with three standard antihypertensive agents.[3][4][5][6][7][8][9][10]

Understanding the diagnosis and differentiation of hyperaldosteronism is crucial for effective management—whether surgical for unilateral primary hyperaldosteronism or medical for bilateral adrenal disease and secondary hyperaldosteronism.

Etiology

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Etiology

Aldosterone secretion from the zona glomerulosa of the adrenal cortex is primarily stimulated by increased serum angiotensin II, potassium, and ACTH.[1] Under normal conditions, a decrease in glomerular filtration rate (GFR) stimulates the release of renin from the renal juxtaglomerular cells. Renin converts angiotensinogen to angiotensin I, which is then converted into vasoactive angiotensin II by pulmonary angiotensin-converting enzyme (ACE) activity.[11] Angiotensin II raises blood pressure by acting as a potent vasoconstrictor.[11] Additionally, it directly stimulates aldosterone production, enhances sodium and water reabsorption in the proximal renal tubule and loop of Henle, and promotes the release of antidiuretic hormone from the hypothalamus.[1][11] Please see StatPearls' companion resources, "Primary Hyperaldosteronism" and "Angiotensin II," for more information.

Aldosterone acts on the distal renal tubules and collecting ducts to promote sodium and water reabsorption while facilitating potassium excretion.[1][11] This leads to increased intravascular volume and higher systemic blood pressure. The net effect of these physiological changes is to increase renal arterial blood flow, thereby improving the GFR of the kidneys.[1][11] The increased GFR subsequently reduces renin production, completing the feedback loop that regulates blood pressure.[1][11]

The underlying cause of the excess aldosterone production differentiates primary from secondary hyperaldosteronism.[12] Elevated serum aldosterone with suppressed renin levels indicates primary hyperaldosteronism, whereas increased plasma renin suggests a secondary form of the condition.[1][12]

Please see StatPearls' companion resources, "Physiology, Renin Angiotensin System" and "Physiology, Aldosterone," for more information.

Primary Hyperaldosteronism

Primary hyperaldosteronism is the most common cause of secondary hypertension.[13] Also known as Conn syndrome, this condition was first described in 1956 and is caused by excessive autonomous aldosterone production by the adrenal gland, specifically the zona glomerulosa.[14] Somatic genetic mutations have been identified in the vast majority of patients (88%-93%) with aldosterone-secreting adrenal adenomas.[1][15][16][17] Please see StatPearls' companion resource, "Conn Syndrome," for more information.

In approximately 60% of primary hyperaldosteronism cases, the condition is caused by bilateral adrenal hyperplasia, while about 30% present with a unilateral hypersecreting glandular adrenal nodule.[1][18][19] Other less frequent causes include aldosterone-producing adrenal carcinoma and ectopic aldosterone secretion from the kidneys or ovaries. Please see StatPearls' companion resource, "Conn Syndrome," for more information.

"Primary hyperaldosteronism" is the preferred terminology, whether the condition results from a unilateral primary adenoma, which is generally treated surgically, or bilateral idiopathic adrenal hyperplasia, typically managed medically.[8][20] Please see StatPearls' companion resources, "Physiology, Adrenal Gland," "Conn Syndrome," and "Primary Hyperaldosteronism" for more information.[2][21][22]

Less common forms of primary hyperaldosteronism include ectopic aldosterone-secreting tumors (typically originating in the kidneys or ovaries), aldosterone-producing adrenocortical carcinomas, the (extremely) rare unilateral adrenal hyperplasia, and familial hyperaldosteronism—of which type I is the most prevalent inherited form.[22] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Although genetic mutations of primary hyperaldosteronism are quite common, inheritable, familial forms of the disorder are relatively rare, accounting for approximately 6% of all cases.[1][23] The 4 specific types of autosomal dominant familial hyperaldosteronism described in the medical literature are discussed below.[1][24][25]

  • Familial primary hyperaldosteronism type I: This subtype results from the fusion of a 2-part chimeric gene (CYP11B1/CYP11B2), combining the regulatory segment of 11β-hydroxylase (CYP11B1) and the synthesis portion from aldosterone synthase (CYP11B2).[26] As a result, aldosterone synthase becomes aberrantly regulated by ACTH, leading to increased aldosterone production. Type I familial primary hyperaldosteronism is a rare, autosomal dominant, heritable disorder characterized by elevated levels of 18-oxocortisol and 18-hydroxycortisol.[26] This is the only type of familial primary hyperaldosteronism that is glucocorticoid-remediable.[24][25][26][27][28][29] Please see StatPearls' companion resource, "Conn Syndrome," for more information.
  • Familial primary hyperaldosteronism type II: This subtype is associated with chromosomes 7p22 and 11q13 and typically presents with histological features consistent with adrenal hyperplasia.[26] Unlike type I, familial primary hyperaldosteronism type II is not glucocorticoid-remediable.[24][25][26][27][28][29] Please see StatPearls' companion resource, "Conn Syndrome," for more information.
  • Familial primary hyperaldosteronism type III: This subtype results from a T158A mutation in the potassium channel gene KCNJ5, which increases intracellular calcium levels, leading to increased aldosterone production by the glomerulosa cells.[26][28][30] Type III familial primary hyperaldosteronism is not glucocorticoid-remediable.[24][25][26][27][28][29] Please see StatPearls' companion resource, "Conn Syndrome," for more information.
  • Familial primary hyperaldosteronism type IV: This subtype is caused by mutations in the CACNA1H gene, which changes calcium current characteristics, leading to increased intracellular calcium and elevated aldosterone production.[1] This is characterized by early-onset hypertension accompanied by complex neurological problems or developmental delay. The onset is variable, but it usually occurs before the age of 20.[1][24][25] Type IV familial primary hyperaldosteronism is not glucocorticoid-remediable.[1][24][25]

Secondary Hyperaldosteronism

Secondary hyperaldosteronism occurs due to excessive and inappropriate activation of the renin-angiotensin-aldosterone system (RAAS). Any condition that reduces renal blood flow can trigger the activation of the RAAS, leading to increased aldosterone production and secretion. This overproduction can result from renin-producing tumors, renal artery stenosis, renal tubular acidosis, pheochromocytoma, nutcracker syndrome, or hyperkalemia due to chronic renal failure. This condition can also arise from generalized edematous states such as left ventricular heart failure, pregnancy, cor pulmonale, Bartter or Gitelman syndromes, hepatic cirrhosis with ascites, obstructive sleep apnea, and nephrotic syndrome.[31][32] 

Please see StatPearls' companion resources, "Physiology, Renin Angiotensin System," "Bartter Syndrome," and "Gitelman Syndrome," for more information.

In some cases, such as heart failure, aldosterone production may remain within the normal range; however, reduced hepatic blood flow can impair its metabolism by the liver, leading to elevated serum aldosterone levels. Additionally, liver failure can decrease hepatic production of angiotensinogen, which directly lowers angiotensin I and II levels, thereby increasing serum renin levels and ultimately leading to hyperaldosteronism.

Epidemiology

Primary Hyperaldosteronism

This condition occurs in at least 10% of all patients with hypertension, although statistics on the prevalence estimates vary widely.[5][33][34][35] The incidence of primary hyperaldosteronism increases with the severity of the associated hypertension.[8] The prevalence exceeds 20% in patients with medically resistant hypertension and may reach as high as 50%, particularly in those aged 40 or younger or those with hypokalemia.[2][8][36][37][38][39] In newly diagnosed hypertensive patients, primary hyperaldosteronism is found in approximately 11,200 per 100,000 individuals.[40]

Earlier studies significantly underestimated the incidence of hyperaldosteronism due to variations in patient selection, diagnostic methods, definitions of both hyperaldosteronism and hypertension, and a general lack of screening in patients who met the recommended screening criteria.[2][18][38][41][42][43][44]

Black individuals may exhibit increased sensitivity to aldosterone compared to the general population, which can result in hyperaldosteronism even without significantly elevated plasma aldosterone levels.[45][46][47][48][49]

The reported prevalence largely depends on the incidence of screening tests performed and the criteria used to determine a positive result warranting further investigation.[1] In a study, lowering the threshold aldosterone-to-renin ratio from above 30 to above 20 increased the detection rates of hyperaldosteronism from 13.8% to nearly 33%.[50] Tertiary care centers that treat patients with refractory hypertension have reported that almost half of their referrals could potentially have primary hyperaldosteronism.[1][51] 

Secondary Hyperaldosteronism

This condition is diagnosed less frequently than primary hyperaldosteronism. Both forms are more prevalent in women. Aldosterone-producing adrenal adenomas are more common in females, whereas males are more likely to have unilateral adrenal hyperplasia by a factor of 4:1.[52][53] Africans and Black Americans tend to have a higher prevalence of hyperaldosteronism than the general population, particularly idiopathic bilateral adrenal hyperplasia.[54][55]

Although the exact incidence of hyperaldosteronism remains uncertain, primary aldosteronism is highly prevalent and frequently underrecognized among individuals with hypertension, with evidence suggesting a steadily increasing incidence.[2][18][42]

Pathophysiology

Aldosterone is the primary mineralocorticoid in the body, exerting its effects primarily on epithelial sodium channels in the collecting tubules and causing sodium reabsorption. This sodium uptake generates a negative potential within the tubular lumen, causing the movement of cations, primarily potassium and hydrogen ions, into the lumen to maintain electrical neutrality. Consequently, this process results in hypokalemia, aciduria, and metabolic alkalosis. The increased reabsorption of sodium and water leads to intravascular volume expansion and elevated blood pressure.[41] Please see StatPearls' companion resource, "Physiology, Aldosterone," for more detailed information.

Aldosterone production primarily occurs in the zona glomerulosa of the adrenal glands, where aldosterone synthase enzymatically converts 11-deoxycorticosterone to aldosterone. This process is regulated mainly by serum potassium and angiotensin II levels. ACTH also stimulates aldosterone production, contributing to the observed diurnal pattern of hormone secretion.

Primary Hyperaldosteronism

Primary hyperaldosteronism occurs due to excessive autonomous aldosterone production by the adrenal gland. The most common causes of primary hyperaldosteronism are idiopathic bilateral adrenal hyperplasia and a hypersecreting adenomatous tumor in the zona glomerulosa, both of which directly cause an inappropriate increase in serum aldosterone. Patients are often asymptomatic but typically present with hypertension that is difficult to control; hypokalemia may also occur due to increased urinary potassium excretion driven by aldosterone.[42] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Patients who have adequate sodium intake are more likely to develop hypokalemia.[55] Higher salt intake increases sodium delivery to the cortical collecting tubules, which, in the presence of elevated aldosterone levels, promotes urinary potassium excretion.[55] Please see StatPearls' companion resource, "Conn Syndrome," for more information.

Both primary and secondary hyperaldosteronism can present with a wide range of clinical features.[41] Approximately one-fifth of patients with primary hyperaldosteronism exhibit impaired glucose tolerance due to hypokalemia, although the overall prevalence of diabetes remains similar to that of the general population.[56][57][58][59] Metabolic alkalosis may also be present.

Hypertensive patients with primary hyperaldosteronism are at increased risk for atrial fibrillation, cardiovascular events, myocardial infarction, and stroke compared to hypertensive patients without the condition.[7][9][60][61] They also demonstrate higher rates of generalized fibrosis affecting the adrenal glands, heart, lungs, and pancreas.[62] Additional findings include increased albuminuria, oxidative DNA damage, inflammation, nephron loss with a higher incidence of renal failure, vascular injury, and reduced overall survival.[45][63][64][65][66][67]

The following 3 pathophysiological features of primary hyperaldosteronism, originally described by Conn in 1964, remain the mainstay of the diagnostic approach:

  • Autonomous aldosterone production lowers plasma renin, resulting in a high aldosterone-to-renin ratio and low serum renin levels.
  • The renin response to stimuli, such as the administration of an ACE inhibitor, is blunted or reduced.
  • Aldosterone production is not suppressed by volume expansion or salt loading, which is typically assessed through intravenous (IV) saline infusion, oral salt-loading, captopril suppression testing, or similar methods.[8][14][68][69] Please see StatPearls' companion resource, "Conn Syndrome," for more information.

Secondary Hyperaldosteronism

Secondary hyperaldosteronism results from a renal response to decreased vascular perfusion or increased serum renin levels. Juxtaglomerular cells detect reduced renal blood flow and release renin, activating the renin-angiotensin system and promoting the synthesis of angiotensin II. Angiotensin II raises systemic blood pressure by increasing proximal tubular sodium reabsorption, causing generalized vasoconstriction, and stimulating the secretion of aldosterone. The overall effect includes sodium retention, expanded intravascular volume, elevated renin levels, increased blood pressure, and secondary hyperaldosteronism. Please see StatPearls' companion resource, "Physiology, Renin Angiotensin System," for more information.

Secondary hyperaldosteronism occurs due to the excess stimulation of the RAAS. Although the conduction may occur as a physiological response to transient RAAS activation, such as in cases of hypovolemia, it is more commonly associated with pathological conditions involving sustained RAAS activation, as mentioned below.

  • Renin-producing tumors (juxtaglomerular cell tumors): These tumors can stimulate the RAAS activation through juxtaglomerular cells.[70][71][72][73] However, this is an extremely rare condition, with fewer than 300 cases reported in the medical literature.[71]
  • Left-sided congestive heart failure and cor pulmonale: These conditions reduce cardiac output, leading to stimulation of aldosterone production.
  • Poor hepatic blood flow: This may lead to secondary hyperaldosteronism by impairing hepatic metabolism of aldosterone, resulting in elevated serum levels despite normal adrenal production. 
  • Liver failure: This condition reduces hepatic production of angiotensinogen, leading to decreased levels of angiotensin I and II. This reduction stimulates increased renin release, which in turn elevates aldosterone production, resulting in hyperaldosteronism.
  • Renovascular hypertension: This condition (eg, renal artery stenosis due to atherosclerosis or fibromuscular dysplasia) reduces renal blood flow, simulating a false sense of hypovolemia and increasing aldosterone secretion. Please see StatPearls' companion resource, "Renal Artery Stenosis," for more information.
  • Cirrhosis, nephrotic syndrome, and ascites: In patients with these conditions, the reduction in circulating fluid volume leads to decreased renal perfusion, which in turn stimulates aldosterone secretion.
  • Additional conditions: Kidney failure, renal tubular acidosis, cor pulmonale, pregnancy, excessive licorice ingestion, aortic coarctation, and nutcracker syndrome are additional conditions that can lead to secondary hyperaldosteronism.

Histopathology

Histopathology is not typically used as a standard tool for diagnosing hyperaldosteronism, although immunohistochemical staining can be helpful. Up to one-third of aldosterone-producing adrenal adenomas exhibit hyperplasia of the zona glomerulosa, which may be localized or manifest as generalized cortical thickening. Additionally, extensions of the zona glomerulosa can sometimes be seen penetrating centrally.[74]

Bilateral hyperaldosteronism, also known as idiopathic hyperaldosteronism, exhibits a variable histological appearance, ranging from normal hyperplasia to micronodular and macronodular forms. Immunohistochemical staining for cytochrome P450 (CYP11B2) in aldosterone-producing adenomas has proven highly valuable for differentiating among the various types and subtypes of adenomas, micronodules, and aldosterone-producing cell clusters.[74][75][76] In contrast, CYP11B1 staining is positive in cortisol-producing cells.[74]

Atypical or nonclassical histopathological features, such as diffuse hyperplasia, multiple aldosterone-producing nodules, clusters of autonomous hormone-producing cells, or multiple aldosterone-producing micronodules, are associated with a significantly higher recurrence rate of hyperaldosteronism following unilateral adrenalectomy (60% versus 14%).[77][78]

History and Physical

Clinical Features of Hyperaldosteronism

The clinical presentation of hyperaldosteronism varies with severity and can sometimes be asymptomatic. Resistant hypertension is the most common presenting symptom for these patients, especially when associated with hypokalemia. A characteristic presentation of hyperaldosteronism is a young woman whose blood pressure remains uncontrolled despite using 3 or more antihypertensive medications.[42] Other common symptoms include fatigue, headache, weakness, abdominal distension, ileus, polyuria, polydipsia, and nephrogenic diabetes insipidus secondary to hypokalemia.

Although no physical examination findings are specific for diagnosing primary hyperaldosteronism, prolonged uncontrolled hypertension can place stress on the heart, resulting in left ventricular hypertrophy. This may produce an S4 heart sound caused by a noncompliant, stiff left ventricle that restricts blood flow during atrial contraction. Please see StatPearls' companion resource, "Hypertensive Heart Disease," for more information.

Blood pressure in hyperaldosteronism can vary from normal to severe hypertension and is often resistant to standard antihypertensive therapy, typically defined as requiring 3 or more antihypertensive medications. Hypertension in hyperaldosteronism is primarily caused by sodium reabsorption, volume expansion, and increased peripheral vascular resistance.[41] Symptoms typically arise from moderate to severe hypertension or secondary hypokalemia. Elevated blood pressure may cause headaches, dizziness, changes in vision, chest pain, and shortness of breath (dyspnea). Additionally, hypokalemia-induced resistance to antidiuretic hormone in the renal tubules can contribute to nephrogenic diabetes insipidus in patients with hyperaldosteronism.[41]

Hypokalemia can cause muscle weakness, fatigue, cardiac palpitations, cramps, polydipsia, and polyuria due to nephrogenic diabetes insipidus. A comprehensive medical history should be obtained, as there may be a family history of hypertension or early cardiovascular events, such as stroke.[41] Although hypokalemia is a classic feature of primary hyperaldosteronism, fewer than 30% of patients with confirmed disease exhibit significant reductions in serum potassium levels.[79]

Patients with secondary hyperaldosteronism may present with varying blood pressure levels, though most exhibit some degree of hypertension. Conditions such as renal artery stenosis, nutcracker syndrome, and coarctation of the aorta also contribute to elevated blood pressure. Please see StatPearls' companion resources, "Renal Artery Stenosis," "Nutcracker Syndrome and Left Renal Vein Entrapment," and "Coarctation of the Aorta," for more information. 

Hypovolemia may be seen in patients taking diuretics or those with heart failure, cirrhosis, or nephrotic syndrome. In contrast, Gitelman and Bartter syndromes often present with mild hypotension.[41] Please see StatPearls' companion resources, "Bartter Syndrome" and "Gitelman Syndrome," for more information.

Although no specific physical signs diagnose hyperaldosteronism, long-term hypertension can cause left ventricular hypertrophy, which may manifest as an S4 heart sound due to the passage of blood into a stiff and noncompliant left ventricle. Other signs of chronic hypertension may also be observed. Metabolic syndrome is more common in patients with primary hyperaldosteronism compared to controls with similar blood pressure, sex, age, and body mass index (BMI).[80]

Risk Factors for Hyperaldosteronism

Factors associated with an increased risk for hyperaldosteronism in patients with hypertension include:

  • Atrial fibrillation
  • Family history of early-onset hypertension or cardiovascular events at age 35 or younger
  • Family history of hyperaldosteronism
  • Hypertension diagnosed at age 40 or younger
  • Hypokalemia—either spontaneous or induced by thiazide diuretics
  • Incidental discovery of an adrenal adenoma in a hypertensive patient, particularly when blood pressure is difficult to control
  • Obstructive sleep apnea with atrial fibrillation
  • Resistant or intractable hypertension, which remains poorly controlled despite the use of 3 or more standard antihypertensive medications, including a diuretic [8]
  • Sleep apnea [3][4][5][6][7][8][9][10]

Evaluation

Hyperaldosteronism Screening

Screening recommendations for hyperaldosteronism are recommended for all patients newly diagnosed with hypertension, especially those with early-onset significant hypertension, hypokalemia, resistant or intractable high blood pressure, obstructive sleep apnea, or an adrenal mass.[7][33][81][82][83][84][85][86] Given the high prevalence of hyperaldosteronism among hypertensive individuals—many of whom remain undiagnosed—such screening is crucial.[1][5][6][38][42][82][85][86][87][88][89][90][91] However, fewer than 1% of hypertensive patients are ever screened or evaluated for this disorder.[92]

Hyperaldosteronism screening remains significantly underutilized. Only about 3% of patients with resistant hypertension who meet established screening criteria undergo appropriate testing, and less than 1% of all hypertensive patients are ever screened or evaluated for the disorder.[44][92][93][94][95][96] An international survey revealed that over one-third of patients waited more than 5 years for an accurate diagnosis.[3][95]

The frequent delay in diagnosing hyperaldosteronism stems from multiple factors, including the misconception that the condition is rare, limited awareness of the serious clinical consequences of delayed treatment, and the presence of subclinical or normotensive hyperaldosteronism in about 11% of the population. Additional challenges include the perceived complexity of confirmatory testing, lack of standardized screening protocols, failure to recognize that hyperaldosteronism often occurs without hypokalemia, inconsistent definitions of hypertension and hyperaldosteronism across guidelines, a high prevalence of atypical presentations, and difficulties in interpreting test results.[1][2][38][45][97][98][99]

Optimal screening for hyperaldosteronism typically involves a straightforward blood test measuring plasma renin and aldosterone levels, which can be easily performed in primary care settings.[100][101] An aldosterone-to-renin ratio of more than 20 or a plasma aldosterone level of 20 ng/dL or more is commonly used to indicate likely hyperaldosteronism.[82][102] An aldosterone-to-renin ratio of 30 or more highly suggests the diagnosis.[1] This test can now be performed without discontinuing most antihypertensive medications.[103] Many guidelines advise discontinuing mineralocorticoid receptor antagonists, such as spironolactone, before measuring the aldosterone-to-renin ratio.[42] However, recent large studies have demonstrated that these medications do not significantly alter aldosterone-to-renin ratio results, making discontinuation before testing unnecessary.[45][104][105][106][107] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

A simple serum aldosterone level can also be quite informative. Serum aldosterone levels of 30 ng/dL or more are highly indicative and almost diagnostic of hyperaldosteronism, but even titers of 15 ng/dL are suggestive of the disorder and warrant further evaluation, typically beginning with an aldosterone-to-renin ratio.[1][45][82] As aldosterone levels can fluctuate, some experts recommend using a cutoff of 15 ng/dL to reduce missed diagnoses, although 20 ng/dL remains the more common threshold.[1][108] A serum aldosterone level of less than 5 ng/dL effectively eliminates hyperaldosteronism as a possible diagnosis. Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

A 24-hour urine test for aldosterone may be used as an alternative to blood testing.[109][110] A 24-hour urinary aldosterone level exceeding 25 mcg per 24 hours is considered abnormal and indicative of excess production. Following this, confirmatory testing, computed tomography (CT) imaging, and selective bilateral adrenal venous sampling may be performed.[82][100][102][111] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

A simplified alternative screening method has been proposed, involving a trial of spironolactone 25 mg/d for 1 month, with monitoring of the antihypertensive response.[92][95] A blood pressure reduction of less than 10 mm Hg suggests that primary hyperaldosteronism is unlikely, while a decrease greater than 12 mm Hg is indicative of the disorder.[92][95]

Laboratory Findings Suggestive of Hyperaldosteronism 

The aldosterone-to-renin ratio remains a widely used and reliable screening tool for hyperaldosteronism, though its accuracy can vary under certain conditions.[8][112][113] Blood samples should ideally be drawn in the morning with the patient in an upright position, and any interfering medications should be discontinued, although this is not always safe or practical.[8][42][114] The aldosterone-to-renin ratio can be influenced by factors such as posture, diurnal variations, electrolyte levels (eg, potassium), and various medications other than antihypertensives, including antidepressants, antihistamines, dopaminergic medications, estrogens, licorice, and nonsteroidal anti-inflammatory drugs (NSAIDs).[8][42][114][115][116][117] Additional laboratory findings may include hypokalemia, mild hypernatremia, and hypomagnesemia, although these are nonspecific and not diagnostic.[118][119][120]

The absence of hypokalemia should not exclude a diagnosis of hyperaldosteronism, even though low serum potassium levels have historically been considered a hallmark associated with the disorder.[8][13][121][122] Current estimates indicate that fewer than 30% of individuals with confirmed primary hyperaldosteronism will exhibit low serum potassium levels.[55] 

Metabolic alkalosis is frequently observed in individuals with hyperaldosteronism due to the net loss of hydrogen ions in the urine, which occurs as a result of aldosterone-induced renal sodium retention, where hydrogen is exchanged for urinary sodium.[123] 

The role of 24-hour urine collection in hyperaldosteronism remains controversial, though it can aid in detecting inappropriate potassium wasting, typically defined as more than 30 mEq/d.[124][125][126] This test is particularly useful for evaluating potential extrarenal potassium losses and diuretic abuse in cases of hypokalemia, especially when aldosterone elevations are minimal or borderline. A urinary aldosterone-to-creatinine ratio has also been proposed to assist in the initial diagnosis of primary hyperaldosteronism, using a threshold of 3 ng aldosterone per 1 mg creatinine.[127] However, the clinical validity of this test has yet to be fully established.[127]

Diagnostic evaluation of primary hyperaldosteronism

In primary hyperaldosteronism, PRA is typically less than 1 ng/mL/h, and the PRC is either very low or undetectable. Aldosterone overproduction originates within the zona glomerulosa rather than from an extrinsic source. Consequently, a morning serum aldosterone-to-renin ratio greater than 20:1 indicates a renin-independent etiology consistent with primary hyperaldosteronism.

The plasma aldosterone concentration-to-plasma renin activity (PAC/PRA) ratio is a widely used confirmatory test for diagnosing primary hyperaldosteronism. Most studies support an elevated PAC/PRA ratio of more than 30:1 and a PAC of more than 20 ng/dL, which yields a sensitivity and specificity of over 90% for the diagnosis of primary hyperaldosteronism.[128][129] However, a PAC/PRA ratio above 20:1 and a PAC of more than 15 ng/dL are reportedly sufficient to support the diagnosis.[128][129] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Diagnostic evaluation of secondary hyperaldosteronism

In secondary hyperaldosteronism, both the PRC and PRA levels are elevated, as renin is the primary stimulator for the excess aldosterone production. Consequently, the serum aldosterone-to-renin ratio is lower than in primary hyperaldosteronism. These levels are best measured in the morning after the patient has been upright for at least 2 hours and seated for 5 minutes to improve accuracy. Typically, the serum aldosterone-to-renin ratio is less than 20:1 in secondary hyperaldosteronism. Although PRA, PRC, and serum renin levels rise, the PAC/PRA ratio remains lower than that seen in primary hyperaldosteronism.[42][128][129][130] 

Differentiating primary from secondary hyperaldosteronism

Serum renin levels are the most effective method for differentiating between primary and secondary hyperaldosteronism.[14] Primary hyperaldosteronism significantly suppresses renal renin production, whereas secondary hyperaldosteronism is associated with elevated serum renin concentrations.[58]

Confirmation Testing for Hyperaldosteronism

Confirmatory testing is generally recommended for most patients with possible or presumptive hyperaldosteronism.[131] This testing typically involves measuring elevated serum aldosterone levels, 24-hour urinary aldosterone excretion, or performing an aldosterone suppression test using intravenous saline, oral salt loading, captopril, or fludrocortisone. Normally, these tests cause a decrease in serum aldosterone levels.[131] All of these tests, except for the captopril suppression test, may increase hypertension, induce fluid overload, and produce hypokalemia.[82] Although no single confirmatory test is officially preferred, a comparative meta-analysis suggests that the captopril challenge test is the most feasible, as it is easy to perform and considered relatively safe.[82][132]

Before performing confirmatory testing, any existing hypokalemia should be corrected.[82] If confirmatory tests are negative or equivocal in patients with a positive screening ratio (aldosterone-to-renin >20 with low serum renin), they likely have mild hyperaldosteronism. These patients are typically treated medically with mineralocorticoid receptor antagonists, such as spironolactone.[82] 

Confirmatory testing is unnecessary in older patients whose blood pressure is well controlled on antihypertensive medication and who are unlikely surgical candidates, even if unilateral hyperaldosteronism is identified. In selected surgical cases showing markedly elevated plasma aldosterone, suppressed serum renin, hypokalemia, and resistant hypertension, confirmation of primary hyperaldosteronism may not be required, although localization studies are still necessary.[82][133][134][135] 

Confirmatory testing may be omitted in select cases where laboratory findings are clearly and exclusively attributed to hyperaldosteronism, with no other underlying condition.[131][136][137][138][139][140][141] This requires that the patient, while upright, meets all of the following laboratory criteria:[42][131][139][141]

  • Plasma aldosterone concentration of ≥20 ng/dL
  • Hypokalemia
  • Suppressed plasma renin activity (PRA) of <1 ng/mL/h or an undetectable plasma renin concentration (PRC)

Additionally, it has been suggested that confirmatory testing may be unnecessary for a definitive diagnosis of primary hyperaldosteronism when the serum aldosterone level is ≥17 ng/dL and is associated with either an aldosterone-to-plasma renin activity ratio ≥29.88 or an aldosterone-to-plasma renin concentration ratio ≥2.44.[142]

Confirmatory testing for hyperaldosteronism is conducted using one of the methods, as mentioned below.[42][143] 

Captopril suppression test

This test confirms primary hyperaldosteronism by evaluating the response to captopril—an angiotensin II blocker. In patients with primary hyperaldosteronism, aldosterone levels remain elevated, whereas they decrease in other conditions. Patients receive 25 to 50 mg of captopril, and serum aldosterone, renin, and cortisol levels are measured before and 1 to 2 hours after administration of captopril.[68]

In primary hyperaldosteronism, aldosterone levels are expected to decrease by at least 30%, resulting in an aldosterone-to-renin ratio of less than 30:1. However, affected patients typically maintain elevated serum aldosterone levels (≥8.5 ng/dL), with a persistently high aldosterone-to-renin ratio (>30:1) and low renin levels. The captopril suppression test is generally safe, inexpensive, and easily performed in an outpatient setting. Nonetheless, it has a relatively high rate of equivocal and false-negative results. This is also contraindicated in suspected renovascular hypertension and carries a risk of angioedema.[82]

Fludrocortisone suppression test

This test aims to lower aldosterone levels by administering oral fludrocortisone, supplementing with potassium, and following a high-sodium diet. If aldosterone levels remain inadequately suppressed after 4 days of treatment, the result is considered confirmatory for primary hyperaldosteronism.[144][145] Oral fludrocortisone (0.1 mg) is administered every 6 hours. Potassium and sodium chloride tablets are taken daily with meals, and patients follow a high-sodium diet during the testing period.[144][145]

Aldosterone and renin levels are measured after 4 days of testing. A serum aldosterone level greater than 6 ng/dL is considered a positive result, indicating primary hyperaldosteronism.[144][145] However, this test is labor-intensive and relatively expensive. The addition of a 2 mg dose of dexamethasone at midnight has been shown to improve the reliability, sensitivity, and specificity of the fludrocortisone suppression test, enhancing its ability to detect milder forms of primary hyperaldosteronism.[146][147][148][149][150][151] 

Negative or equivocal confirmatory test results in patients with positive blood screenings—characterized by an aldosterone-to-renin ratio greater than 20 and low serum renin—suggest probable mild hyperaldosteronism. These cases are typically managed medically with mineralocorticoid receptor antagonists, such as spironolactone.[82]

Intravenous salt-loading test

This test involves administering 2 liters of isotonic saline intravenously over a 4-hour period. Plasma aldosterone levels exceeding 10 ng/dL after the infusion are indicative of primary hyperaldosteronism; however, the test has a false-negative rate of 30%.[42] A modified version of the saline infusion test, which includes 0.5 mg of oral dexamethasone every 6 hours for 2 days, has demonstrated greater sensitivity.[152] Limitations of this test include the need for hospitalization and potential risks such as fluid overload, exacerbation of heart failure, hypokalemia, and increased blood pressure.

The oral salt-loading test typically involves a significant increase in dietary sodium intake over 3 days, followed by the measurement of aldosterone levels. This test also involves taking 5000 to 6000 mg of dietary sodium daily, or 90 mEq of sodium tablets, over 3 days. Potassium supplements are provided to those who develop hypokalemia. After sodium loading, a 24-hour urine aldosterone measurement is taken, with a value of greater than 12 mcg/d commonly used to confirm primary hyperaldosteronism.

A 24-hour urine sodium test of 200 mEq or more indicates adequate oral salt intake. However, some considerations with this test include the potential for false-negative results in patients with renal failure. This test should not be administered to individuals with a history of congestive heart failure, uncontrolled significant hypertension, or cardiac arrhythmias.[82]

The choice of the best confirmatory test for hyperaldosteronism remains a topic of debate. Several comparative analyses suggest that the captopril suppression test and the intravenous salt-loading test are the most consistent and reliable methods.[68][131][132] Of the 2 tests, the captopril suppression test is generally considered safer and easier to perform.[68][132] However, several large studies have questioned the added value of both captopril and intravenous saline infusion tests, finding that they may not provide significant diagnostic benefit beyond a carefully conducted and properly interpreted aldosterone-to-renin ratio.[42][45][153][154]

Differentiating Unilateral From Bilateral Adrenal Disease

Determining laterality is critical, as it directly influences treatment decisions and patient outcomes. Distinguishing between an adrenal adenoma and adrenal hyperplasia also helps clarify the underlying pathology. The following considerations may be useful:

  • Adrenal adenomas that autonomously overproduce aldosterone are typically glucocorticoid-responsive, whereas bilateral idiopathic adrenal hyperplasia generally is not, although it may still exhibit some responsiveness to serum renin levels.[155]
  • An adrenal adenoma shows a paradoxical decrease in serum aldosterone levels after 2 hours of upright positioning, whereas adrenal hyperplasia generally results in a normal postural increase. Please see the companion StatPearls' reference resource, "Conn Syndrome," for more information.
  • Serum 18-hydroxycorticosterone levels are elevated in adenomas but remain normal in bilateral adrenal hyperplasia. Please see the companion StatPearls' reference resource, "Conn Syndrome," for more information.

None of these findings alone is definitive for determining laterality, which typically requires imaging studies or the more complex but conclusive adrenal vein sampling procedure. Additionally, many patients with hyperaldosteronism, such as those who are not surgical candidates, do not require lateralization testing.

Diagnostic Studies

Radiological imaging—most commonly a CT scan—is the preferred modality for identifying adrenal adenomas, distinguishing them from bilateral adrenal hyperplasia, and detecting rare adrenal malignancies.[156][157][158] However, studies have found that CT imaging alone may not reliably differentiate between these conditions.[159] The overall reported sensitivity and specificity of CT imaging for detecting aldosterone-producing adenomas are about 78% and 75%, respectively.[160]

All patients with primary aldosteronism should undergo imaging to exclude large adrenal masses or carcinomas.[1][42] Aldosterone-producing adrenal tumors tend to be homogenous and lipid-rich and demonstrate low Hounsfield density values. However, imaging alone cannot reliably differentiate between functioning and nonfunctioning adrenal adenomas.[161][162][163] However, nonfunctional adrenal adenomas are extremely rare in children and young adults.[42]

Adrenal vein sampling

This definitive method is used to differentiate unilateral from bilateral pathology when radiological imaging is inconclusive and the patient is potentially a candidate for adrenal surgery.[82] Cortisol and aldosterone levels are measured from both the right and left adrenal veins, with cortisol serving to confirm proper catheter placement.[164] Bilateral adrenal hyperplasia typically shows similar hormone levels on both sides. In contrast, a significant difference, such as a 2-fold or greater difference in aldosterone concentration or an aldosterone-to-cortisol ratio at least five times higher on one side, indicates unilateral disease.[42][164][165] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Cosyntropin

Cosyntropin, a synthetic ACTH analog, may be administered during adrenal vein sampling either as a continuous intravenous infusion (50 µg/h starting 30 minutes before sampling) or as a single intravenous bolus (250 µg).[166] This has the following potentially beneficial effects:[166][167][168][169]

  • Increases the plasma cortisol concentration gradient between the adrenal vein and the inferior vena cava, improving the selectivity index.
  • Reduces cortisol and aldosterone fluctuations during the procedure.
  • Increases aldosterone secretion from aldosterone-producing adenomas.

When cosyntropin stimulation is administered, a 4-fold difference in adrenal vein aldosterone levels is used as the cutoff threshold.[42][164][165] However, no conclusive evidence exists that cosyntropin stimulation leads to improved diagnosis or better outcomes, and there is no consensus on whether it should be administered; therefore, its use remains optional.[166][168][170] If cosyntropin is not administered during adrenal vein sampling, simultaneous bilateral sampling is recommended to ensure accuracy.[166]

Adrenal vein sampling may be unnecessary in certain surgical candidates with hyperaldosteronism. This technique is generally not required in patients aged 35 or younger who present with spontaneous hypokalemia, resistant hypertension, markedly elevated aldosterone levels, and a clearly suspicious unilateral adrenal adenoma on CT imaging, as nonfunctioning adrenal adenomas are rare in this age group.[1][45][166][171][172][173][174][175][176][177][178][179][180] Similarly, adrenal vein sampling is unnecessary in patients aged 40 or older who have marked hyperaldosteronism and a clearly defined solitary, unilateral adrenal adenoma on CT imaging. This is also not required in individuals who are not surgical candidates, those with suspected adrenal cancer, or patients with known familial hyperaldosteronism.[166] 

Adrenal vein sampling remains the gold standard for differentiating unilateral from bilateral adrenal hyperaldosteronism.[1][82][164] This technique should ideally be performed in all potential adrenalectomy patients to avoid inappropriate procedures and to identify the 40% of patients with primary hyperaldosterone who would benefit from surgery but might otherwise be missed based on imaging studies alone.[45][180][181][182][183][184]  

However, expertise in this technically demanding procedure is often limited, and it may be unnecessary in clearly defined surgical cases. (The technique is best reviewed in detail elsewhere.[164]) The adrenal veins are relatively small, making the interpretation of the results difficult. The procedure is expensive, carries a significant risk of complications, and many institutions lack experience in this challenging technique. Therefore, patients should ideally be referred to specialized centers with expertise in adrenal vein sampling.[1][164] The right adrenal vein is particularly challenging to cannulate; nonetheless, even unilateral sampling can yield valuable diagnostic information.[185][186][187][188][189][190]

In 2016, Pasternak proposed a method for interpreting results when only unilateral adrenal vein sampling is achieved, as outlined below:[186]

  • The formula (adrenal vein aldosterone [AVA] ÷ cortisol) / (inferior vena cava [IVC] aldosterone ÷ IVC cortisol) is used to calculate the AVA/IVC ratio cutoff value.[186]
  • A value greater than 5.5 indicates unilateral hyperaldosteronism on the sampled side, while a value less than 0.5 suggests unilateral disease on the contralateral side.[186]
  • Values between 5.5 and 0.5 are considered uninterpretable and may indicate either bilateral or unilateral disease.[186] 

This method has an estimated specificity of 100% but a sensitivity of only 50%. Additional studies have confirmed these findings.[185][186][191]

Adrenal venous sampling carries risks, including adrenal venous rupture, infarction, thrombus formation, bleeding, and hematoma formation. Therefore, this procedure should ideally be performed at centers of excellence with specialized experience and expertise.[166] Due to these risks, various noninvasive alternative diagnostic methods are being explored. Although these alternatives can be cumbersome and have somewhat limited accuracy, they may be useful when performed by experienced practitioners and when available.

The overall consensus is that adrenal vein sampling may not be necessary in all potential adrenalectomy candidates and can be safely omitted in selected patients; however, this remains a topic of controversy.

Alternative diagnostic modalities

Alternative diagnostic modalities for determining laterality in hyperaldosteronism include:[192][193]

  • Scintigraphy using NP-59 (131 I-6-β-iodomethyl-19-norcholesterol) with dexamethasone suppression may be useful in selected cases to help differentiate between unilateral functioning adenomas and bilateral hyperplasia. This technique is particularly useful when adrenal vein sampling is unsuccessful or not feasible, and the patient would otherwise remain a potential candidate for surgical intervention.[160][194][195] This modality can also help identify laterality in primary hyperaldosteronism and may be particularly beneficial for patients with chronic kidney disease, where standard biochemical testing is more problematic.[194][195] Despite its high positive predictive value and sensitivity of approximately 92%,[194] this test is technically challenging and is not available in many centers.
  • The 11C-metomidate positron emission tomography (PET)-CT scanning modality, with and without dexamethasone suppression, appears to be a sensitive and specific tool for detecting primary hyperaldosteronism and adrenocortical tumors.[196][197][198][199][200][201] Additionally, this scan can reliably predict the response to medical therapy for hyperaldosteronism.[199] However, its clinical utility remains uncertain due to limited data, and it is not widely available, requiring ACTH suppression.[45][198][200][202][203][204]
  • Gallium-68 (68Ga) pentixafor PET-CT scanning, which targets CXCR4, has demonstrated an excellent correlation in distinguishing aldosterone-producing from nonfunctional adrenal nodules and in differentiating unilateral from bilateral hyperaldosteronism.[205][206][207][208][209][210][211] 68Ga has also proved useful in rare cases of bilateral aldosterone-producing adenomas.[205][212] In a study, the gallium-68 PET-CT scan demonstrated a 90% correlation with adrenal vein sampling, compared to 54% with CT scans.[205]

Genetic Testing

Genetic testing is recommended for patients with primary aldosteronism who are aged 20 or younger, have a family history of the disorder, or when lateralization cannot be determined.[25][143][213][214][215][216][217][218][219] Familial hyperaldosteronism accounts for approximately 6% of all adult cases of primary hyperaldosteronism.[25][219] Notably, 4 types of familial hyperaldosteronism have been described, with type I (glucocorticoid-responsive hyperaldosteronism) and type III (glucocorticoid-unresponsive hyperaldosteronism) being the most common.[25][42] In severe cases, bilateral adrenalectomy may be necessary to manage blood pressure and severe hypokalemia, which then requires lifelong glucocorticoid and mineralocorticoid replacement therapy.

Summary

All newly diagnosed hypertensive patients should be screened for hyperaldosteronism by checking serum renin and a serum or urine aldosterone level.[92][101] Findings suggestive of hyperaldosteronism include a serum aldosterone level greater than 15 ng/dL, a 24-hour urine aldosterone level exceeding 12 mcg, or an aldosterone-to-renin ratio of more than 20:1.[101] 

The next step is to differentiate between primary and secondary hyperaldosteronism, which is relatively straightforward using serum renin levels. Primary hyperaldosteronism typically shows an aldosterone-to-renin ratio greater than 20:1 with low renin levels, whereas secondary hyperaldosteronism is characterized by elevated serum renin levels.[14]

A confirmatory test is typically recommended for all suspected cases of primary hyperaldosteronism; however, it may be omitted in certain situations.[8][41][133][134]

If primary hyperaldosteronism is diagnosed and confirmed, the next step is to differentiate between unilateral disease, which is optimally treated surgically, and bilateral disease, which is best managed medically.[220][221][222][223] 

  • Unilateral disease is traditionally confirmed with bilateral selective adrenal venous sampling; however, CT scans and other imaging modalities may also be used and can be sufficient for lateralization in selected cases.[42][164] Successful surgical outcomes depend on accurate lateralization.[104]
  • Secondary hyperaldosteronism, characterized by elevated serum renin levels, is best treated by eliminating the underlying etiology and using appropriate medical therapy.

Treatment / Management

Surgical Management of Unilateral Primary Hyperaldosteronism

Total adrenalectomy surgery

This is the preferred treatment of choice for unilateral primary hyperaldosteronism.[1][42][45][224][225][226] Minimally invasive techniques, such as laparoscopic or robotic approaches, are preferred over partial adrenalectomy, as they offer better symptom resolution and treatment efficacy.[161] Complete adrenalectomy is preferred to partial gland removal due to greater efficacy and resolution of symptoms.[42] Notably, primary hyperaldosteronism is the most common surgically curable cause of hypertension.[227] (A1)

Preoperative spironolactone is recommended for 4 to 6 weeks to help control blood pressure. Patients who do not achieve blood pressure normalization on spironolactone before surgery are more likely to remain hypertensive even after surgery. Following surgery, approximately half of patients with unilateral primary hyperaldosteronism will eventually maintain stable, normal blood pressure without further treatment, although this may take up to a year.[228] Various predictive models have been unable to reliably predict which patients with unilateral primary hyperaldosteronism will become normotensive after adrenalectomy surgery.[228][229][230][231][232][233][234] Please see StatPearls' companion resources, "Conn Syndrome" and "Adrenalectomy," for more information.(A1)

Patients with hyperaldosteronism due to unilateral disease experience better long-term outcomes with surgery than with medical therapy, including improved blood pressure control, maintenance of normal serum potassium levels, and enhanced vascular remodeling.[235][236][237][238][239] If hypertension persists after surgery despite normalized aldosterone levels, possible causes include:(A1)

  • Incorrect or incomplete initial diagnosis of unilateral hyperaldosteronism
  • Underlying essential hypertension
  • Vascular abnormalities or damage from chronic hyperaldosteronism
  • Other unrelated causes of hypertension, such as pheochromocytoma or renovascular disease

Partial adrenalectomy

Partial adrenalectomy may be an option for some patients, offering reasonable outcomes with fewer postoperative complications than total adrenalectomy. However, it carries a significant risk of incomplete control of hyperaldosteronism due to residual abnormal aldosterone-secreting tissue.[240][241]

Total adrenalectomy remains the preferred approach in most cases, as partial adrenal resections require technically challenging selective segmental adrenal venous sampling and are associated with lower rates of postoperative biochemical success and blood pressure normalization, with limited supporting data currently available.[1][242][243][244][245][246][247][248] However, several studies suggest that partial adrenalectomy may be appropriate in selected cases of unilateral surgical hyperaldosteronism and can yield satisfactory outcomes.[244][249][250][251](A1)

Percutaneous and transcatheter ablation of unilateral adrenal adenomas 

These newer, less invasive treatment options appear reasonably safe and effective when performed at experienced centers, with early data showing an overall clinical success rate of approximately 75%.[1][252][253][254][255][256][257][258] In a randomized controlled trial, 27% of patients achieved a complete response, 54% had a partial response, and over half showed biochemical success.[259] These new procedures are currently recommended only for patients who are unsuitable for surgery or long-term medication or who decline these options.[252][253][254][255][256][257][260][261] Their long-term outcomes compared to standard surgery or extended medical therapy remain unclear.(A1)

Medical Management of Hyperaldosteronism

Mineralocorticoid receptor antagonists

These are the preferred treatments for primary hyperaldosteronism caused by bilateral adrenal hyperplasia and for patients who are not candidates for surgery.[1][42][45] Spironolactone and eplerenone are the most commonly used agents. The selection of these agents depends on the adverse effect profile, physician experience, and individual patient factors. Spontaneous remission of primary hyperaldosteronism after long-term treatment with mineralocorticoid receptor antagonists is very rare, so medical therapy is generally lifelong.[262][263](A1)

  • Spironolactone: This is typically the preferred medical therapy, starting at 12.5 to 25 mg daily and titrated upward every 2 weeks, according to the 2016 Endocrine Society Guidelines.[84] Spironolactone is favored because it is more effective in controlling blood pressure and has a longer duration of action due to its active metabolites, allowing once-daily dosing.[264][264] Maintenance doses are often around 100 mg daily. Significant adverse effects in men include gynecomastia and decreased libido, which may occur in up to 50% of those taking more than 150 mg daily. In such cases, eplerenone may be the preferred option. Please see StatPearls' companion resource, "Spironolactone," for more information. 
    • (A1)
  • Eplerenone is a more selective medication that, unlike spironolactone, does not block androgen receptors. This makes it more acceptable and preferred for long-term treatment in men, as it avoids side effects such as gynecomastia and erectile dysfunction, especially when low-dose spironolactone is ineffective. Eplerenone has a relatively short half-life of about 4 hours, so twice-daily dosing is generally recommended. Eplerenone treatment usually starts at 50 mg daily and is titrated up to a maximum of about 200 mg twice daily. Although now available as a generic, eplerenone remains more expensive than spironolactone. Please see StatPearls' companion resource, "Eplerenone," for more information.
  • Canrenone is an active metabolite of spironolactone with similar efficacy but a much longer half-life (16.5 hours versus 1.4 hours) and significantly fewer adverse sexual effects.[265][266] Canrenone appears to have direct beneficial effects on the myocardium beyond its antihypertensive properties.[267] Canrenone stabilizes heart failure, reduces harmful cardiac remodeling, improves diastolic function, and may increase ejection fraction.[267][268][269] Although available in Europe, canrenone is not currently approved for use in the United States.
    • (A1)

Patients with bilateral or idiopathic hyperaldosteronism are typically treated medically with spironolactone or eplerenone to control blood pressure. However, they tend to experience higher long-term rates of cardiovascular events compared to other hypertensive patients, as elevated serum aldosterone levels are associated with increased risk.[235] This has prompted investigations into alternative therapies for cases where surgery is not feasible.(A1)

Additional medications

Other medications, particularly amiloride and triamterene—potassium-sparing diuretic antihypertensives—help lower blood pressure and increase serum potassium levels.[82] These medications help maintain normal serum potassium levels and also allow a reduction of the required dosage of the mineralocorticoid antagonist drug. They are also the recommended medical therapy for patients who do not tolerate spironolactone or eplerenone.[270] Amiloride is generally preferred, as triamterene may increase the risk of urinary calculi formation.[271][272][273][274] Please see StatPearls' companion resources, "Amiloride" and "Triamterene," for more information.[276](B3)

Patients with primary hyperaldosteronism are sensitive to salt intake and typically experience a more pronounced beneficial response to dietary sodium restriction compared to other hypertensive patients.[1][275] Another goal of medical therapy, besides normalizing blood pressure and regulating potassium levels, is to increase renin levels—typically to above 1 ng/mL/h—as this is associated with a significantly lower risk of atrial fibrillation, reduced long-term cardiovascular complications, and improved overall outcomes. Achieving this target is associated with a significantly lower risk of atrial fibrillation, reduced long-term cardiovascular complications, and improved overall outcomes.[1][10][276][277][278] (B2)

Surgery plays a limited role in bilateral hyperaldosteronism. However, unilateral adrenalectomy may be considered in cases where medical therapy is insufficient, particularly if selective adrenal venous sampling reveals a significant difference in aldosterone secretion between the right and left sides of the adrenal glands.[279][280][281]

Unilateral adrenalectomy with contralateral partial adrenalectomy, as well as bilateral partial adrenalectomies, have been successfully performed in carefully selected cases and may be considered in otherwise refractory situations.[282][283][284](B2)

Bilateral adrenalectomy

Bilateral adrenalectomy, even in severe cases of medically intractable bilateral hyperaldosteronism, is generally not recommended due to the risks and complications associated with lifelong adrenal hormone replacement therapy.[1] However, in extremely rare and refractory cases, it may be considered for selected patients with severe symptomatic hyperaldosteronism when the potential benefits outweigh the risks of long-term adrenal insufficiency.[285][286] Notably, it is suggested that endocrinologists experienced in both primary adrenal insufficiency and hyperaldosteronism guide patients through these complex decisions, following thorough shared decision-making discussions with the patient and family about the trade-offs involved in this unconventional and controversial surgery.[286]

Bilateral super-selective adrenal artery embolization has been successfully used to treat idiopathic primary hyperaldosteronism.[287][288][289][290][291][292][293][294][295][296] Early studies suggest that this selective embolization therapy can lead to long-term, sustained improvements in serum aldosterone levels, aldosterone-to-renin ratios, hypokalemia, and blood pressure, with no significant adverse effects or adverse events reported after 1 year of follow-up.[287][288][289][290][291][292] These findings suggest that bilateral super-selective adrenal artery embolization may represent a promising and effective alternative therapy for idiopathic primary hyperaldosteronism in the future.[287][288][289][290][291][292](B2)

Investigational therapies

Investigational therapies, including aldosterone synthase inhibitors and nonsteroidal mineralocorticoid receptor antagonists, are currently under development.[1][297][298] Aldosterone synthase inhibitors are particularly promising, as they directly suppress aldosterone production and may offer improved outcomes compared to traditional mineralocorticoid receptor antagonists.[1][297][298][299][300][301][302][303][304][305](A1)

Experience with percutaneous thermal and microwave ablation for unilateral hyperaldosteronism remains limited. Success rates appear lower than those of standard surgery; the procedure requires general anesthesia, and the risk of complications is relatively significant.[306][307][308][309][310][311](A1)

Combination therapy

Drug selection, dosage, and administration frequency are ultimately guided by the patient’s clinical response. Combining medications with lifestyle modifications—such as sodium restriction, alcohol avoidance, smoking cessation, regular aerobic exercise, and maintaining an ideal body weight—generally produces the best outcomes.[84][312][313][314] Additional treatments, including glucocorticoids, amiloride, triamterene, and calcium channel blockers, may be added to manage hypertension and symptoms not fully controlled by mineralocorticoid receptor antagonists alone.[82] (B3)

Secondary Hyperaldosteronism Management

Addressing the underlying cause is the primary approach to managing secondary hyperaldosteronism, often leading to symptom resolution. For blood pressure control, ACE inhibitors (ACEIs) and angiotensin receptor blockers are preferred because of their renal protective effects.[315] Additionally, dietary salt restriction is recommended for better blood pressure management.[315] Please see StatPearls' companion resource, "Spironolactone," for more information.(A1)

Potassium supplements and potassium-sparing diuretics can be used to manage secondary hyperaldosteronism, with a treatment approach similar to that for primary hyperaldosteronism due to idiopathic adrenal hyperplasia. In cases involving renal artery stenosis, surgical intervention or revascularization may be required to achieve optimal blood pressure control. Please see StatPearls' companion resource, "Renal Artery Stenosis," for more information.

Differential Diagnosis

Presentations similar to hyperaldosteronism can be observed in various conditions, including essential hypertension, Liddle syndrome, syndrome of apparent mineralocorticoid excess, congenital adrenal hyperplasia, primary glucocorticoid resistance, Cushing syndrome (hypercortisolism), aldosterone-producing renin-responsive adenomas, adrenocortical carcinomas, metabolic alkalosis, diabetes insipidus, preeclampsia, Gitelman syndrome, renal artery stenosis, Bartter syndrome, pheochromocytoma, Chrétien syndrome, excessive licorice intake, and ectopic ACTH syndrome.

Please see StatPearls' companion resources "Bartter Syndrome," "Gitelman Syndrome," "Renal Artery Stenosis," "Primary Hyperaldosteronism," "Adrenal Cancer," "Hypercortisolism," "Pheochromocytoma," "Gitelman Syndrome," and "Arginine Vasopressin Disorder (Diabetes Insipidus)," for more information.[38]

The following presentations are some of the shared clinical features:

  • 17-Alpha-hydroxylase deficiency: This condition can closely mimic hyperaldosteronism.[316] Affected patients typically present with hypogonadism and immature genitalia.[316] Genetic testing is often required for a definitive diagnosis.[316] Please see StatPearls' companion resource, "17-Hydroxylase Deficiency," for additional information.
  • Bartter syndrome: This autosomal recessive genetic disorder affects renal salt and water reabsorption, resulting in a low extracellular fluid volume, decreased blood pressure, hypokalemia, and compensatory elevations in serum aldosterone and renin levels. This condition is distinguished from Gitelman syndrome by elevated 24-hour urinary calcium excretion. Genetic testing may be necessary to confirm the diagnosis. Please see StatPearls' companion resource, "Bartter Syndrome," for more information. 
  • Chrétien syndrome: This rare disorder is caused by excessive secretion of proopiomelanocortin, the precursor of ACTH, typically from a pituitary adenoma. The resulting ACTH overproduction leads to adrenocortical hypertension.[317]
  • Congenital adrenal hyperplasia: This condition is typically associated with a family history of 11-beta-hydroxylase or 17-alpha-hydroxylase deficiency and is characterized by low aldosterone levels. Please see StatPearls' companion resources, "Congenital Adrenal Hyperplasia" and "17-Hydroxylase Deficiency," for additional information.
  • Cushing syndrome: Cushing syndrome may present with hypertension and hypokalemia, mimicking hyperaldosteronism; however, these findings result from excessive adrenal cortisol production. A low-dose dexamethasone suppression test helps identify Cushing syndrome in cases that are equivocal or subclinical.[318] Please see StatPearls' companion resources, "Hypercortisolism," and "Dexamethasone Suppression Test," for more information.
  • Ectopic ACTH syndrome: This condition is characterized by elevated ACTH levels that remain unsuppressed despite high-dose dexamethasone administration. This is often associated with an underlying tumor.[319][320][321][322] 
  • Essential hypertension: This condition typically presents with a normal PAC/PRA ratio. Please see StatPearls' companion resource, "Essential Hypertension," for additional information.
  • Excessive licorice intake: This condition inhibits the renal enzyme 11β-hydroxysteroid dehydrogenase type 2, preventing the conversion of cortisol to cortisone. The resulting cortisol excess acts as a mineralocorticoid agonist, mimicking the effects of hyperaldosteronism.[323][324]
  • Gitelman syndrome: This is a genetic disorder similar to Bartter syndrome, as both are inherited in an autosomal recessive manner and cause hypokalemia due to renal salt and water wasting. This inappropriate fluid depletion causes compensatory elevations in renin and aldosterone levels. Unlike Bartter syndrome, Gitelman syndrome is characterized by hypocalciuria on 24-hour urine testing. Genetic testing can be used for diagnosis. Please see StatPearls' companion resource, "Gitelman Syndrome," for more information. 
  • Liddle syndrome: This is a rare genetic disorder that typically presents in childhood with low aldosterone levels. This condition manifests as hypertension, hypokalemia, and metabolic alkalosis, resembling mineralocorticoid excess disorders. Liddle syndrome is often referred to as pseudohyperaldosteronism and is characterized by increased urinary potassium excretion and sodium reabsorption in the renal collecting tubules despite low aldosterone levels. Please see StatPearls' companion resource, "Liddle Syndrome (Pseudohyperaldosteronism)," for additional information.
  • Pheochromocytomas (80%–85%) and sympathetic paragangliomas (15%–20%) are benign neuroendocrine tumors that secrete excessive catecholamines—dopamine, epinephrine, and norepinephrine—leading to hypertension. This hypertension may be episodic or sustained and, similar to hyperaldosteronism, is often resistant to standard antihypertensive therapy. Surgical resection is the primary treatment. Please see StatPearls' companion reference resources, "Pheochromocytoma" and "Paraganglioma," for additional information.
  • Primary glucocorticoid resistance: This condition is characterized by low aldosterone levels and is accompanied by elevated ACTH and cortisol levels. A positive family history is often present, reflecting the hereditary nature of the syndrome.[325][326][327]
  • Syndrome of apparent mineralocorticoid excess: Patients with this syndrome present with hypertension, low aldosterone levels, high urinary free cortisol levels, hypokalemia, suppressed ACTH, and may have hereditary links or a history of excessive licorice consumption.[328] Genetically, it is an autosomal recessive disorder.[328]

Hyperaldosteronism and Hypercortisolism

Hyperaldosteronism and hypercortisolism (ie, Cushing syndrome and disease) share overlapping clinical and laboratory features due to adrenal dysfunction. Both conditions are 3 times more common in women than in men, are most frequently diagnosed in patients aged 25 to 50, and often present with hypertension, hypokalemia, and hypernatremia.

In hyperaldosteronism, patients typically present with intractable hypertension resistant to standard drug therapies.[42] Hyperaldosteronism is a relatively common disorder, affecting approximately 10% of all hypertensive individuals, with over 20% experiencing resistant hypertension.[2][329] Therefore, hyperaldosteronism should be considered in any patient with difficult-to-control hypertension. Diagnosis often begins with blood tests showing elevated serum aldosterone (at least 15 ng/mL), a high aldosterone-to-renin ratio, and low plasma renin levels, as previously described.[1][23][35] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.

Conversely, patients with hypercortisolism often present with less severe hypertension. Hypercortisolism is rare, with an estimated prevalence of approximately 60 cases per million individuals.[330] Hypercortisolism is initially suspected based on clinical features such as weight gain, muscle weakness, thin extremities, a rounded face, a fat pad at the base of the neck, easy bruising, thin skin, acne, hirsutism, and purplish stretch marks. A 24-hour urine test for free cortisol is typically used for initial diagnosis, while a dexamethasone suppression test serves as a confirmatory measure. Please see StatPearls' companion resources, "Dexamethasone Suppression Test," "Cushing Syndrome," and "Hypercortisolism," for additional information.[146][161][163]

Prognosis

Few studies have examined mortality rates for either form of hyperaldosteronism, but available data suggest 10-year survival rates for treated patients range from 90% to 95%. The most common morbidity associated with hyperaldosteronism is cardiovascular-related; however, overall mortality rates do not significantly differ from those of the general population.[331] Patients with hyperaldosteronism treated medically experience higher cardiovascular and overall mortality compared to those treated surgically.[332][333][334]

Although biochemical success—defined by normalization of the aldosterone-to-renin ratio and potassium levels—was achieved in 94% of patients following adrenalectomy, only 37% attained complete clinical success, characterized by normal blood pressure without the need for antihypertensive medications. An additional 47% experienced partial clinical success, with improved blood pressure still requiring medication.[1][335] These improvements may take up to a year, and by 5 years post-surgery, approximately half of the patients remain normotensive without medication.[1]

Hypokalemia in patients with primary unilateral hyperaldosteronism is typically well-controlled following adrenalectomy.[1] However, if hypokalemia persists, it may cause symptoms such as muscle weakness, paralysis, constipation, and polyuria. Both primary hyperaldosteronism and associated hypokalemia can also impair insulin secretion, thereby increasing the risk of developing diabetes mellitus.[56][57][58] 

Untreated hyperaldosteronism is linked to substantial morbidity and mortality, primarily due to uncontrolled hypertension, stroke, congestive heart failure, and cardiac arrhythmias.[1] Additional risks include coronary artery disease, atrial fibrillation, increased proteinuria, chronic kidney disease, type 2 diabetes, metabolic syndrome, and osteoporosis secondary to hypercalciuria.[1][9][276][336][337][338][339][340][341][342][343][344][345][346]

Complications

The most common complication and comorbidity of hyperaldosteronism is an increased risk of cardiovascular mortality resulting from excessive aldosterone secretion. Clinical manifestations may include atrial fibrillation, left ventricular hypertrophy, hypertension, myocardial infarction, and stroke.[347][348][349][350][351] Myocardial fibrosis has also been observed in patients with long-standing hyperaldosteronism.[352][353]

Secondary adrenal insufficiency requiring glucocorticoid supplementation may develop in 30% to 50% of patients following unilateral adrenalectomy, particularly in those with mild autonomous cortisol secretion before surgery.[354]

Some patients may experience severe hyperkalemia immediately following unilateral adrenalectomy due to prolonged suppression of the adrenal zona glomerulosa and insufficient aldosterone production from the remaining adrenal gland.[1][355][356][357][358][359][360]

Residual or recurrent hyperaldosteronism may occur after adrenalectomy surgery due to many factors. Known risk factors include:[45][77][335][361][362][363][364][365][366][367][368][369]

  • Omission of adrenal venous sampling
  • Atypical or nonclassical histopathology (60% versus 14% recurrence rate)
  • Black ethnicity
  • Undetected contralateral disease preoperatively
  • Delayed diagnosis leading to chronic kidney disease and essential hypertension
  • Coexisting diabetes
  • Evidence of vascular remodeling
  • Extended duration of hypertension
  • Family history of hypertension
  • Higher serum potassium
  • History of cerebrovascular and cardiovascular diseases
  • Use of multiple antihypertensive drugs to control preoperative blood pressure
  • Larger adrenal nodule size
  • Lateralization changes observed on adrenal venous sampling at baseline, but absent after cosyntropin stimulation
  • Left ventricular hypertrophy
  • Longer duration of hypertension before surgery (≥5 years)
  • Lower aldosterone-to-renin ratio
  • Male gender
  • Multiple adrenal nodules
  • Obesity
  • Older age (individuals aged more than 50)
  • Poor clinical response to preoperative spironolactone
  • Proteinuria
  • Renal failure
  • Significant discrepancy between the adrenal vein sampling and imaging findings
  • Underlying essential hypertension (present in about 30% of patients with primary hyperaldosteronism)

Postoperative and Rehabilitation Care

The day after adrenalectomy, serum aldosterone levels should be measured. Successful surgery is indicated by a serum aldosterone level of less than 5 ng/mL.[335] 

Serum potassium levels require close monitoring during hospitalization and at least weekly for 1 month postoperatively, as some patients may develop significant hyperkalemia.[355][357][358][359][360][370]

Serum creatinine should also be monitored, as renal function may initially decline following surgery but typically stabilizes within 3 to 6 months.

Restricting sodium intake, avoiding alcohol, quitting smoking, maintaining a healthy body weight, and engaging in regular aerobic exercise all contribute to optimal postoperative care and overall health maintenance.

Quality of life scores typically improve within 3 months of successful surgery, with continued improvement possible up to 12 months.[224][371] Surgical treatment has been shown to significantly enhance quality of life compared to medical therapy.[371]

Consultations

Effective management of hyperaldosteronism often requires a coordinated, multidisciplinary approach tailored to each patient's specific needs.

  • Consultations with endocrinologists, hypertension specialists, and nutritionists are essential for the comprehensive management of hyperaldosteronism.
  • Surgical candidates with unilateral primary hyperaldosteronism should be evaluated by general surgery and/or urology.
  • Additionally, collaboration with radiology or interventional radiology is often warranted for imaging interpretation and guidance on adrenal vein sampling.

Deterrence and Patient Education

Patients should receive thorough education about their condition, highlighting the importance of adhering to long-term treatment plans, including dietary modifications such as salt restriction, attending follow-up appointments, and fully complying with prescribed medications.

Pearls and Other Issues

Key facts to bear in mind when screening for, diagnosing, and managing hyperaldosteronism include:

  • Hyperaldosteronism testing should be routinely considered in all newly diagnosed patients with hypertension that is difficult to control with 3 or more standard antihypertensive agents, particularly those aged 40 or younger, those with hypokalemia, or those with obstructive sleep apnea.[4][42][91][372] The Endocrine Society recommends screening for primary hyperaldosteronism in these patients, as it is a common yet frequently underdiagnosed cause of resistant hypertension.[84] 
  • A morning plasma aldosterone-to-renin ratio (PAC/PRA) is a useful initial screening test for hyperaldosteronism. A ratio greater than 20:1, combined with a PAC above 20 ng/dL, strongly suggests primary hyperaldosteronism, particularly when accompanied by low renin levels and/or hypokalemia.[82][102] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.
  • Serum renin levels provide a straightforward method to differentiate primary from secondary hyperaldosteronism. In primary hyperaldosteronism, renin activity is typically suppressed, whereas it is elevated in secondary hyperaldosteronism. Additionally, blood pressure and aldosterone levels are generally higher in secondary hyperaldosteronism compared to primary hyperaldosteronism.
  • A simple serum aldosterone level can serve as an initial screening tool for evaluating aldosterone levels. Levels above 30 ng/dL are highly suggestive of hyperaldosteronism, while levels as low as 15 ng/dL warrant further investigation, starting with an aldosterone-to-renin ratio.[1][45][82] As aldosterone levels can fluctuate, some experts recommend using a cutoff of 15 ng/dL to minimize missed diagnoses.[1][45][108] Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.
  • 17-Alpha-hydroxylase deficiency can closely mimic primary or secondary hyperaldosteronism.[316] Patients with this deficiency will often present with juvenile, undeveloped genitalia and hypogonadism.[316] Please see StatPearls' companion resource, "17-Hydroxylase Deficiency," for additional information.
  • Normal serum potassium in a patient with hypertension does not exclude hyperaldosteronism.[1] Please see StatPearls' companion resources, "Primary Hyperaldosteronism" and "Conn Syndrome," for more information
  • A significant overlap in aldosterone-to-renin ratios exists between primary hyperaldosteronism and essential resistant hypertension. However, in patients with hypokalemia, the aldosterone-to-renin ratio is often sufficient for diagnosing hyperaldosteronism. Please see StatPearls' companion resource, "Primary Hyperaldosteronism," for more information.
  • Hypokalemia has traditionally been considered a key indicator of hyperaldosteronism; however, it is present in fewer than 30% of cases.[55][373] 
  • Hypokalemia may be masked in patients adhering to a salt-restricted diet or affected by conditions such as hemolysis (eg, prolonged tourniquet application before blood draw), magnesium deficiency, Bartter, Cushing, Fanconi, and Liddle syndromes, renal tubular acidosis, or when whole blood is used for testing.[374][375] 
  • Severe hypokalemia may also obscure the diagnosis of hyperaldosteronism until potassium levels are corrected.[376]
  • Patients with primary hyperaldosteronism due to functional adrenal adenomas are more likely to demonstrate hypokalemia.[377]
  • Hyperaldosteronism causes renal hyperfiltration. Postoperatively, when aldosterone levels normalize, this may uncover some degree of preexisting renal failure.[378] Consequently, renal function should be closely monitored following adrenalectomy for hyperaldosteronism.[378][379]
  • Hyperaldosteronism is present in approximately 10% of all individuals with hypertension, but the prevalence increases to over 20% in patients with medication-resistant hypertension and up to 50% among those referred to hypertension specialty centers.[2][8][36][37][38][39]
  • A patient's clinical history and presentation, family history, and response to prior treatments will help guide the selection of appropriate diagnostic tests for suspected disorders.[130]
  • Obstructive sleep apnea with unexplained atrial fibrillation is considered a high-risk factor for hyperaldosteronism.[380] 
  • Obstructive sleep apnea doubles the risk of hyperaldosteronism by increasing endothelin-1 levels through hypoxia, which in turn stimulates aldosterone production.[45][381][382]
  • Genetic testing for familial hyperaldosteronism should be considered in patients with confirmed primary hyperaldosteronism who are aged 20 or younger, have a suggestive family history, or when imaging fails to demonstrate lateralization.[25][143][213][214][215][216][217][218][219]
  • Various computerized models using machine learning that integrate CT findings with clinical and biochemical data are being developed to improve the classification, subtyping, and lateralization of primary hyperaldosteronism.[383][384][385][386][387][388]
  • Bilateral super-selective adrenal artery embolization may be considered for patients with bilateral or idiopathic primary hyperaldosteronism, if available.[287][288][289][290][291][292]

Enhancing Healthcare Team Outcomes

Diagnosing and managing hyperaldosteronism is a complex process that is best approached by an interprofessional healthcare team, comprising a radiologist, pathologist, internist, endocrinologist, nurse practitioner, pharmacist, nurse, and surgeon. For primary hyperaldosteronism caused by unilateral disease, surgery is the preferred treatment. Robotic adrenalectomy is favored because it is associated with fewer complications and shorter hospital stays compared to laparoscopic or open adrenal surgery. Complete adrenalectomy is preferred over partial adrenalectomy due to its greater efficacy and more complete symptom resolution.

For nonsurgical candidates, mineralocorticoid receptor antagonists are the preferred medical therapy. In bilateral hyperaldosteronism, medical treatment is recommended, with spironolactone as the initial drug of choice. However, eplerenone may be preferred for long-term management in men because it has a lower risk of gynecomastia and sexual dysfunction.

Pharmacists play a key role in supporting the clinical team by counseling patients on the importance of long-term adherence to medical therapy. They should also inform patients about the potential adverse effects of spironolactone, particularly the risk of gynecomastia and sexual dysfunction at higher doses (>150 mg/d).

Primary care clinicians, nurses, and dietitians should educate patients and their families on the importance of salt restriction, alcohol cessation, smoking cessation, maintaining an optimal body weight, and engaging in regular aerobic exercise. Regular follow-up is essential due to the high risk of adverse cardiac events in these patients. A coordinated interprofessional team approach with close communication among members is crucial to reducing the morbidity associated with hyperaldosteronism.

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