Endocrinology ICD-10: E26.01

Primary Aldosteronism

Also known as: Conn Syndrome, Primary Hyperaldosteronism

A hormonal disorder where the adrenal glands produce too much aldosterone, causing hard-to-treat high blood pressure and low potassium levels.

Source: Endocrine Society Clinical Practice Guideline for Primary Aldosteronism

Updated: Aug 05, 2026

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Red Flag Warning & Emergency Situations

Profound muscle weakness or paralysis indicating life-threatening hypokalemia.
Hypertensive crisis symptoms (chest pain, neurologic deficits).

Emergency Management: Severe symptomatic hypokalemia (K < 2.5 mEq/L) requires careful IV Potassium Chloride repletion (max 10-20 mEq/hour) with continuous ECG monitoring to prevent arrhythmias.

Core Definition:

Primary aldosteronism (PA) is a group of disorders characterized by autonomous, inappropriate overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands, independent of the normal renin-angiotensin regulatory system.

Detailed Overview

It is the most common cause of secondary hypertension. The excessive aldosterone causes renal sodium retention (leading to volume expansion and hypertension) and potassium excretion (leading to hypokalemia). PA causes significantly higher cardiovascular morbidity and mortality compared to age- and blood pressure-matched essential hypertension due to the direct fibrotic effects of aldosterone on the heart and vasculature. Early identification and targeted treatment (surgical resection or mineralocorticoid receptor antagonists) can cure or vastly improve the hypertension.

Epidemiology & Demographics

Prevalence is 5-10% of all hypertensive patients, and up to 20% in patients with resistant hypertension. Often diagnosed between ages 30 and 50.

Etiological Mechanism

The two main causes are Bilateral Idiopathic Adrenal Hyperplasia (IHA) accounting for 60-70% of cases, and Aldosterone-Producing Adenoma (Conn's adenoma) accounting for 30-40%. Rare causes include unilateral hyperplasia or familial hyperaldosteronism.

Primary Causes

Somatic mutations (e.g., KCNJ5, ATP1A1, CACNA1D) in adrenal cortical cells leading to autonomous aldosterone hypersecretion.

Resistant Hypertension: Blood pressure >140/90 despite 3 antihypertensive drugs including a diuretic.
Hypokalemia: Spontaneous or diuretic-induced low potassium in the setting of hypertension is a strong indicator.
Incidentaloma: Hypertension in a patient with a previously discovered adrenal mass.
Family History: Early-onset hypertension or cerebrovascular accidents at young ages (<40 years).

Aldosterone binds to mineralocorticoid receptors in the principal cells of the distal tubule and collecting duct of the kidney. This upregulates the epithelial sodium channel (ENaC) and the basolateral Na+/K+-ATPase. The resulting massive sodium reabsorption expands the intravascular volume, suppressing renin secretion from the juxtaglomerular apparatus (classic profile: high aldosterone, low plasma renin activity). To maintain electroneutrality, potassium and hydrogen ions are secreted into the tubular lumen, resulting in hypokalemia and a metabolic alkalosis. Sustained excess aldosterone also exerts direct pro-inflammatory and pro-fibrotic effects on the myocardium and blood vessels.

Characteristic Clinical Presentation

Hypertension: Often asymptomatic but severe or resistant to standard multidrug therapy.
Muscle Weakness / Cramps: Due to severe hypokalemia altering resting membrane potentials.
Polyuria and Polydipsia: Hypokalemia can induce a state of nephrogenic diabetes insipidus, causing frequent urination and thirst.
Palpitations: Arrhythmias secondary to hypokalemia.

Physical Examination Signs

Severe hypertension (>160/100 mmHg).
Absence of peripheral edema (due to 'aldosterone escape' mechanism via ANP).
Signs of hypokalemia on exam, such as diminished deep tendon reflexes or muscle paresis.

Clinical Risk: Uncontrolled or untreated conditions may progress to the following complications:

Cardiovascular Events: Higher rates of stroke, atrial fibrillation, and myocardial infarction than essential hypertension.
Target Organ Damage: Left ventricular hypertrophy and chronic kidney disease (proteinuria).
Severe Hypokalemia: Can cause fatal cardiac arrhythmias or paralysis.

Diagnostic Criteria & Guidelines

Requires three steps: 1) Screening with Plasma Aldosterone Concentration to Plasma Renin Activity Ratio (ARR). 2) Confirmation with a suppression test (e.g., Oral Sodium Loading). 3) Subtyping via CT scan and Adrenal Vein Sampling.

Differential Diagnosis

Essential Hypertension
Renovascular Hypertension (Renal artery stenosis - causes high renin AND high aldosterone)
Cushing Syndrome
Liddle Syndrome (genetic ENaC overactivation mimicking hyperaldosteronism)

Laboratory Tests & Biomarkers

Plasma Aldosterone to Renin Ratio (ARR): Elevated ARR > 20 (with PAC usually >15 ng/dL and suppressed PRA <1.0 ng/mL/hr) is a positive screen.
Basic Metabolic Panel: Hypokalemia (K+ < 3.5 mEq/L, present in only ~30% of patients) and mild hypernatremia (Na+ ~ 144 mEq/L) with metabolic alkalosis (elevated HCO3- > 28 mEq/L).
Saline Infusion Test (Confirmation): Failure of PAC to suppress < 5 ng/dL after infusion of 2 Liters of normal saline over 4 hours confirms autonomous production.

Imaging Modalities & Findings

CT Abdomen (Adrenal Protocol): May show a discrete unilateral adrenal adenoma (typically small, <2 cm, lipid-rich) or bilateral thickening/nodularity. Note: CT is often misleading in older patients due to non-functioning incidentalomas.
Adrenal Vein Sampling (AVS): The gold standard to distinguish unilateral from bilateral disease. Shows a lateralization ratio > 4:1 (aldosterone/cortisol ratio of dominant over non-dominant adrenal vein).

Unilateral Disease
Aldosterone-producing adenoma (Conn syndrome); curable with surgery.
Bilateral Disease
Bilateral adrenal hyperplasia; requires lifelong medical therapy.

First-Line Treatment:

For Unilateral Adenoma: Laparoscopic adrenalectomy is the definitive cure. Cures hypokalemia in 100% and hypertension in 30-60%. For Bilateral Hyperplasia: Mineralocorticoid receptor antagonists. Spironolactone (starting at 12.5-25 mg PO daily, up to 100 mg). Eplerenone (50 mg PO BID) is an alternative with fewer anti-androgenic side effects.

Second-Line & Adjunctive Therapy

Amiloride (5-10 mg daily), an ENaC inhibitor, can be used if MRA therapy is poorly tolerated or contraindicated.

Surgical & Procedural Management

Unilateral laparoscopic adrenalectomy. Post-operatively, monitor closely for hyperkalemia due to transient hypoaldosteronism from the suppression of the contralateral normal gland.

Recommended Lifestyle Changes

Sodium restriction (<2 grams/day) is critical, as a high salt diet exacerbates potassium wasting and hypertension.
Weight management and regular aerobic exercise to assist in blood pressure control.

Patient Counseling & Advice

Men taking spironolactone should be warned about side effects like gynecomastia, breast tenderness, and decreased libido. If these occur, they can be switched to Eplerenone.

Follow-Up & Monitoring Schedule

Monitor blood pressure, serum potassium, and creatinine 1, 2, and 4 weeks after starting an MRA or post-adrenalectomy. Long-term monitoring of BP and renal function is necessary.

Preventive Strategies

No specific prevention. Routine screening (ARR) in high-risk groups (e.g., severe hypertension, hypokalemia) is the best strategy to prevent long-term cardiovascular damage.

Surgery cures hypokalemia universally and cures hypertension in about 50% of unilateral cases. Medical therapy effectively controls BP and potassium in bilateral disease but requires lifelong adherence.

Frequently Asked Questions

CT scans can be misleading. Adrenal vein sampling is the only way to be 100% sure which adrenal gland is actually producing the excess hormone before we remove it.

It will definitely fix the low potassium. It cures high blood pressure completely in about 50% of people; the other 50% still need medications, but usually fewer than before.

Authoritative Sources & Evidence References

Endocrine Society Clinical Practice Guideline for Primary Aldosteronism:
View Official Guideline

Key Literature & References:

Evidence Primary Aldosteronism: JACC State-of-the-Art Review