Hyperaldosteronism for USMLE Step 2
Hyperaldosteronism for the USMLE Step 2 Exam
- Pathophysiology
- Excess Aldosterone Production: Hyperaldosteronism is characterized by overproduction of aldosterone, a mineralocorticoid that promotes sodium retention and potassium excretion in the kidneys. This leads to hypertension and hypokalemia.
- Types:
- Primary Hyperaldosteronism: Excess aldosterone secretion occurs independent of renin-angiotensin system regulation. It is also called Conn’s syndrome.
- Secondary Hyperaldosteronism: Increased aldosterone is driven by high renin levels, often secondary to reduced renal perfusion, as seen in conditions like renal artery stenosis or heart failure.
- Etiology
- Primary Hyperaldosteronism:
- Aldosterone-Producing Adenoma (APA): The most common cause of primary hyperaldosteronism, involving a unilateral adrenal adenoma.
- Bilateral Adrenal Hyperplasia (BAH): Another frequent cause, with diffuse enlargement of both adrenal glands producing aldosterone.
- Familial Hyperaldosteronism: A genetic form, such as glucocorticoid-remediable aldosteronism.
- Secondary Hyperaldosteronism:
- Renal Artery Stenosis: Reduced blood flow to the kidneys stimulates renin production, activating aldosterone secretion.
- Heart Failure: Perceived low blood volume in the kidneys activates the renin-angiotensin system, leading to elevated aldosterone.
- Clinical Features
- Hypertension: Often resistant to standard antihypertensive medications. It is a key feature of hyperaldosteronism and is driven by sodium retention.
- Hypokalemia: Excessive potassium excretion leads to low serum potassium levels, causing symptoms like muscle weakness, fatigue, cramps, and, in severe cases, cardiac arrhythmias.
- Polyuria and Polydipsia: Hypokalemia impairs the kidney’s ability to concentrate urine, leading to excessive urination and thirst.
- Metabolic Alkalosis: Due to increased excretion of hydrogen ions in exchange for sodium, resulting in an elevated bicarbonate level.
- Diagnosis
- Screening:
- Aldosterone-to-Renin Ratio (ARR): The first-line screening test. An elevated ratio suggests primary hyperaldosteronism, especially when aldosterone levels are high and renin is low.
- Confirmatory Testing:
- Oral Sodium Loading Test: After high sodium intake, 24-hour urinary aldosterone levels are measured. Elevated aldosterone confirms the diagnosis.
- Saline Infusion Test: Failure of aldosterone suppression after intravenous saline confirms primary hyperaldosteronism.
- Imaging:
- Adrenal CT Scan: To identify adrenal adenomas or hyperplasia.
- Adrenal Venous Sampling (AVS): Used to differentiate between unilateral and bilateral disease, especially before surgical intervention.
- Differential Diagnosis
- Essential Hypertension: The most common cause of high blood pressure, usually without hypokalemia or metabolic alkalosis.
- Liddle Syndrome: A genetic condition causing hypertension and hypokalemia, but with low aldosterone levels.
- Cushing’s Syndrome: Excess cortisol can mimic aldosterone by activating mineralocorticoid receptors, leading to hypertension and hypokalemia.
- Treatment
- Primary Hyperaldosteronism:
- Aldosterone-Producing Adenoma: Laparoscopic adrenalectomy is the treatment of choice for unilateral adenomas. This often cures hypertension and hypokalemia.
- Bilateral Adrenal Hyperplasia: Medical management with mineralocorticoid receptor antagonists, like spironolactone or eplerenone, is preferred since both glands are involved.
- Spironolactone: Non-selective antagonist of aldosterone but may cause gynecomastia in men due to anti-androgenic effects.
- Eplerenone: A selective aldosterone antagonist with fewer side effects on androgens.
- Secondary Hyperaldosteronism:
- Renal Artery Stenosis: Managed with angioplasty or stenting to restore renal blood flow. Medical therapy with RAAS inhibitors (ACE inhibitors or ARBs) is often used.
- Heart Failure: Treated with diuretics, RAAS inhibitors, and lifestyle modifications to reduce volume overload.
- Complications
- Cardiovascular Risk: Long-standing hyperaldosteronism increases the risk of left ventricular hypertrophy, myocardial infarction, stroke, and atrial fibrillation.
- Renal Impairment: Chronic hypokalemia and hypertension can lead to renal damage and chronic kidney disease.
- Electrolyte Imbalances: Severe hypokalemia can cause muscle cramps, weakness, and life-threatening arrhythmias.
Key Points
- Pathophysiology: Hyperaldosteronism results from excessive aldosterone production, leading to hypertension, sodium retention, and potassium excretion.
- Etiology: Primary causes include aldosterone-producing adenomas and bilateral adrenal hyperplasia. Secondary causes involve conditions that activate the renin-angiotensin system, such as renal artery stenosis.
- Clinical Features: Resistant hypertension, hypokalemia, muscle weakness, and metabolic alkalosis are common findings.
- Diagnosis: Screening with an aldosterone-to-renin ratio (ARR), followed by confirmatory testing like the saline infusion or sodium loading test. Imaging helps identify adrenal pathology.
- Treatment: Unilateral adenomas are treated with adrenalectomy, while bilateral disease requires mineralocorticoid receptor antagonists. Secondary hyperaldosteronism is managed by treating the underlying condition.
- Complications: Untreated hyperaldosteronism can result in cardiovascular disease, renal damage, and severe electrolyte imbalances.