Hyperaldosteronism for USMLE Step 3
Hyperaldosteronism for the USMLE Step 3 Exam
- Pathophysiology
- Excess Aldosterone Production: Hyperaldosteronism is due to the overproduction of aldosterone, a mineralocorticoid hormone that increases sodium reabsorption and potassium excretion in the kidneys. This leads to hypertension and hypokalemia.
- Types:
- Primary Hyperaldosteronism: Excess aldosterone secretion independent of renin activity. This is also called Conn’s syndrome and is usually caused by an aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia.
- Secondary Hyperaldosteronism: Caused by conditions that activate the renin-angiotensin-aldosterone system (RAAS), such as renal artery stenosis or heart failure, leading to elevated renin and aldosterone levels.
- Etiology
- Primary Hyperaldosteronism:
- Aldosterone-Producing Adenoma (APA): The most common cause, also known as Conn's syndrome, involving unilateral adrenal adenomas.
- Bilateral Adrenal Hyperplasia (BAH): Causes increased aldosterone secretion from both adrenal glands.
- Familial Hyperaldosteronism: Genetic conditions, such as glucocorticoid-remediable aldosteronism, where aldosterone production is under the control of ACTH.
- Secondary Hyperaldosteronism:
- Renal Artery Stenosis: Narrowing of the renal arteries leads to decreased renal perfusion, activating the RAAS and stimulating aldosterone secretion.
- Heart Failure: Reduced cardiac output leads to decreased renal perfusion, causing RAAS activation and secondary aldosterone excess.
- Clinical Features
- Hypertension: The most common presentation, often resistant to standard antihypertensive medications.
- Hypokalemia: Results from excessive potassium excretion, leading to muscle weakness, cramps, paresthesias, and, in severe cases, arrhythmias.
- Polyuria and Polydipsia: Due to hypokalemia impairing renal concentrating ability, leading to increased urination and thirst.
- Metabolic Alkalosis: Caused by increased hydrogen ion excretion, resulting in elevated bicarbonate levels.
- Diagnosis
- Screening:
- Aldosterone-to-Renin Ratio (ARR): A high ARR (>20) with elevated plasma aldosterone and low renin suggests primary hyperaldosteronism.
- Confirmatory Testing:
- Oral Sodium Loading Test: Persistent high aldosterone levels after high salt intake confirm hyperaldosteronism.
- Saline Infusion Test: Failure of aldosterone suppression after intravenous saline administration supports the diagnosis.
- Imaging:
- Adrenal CT Scan: Helps differentiate aldosterone-producing adenomas from bilateral adrenal hyperplasia.
- Adrenal Venous Sampling (AVS): The gold standard for distinguishing between unilateral and bilateral disease, especially when considering surgery.
- Differential Diagnosis
- Essential Hypertension: Common but not associated with hypokalemia or metabolic alkalosis.
- Liddle Syndrome: A rare genetic disorder causing hypertension and hypokalemia with low aldosterone levels.
- Cushing’s Syndrome: Excess cortisol can activate mineralocorticoid receptors, leading to hypertension and hypokalemia.
- Treatment
- Primary Hyperaldosteronism:
- Aldosterone-Producing Adenoma: Laparoscopic adrenalectomy is the treatment of choice for unilateral disease, which can cure hypertension and hypokalemia.
- Bilateral Adrenal Hyperplasia: Medical management with mineralocorticoid receptor antagonists like spironolactone or eplerenone is preferred.
- Spironolactone: Blocks aldosterone but may cause gynecomastia due to anti-androgenic effects.
- Eplerenone: A more selective aldosterone antagonist with fewer side effects.
- Secondary Hyperaldosteronism:
- Renal Artery Stenosis: Managed with angioplasty or stenting to restore renal blood flow, along with RAAS inhibitors like ACE inhibitors or ARBs.
- Heart Failure: Treated with diuretics, ACE inhibitors, and RAAS inhibitors to reduce volume overload.
- Complications
- Cardiovascular Complications: Chronic hypertension due to hyperaldosteronism increases the risk of left ventricular hypertrophy, heart failure, myocardial infarction, and stroke.
- Electrolyte Imbalances: Persistent hypokalemia can cause severe muscle weakness, arrhythmias, and nephropathy.
- Renal Damage: Long-standing hyperaldosteronism can lead to chronic kidney disease.
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, while secondary causes involve conditions that activate the renin-angiotensin system, like renal artery stenosis or heart failure.
- Clinical Features: Resistant hypertension, hypokalemia, muscle weakness, and metabolic alkalosis are common features.
- Diagnosis: Initial screening involves a high aldosterone-to-renin ratio (ARR), followed by confirmatory tests such as the saline infusion test. Imaging identifies adrenal pathology.
- Treatment: Adrenalectomy is the treatment for unilateral adenomas, while medical management with spironolactone or eplerenone is used for bilateral disease. Secondary hyperaldosteronism is managed by treating the underlying cause.
- Complications: Untreated hyperaldosteronism can lead to cardiovascular disease, electrolyte imbalances, and renal damage.