Hyperaldosteronism for USMLE Step 1

Hyperaldosteronism for the USMLE Step 1 Exam

Excess Aldosterone Production: Hyperaldosteronism is characterized by the overproduction of aldosterone, a mineralocorticoid produced by the adrenal cortex. Aldosterone increases sodium reabsorption and potassium excretion in the kidneys, leading to hypertension and hypokalemia.

Types:
Primary Hyperaldosteronism: The excessive secretion of aldosterone is independent of renin. This is also known as Conn's syndrome and is usually caused by an aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia.
Secondary Hyperaldosteronism: Increased aldosterone production occurs due to activation of the renin-angiotensin-aldosterone system (RAAS). This is often due to decreased renal perfusion (e.g., in renal artery stenosis), heart failure, or cirrhosis.

Primary Hyperaldosteronism:
Aldosterone-Producing Adenoma: The most common cause of primary hyperaldosteronism (Conn’s syndrome), involving a unilateral adrenal adenoma that secretes aldosterone autonomously.
Bilateral Adrenal Hyperplasia: Characterized by the diffuse or nodular enlargement of both adrenal glands, causing excess aldosterone production.
Secondary Hyperaldosteronism:
Renal Artery Stenosis: Reduced renal blood flow activates the RAAS, stimulating excess aldosterone release.
Heart Failure or Cirrhosis: Both conditions result in reduced effective arterial blood volume, triggering the RAAS.

Hypertension: Hyperaldosteronism is a common cause of secondary hypertension, which may be resistant to standard antihypertensive treatment.
Hypokalemia: Due to excessive potassium excretion, which can result in symptoms such as muscle weakness, fatigue, paresthesias, or even arrhythmias in severe cases.
Polyuria and Polydipsia: Hypokalemia impairs renal concentrating ability, leading to excessive urine output and increased thirst.
Metabolic Alkalosis: Enhanced hydrogen ion excretion in exchange for sodium contributes to metabolic alkalosis, which can exacerbate muscle weakness.

Screening Tests:
Plasma Aldosterone-to-Renin Ratio (ARR): The primary screening tool for hyperaldosteronism. A high ARR (>20) suggests primary hyperaldosteronism, especially when plasma renin activity (PRA) is low and aldosterone levels are high.
Confirmatory Tests:
Oral Sodium Loading Test: The patient consumes a high-sodium diet or receives salt tablets for several days. Persistent elevation of 24-hour urine aldosterone levels (>12 µg/day) confirms the diagnosis.
Saline Infusion Test: Aldosterone levels are measured after intravenous saline. Failure of aldosterone suppression suggests hyperaldosteronism.
Imaging:
CT or MRI of the Adrenal Glands: Used to detect aldosterone-producing adenomas or adrenal hyperplasia.
Adrenal Venous Sampling (AVS): This is the gold standard for distinguishing between unilateral and bilateral disease in primary hyperaldosteronism and is essential for guiding treatment decisions.

Essential Hypertension: The most common cause of hypertension, not associated with hypokalemia or suppressed renin.
Liddle Syndrome: A genetic condition involving increased sodium reabsorption, which causes hypertension and hypokalemia but with low aldosterone levels.
Cushing's Syndrome: Excess cortisol can mimic aldosterone’s effects, leading to hypertension and hypokalemia.

Primary Hyperaldosteronism:
Aldosterone-Producing Adenoma: Laparoscopic adrenalectomy is the treatment of choice for unilateral disease, leading to a cure of hypertension in many patients.
Bilateral Adrenal Hyperplasia: Medical management with mineralocorticoid receptor antagonists is preferred, as bilateral disease is not amenable to surgery.
Spironolactone: A non-selective aldosterone antagonist that also blocks androgen receptors. It effectively lowers blood pressure and corrects hypokalemia but may cause gynecomastia and impotence in men.
Eplerenone: A more selective aldosterone antagonist with fewer androgenic side effects.
Secondary Hyperaldosteronism:
Renal Artery Stenosis: Treated with percutaneous transluminal angioplasty and stenting to restore renal perfusion.
Heart Failure or Cirrhosis: Treatment focuses on addressing the underlying condition with diuretics, RAAS blockers, and lifestyle modifications.

Cardiovascular Complications: Untreated hyperaldosteronism can result in left ventricular hypertrophy, myocardial infarction, and stroke due to chronic hypertension.
Electrolyte Imbalances: Persistent hypokalemia can lead to severe muscle weakness, arrhythmias, and kidney dysfunction.
Renal Dysfunction: Long-standing hyperaldosteronism may lead to renal damage and impaired kidney function.

Key Points

Pathophysiology: Hyperaldosteronism results from excessive aldosterone production, leading to sodium retention, hypertension, and potassium excretion.
Etiology: Primary hyperaldosteronism is usually caused by an aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia. Secondary hyperaldosteronism is due to conditions that activate the RAAS, such as renal artery stenosis or heart failure.
Clinical Features: Resistant hypertension, hypokalemia, muscle weakness, polyuria, and metabolic alkalosis.
Diagnosis: A high aldosterone-to-renin ratio (ARR) is the initial screening test, followed by confirmatory tests (e.g., oral sodium loading test). Imaging and adrenal venous sampling help differentiate between unilateral and bilateral disease.
Treatment: Unilateral disease is treated with adrenalectomy, while bilateral disease is managed with mineralocorticoid receptor antagonists such as spironolactone or eplerenone.
Complications: Cardiovascular disease, electrolyte imbalances, and renal dysfunction can result from untreated hyperaldosteronism.