Adrenal

Hyperaldosteronism

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Hyperaldosteronism, Aldosteronism, Conn's Disease, Conn's Syndrome

Epidemiology

Represents under 6% of Hypertension Causes
1. Most common cause of drug Resistant Hypertension
Peak age 30-50 years
More common in women

Pathophysiology

Inappropriate Aldosterone Hypersecretion
1. Primary Hyperaldosteronism (See Causes below)
  1. Increased Aldosterone is initiating event
  2. Results in Sodium retention and volume increase
  3. Renin decreases
2. Secondary Hyperaldosteronism (See Causes below)
  1. Decreased circulating volume is initiating event
  2. Results in increased renin and Aldosterone
  3. Results in Sodium retention
Physiologic response to Aldosterone Excess
1. Increased renal distal tubular Sodium reabsorption
  1. Increased total body Sodium content
  2. Increased water retention
2. Escape phenomenon
  1. Compensatory increased ANF secretion
  2. Hypertension may not be solely volume expansion
3. Increased Peripheral Vascular Resistance
  1. Hypokalemia: Potassium lost in distal renal tubule (Potassium wasting)
  2. Alkalosis: Ammoniagenesis
4. Hydrogen Ion loss (avid Sodium retention)
5. Polyuria: Decreased renal concentrating ability
6. Plasma renin suppressed
  1. Unresponsive to intravascular volume depletion

Causes

Primary Hyperaldosteronism (Conn's Disease)
1. Solitary Adrenal Adenomas (80-90%)
2. Bilateral adrenal hyperplasia (10-20%)
  1. Idiopathic Hyperaldosteronism
  2. Accounts for 50% of cases at some referral centers
3. Adrenal Carcinoma (rare)
4. Unilateral Adrenal Hyperplasia (very rare)
Secondary Hyperaldosteronism
1. Hypertensive States
  1. Primary Reninism (rare renin producing tumor)
  2. Secondary reninism due to decreased renal perfusion
2. Edematous States
  1. Cirrhosis
  2. Nephrotic Syndrome
3. Miscellaneous causes
  1. Excessive Growth Hormone (Acromegaly)

Symptoms

Often Asymptomatic
Frontal Headache
Muscle Weakness to Flaccid Paralysis (Hypokalemia)
Polyuria and Polydipsia (carbohydrate intolerance)

Signs

Hypertension
1. May be severe
2. Rarely malignant
Motor Exam with decreased Muscle Strength

Labs

Serum Electrolytes
1. Serum Potassium decreased (Hypokalemia)
  1. Hypokalemia is the most prominent feature of Hyperaldosteronism
  2. However, Potassium is normal in 50% of Hyperaldosteronism causes
2. Serum Sodium increased (Mild)
3. Metabolic Alkalosis
Morning Aldosterone to PRA ratio
1. Ratio over 20-25 (esp if >100) suggests Hyperaldosteronism
2. Aldosterone >15 ng/dl and plasma renin low
  1. Serum Aldosterone alone may be normal in 25% of Hyperaldosteronism patients
3. Technique
  1. Obtain 2 hours after waking and in upright position
  2. Stop Spironolactone, Eplerenone, Amiloride, Triamterene, Potassium-wasting Diuretics 4 weeks before test
  3. Consider stopping antihypertensives and NSAIDs before test
    1. May use Verapamil XR, Hydralazine or Alpha Adrenergic Antagonist for Blood Pressure control
Saline suppression
1. IVF: 300-500 cc/hour for 4 hours
2. Normal response
  1. Aldosterone usually under 0.28
  2. Renin usually suppressed

Differential Diagnosis
Hypertension with Hypokalemia

Cushing's Disease
1. Low Aldosterone and Low Plasma Renin
Renal Artery Stenosis or other renal cause
1. High Aldosterone and High Plasma Renin

Management

Adrenal Adenoma
1. Surgical excision
Adrenal Hyperplasia
1. First-Line Agents
  1. Spironolactone (Aldactone)
2. Alternative agents if Gynecomastia develops on Spironolactone
  1. Eplerenone (Inspra)
  2. Amiloride (Midamor)
3. Precautions
  1. Follow Serum Potassium and Serum Creatinine every 6 months with these agents

References