II. Epidemiology
- Represents under 6% of Hypertension Causes
- Most common cause of drug Resistant Hypertension
- Peak age 30-50 years
- More common in women
III. Pathophysiology
- Inappropriate Aldosterone Hypersecretion
- Primary Hyperaldosteronism (See Causes below)
- Increased Aldosterone is initiating event
- Results in Sodium retention and volume increase
- Renin decreases
- Secondary Hyperaldosteronism (See Causes below)
- Decreased circulating volume is initiating event
- Results in increased renin and Aldosterone
- Results in Sodium retention
- Primary Hyperaldosteronism (See Causes below)
- Physiologic response to Aldosterone Excess
- Increased renal distal tubular Sodium reabsorption
- Increased total body Sodium content
- Increased water retention
- Escape phenomenon
- Compensatory increased ANF secretion
- Hypertension may not be solely volume expansion
- Increased Peripheral Vascular Resistance
- Hypokalemia: Potassium lost in distal renal tubule (Potassium wasting)
- Alkalosis: Ammoniagenesis
- Hydrogen Ion loss (avid Sodium retention)
- Polyuria: Decreased renal concentrating ability
- Plasma renin suppressed
- Unresponsive to intravascular volume depletion
- Increased renal distal tubular Sodium reabsorption
IV. Causes
- Primary Hyperaldosteronism (Conn's Disease)
- Solitary Adrenal Adenomas (80-90%)
- Bilateral adrenal hyperplasia (10-20%)
- Idiopathic Hyperaldosteronism
- Accounts for 50% of cases at some referral centers
- Adrenal Carcinoma (rare)
- Unilateral Adrenal Hyperplasia (very rare)
- Secondary Hyperaldosteronism
- Hypertensive States
- Primary Reninism (rare renin producing tumor)
- Secondary reninism due to decreased renal perfusion
- Edematous States
- Miscellaneous causes
- Excessive Growth Hormone (Acromegaly)
- Hypertensive States
V. Symptoms
- Often Asymptomatic
- Frontal Headache
- Muscle Weakness to Flaccid Paralysis (Hypokalemia)
- Polyuria and Polydipsia (Carbohydrate intolerance)
VI. Signs
-
Hypertension
- May be severe
- Rarely malignant
- Motor Exam with decreased Muscle Strength
VII. Labs
- Serum Electrolytes
- Serum Potassium decreased (Hypokalemia)
- Hypokalemia is the most prominent feature of Hyperaldosteronism
- However, Potassium is normal in 50% of Hyperaldosteronism causes
- Serum Sodium increased (Mild)
- Metabolic Alkalosis
- Serum Potassium decreased (Hypokalemia)
- Morning Aldosterone to PRA ratio
- Ratio over 20-25 (esp if >100) suggests Hyperaldosteronism
- Aldosterone >15 ng/dl and plasma renin low
- Serum Aldosterone alone may be normal in 25% of Hyperaldosteronism patients
- Technique
- Obtain 2 hours after waking and in upright position
- Stop Spironolactone, Eplerenone, Amiloride, Triamterene, Potassium-wasting Diuretics 4 weeks before test
- Consider stopping antihypertensives and NSAIDs before test
- May use Verapamil XR, Hydralazine or Alpha Adrenergic Antagonist for Blood Pressure control
- Saline suppression
- IVF: 300-500 cc/hour for 4 hours
- Normal response
- Aldosterone usually under 0.28
- Renin usually suppressed
VIII. Differential Diagnosis: Hypertension with Hypokalemia
-
Cushing's Disease
- Low Aldosterone and Low Plasma Renin
-
Renal Artery Stenosis or other renal cause
- High Aldosterone and High Plasma Renin
IX. Management
-
Adrenal Adenoma
- Surgical excision
- Adrenal Hyperplasia
- First-Line Agents
- Alternative agents if Gynecomastia develops on Spironolactone
- Precautions
- Follow Serum Potassium and Serum Creatinine every 6 months with these agents