Aldosteronism, Primary

Key Features

Essentials of Diagnosis

• Hypertension may be severe or drug-resistant

• Hypokalemia (in minority of patients) may cause polyuria, polydipsia, muscle weakness

• Low plasma renin; elevated plasma and urine aldosterone levels

General Considerations

• Excessive aldosterone production

  • Increases sodium retention and suppresses plasma renin

  • Increases renal potassium excretion that can lead to hypokalemia

• Cardiovascular events are more prevalent in patients with aldosteronism (35%) than in those with essential hypertension (11%)

• May be caused by a unilateral aldosterone-producing adrenal cortical adenoma (Conn syndrome, 25%)

  • More common in women with a 2:1 ratio

  • Peaks between ages 30 and 50 years

• More commonly caused by adrenal cortical hyperplasia (75%)

  • More common in men with a 4:1 ratio

  • Peaks between ages 50 and 60 years

• Bilateral aldosteronism may be corticosteroid suppressible due to an autosomal-dominant genetic defect allowing ACTH stimulation of aldosterone production

• Malignant ovarian tumors are rare cause of hyperaldosteronism

Demographics

• Accounts for about 8% of cases of stage 2 (mild) hypertension and about 13% of cases of stage 3 (moderate) hypertension

• Should also be suspected with early onset hypertension or stroke before age 50 years (or both)

• Patients of all ages may be affected, but the peak incidence is between 30–60 years

Clinical Findings

Symptoms and Signs

• Hypertension is typically moderate but may be severe

• Some patients have only diastolic hypertension, without other symptoms and signs

• Edema (rare)

• Muscle weakness (at times with paralysis simulating periodic paralysis), paresthesias with frank tetany, headache, polyuria, and polydipsia may be seen in patients with hypokalemia

Differential Diagnosis

• Essential hypertension

• Hypokalemic thyrotoxic periodic paralysis

• Renal vascular hypertension (hypertension and hypokalemia, but plasma renin activity is high)

• Hypokalemia due to other cause, eg, diuretics

• Secondary hyperaldosteronism (dehydration, heart failure)

• Congenital adrenal hyperplasia: 11beta-hydroxylase deficiency, 17alpha-hydroxylase deficiency

• Cushing syndrome

• Excessive real licorice ingestion

• Syndrome of cortisol resistance

Diagnosis

Laboratory Tests

• Plasma potassium should be determined in hypertensive individuals; however, hypokalemia is present in only 37% of affected patients

• An elevated serum bicarbonate (HCO₃) concentration indicates metabolic alkalosis and is commonly present

• Testing for primary aldosteronism should be considered for all hypertensive patients with any of the following:

  • Sustained hypertension above 150/100 mm Hg on 3 different days

  • Hypertension resistant to three conventional antihypertensive drugs, including a diuretic

  • Controlled blood pressure requiring four or more antihypertensive drugs

  • Hypokalemia, particularly when unrelated to diuretics

  • Personal or family history of early onset hypertension or CVA at age ≤ 40 years

  • First-degree relative with primary aldosteronism

  • Presence of an adrenal mass

  • Low plasma renin activity

• Testing protocol

  • For at least 2 weeks prior to testing, patients ...