PRIMARY
ALDOSTERONISM

DEFINITION

Renin-independent overproduction of the adrenocorticol hormone aldosterone, which is formed in the zona glomerulora, with resultant hypertension, hypokalemia, hyporeninemia and metabolic alkalosis.

PREVALENCE

· Among patients with hypertension the prevalence of primary aldosteronism ranges between 0.6 and 20%.

· The presence of hypokalemia in patients with primary aldosteronism varies between 0 to 37.5%.

ETIOLOGY

1. Adenema of the supra renal cortex-aldosterone producing adenema (Conn's syndrome) in 70-80% of cases of primary aldosteronism.

2. Primary hyperplasia of the adrenal cortex-primary adrenal hyperplasia in 20-30% of cases.

3. Adrenocorticol carcinoma.

4. Dexamethazone-suppressible hyperaldosteronism.

MECHANISM OF HYPERTENSION

- Increased renal absorption of sodium resulting in increase in intravascular volume.

- Potentially pressor effects of aldosterone.

CLINICAL SUSPICION

· Primary Aldosteronism

Hypertension in association with hypokalemia (serum potassium less than 3.2 mEq/L) in absence of diuretic therapy justifies the tentative diagnosis of primary aldosteronism.

· Hypertension which is difficult to treat.

CLINICAL SYMPTOMS

Nonspecific and of limited value in diagnosis.

- Hypokalemia is present in 80 to 90% of patients.

- ECG abnormalities: 80%

- Muscle weakness: 80%

- Polyurea: 70%

- Headache: 65%

- Polydipsia: 45%

- Parasthesia: 25%

- Intermittent paralytic symptoms: 20%

- Intermittent tetany: 20%

Diagnosis

1. Repeated serum potassium estimation

Levels below 3.5 mEq/L in absence of diuretics, or potassium loss through gastrointestinal tract are suggestive of primary aldosteronism.

2. Urinary potassium estimation

24-Hour urine collection for potassium content.

An excess of urinary potassium excretion (>30 mEq/24hr) when the serum potassium is less than 3.5 mEq/L reflects renal potassium wasting and suggests primary aldosteronism.

3. Measurement of plasma aldosterone and plasma renin activity

- The ratio of plasma aldosterone to renin activity (ARR) is a good

Primary Aldosteronism
screening test, a ratio greater than 20 is suggestive of inappropriate aldosterone excretion.

- Misleading ARR results can occur unless the blood is collected under standardized conditions of diet, posture and time of the day, and withdrawal of antihypertensive therapy for 14 days before investigation.

4. Salt Loading

- Salt loading leads to an increased renal sodium/potassium exchange, allowing the unmasking of latent hypokalemia.

- It increases the specificity of plasma aldosterone measurement, which remains elevated.

- Urine collection for 24-hours: 24-hour urinary aldosterone excretion greater than 14 mg/24 hours following salt loading is almost diagnostic.

DIAGNOSTIC LABORATORY FINDINGS

1. In untreated patient with spontaneous hypokalemia (serum potassium < 3m Eq/L)

- Inappropriate loss of potassium in urine (urinary potassium > 30 mEq/24hr).

- PRA below 1 ng/ml/hr, plasma aldosterone > 22 ng/dl.

- Urinary aldosterone excretion rate greater than 14 mg/24hr when the urinary sodium is 250mEq/24hr or greater.

2. Patients who are normokalemic but who have a history of becoming significantly hypokalemic on convential diuretic therapy or who have persistant hypokalemia despite attempts of potassium repletion should undergo salt loading by increasing oral sodium chloride intake by one tea spoon full daily for 5 days and collecting blood and 24 hour urine for sodium, potassium and aldosterone.

Aldosterone excretion rate greater than 14 mg/24hr when the urinary sodium is at least 250 mEq/24hr suggests excessive aldosterone production.

Primary Aldosteronism

3. Raised ARR is in 90% specific for primary aldosteronism.

IMAGING PROCEDURES

1. Computed Tomography Scanning (CT)

- The technique detects only 50% of aldosterone producing adenomas and excludes large (>2.5cm) adrenal masses.

- Unilateral adrenal gland alterations indicate an adenoma and bilateral alterations of less than 1 cm suggest idiopathic hyperplasia.

- 20% of adenomas measure less than 1 cm.

2. Magnetic Resonance Imaging (MRI)

Performed as a supplemental method in exceptional cases when there is negative CT findings with biochemically verified primary aldosteronism

TREATMENT

- Successful medical treatment of primary aldosteronism can be achieved with spironolactone (aldactone) or amiloride without side effects by using low doses initially, e.g., 12.5 mg daily and 2.5 mg daily respectively, and giving these medications adequate time (weeks) to demonstrate effect. The dose of spironolactone can be increased to 100 mg/day if necessary. The incidence of gynecomastia is related to the dose used.

- Eplerenone, a new and better-tolerated specific mineralocorticoid receptor blocker is under trial for treatment of primary aldosteronism.

- Primary Aldosteronism

- Role of Surgery

- Aldosterone producing adenoma and unilateral adrenal hyperplasia are treated with unilateral adrenalectomy. Laparoscopic adrenolectomy is the surgical treatment of choice.

- One approach is to treat all CT-scan-negative patients with raised ARR medically and another approach is to exclude the presence of adenoma systemically for possible surgical intervention.