What is the diagnosis and treatment approach for a patient with suspected aldosteronism?

Diagnosis and Treatment of Aldosteronism

Initial Screening

Screen all patients with resistant hypertension (BP uncontrolled on 3 medications including a diuretic), severe hypertension (BP >180/110 mmHg), spontaneous or diuretic-induced hypokalemia, incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke at age <40 years using the aldosterone-to-renin ratio (ARR). 1

Patient Preparation Before Testing

• Correct hypokalemia before testing because low potassium suppresses aldosterone production and causes false-negative results 1
• Discontinue mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing 2, 1
• Stop beta-blockers, centrally acting drugs, and diuretics when clinically feasible, as these suppress renin and cause false-positive results 1
• Use long-acting calcium channel blockers or alpha-receptor antagonists as alternatives during the testing period, as they minimally interfere with ARR 1
• Ensure unrestricted salt intake and normal serum potassium levels before testing 2, 1

Blood Collection Technique

• Collect blood in the morning (ideally 0800-1000 hours) with the patient out of bed for 2 hours prior and seated for 5-15 minutes immediately before blood draw 1
• Draw blood with the patient in a seated position 1

Interpreting the ARR

A positive screening test requires BOTH an ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) AND a plasma aldosterone concentration ≥10 ng/dL. 2, 1

• The specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1
• Do not rely on hypokalemia alone for screening, as it is absent in approximately 50% of primary aldosteronism cases 1, 3

Confirmatory Testing

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 2, 1

Confirmatory Test Options

• Intravenous saline suppression test: Infuse 2L of normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis 1
• Oral sodium loading test: Administer oral salt loading with measurement of 24-hour urine aldosterone 2, 1
• Maintain potassium repletion during salt challenge testing to avoid false-negative results 1

Subtype Determination

After biochemical confirmation, determine whether the disease is unilateral or bilateral, as this dictates treatment. 1, 4

Imaging

• Obtain non-contrast CT scan of the adrenal glands as initial imaging 1
• Do not proceed to surgery based on CT findings alone, as up to 25% of patients might undergo unnecessary adrenalectomy based on imaging alone 1

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, except in patients <40 years when imaging shows a single affected gland, as bilateral hyperplasia is rare in this population 1

• Refer to specialized centers with expertise in AVS for this procedure 1

Treatment Algorithm

For Unilateral Disease (Aldosterone-Producing Adenoma)

Laparoscopic unilateral adrenalectomy is the treatment of choice for unilateral aldosterone production. 2, 4, 3

• Surgery improves blood pressure in virtually 100% of patients and results in complete cure of hypertension in approximately 50% 2, 4
• Adrenalectomy normalizes hypokalemia, lowers blood pressure, reduces antihypertensive medication requirements, and improves cardiac and kidney function parameters 2
• Early diagnosis and treatment improve cure rates, as delayed diagnosis causes irreversible vascular remodeling that results in residual hypertension even after successful surgery 1, 4, 3

For Bilateral Disease (Idiopathic Hyperaldosteronism)

Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of lifelong treatment for bilateral disease. 2, 4, 3

Spironolactone (First-Line)

• Start spironolactone 25-50 mg once daily 5
• Titrate dose at two-week intervals up to 100-400 mg daily as needed for blood pressure and biochemical control 4, 5
• Doses greater than 100 mg/day generally do not provide additional blood pressure reductions 5

Eplerenone (Alternative)

• Use eplerenone 50-100 mg daily for patients who develop gynecomastia, breast tenderness, or sexual dysfunction on spironolactone 3
• Eplerenone has equal effectiveness to spironolactone for blood pressure control but requires twice-daily administration 3

Special Consideration: Familial Hyperaldosteronism Type 1

• Treat with low-dose dexamethasone, which is free of glucocorticoid effects and safe during pregnancy 1, 4

Safety Monitoring for MRA Therapy

Pre-Treatment Requirements

• Verify serum potassium ≤5.0 mEq/L before initiating any aldosterone antagonist 3
• Confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 3
• Discontinue potassium supplements before starting MRAs 3

Monitoring Schedule

• Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months 3
• Subsequently monitor every 3 months if stable 3

Critical Drug Interactions to Avoid

• Do not combine MRAs with potassium supplements or potassium-sparing diuretics 3
• Avoid combining with ACE inhibitors or ARBs without close monitoring due to increased risk of hyperkalemia 3
• Avoid NSAIDs or COX-2 inhibitors due to increased risk of hyperkalemia and renal dysfunction 3
• Use MRAs with caution in patients with eGFR <45 mL/min 3

Treatment Targets

Blood Pressure Goals

• Achieve blood pressure <140/90 mmHg 6
• In resistant hypertension, adding spironolactone 25-50 mg daily provides significant additional BP reduction of 25/12 mmHg when added to multidrug regimens 1

Biochemical Goals

• Achieve normokalemia (ideally potassium ≥4.3 mmol/L) 6
• Achieve renin >1 ng/mL/h 6

Common Pitfalls to Avoid

• Never rely solely on presence or absence of hypokalemia to screen for primary aldosteronism, as 50% of cases have normal potassium 1
• Never proceed to adrenalectomy based on CT findings alone without AVS (except in patients <40 years with unilateral adenoma on imaging) 1
• Never test patients while on mineralocorticoid receptor antagonists, as these must be withdrawn for at least 4 weeks 2, 1
• Never ignore the dramatically increased cardiovascular risk in primary aldosteronism, including 3.7-fold increase in heart failure, 4.2-fold increase in stroke, 6.5-fold increase in myocardial infarction, and 12.1-fold increase in atrial fibrillation compared to essential hypertension at equivalent blood pressure levels 1

Referral Recommendations

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 3