What are the diagnostic criteria for secondary hyperaldosteronism in a patient with resistant hypertension or hypokalemia?

Diagnostic Criteria for Secondary Hyperaldosteronism

Secondary hyperaldosteronism is diagnosed by demonstrating elevated aldosterone levels with elevated (not suppressed) renin levels, distinguishing it from primary aldosteronism where renin is suppressed. 1

Key Distinguishing Features from Primary Hyperaldosteronism

The fundamental difference is the renin level: secondary hyperaldosteronism shows both aldosterone AND renin elevated together, reflecting appropriate physiologic response to renin-angiotensin system activation, whereas primary aldosteronism shows elevated aldosterone with suppressed renin (aldosterone-to-renin ratio >30). 1

Laboratory Findings

• Elevated plasma aldosterone concentration with elevated plasma renin activity - this is the hallmark that distinguishes secondary from primary hyperaldosteronism 1
• Low aldosterone-to-renin ratio (ARR <20-30) effectively rules out primary aldosteronism 1
• Hypokalemia may be present but is not required for diagnosis 2
• Metabolic alkalosis may accompany the hypokalemia 3

Common Clinical Scenarios Leading to Secondary Hyperaldosteronism

Renovascular Hypertension

• Renal artery stenosis stimulates renin release from the juxtaglomerular apparatus, leading to secondary hyperaldosteronism 1
• Accessory renal arteries can cause renovascular hypertension with secondary hyperaldosteronism, presenting with hypokalemia and unsuppressed renin levels 2
• Screen with renal Duplex Doppler ultrasound initially, followed by MRA or CT angiography if positive 1

Volume Depletion States

• Diuretic use is a common iatrogenic cause, increasing both renin and aldosterone 1, 3
• Heart failure with reduced cardiac output activates the renin-angiotensin-aldosterone system 1, 3
• Cirrhosis with ascites causes effective arterial underfilling, triggering secondary hyperaldosteronism 1, 3

Renal Parenchymal Disease

• Chronic kidney disease can lead to secondary hyperaldosteronism through multiple mechanisms 1
• Assess with serum creatinine, eGFR, urinalysis with microscopy, and urinary albumin-to-creatinine ratio 1
• Perform renal ultrasound to evaluate for structural abnormalities, obstruction, or polycystic kidney disease 1

Diagnostic Workup Algorithm

Step 1: Measure Both Aldosterone and Renin

• Collect morning blood sample (0800-1000 hours) with patient seated for 5-15 minutes 4
• Measure simultaneous plasma aldosterone concentration and plasma renin activity 4
• Calculate the aldosterone-to-renin ratio 4

Step 2: Interpret the Pattern

• If ARR <20-30 with both aldosterone and renin elevated: consistent with secondary hyperaldosteronism 1
• If ARR >30 with aldosterone ≥10-15 ng/dL and suppressed renin: suggests primary aldosteronism requiring different workup 4

Step 3: Identify the Underlying Cause

• Review medications: diuretics, ACE inhibitors, ARBs, beta-blockers all affect the renin-angiotensin-aldosterone system 1
• Assess volume status: look for heart failure, cirrhosis, or nephrotic syndrome 3
• Evaluate for renovascular disease: particularly in patients with resistant hypertension, abrupt onset or worsening of hypertension, or onset of diastolic hypertension in older adults 5
• Check renal function: measure creatinine, eGFR, and perform urinalysis 1

Critical Pitfalls to Avoid

• Do not assume primary aldosteronism based on elevated aldosterone alone - the suppressed renin is the defining feature of primary aldosteronism 1
• Do not rely on hypokalemia presence or absence - it occurs in only 50% of primary aldosteronism cases and can be present in secondary hyperaldosteronism 1, 2
• Do not overlook renovascular disease - it is the most common cause of secondary hyperaldosteronism with elevated renin and is potentially curable with revascularization in fibromuscular dysplasia 1
• Consider medication effects - withdraw interfering drugs when feasible before definitive testing, including diuretics and ACE inhibitors/ARBs 1

When to Suspect Secondary vs Primary Hyperaldosteronism

Suspect secondary hyperaldosteronism when:

• Patient has known heart failure, cirrhosis, or chronic kidney disease 1, 3
• Patient is taking diuretics or other medications affecting the renin-angiotensin system 1
• Clinical context suggests volume depletion or reduced effective arterial blood volume 3
• Both renin and aldosterone are elevated together 1

Suspect primary hyperaldosteronism when:

• Resistant hypertension (up to 20% prevalence) 5, 4
• Severe hypertension (BP >180/110 mmHg, up to 12% prevalence) 5
• Spontaneous or diuretic-induced hypokalemia with hypertension 5
• Adrenal incidentaloma discovered on imaging 5
• Family history of early-onset hypertension or stroke at young age 5