What is the recommended test order to diagnose secondary hypertension?

Diagnostic Test Order for Secondary Hypertension

Begin with routine laboratory screening in all suspected cases, then proceed to targeted investigations based on clinical clues and initial test results, with plasma aldosterone-to-renin ratio now recommended for all adults with confirmed hypertension as a major shift in diagnostic approach. 1, 2

Initial Clinical Assessment

Before ordering any tests, identify patients who warrant evaluation for secondary hypertension based on these specific features:

• Age of onset <30 years or >50 years (suggesting fibromuscular dysplasia in younger patients or atherosclerotic renovascular disease in older patients) 2, 3
• Resistant hypertension requiring ≥3 medications from different classes including a diuretic 4, 2
• Sudden onset or sudden deterioration of previously controlled blood pressure 1, 2
• Severe hypertension with disproportionate target organ damage relative to duration 1, 2

Physical examination should specifically assess for: Cushing syndrome features (truncal obesity, purple striae), enlarged kidneys on palpation (polycystic kidney disease), abdominal bruits (renovascular disease), diminished/delayed femoral pulses (coarctation), and left-right arm blood pressure differences 5, 3

Step 1: Routine Laboratory Tests (All Patients)

Order these basic screening tests first in all suspected cases:

• Serum electrolytes (sodium and potassium—hypokalemia suggests primary aldosteronism) 5, 4
• Serum creatinine with eGFR calculation (assess renal function) 5, 4
• Fasting blood glucose or HbA1c (screen for diabetes and Cushing syndrome) 5, 4
• Lipid profile (total cholesterol, LDL, HDL, triglycerides) 5
• Thyroid-stimulating hormone (TSH) (screen for thyroid disorders) 4, 2
• Urinalysis with dipstick for blood and protein 5, 4
• Urinary albumin-to-creatinine ratio (assess kidney damage) 1, 4
• 12-lead ECG (evaluate for left ventricular hypertrophy) 5, 1

Step 2: Universal Screening Test (Major Guideline Change)

The European Society of Cardiology 2024 guidelines now recommend measuring plasma aldosterone-to-renin ratio in ALL adults with confirmed hypertension (Class IIa recommendation), representing a significant departure from traditional selective screening. 1 This test has high negative predictive value and identifies primary aldosteronism, which affects 8-20% of resistant hypertension cases. 1, 4

Critical caveat: Certain medications affect interpretation—mineralocorticoid receptor antagonists raise aldosterone levels, while beta-blockers and direct renin inhibitors lower renin levels. 1 Consider medication adjustments before testing when feasible.

Step 3: Targeted Investigations Based on Clinical Suspicion

For Primary Aldosteronism (if ARR >20 with elevated aldosterone and suppressed renin):

1. Confirmatory testing with IV saline suppression test or oral sodium loading test 4, 2
2. Adrenal CT scan for localization 4, 2
3. Adrenal vein sampling to distinguish unilateral from bilateral disease 4, 2

For Renovascular Disease (abrupt onset, flash pulmonary edema, abdominal bruits):

1. Renal ultrasound with Duplex Doppler as initial imaging 1, 4
2. CT or MR renal angiography for confirmation 1, 4
3. Consider if creatinine increases ≥50% within one week of starting ACE inhibitor/ARB 6

For Pheochromocytoma (episodic symptoms, labile hypertension, sweating, palpitations):

1. Plasma free metanephrines or 24-hour urinary metanephrines/catecholamines 1, 2
2. Abdominal/adrenal imaging (CT or MRI) if biochemical tests positive 2

For Obstructive Sleep Apnea (25-50% of resistant hypertension, snoring, daytime sleepiness, non-dipping BP pattern):

1. Home sleep apnea testing as initial screen 4, 2
2. Overnight polysomnography for definitive diagnosis 4, 2

For Cushing Syndrome (truncal obesity, purple striae, fatty deposits):

1. 24-hour urinary free cortisol or overnight dexamethasone suppression test 2

Step 4: Advanced Imaging (Selected Cases)

Order these only after basic screening and when specific conditions are suspected:

• Echocardiography for patients with ECG abnormalities, suspected left ventricular hypertrophy, or aortic coarctation 1, 2
• Fundoscopy if blood pressure >180/110 mmHg to evaluate for hypertensive emergency 1
• Carotid ultrasound to assess for plaques and stenosis in patients with vascular disease 2

Critical Pitfalls to Avoid

• Do not perform expensive imaging studies before completing basic laboratory screening 1
• Do not miss medication-induced hypertension (NSAIDs, oral contraceptives, decongestants, steroids)—review all medications before extensive workup 1, 2
• Delayed diagnosis leads to vascular remodeling and residual hypertension even after treating the underlying cause 4
• Secondary hypertension is underrecognized despite affecting 5-10% of all hypertensive patients, increasing to 10-20% in resistant cases 4, 7
• Refer complex cases to specialized centers with appropriate expertise rather than pursuing extensive testing in primary care 1, 7