What investigations are needed for a patient with secondary hypertension?

Investigations for Secondary Hypertension

When to Investigate

All patients with confirmed hypertension should undergo basic screening investigations, with the 2024 European Society of Cardiology now recommending aldosterone-to-renin ratio measurement in all adults with confirmed hypertension—a major shift from previous selective screening approaches. 1

Pursue comprehensive workup when patients present with:

• Age of onset <30 years or >50 years 2, 1
• Resistant hypertension (BP >140/90 mmHg despite ≥3 medications including a diuretic) 1, 3
• Sudden onset or deterioration of previously controlled hypertension 2, 3
• Hypertensive urgency/emergency 1, 3
• Target organ damage disproportionate to hypertension duration 1, 3

Basic Laboratory Investigations (Required for All Patients)

Blood Tests

• Serum electrolytes: Sodium and potassium (unprovoked hypokalemia suggests primary aldosteronism or renovascular disease) 2
• Renal function: Serum creatinine with estimated glomerular filtration rate (eGFR) 2
• Fasting glucose and lipid profile (total cholesterol, LDL, HDL, triglycerides) 2
• Serum uric acid 2
• Thyroid function tests 3
• Aldosterone-to-renin ratio (now recommended for all hypertensive patients per ESC 2024 guidelines) 1, 4

Urine Tests

• Dipstick urinalysis with microscopic examination 2
• Urinary albumin-to-creatinine ratio 2, 3

Electrocardiography

• 12-lead ECG to detect left ventricular hypertrophy, atrial fibrillation, and ischemic heart disease 2

Targeted Advanced Investigations (Based on Clinical Suspicion)

For Primary Aldosteronism (8-20% of resistant hypertension)

Clinical clues: Muscle weakness, tetany, cramps, arrhythmias, unprovoked hypokalemia 2, 1

• Aldosterone-to-renin ratio (ARR >20 with elevated aldosterone and suppressed renin is suggestive) 1, 4
• Confirmatory testing: Intravenous saline suppression test or oral sodium loading test 1, 3
• Adrenal CT imaging for localization after biochemical confirmation 1, 4
• Adrenal vein sampling for lateralization in surgical candidates 3, 4

Critical pitfall: Measure ARR before starting interfering medications (mineralocorticoid receptor antagonists, beta-blockers, direct renin inhibitors) when possible 4

For Renovascular Disease

Clinical clues: Abrupt onset or worsening hypertension, flash pulmonary edema, abdominal bruit, serum creatinine increase ≥50% within one week of starting ACE inhibitor/ARB 1, 3

• Renal ultrasound with Doppler duplex as initial non-invasive screening 1, 3
• CT or MR angiography for precise localization of stenosis 2, 1
• Assess for kidney size asymmetry (>1.5 cm difference suggests renovascular disease) 5

For Pheochromocytoma

Clinical clues: Episodic sweating, palpitations, frequent headaches, labile hypertension 2, 1

• Plasma free metanephrines or 24-hour urinary catecholamines/metanephrines 2, 1
• Abdominal/adrenal imaging (CT or MRI) only after biochemical confirmation 1, 3

For Obstructive Sleep Apnea (25-50% of resistant hypertension)

Clinical clues: Snoring, daytime sleepiness, obesity, neck circumference >40 cm, non-dipping nocturnal BP pattern 2, 4

• Home sleep apnea testing or polysomnography 4

For Cushing Syndrome

Clinical clues: Fatty deposits, colored striae, central obesity, moon facies 2

• Late-night salivary cortisol or other screening tests for cortisol excess 2

Imaging Studies (When Clinically Indicated)

Cardiovascular Imaging

• Echocardiography: Evaluate left ventricular hypertrophy, systolic/diastolic dysfunction, atrial dilation, aortic coarctation 2, 1
• Carotid ultrasound: Assess for atherosclerotic plaques and stenosis 2, 1

Renal and Adrenal Imaging

• Renal ultrasound: Evaluate for parenchymal disease, kidney size asymmetry, masses 2, 1
• CT/MR angiography: Precise visualization of renal artery stenosis and adrenal lesions 2, 1

Other Imaging

• Fundoscopy: Detect retinal changes, hemorrhages, papilledema, arteriovenous nipping 2, 3
• Ankle-brachial index: Screen for peripheral artery disease 2

Diagnostic Algorithm

Follow a stepwise approach: 1, 3

1. Complete medication review first (oral contraceptives, NSAIDs, decongestants, glucocorticoids, cyclosporine, cocaine, amphetamines can all cause hypertension—failure to recognize drug-induced hypertension before extensive workup is a common and costly error) 1, 3

2. Perform basic screening (electrolytes, renal function, glucose, lipids, urinalysis, ECG, aldosterone-to-renin ratio) 2, 1

3. Advance to specialized testing only when clinical clues or abnormal basic screening warrant further investigation 2

4. Refer to specialist centers for complex cases requiring adrenal vein sampling, renal angiography, or other advanced procedures 3, 4

Critical Pitfalls to Avoid

• Do not perform expensive imaging studies before completing basic laboratory screening 4
• Recognize that even after treating the underlying cause, some patients require ongoing antihypertensive therapy due to irreversible vascular remodeling—early detection is crucial 6
• Do not combine two RAS blockers (ACE inhibitor and ARB) during evaluation 3
• Interpret aldosterone-to-renin ratio carefully in patients already taking interfering antihypertensive medications 4