What investigations are recommended for patients with suspected secondary hypertension?

Investigations for Suspected Secondary Hypertension

When to Investigate

All patients with suspected secondary hypertension should undergo basic laboratory screening first, followed by targeted investigations based on clinical clues and initial findings. 1, 2

Key clinical indicators warranting investigation include:

• 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 (BP >140/90 mmHg despite ≥3 medications including a diuretic) 1, 4
• Sudden onset or deterioration of previously controlled hypertension 1, 2
• Hypertensive urgency or emergency 1, 2
• Target organ damage disproportionate to duration or severity of hypertension 1, 2

Basic Screening Tests (For All Suspected Cases)

The initial workup must include comprehensive laboratory screening before proceeding to expensive imaging studies. 1

Essential Laboratory Tests:

• Serum electrolytes (sodium and potassium) 1, 4
• Serum creatinine and estimated glomerular filtration rate (eGFR) 1, 4
• Fasting blood glucose or HbA1c 1, 4
• Lipid profile 2
• Thyroid-stimulating hormone (TSH) 1, 4
• Urinalysis with dipstick for blood and protein 4
• Urinary albumin-to-creatinine ratio 4
• 12-lead ECG 1, 2

Notable Guideline Update:

The European Society of Cardiology 2024 guidelines now recommend measuring renin and aldosterone in all adults with confirmed hypertension (Class IIa recommendation), representing a significant shift from traditional selective screening. 1

Targeted Investigations Based on Clinical Suspicion

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

Clinical clues: Resistant hypertension with spontaneous or diuretic-induced hypokalemia, muscle cramps/weakness, arrhythmias 1, 4

Investigations:

• Plasma aldosterone-to-renin ratio (ARR) as initial screening (high negative predictive value; ratio >20 with elevated aldosterone and low renin is suggestive) 1, 4
• Confirmatory testing: IV saline suppression test or oral sodium loading test 1, 4
• Adrenal CT imaging for localization 1, 4
• Adrenal vein sampling for lateralization in surgical candidates 1, 4

Critical pitfall: ARR interpretation can be affected by medications—mineralocorticoid receptor antagonists raise aldosterone, while beta-blockers and direct renin inhibitors lower renin. 1

For Renovascular Disease (5-34% in selected populations):

Clinical clues: Abrupt onset or worsening hypertension, flash pulmonary edema, abdominal bruits, early-onset hypertension in women (fibromuscular dysplasia), serum creatinine increase ≥50% within one week of starting ACE inhibitor/ARB 1, 4, 5

Investigations:

• Renal ultrasound with Duplex Doppler as initial imaging 1, 4
• CT or MR renal angiography for confirmation 1, 4
• Bilateral selective renal intra-arterial angiography if intervention is planned 4

For Renal Parenchymal Disease (1-2% prevalence):

Clinical clues: History of urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, analgesic abuse, family history of polycystic kidney disease 1, 4

Investigations:

• Urinalysis and urinary albumin-to-creatinine ratio (already part of basic screening) 1
• Renal ultrasound to assess kidney size and structure 1
• Serum creatinine and eGFR monitoring 4

For Pheochromocytoma (uncommon but dangerous):

Clinical clues: Episodic symptoms (sweating, palpitations, headaches), labile hypertension 1, 2

Investigations:

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

Important note: These tests should only be ordered when pheochromocytoma is specifically suspected based on clinical features, not routinely. 1

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

Clinical clues: Snoring, daytime sleepiness, obesity, non-dipping nocturnal BP pattern 1, 4

Investigations:

• Home sleep apnea testing or overnight polysomnography 1, 4

For Cushing Syndrome:

Clinical clues: Truncal obesity, purple striae, fatty deposits, hyperglycemia 2, 3

Investigations:

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

For Coarctation of the Aorta:

Clinical clues: Radio-femoral delay, decreased femoral pulses, upper extremity hypertension with lower extremity hypotension 1, 3

Investigations:

• Echocardiography to visualize the coarctation 2
• CT or MR angiography for detailed anatomical assessment 2

Additional Imaging Studies

Cardiovascular Assessment:

• Echocardiography to evaluate left ventricular hypertrophy, systolic/diastolic dysfunction, atrial dilation, and aortic coarctation 1, 2
• Carotid ultrasound to evaluate plaques and stenosis 2

Ophthalmologic Assessment:

• Fundoscopy to evaluate retinal changes, hemorrhages, and papilledema (grade III or IV retinopathy suggests renovascular hypertension or pheochromocytoma) 1, 3

Critical Pitfalls to Avoid

• Do not perform expensive imaging studies before completing basic laboratory screening 1
• Exclude medication-induced or substance-induced hypertension (including oral contraceptives, NSAIDs, decongestants, alcohol) before extensive workup 1, 2
• Do not combine two RAS blockers (ACE inhibitor and ARB) during evaluation 1, 2
• Early detection is crucial—delayed diagnosis leads to irreversible vascular remodeling and residual hypertension even after treating the underlying cause 4, 6
• Secondary hypertension is often underrecognized despite affecting 5-10% of all hypertensive patients (10-20% in resistant cases) 4, 7

Referral Considerations

Refer to specialized centers with appropriate expertise for complex cases requiring confirmatory testing, adrenal vein sampling, or consideration of interventional procedures. 1, 7