What is the appropriate workup for a patient with suspected secondary hypertension?

Workup for Secondary Hypertension

Screen for secondary hypertension when patients present with resistant hypertension (BP >140/90 mmHg on ≥3 drugs including a diuretic), early-onset hypertension (<30-40 years), sudden onset or deterioration of previously controlled BP, or hypertensive emergency. 1, 2

When to Suspect Secondary Hypertension

High-Risk Clinical Scenarios

• Age of onset <30 years (especially before puberty) warrants comprehensive screening 1, 2
• Resistant hypertension despite optimal doses of three antihypertensive drugs including a diuretic 1, 2
• Abrupt onset or sudden worsening of previously controlled hypertension 1, 2
• Hypertensive urgency or emergency (BP ≥180/110 mmHg) 1
• Target organ damage disproportionate to duration or severity of hypertension 1

Specific Clinical Clues by Etiology

• Renal parenchymal disease: History of UTIs, obstruction, hematuria, urinary frequency, nocturia, or family history of polycystic kidney disease 1, 2
• Renovascular disease: Flash pulmonary edema, abdominal bruits, serum creatinine increase ≥50% within one week of starting ACE inhibitor/ARB, unilateral smaller kidney or size difference >1.5 cm 1, 3
• Primary aldosteronism: Spontaneous or diuretic-induced hypokalemia, muscle cramps/weakness, family history of early-onset hypertension 1, 2
• Pheochromocytoma: Episodic symptoms (headaches, palpitations, sweating), labile hypertension 1
• Obstructive sleep apnea: Snoring, daytime sleepiness, obesity, non-dipping nocturnal BP pattern (affects 25-50% of resistant hypertension) 1
• Cushing syndrome: Fatty deposits, colored striae, central obesity 1

Initial Screening Tests for All Suspected Cases

Basic Laboratory Panel

• Serum creatinine and eGFR to assess renal function 4, 1, 2
• Serum sodium and potassium (hypokalemia suggests primary aldosteronism) 1, 2
• Urinalysis and urinary albumin-to-creatinine ratio to detect proteinuria and kidney damage 4, 1, 2
• Fasting blood glucose or HbA1c 1, 2
• Thyroid-stimulating hormone (TSH) 1, 2
• Serum lipids 1
• 12-lead ECG for all patients with hypertension 4, 1

Critical 2024 Guideline Update

The 2024 ESC guidelines now recommend measuring renin and aldosterone in ALL adults with confirmed hypertension (Class IIa recommendation), representing a major shift from traditional selective screening. 1 This reflects growing recognition that primary aldosteronism affects 8-20% of resistant hypertension cases and is significantly underdiagnosed. 1, 2

Targeted Investigations Based on Clinical Suspicion

Primary Aldosteronism (Most Common Endocrine Cause)

• Plasma aldosterone-to-renin ratio (ARR) as initial screening test 1, 2
  • High ratio (>20) with elevated aldosterone and low renin is suggestive 1
  • Pitfall: Beta-blockers and direct renin inhibitors lower renin; mineralocorticoid receptor antagonists raise aldosterone—consider medication effects on interpretation 1
• Confirmatory testing: IV saline suppression test or oral sodium loading test 1, 2
• Adrenal CT scan for localization 1, 2
• Adrenal vein sampling to distinguish unilateral from bilateral disease 1, 2

Renovascular Disease

• Renal ultrasound with Duplex Doppler as initial imaging 1, 2
• CT or MR renal angiography for confirmation 1, 2
• Consider in patients with abrupt onset, flash pulmonary edema, or creatinine rise with RAS blockers 1, 3

Obstructive Sleep Apnea

• Home sleep apnea testing or overnight polysomnography 1, 2
• Screen patients with resistant hypertension, snoring, daytime sleepiness, and obesity 1

Pheochromocytoma (Only When Specifically Suspected)

• 24-hour urinary metanephrines or plasma metanephrines 1
• Abdominal/adrenal imaging if biochemical testing positive 1
• Do not order routinely—only when episodic symptoms and labile hypertension present 1

Additional Imaging When Indicated

• Echocardiography for patients with ECG abnormalities or signs/symptoms of cardiac disease 4, 1
• Fundoscopy if BP >180/110 mmHg to evaluate for hypertensive emergency and malignant hypertension 4, 1

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Failing to consider medication-induced hypertension before extensive workup (NSAIDs, oral contraceptives, decongestants, stimulants) 1
• Performing expensive imaging before completing basic laboratory screening 1
• Underrecognizing secondary hypertension despite affecting 5-10% of all hypertensive patients (up to 10-20% in resistant cases) 2, 5
• Delayed diagnosis leads to irreversible vascular remodeling, resulting in residual hypertension even after treating the underlying cause 1, 2, 6

Medication Considerations

• Do not combine two RAS blockers (ACE inhibitor + ARB) 1
• Monitor renal function carefully when using RAS blockers, especially in suspected renovascular disease 1

Algorithmic Approach Summary

1. Identify high-risk features (age <30, resistant HTN, sudden onset/worsening, hypertensive emergency) 1, 2
2. Perform basic screening panel (electrolytes, creatinine/eGFR, urinalysis, TSH, glucose, ECG) on all suspected cases 1, 2
3. Measure aldosterone-to-renin ratio in all confirmed hypertension per 2024 ESC guidelines 1
4. Order targeted investigations based on specific clinical clues:
   • Renal ultrasound for renovascular disease 1, 2
   • Sleep study for OSA symptoms 1, 2
   • Urinary/plasma metanephrines only for episodic symptoms 1
5. Refer to specialist centers for complex cases requiring adrenal vein sampling, renal angiography, or surgical intervention 1, 2

Management After Diagnosis

• Unilateral primary aldosteronism: Surgical adrenalectomy 1
• Bilateral primary aldosteronism: Spironolactone 50-100 mg daily 1
• Atherosclerotic renovascular disease: Medical therapy (not revascularization) 1
• Fibromuscular dysplasia: Percutaneous transluminal renal angioplasty without stenting 1
• Obstructive sleep apnea: CPAP therapy for moderate-severe cases 1

Even after treating the underlying cause, many patients require ongoing antihypertensive therapy due to concomitant essential hypertension or irreversible vascular changes. 1, 6