What is the diagnostic workup for patients with secondary hypertension?

Diagnostic Workup for Secondary Hypertension

Secondary hypertension affects 5-10% of all hypertensive patients and requires a systematic approach to diagnosis. The diagnostic workup for secondary hypertension should include targeted screening based on clinical suspicion, starting with basic laboratory tests and advancing to specialized imaging and functional tests for patients with specific clinical clues. 1

Clinical Clues Suggesting Secondary Hypertension

• Age of onset <30 years or >50 years (young age suggests coarctation, fibromuscular dysplasia, or endocrine disorders; older age onset suggests atherosclerotic renovascular disease) 1, 2
• Resistant hypertension (requiring >3 medications from different classes) 1, 2
• Sudden deterioration in previously controlled hypertension 3
• Hypertensive urgency or emergency 3
• Target organ damage disproportionate to duration or severity of hypertension 1
• Specific symptoms suggesting secondary causes 3

Symptoms Suggestive of Specific Secondary Causes

• Muscle weakness, tetany, cramps, arrhythmias (hypokalemia/primary aldosteronism) 3
• Flash pulmonary edema (renal artery stenosis) 3
• Sweating, palpitations, frequent headaches (pheochromocytoma) 3
• Snoring, daytime sleepiness (obstructive sleep apnea) 3
• Symptoms of thyroid disease 3
• Truncal obesity, purple striae (Cushing syndrome) 2

Physical Examination

• Circulation and heart: Pulse rate/rhythm/character, jugular venous pressure, apex beat, extra heart sounds, peripheral edema, bruits (carotid, abdominal, femoral), radio-femoral delay 3
• Other systems: Enlarged kidneys, neck circumference >40 cm (obstructive sleep apnea), enlarged thyroid, increased BMI/waist circumference, fatty deposits and colored striae (Cushing disease/syndrome) 3
• Decreased femoral pulses (coarctation of aorta) 2

Basic Laboratory Investigations

• Blood tests: Sodium, potassium, serum creatinine, estimated glomerular filtration rate (eGFR) 3
• Lipid profile and fasting glucose 3
• Urinalysis (dipstick urine test) 3
• 12-lead ECG: Detection of atrial fibrillation, left ventricular hypertrophy, ischemic heart disease 3
• Thyroid function tests 1

Advanced Diagnostic Tests Based on Clinical Suspicion

For Primary Aldosteronism

• Aldosterone-renin ratio 3
• Confirmatory testing (intravenous saline suppression test) 3
• Adrenal CT imaging 3
• Adrenal vein sampling (to determine if unilateral or bilateral) 3

For Renovascular Disease

• Renal ultrasound/renal artery duplex 3
• CT or MR angiography (depending on renal function) 3

For Pheochromocytoma

• Plasma free metanephrines 3
• 24-hour urinary free catecholamines 3
• Abdominal/adrenal imaging 3

For Cushing Syndrome

• Late-night salivary cortisol 3
• Dexamethasone suppression tests 3
• 24-hour urinary free cortisol 3
• Abdominal/pituitary imaging 3

For Obstructive Sleep Apnea

• Home sleep apnea testing (level 3 sleep study) 3
• Overnight polysomnography 3

For Coarctation of Aorta

• Echocardiography 3
• CT or MR angiogram 3

Imaging Techniques

• Echocardiography: Left ventricular hypertrophy, systolic/diastolic dysfunction, atrial dilation, aortic coarctation 3
• Carotid ultrasound: Plaques, stenosis 3
• Kidney/renal artery and adrenal imaging: Ultrasound, CT/MR angiography for renal parenchymal disease, renal artery stenosis, adrenal lesions 3
• Fundoscopy: Retinal changes, hemorrhages, papilledema 3
• Brain CT/MRI: Ischemic or hemorrhagic brain injury due to hypertension 3

Additional Functional Tests

• Ankle-brachial index: Peripheral artery disease 3
• Urinary albumin/creatinine ratio 3
• Serum uric acid levels 3
• Liver function tests 3

Diagnostic Algorithm

1. Identify patients with clinical clues suggesting secondary hypertension 3
2. Perform basic screening with history, physical examination, basic blood biochemistry, and urinalysis 3
3. Based on initial findings, proceed with targeted testing:
   • Hypokalemia → Aldosterone-renin ratio 1
   • Abdominal bruit → Renal artery imaging 1
   • Snoring, obesity → Sleep study 1
   • Paroxysmal symptoms → Plasma metanephrines 1
   • Cushingoid features → Cortisol testing 1
4. Refer to specialist centers for complex cases or when initial testing suggests secondary causes 3

Common Pitfalls to Avoid

• Indiscriminate screening of all hypertensive patients is costly and inefficient; focus on those with clinical suspicion 4, 5
• Delayed diagnosis can lead to irreversible vascular remodeling, affecting long-term outcomes 5
• Even after treating the underlying cause, some patients may require ongoing antihypertensive therapy due to residual essential hypertension or vascular remodeling 5
• Combining two RAS blockers (ACE inhibitor and ARB) is not recommended during evaluation 1
• Failure to recognize drug-induced or substance-induced hypertension before extensive workup 3