What is the initial workup for a patient with secondary hypertension?

Initial Workup for Secondary Hypertension

The initial workup for a patient with suspected secondary hypertension should include a thorough history, physical examination, basic laboratory tests, and a 12-lead ECG to identify potential underlying causes and assess for hypertension-mediated organ damage.

When to Suspect Secondary Hypertension

Secondary hypertension occurs in approximately 5-10% of all hypertensive patients 1. Consider screening for secondary causes in patients with:

• Early-onset hypertension (<30 years of age), particularly without typical risk factors
• Resistant hypertension (BP >140/90 mmHg despite ≥3 antihypertensive medications including a diuretic)
• Sudden deterioration in previously well-controlled BP
• Hypertensive urgency or emergency
• Clinical features suggesting a specific secondary cause
• Severe hypertension (≥180/110 mmHg)

Initial Diagnostic Workup

History and Physical Examination

Focus on:

• Family history of hypertension or cardiovascular disease

• Medication use (including OTC, herbal supplements, illicit drugs)

• Symptoms suggesting secondary causes:

  • Episodic headaches, palpitations, sweating (pheochromocytoma)
  • Snoring, daytime sleepiness (obstructive sleep apnea)
  • Muscle weakness, polyuria (primary aldosteronism)
  • Weight gain, hirsutism, easy bruising (Cushing's syndrome)

• Physical examination should include:

  • BP measurement in both arms
  • BMI and waist circumference
  • Heart and lung examination
  • Abdominal examination (including renal artery bruits)
  • Peripheral pulses
  • Signs of endocrine disorders (moon facies, buffalo hump, striae)

Basic Laboratory Tests

According to the 2024 ESC guidelines 2 and 2020 ISH guidelines 2, routine tests should include:

• Blood tests:

  • Fasting blood glucose (and HbA1c if elevated)
  • Serum lipids (total cholesterol, LDL, HDL, triglycerides)
  • Serum sodium and potassium
  • Blood creatinine and eGFR
  • Thyroid-stimulating hormone (TSH)
  • Hemoglobin/hematocrit
  • Serum calcium
  • Serum uric acid (if available)
  • Liver function tests (if indicated)

• Urine tests:

  • Urinalysis (dipstick)
  • Urinary albumin-to-creatinine ratio

• 12-lead ECG:

  • To detect atrial fibrillation, left ventricular hypertrophy, ischemic heart disease

Additional Investigations Based on Initial Findings

If the initial evaluation suggests a specific secondary cause, further targeted investigations should be considered 2:

For Suspected Primary Aldosteronism

• Plasma aldosterone-to-renin ratio
• Confirmatory testing (e.g., intravenous saline suppression test)
• Adrenal imaging (CT)
• Adrenal vein sampling in selected cases

For Suspected Renal Causes

• Kidney ultrasound
• Renal artery imaging (duplex ultrasound, CT or MR angiography)

For Suspected Pheochromocytoma

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

For Suspected Cushing's Syndrome

• Late-night salivary cortisol
• Dexamethasone suppression test
• 24-hour urinary free cortisol

For Suspected Obstructive Sleep Apnea

• Home sleep apnea testing
• Overnight polysomnography

Assessment for Hypertension-Mediated Organ Damage

Optional tests to assess for target organ damage include 2:

• Echocardiography (LVH, systolic/diastolic dysfunction)
• Carotid ultrasound (atherosclerotic plaques)
• Fundoscopy (retinal changes, particularly if BP >180/110 mmHg)
• Ankle-brachial index (peripheral artery disease)
• Brain CT/MRI (if neurological symptoms present)

Important Considerations

• The prevalence of abnormal findings and end-organ damage is higher than previously thought, with recent studies showing up to 8.3% of patients with asymptomatic severe hypertension having evidence of end-organ damage 3.

• Age >60 years and comorbidities such as diabetes, ischemic heart disease, and prior cerebrovascular events significantly increase the risk of end-organ damage in patients with severe hypertension 3.

• Even with appropriate treatment of secondary causes, blood pressure rarely returns to completely normal levels with long-term follow-up, suggesting either concomitant essential hypertension or irreversible vascular remodeling 1.

• Consider referral to a specialist center for further investigation and management of suspected secondary hypertension, particularly for complex cases or when initial workup suggests a specific cause 2.