What is the approach to a secondary hypertension (HTN) work-up?

Secondary Hypertension Work-up

The approach to secondary hypertension work-up should begin with targeted screening in patients with specific risk factors, followed by systematic testing for the most common causes including renal disease, primary aldosteronism, and obstructive sleep apnea. 1, 2

When to Suspect Secondary Hypertension

Secondary hypertension should be considered in patients with:

• Early-onset hypertension (<30 years of age), especially without typical risk factors 1
• Resistant hypertension (BP >140/90 mmHg despite three optimal-dose medications including a diuretic) 1
• Sudden deterioration in previously well-controlled BP 1
• Hypertensive urgency or emergency 1
• Clinical features suggesting a specific secondary cause 2

Initial Evaluation

History and Physical Examination

• History:

  • Duration and previous levels of high blood pressure 1
  • Symptoms suggesting secondary causes (headaches, palpitations, sweating for pheochromocytoma; snoring for sleep apnea) 1
  • Medication use (oral contraceptives, NSAIDs, steroids, sympathomimetics) 1
  • Family history of hypertension or early cardiovascular disease 2

• Physical Examination:

  • BP measurement in both arms 2
  • BMI and waist circumference (>40 cm neck circumference suggests OSA) 1
  • Heart examination (extra sounds, murmurs) 1
  • Abdominal examination (bruits, enlarged kidneys) 1
  • Peripheral pulses (diminished femoral pulses suggest coarctation) 1
  • Signs of endocrine disorders (Cushing's features, thyroid abnormalities) 1

Basic Laboratory Tests

• Blood tests: 1, 2

  • Serum sodium and potassium (hypokalemia suggests hyperaldosteronism)
  • Serum creatinine and eGFR (renal disease)
  • Fasting glucose (diabetes, Cushing's)
  • Lipid profile
  • TSH (thyroid disease)

• Urine tests: 1

  • Urinalysis (protein, blood suggests renal disease)
  • Urinary albumin-to-creatinine ratio

• 12-lead ECG: To detect atrial fibrillation, left ventricular hypertrophy, ischemic heart disease 1

Targeted Investigations for Specific Causes

Renal Causes

• Renal parenchymal disease:

  • Kidney ultrasound 1, 2
  • Urine protein quantification 1

• Renovascular disease:

  • Duplex ultrasound of renal arteries 1
  • CT or MR angiography (if ultrasound suggestive or high clinical suspicion) 1
  • Consider in patients with abdominal bruits, sudden-onset or resistant hypertension, or acute kidney injury after ACE inhibitor/ARB initiation 3

Endocrine Causes

• Primary aldosteronism:

  • Aldosterone-to-renin ratio (ARR) as initial screening 1, 2
  • Confirmatory testing (saline suppression test) if ARR elevated 2
  • Adrenal CT if confirmed 2
  • Adrenal vein sampling to determine laterality before surgery 1, 2
  • Consider in patients with hypokalemia or resistant hypertension 3

• Pheochromocytoma:

  • Plasma free metanephrines or 24-hour urinary metanephrines 1, 2
  • Abdominal/adrenal imaging if biochemically confirmed 2
  • Consider in patients with episodic symptoms (headaches, sweating, palpitations) 3

• Cushing's syndrome:

  • Late-night salivary cortisol or overnight dexamethasone suppression test 1, 2
  • 24-hour urinary free cortisol 2
  • Consider in patients with typical cushingoid features 3

Other Common Causes

• Obstructive sleep apnea:

  • Home sleep apnea testing or overnight polysomnography 1, 2
  • Consider in patients with obesity, snoring, daytime sleepiness 3

• Coarctation of the aorta:

  • Echocardiography 1
  • CT or MR angiography if echocardiography suggestive 2
  • Consider in young patients with diminished femoral pulses or BP differential between arms and legs 1, 3

Additional Evaluation for Target Organ Damage

• Echocardiography (LVH, systolic/diastolic dysfunction) 1
• Carotid ultrasound (atherosclerosis) 1
• Fundoscopy (retinal changes) 1
• Brain CT/MRI if neurological symptoms present 1

Management Approach

1. Identify patients at high risk for secondary hypertension
2. Perform basic screening tests
3. Order targeted investigations based on clinical suspicion
4. Refer to specialists when appropriate (endocrinology, nephrology, vascular surgery)
5. Consider referral to specialized hypertension centers for complex cases 1

Important Considerations

• Secondary hypertension affects approximately 5-10% of all hypertensive patients 4, 3
• Early detection is crucial as some causes are potentially curable 5
• Even after treating the underlying cause, some patients may have residual hypertension due to vascular remodeling or concomitant essential hypertension 6
• Medication-induced hypertension should always be considered and medication review performed 7