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

Initial Workup for Secondary Hypertension

Begin with basic laboratory screening in all patients with clinical suspicion, then proceed to targeted investigations based on specific clinical clues rather than performing expensive imaging studies upfront. 1

When to Screen for Secondary Hypertension

Screen patients who meet any of these criteria:

• Age of onset <30 years 1
• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic) 1, 2
• Abrupt onset or sudden deterioration of previously controlled hypertension 1, 3
• Hypertensive urgency or emergency 1
• Target organ damage disproportionate to duration or severity of hypertension 1

Secondary hypertension affects 5-10% of all hypertensive patients, increasing to 10-20% in resistant cases, making selective screening essential rather than universal testing. 3, 4

Basic Laboratory Screening (Perform First in All Suspected Cases)

Complete these tests before proceeding to expensive imaging studies: 1

• Serum electrolytes (sodium and potassium) 1, 3
• Serum creatinine and estimated GFR (eGFR) 1, 3
• Urinalysis with dipstick for blood and protein 1, 3
• Urinary albumin-to-creatinine ratio 1, 3
• Fasting blood glucose or HbA1c 1, 3
• Serum lipids 1
• Thyroid-stimulating hormone (TSH) 1, 3
• 12-lead ECG 1, 2

Comprehensive History and Physical Examination

History Should Focus On:

• Duration and previous levels of blood pressure 1
• Medication use (including NSAIDs, oral contraceptives, decongestants, stimulants) - evaluate for medication-induced hypertension before extensive workup 1
• Symptoms suggesting specific causes:
  • Urinary tract infections, obstruction, hematuria, urinary frequency, nocturia (renal parenchymal disease) 1, 3
  • Episodic headaches, palpitations, sweating, pallor (pheochromocytoma) 1
  • Snoring, daytime sleepiness, witnessed apneas (obstructive sleep apnea) 1, 3
  • Muscle cramps or weakness (primary aldosteronism) 1, 3
• Family history of polycystic kidney disease, early-onset hypertension, or stroke at young age 1, 3

Physical Examination Should Include:

• Radio-femoral delay and assessment of femoral pulses (coarctation of aorta) 1, 4
• Abdominal bruits (renovascular disease) 1, 3
• Palpation for enlarged kidneys (polycystic kidney disease) 1
• Features of Cushing syndrome (fatty deposits, colored striae, moon facies) 1, 4
• Skin stigmata of neurofibromatosis 1
• Fundoscopy for retinal changes, hemorrhages, papilledema 4

Targeted Investigations Based on Clinical Suspicion

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

Screen if: Resistant hypertension with spontaneous or diuretic-induced hypokalemia, muscle cramps/weakness, or family history of early-onset hypertension 1, 3

• Plasma aldosterone-to-renin ratio (initial screening test) 1, 3
• Confirmatory testing: IV saline suppression test or oral sodium loading test 1, 3
• Adrenal CT scan (if confirmatory test positive) 1, 3
• Adrenal vein sampling (to distinguish unilateral from bilateral disease) 1, 3

For Renovascular Disease:

Screen if: Abrupt onset or worsening hypertension, flash pulmonary edema, early-onset hypertension (especially fibromuscular dysplasia in women), or abdominal bruits 1, 3

• Renal ultrasound with Duplex Doppler (initial imaging) 1, 3, 4
• CT or MR renal angiography (if ultrasound suggests stenosis) 1, 3
• Bilateral selective renal intra-arterial angiography (gold standard if intervention planned) 3

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

Screen if: Snoring, daytime sleepiness, obesity, non-dipping nocturnal BP pattern 1, 3

• Home sleep apnea testing (initial screening) 1, 3
• Overnight polysomnography (if home testing inconclusive or for comprehensive evaluation) 1, 3

For Pheochromocytoma:

Screen if: Episodic symptoms (headaches, palpitations, sweating), labile hypertension 1

• 24-hour urinary catecholamines or metanephrines 1
• Abdominal/adrenal imaging (CT or MRI if biochemical testing positive) 1

For Renal Parenchymal Disease:

Screen if: History of urinary tract infections, obstruction, hematuria, analgesic abuse, family history of polycystic kidney disease 1, 3

• Renal ultrasound 1
• Urinalysis findings from basic screening will guide further evaluation 1

Additional Imaging When Indicated

• Echocardiography to assess for left ventricular hypertrophy, aortic coarctation, and systolic/diastolic dysfunction 4

Critical Pitfalls to Avoid

• Do not perform expensive imaging studies before completing basic laboratory screening - this wastes resources and may lead to incidental findings that complicate management 1
• Do not miss medication-induced hypertension - evaluate current medications before extensive workup 1
• Recognize that delayed diagnosis leads to vascular remodeling - even after treating the underlying cause, residual hypertension may persist due to irreversible vascular changes 3, 5
• Refer complex cases to specialized centers with appropriate expertise rather than pursuing extensive testing without clear direction 1, 4
• Do not screen all hypertensive patients - only those with specific clinical clues, as secondary hypertension affects only 5-10% of cases 3, 4, 6

Algorithmic Approach Summary

1. Identify clinical clues suggesting secondary hypertension (age <30, resistant HTN, abrupt onset, etc.)
2. Complete basic laboratory screening in all suspected cases (electrolytes, creatinine, eGFR, urinalysis, glucose, TSH, ECG)
3. Perform targeted history and physical focusing on symptoms and signs of specific causes
4. Order targeted investigations based on clinical suspicion from steps 1-3
5. Refer to specialized centers if diagnosis remains unclear or intervention is needed

This stepwise approach maximizes diagnostic yield while minimizing unnecessary testing and cost. 1, 4, 5