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

Secondary Hypertension Workup

Begin with a targeted clinical assessment focusing on specific red flags, followed by basic laboratory screening in all suspected cases, then pursue cause-specific testing based on clinical clues rather than shotgun testing. 1, 2

When to Suspect Secondary Hypertension

Screen patients who present with these high-risk features 1, 2:

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

Initial Clinical Assessment

History - Look for Cause-Specific Symptoms

Renal parenchymal disease 1:

• Urinary tract infections, obstruction, hematuria, urinary frequency, nocturia
• Family history of polycystic kidney disease

Renovascular disease 1:

• Flash pulmonary edema
• Early-onset hypertension (especially fibromuscular dysplasia in young women)

Primary aldosteronism 1:

• Muscle weakness, tetany, cramps (from hypokalemia)
• Arrhythmias
• Family history of early-onset hypertension or stroke at young age

Pheochromocytoma 3, 1:

• Episodic sweating, palpitations, frequent headaches
• Labile hypertension

Obstructive sleep apnea 3, 1:

• Snoring, daytime sleepiness
• Non-dipping nocturnal BP pattern

Cushing syndrome 3:

• Weight gain, easy bruising, proximal muscle weakness

Physical Examination - Key Findings

Cardiovascular 3:

• Radio-femoral delay (coarctation)
• Abdominal bruits (renovascular disease)
• Peripheral edema

Endocrine/metabolic 3:

• Neck circumference >40 cm (obstructive sleep apnea)
• Fatty deposits and colored striae (Cushing syndrome)
• Enlarged thyroid

Renal 3:

• Enlarged kidneys on palpation

Basic Laboratory Screening - Perform in ALL Suspected Cases

Essential initial tests 3, 2:

• Serum sodium and potassium
• Serum creatinine and eGFR
• Urinalysis with dipstick for blood and protein
• Urinary albumin-to-creatinine ratio
• Fasting blood glucose or HbA1c
• Thyroid-stimulating hormone (TSH)
• 12-lead ECG

Critical pitfall: Do not proceed to expensive imaging before completing basic laboratory screening 1. Also evaluate for medication-induced hypertension before extensive workup 1.

Cause-Specific Testing - Based on Clinical Suspicion

Primary Aldosteronism (8-20% of resistant hypertension)

When to test 1, 2:

• Resistant hypertension with spontaneous or diuretic-induced hypokalemia
• Muscle cramps or weakness

Testing sequence 3, 2:

1. Plasma aldosterone-to-renin ratio (best done BEFORE starting interfering antihypertensive drugs) 4
2. Confirmatory testing: IV saline suppression test or oral sodium loading test 2
3. Adrenal CT scan for localization 2
4. Adrenal vein sampling to distinguish unilateral from bilateral disease 2

Renovascular Disease (5-34% in selected populations)

When to test 1, 2:

• Abrupt onset or worsening hypertension
• Flash pulmonary edema
• Abdominal bruits

Testing sequence 3, 2:

1. Renal ultrasound with Duplex Doppler 2
2. CT or MR renal angiography 3, 2
3. Bilateral selective renal intra-arterial angiography if intervention planned 2

Pheochromocytoma

When to test 3, 1:

• Episodic symptoms (sweating, palpitations, headaches)
• Labile hypertension

Testing sequence 1:

1. Plasma free metanephrines or 24-hour urinary catecholamines/metanephrines 3
2. Abdominal/adrenal imaging (CT or MRI) 1

Cushing Syndrome

When to test 3:

• Fatty deposits and colored striae
• Central obesity with proximal muscle weakness

Testing sequence 3:

• Late-night salivary cortisol or other screening tests for cortisol excess 3

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

When to test 1:

• Snoring, daytime sleepiness, obesity
• Neck circumference >40 cm

Testing sequence 1, 2:

1. Home sleep apnea testing 2
2. Overnight polysomnography if home testing inconclusive 2

Additional Imaging When Indicated

Echocardiography 3:

• Assess for LVH, aortic coarctation, systolic/diastolic dysfunction

Fundoscopy 3:

• Retinal changes, hemorrhages, papilledema

Critical Pitfalls to Avoid

Delayed diagnosis leads to irreversible vascular remodeling 2, 5. Even after treating the underlying cause, BP rarely returns to normal with long-term follow-up, indicating either concomitant essential hypertension or irreversible vascular changes 5. Therefore, early detection and treatment are crucial to minimize permanent target organ damage 5.

Secondary hypertension is markedly underrecognized despite affecting 5-10% of all hypertensive patients, increasing to 10-20% in resistant cases 2, 5. Maintain high clinical suspicion in appropriate patients 6.

Refer complex cases to specialized centers with appropriate expertise rather than pursuing extensive workup in primary care 1.