What is the appropriate workup for an adult patient with newly diagnosed secondary hypertension and no prior history of hypertension?

Workup for Secondary Hypertension

When to Suspect Secondary Hypertension

Screen for secondary hypertension when patients present with age of onset <30 years, resistant hypertension (BP >140/90 mmHg despite ≥3 drugs including a diuretic), abrupt onset or sudden worsening of previously controlled hypertension, or hypertensive emergency. 1, 2

Additional red flags include: 1, 3

• Target organ damage disproportionate to duration of hypertension
• Serum creatinine increase ≥50% within one week of starting ACE inhibitor or ARB
• Flash pulmonary edema
• Family history of early-onset hypertension or stroke at young age

Initial Laboratory Screening (Order for ALL Suspected Cases)

The 2024 ESC guidelines now recommend measuring plasma aldosterone-to-renin ratio (ARR) in all adults with confirmed hypertension (Class IIa), representing a major shift from traditional selective screening. 1, 2 This reflects that primary aldosteronism affects 8-20% of resistant hypertension cases and is the most common treatable cause. 1, 2

Complete the following basic panel first: 1, 2

• Serum electrolytes (sodium, potassium) - hypokalemia strongly suggests primary aldosteronism
• Serum creatinine and eGFR
• Urinalysis with microscopy - look for blood, protein, casts suggesting renal parenchymal disease
• Urinary albumin-to-creatinine ratio
• Fasting blood glucose or HbA1c
• Thyroid-stimulating hormone (TSH)
• Fasting lipid panel
• 12-lead ECG - assess for left ventricular hypertrophy and strain patterns

Physical Examination Findings to Document

Focus on specific findings rather than general examination: 1, 4

• Radio-femoral delay - indicates coarctation of aorta
• Abdominal systolic-diastolic bruit - suggests renovascular disease
• Central obesity with thin extremities, purple striae, easy bruising, proximal muscle weakness, moon facies, buffalo hump - Cushing syndrome
• Enlarged kidneys on palpation - polycystic kidney disease
• Skin stigmata of neurofibromatosis - associated with pheochromocytoma

Targeted Investigations Based on Clinical Clues

For Primary Aldosteronism (if ARR positive: ratio >20 with elevated aldosterone and suppressed renin):

1, 2

• Confirmatory testing: oral sodium loading test with 24-hour urine aldosterone OR IV saline infusion test with plasma aldosterone at 4 hours
• Localization: adrenal CT scan, then adrenal vein sampling if surgical candidate

For Renovascular Disease (if abrupt onset/worsening, flash pulmonary edema, creatinine rise with ACE-I/ARB, unilateral small kidney, or abdominal bruit):

1, 2

• Initial: renal ultrasound with Duplex Doppler
• Confirmatory: CT or MR renal angiography

For Pheochromocytoma (if episodic symptoms, labile/paroxysmal hypertension, hypertensive crisis during anesthesia):

1, 2

• 24-hour urinary catecholamines or metanephrines
• Abdominal/adrenal imaging if biochemically positive

For Obstructive Sleep Apnea (if resistant hypertension, snoring, witnessed apneas, daytime sleepiness, BMI >30, non-dipping nocturnal BP):

1, 2

• Home sleep apnea testing or polysomnography
• Note: OSA present in 25-50% of resistant hypertension cases

For Cushing Syndrome (if characteristic physical findings):

2

• Targeted endocrine workup based on clinical presentation

Critical Pitfalls to Avoid

Do not order expensive imaging (CT, MRI, angiography) before completing basic laboratory screening. 2 This wastes resources and delays diagnosis.

Avoid combining two RAS blockers (ACE inhibitor + ARB) - increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit. 2

Do not dismiss medication-induced hypertension - review all medications, supplements, and substances (NSAIDs, decongestants, oral contraceptives, steroids, licorice) before extensive workup. 1

Recognize that certain medications affect ARR interpretation: mineralocorticoid receptor antagonists raise aldosterone levels; beta-blockers and direct renin inhibitors lower renin levels. 1 Ideally discontinue these 2-4 weeks before testing if safe to do so.

When to Refer

Refer to specialist centers when: 1, 4

• Positive screening tests require confirmatory testing or specialized procedures (adrenal vein sampling, renal angiography)
• Complex cases requiring multidisciplinary management
• Resistant hypertension uncontrolled despite optimal medical therapy

Important Context

Secondary hypertension affects 5-10% of all hypertensive patients, increasing to 10-20% in resistant cases. 2, 5 Early detection is crucial because delayed diagnosis leads to irreversible vascular remodeling, affecting renal function and resulting in residual hypertension even after treating the underlying cause. 6 Even with successful treatment of the secondary cause, many patients require ongoing antihypertensive therapy due to concomitant essential hypertension or irreversible vascular changes. 1, 6