What laboratory tests are recommended for evaluating secondary hypertension (hypertension)?

Laboratory Tests for Secondary Hypertension Evaluation

Screen all hypertensive patients with basic labs (electrolytes, creatinine, glucose, lipids, urinalysis, TSH, ECG), then pursue targeted testing based on clinical suspicion—with the notable exception that aldosterone-to-renin ratio should be considered in all confirmed hypertensive patients given primary aldosteronism affects 5-20% of cases. 1

Basic Screening Labs (Perform in All Hypertensive Patients)

Routine laboratory evaluation should include: 1

• Serum electrolytes (sodium and potassium) - hypokalemia suggests primary aldosteronism 1
• Serum creatinine with eGFR calculation - identifies renal parenchymal disease 1
• Fasting blood glucose or HbA1c - assesses metabolic status 1, 2
• Serum lipid panel (total cholesterol, LDL, HDL, triglycerides) 1
• Urinalysis with microscopy - detects hematuria, proteinuria suggesting renal disease 1
• Urinary albumin-to-creatinine ratio - identifies early kidney damage 1, 2
• Serum uric acid 1
• Thyroid-stimulating hormone (TSH) - screens for thyroid disorders 1, 2
• 12-lead ECG - all hypertensive patients require this 1

Targeted Testing Based on Clinical Suspicion

Primary Aldosteronism (Most Common Endocrine Cause)

The 2024 ESC guidelines represent a major shift: screening for primary aldosteronism with aldosterone-to-renin ratio should be considered in ALL adults with confirmed hypertension (Class IIa), not just those with traditional risk factors. 1 This recommendation reflects evidence that primary aldosteronism affects 5-20% of hypertensive patients, most lack hypokalemia, and targeted treatment reduces cardiovascular risk beyond blood pressure lowering alone. 1

Mandatory screening indications (Class I): 1

• Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including diuretic)
• Hypokalemia (spontaneous or substantial if diuretic-induced)
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension or stroke at age <40 years
• Obstructive sleep apnea

Screening test: 1

• Plasma aldosterone-to-renin ratio (ARR) under standardized conditions

Critical preparation requirements: 1

• Correct hypokalemia before testing (low potassium causes false negatives)
• Withdraw aldosterone antagonists for 4-6 weeks
• Be aware of medication effects on ARR (see Table 12 in evidence): beta-blockers, NSAIDs, alpha-2 agonists cause false positives; ACE inhibitors, ARBs, diuretics cause false negatives 1

Confirmatory testing if ARR positive: 1

• Oral sodium loading test with 24-hour urine aldosterone, OR
• IV saline infusion test with plasma aldosterone at 4 hours
• Adrenal CT scan
• Adrenal vein sampling for lateralization

Renovascular Hypertension

Clinical triggers for screening: 1, 2

• Age <40 years (suggests fibromuscular dysplasia, especially in women)
• Age >60 years with acute BP change or flash pulmonary edema (suggests atherosclerosis)
• Resistant hypertension
• Abrupt onset or sudden worsening of previously controlled hypertension
• Acute eGFR decline after starting ACE inhibitor or ARB

Screening tests: 1

• Renal Doppler ultrasound (initial screening)
• CT angiography or MR angiography of renal arteries (confirmatory)
• Plasma renin level
• Monitor eGFR and albuminuria

Important caveat: For fibromuscular dysplasia (systemic disease), CT or MRI angiography from head to pelvis is recommended. 1

Pheochromocytoma/Paraganglioma

Clinical triggers: 1, 2

• Episodic symptoms (headache, sweating, palpitations, pallor)
• Labile or paroxysmal hypertension
• Hypertensive crisis during anesthesia or surgery
• Incidentally discovered adrenal mass

Screening test: 1

• 24-hour urinary metanephrines and normetanephrines, AND/OR
• Plasma free metanephrines and normetanephrines

Renal Parenchymal Disease

Clinical triggers: 1, 2

• History of urinary tract infections, obstruction, hematuria
• Urinary frequency and nocturia
• Analgesic abuse
• Family history of polycystic kidney disease
• Elevated serum creatinine
• Abnormal urinalysis

Screening tests: 1

• Plasma creatinine with eGFR calculation
• Serum sodium and potassium
• Urine dipstick for blood and protein
• Urinary albumin-to-creatinine ratio
• Renal ultrasound

Cushing's Syndrome

Clinical triggers: 1, 2

• Central obesity with thin extremities
• Purple striae
• Easy bruising
• Proximal muscle weakness
• Moon facies and buffalo hump

Screening tests: 1

• 24-hour urinary free cortisol
• Low-dose dexamethasone suppression test

Obstructive Sleep Apnea (Highly Prevalent in Resistant Hypertension)

Clinical triggers: 1, 2

• Resistant hypertension (present in up to 60% of cases)
• Snoring, witnessed apneas, daytime sleepiness
• Obesity
• Non-dipping or reverse-dipping pattern on 24-hour BP monitoring

Screening test: 1

• Validated questionnaires (initial)
• Overnight ambulatory polysomnography (confirmatory)
• Apnea-hypopnea index (AHI) >5 confirms diagnosis; severity: mild <15, moderate 15-30, severe >30

Important note: Lack of symptoms does not rule out obstructive sleep apnea. 1

Hyperparathyroidism

Screening tests: 1

• Parathyroid hormone level
• Serum calcium and phosphate

Coarctation of the Aorta

Clinical triggers: 1, 2

• Young age at presentation
• Differential blood pressure between arms and legs
• Diminished or delayed femoral pulses
• Systolic murmur over the back

Screening tests: 1

• Echocardiogram
• Aortic CT angiography

Age-Based Screening Approach

For young adults (<40 years): 1

• The 2024 ESC guidelines recommend comprehensive screening for main causes of secondary hypertension (Class I)
• Exception: Young adults with obesity should start with obstructive sleep apnea evaluation

For children with confirmed hypertension: 3

• Up to 85% have identifiable secondary cause, most commonly renal parenchymal disease
• All children require evaluation including renal ultrasonography

Common Pitfalls to Avoid

• Don't perform expensive imaging before completing basic laboratory screening 2
• Don't overlook medication-induced hypertension - review all prescription medications, over-the-counter drugs, NSAIDs, oral contraceptives, steroids, and herbal supplements before extensive workup 1, 2
• Don't assume normal potassium excludes primary aldosteronism - hypokalemia is absent in the majority of cases 1
• Don't delay screening in resistant hypertension - approximately 10% of adults with hypertension have secondary causes, but this increases substantially in resistant cases 4, 5
• Refer complex cases to specialized hypertension centers for diagnostic confirmation and comprehensive management 1, 2, 4

When to Pursue Secondary Hypertension Workup

Strong clinical indications (Class I recommendation): 1

• Resistant hypertension despite optimal 3-drug therapy including diuretic
• Age of onset <30 years
• Severe hypertension (BP ≥180/110 mmHg)
• Abrupt onset or sudden deterioration of previously controlled hypertension
• Hypertensive urgency or emergency
• Target organ damage disproportionate to duration/severity of hypertension
• Presence of clinical features specific to secondary causes

Early detection and treatment are critical because delayed diagnosis leads to irreversible vascular remodeling, affecting renal function and resulting in residual hypertension even after treating the underlying cause. 6