What screening tests are recommended for a patient with newly diagnosed or resistant hypertension to evaluate secondary causes?

Screening Tests for Secondary Hypertension

Universal Baseline Laboratory Panel

All patients with confirmed hypertension should undergo a comprehensive baseline laboratory evaluation before proceeding to targeted testing. 1, 2

• Plasma aldosterone-to-renin ratio (ARR) – The European Society of Cardiology 2024 guidelines now recommend measuring this in all adults with confirmed hypertension (Class IIa recommendation), representing a major shift from traditional selective screening. 1, 2

• Serum electrolytes (sodium and potassium) – Spontaneous or diuretic-induced hypokalemia strongly suggests primary aldosteronism. 1, 3

• Serum creatinine and estimated glomerular filtration rate (eGFR) – Essential for detecting renal parenchymal disease. 1, 3, 2

• Urinalysis with albumin-to-creatinine ratio – Screens for proteinuria and kidney damage. 1, 3

• Fasting glucose or HbA1c – Part of cardiovascular risk stratification. 1, 3

• Thyroid-stimulating hormone (TSH) – Screens for thyroid-related hypertension. 1, 3, 2

• Fasting lipid panel – Completes cardiovascular risk assessment. 1, 3

• 12-lead ECG – Evaluates for left ventricular hypertrophy and cardiac abnormalities. 1, 3, 2

Clinical Red Flags Requiring Aggressive Workup

Pursue targeted secondary hypertension screening when any of the following are present:

• Age of onset < 30 years (especially without family history) or > 50 years (suggests atherosclerotic renovascular disease in older patients). 1, 3, 4

• Resistant hypertension – Blood pressure > 140/90 mmHg despite optimal doses of ≥ 3 antihypertensive drugs including a diuretic. 1, 3, 2, 4

• Abrupt onset or sudden deterioration of previously controlled hypertension. 1, 3, 2, 4

• Severe hypertension (> 180/110 mmHg) or hypertensive emergency. 1, 3, 5

• Target organ damage disproportionate to duration or severity of hypertension. 1, 3

Targeted Testing Based on Clinical Suspicion

Primary Aldosteronism (Most Common Treatable Cause)

Primary aldosteronism accounts for 8–20% of resistant hypertension cases. 1, 2

• Initial screening: Plasma aldosterone-to-renin ratio (ARR) – A ratio > 20 with elevated aldosterone and suppressed renin is suggestive. 1

• Confirmatory testing: Intravenous saline suppression test or oral sodium-loading test (24-hour urine aldosterone). 1, 3, 6

• Localization: Adrenal CT scan after biochemical confirmation. 1, 3

• Adrenal vein sampling when surgical intervention is contemplated to differentiate unilateral from bilateral disease. 1, 3

Clinical clues: Spontaneous or diuretic-induced hypokalemia, muscle weakness, tetany, cramps, arrhythmias, or family history of early-onset hypertension/stroke < 40 years. 1, 3

Medication effects: ACE inhibitors and ARBs lower aldosterone and raise renin, potentially causing false-negative ARR results; beta-blockers and direct renin inhibitors lower renin levels. 1

Renovascular Disease

• Initial imaging: Renal Duplex Doppler ultrasound. 1, 3, 2

• Confirmatory imaging: CT or MR renal angiography. 1, 3, 2, 7

Clinical clues: Abrupt onset or worsening hypertension, flash pulmonary edema, serum creatinine increase ≥ 50% within one week of starting ACE inhibitor or ARB, abdominal systolic-diastolic bruits, unilateral smaller kidney or size difference > 1.5 cm. 1, 2, 4

Pheochromocytoma

• Biochemical screening: 24-hour urinary metanephrines/normetanephrines or plasma free metanephrines. 1, 3, 8

• Imaging: Abdominal/adrenal CT or MRI after biochemical confirmation. 1, 3

Clinical clues: Classic triad of episodic sweating, palpitations, and frequent headaches; labile or paroxysmal hypertension. 1, 3

Obstructive Sleep Apnea

Present in 25–50% of resistant hypertension cases. 1

• Diagnostic test: Overnight polysomnography; apnea-hypopnea index (AHI) > 5 confirms OSA, > 30 indicates severe disease. 1, 2

Clinical clues: Snoring, witnessed apneas, daytime sleepiness, obesity with neck circumference > 40 cm, non-dipping or reverse-dipping 24-hour BP pattern. 1, 5

Cushing Syndrome

• Screening tests: 24-hour urinary free cortisol or late-night salivary cortisol or low-dose dexamethasone suppression test. 1

Clinical clues: Central obesity with thin extremities, wide (> 1 cm) purple striae, easy bruising, proximal muscle weakness, moon facies, buffalo hump, fatty deposits. 1, 8

Thyroid Disease

• Screening: TSH with free T4/T3 as indicated. 1, 3

Clinical clues for hypothyroidism: Dry skin, cold intolerance, constipation, weight gain, delayed ankle reflexes, periorbital puffiness. 1

Clinical clues for hyperthyroidism: Warm moist skin, heat intolerance, tremor, weight loss, tachycardia. 1

Coarctation of the Aorta

• Diagnostic imaging: CT angiography or MRI. 1

Clinical clues: Systolic BP difference > 10 mmHg between arm and thigh, radio-femoral delay, especially in patients < 30 years. 1, 4

Critical Pitfalls to Avoid

• Medication non-adherence accounts for a large proportion of apparent resistant hypertension – explicitly ask about missed doses, side effects, and cost barriers before extensive workup. 1

• Drug-induced hypertension from NSAIDs, decongestants, stimulants, oral contraceptives, cyclosporine, erythropoietin, licorice, or ephedra must be excluded. 1

• White-coat hypertension occurs in 20–30% of patients with apparent resistant hypertension – use ambulatory or home BP monitoring to exclude this before pursuing expensive testing. 1

• Do not perform expensive imaging studies before completing the basic laboratory screening panel. 1, 2

When to Refer to a Specialist

Refer to a hypertension specialist or endocrinologist when:

• Screening tests are positive and require confirmatory testing (e.g., positive ARR, elevated metanephrines). 1, 2

• Complex procedures are needed (e.g., adrenal vein sampling). 1, 2

• Surgical intervention is being considered (e.g., unilateral adrenalectomy for primary aldosteronism). 1, 2

• BP remains uncontrolled after ≥ 6 months of optimal medical therapy. 1