What labs are recommended to evaluate secondary causes of hypertension?

From the Guidelines

To evaluate secondary causes of hypertension, I recommend a comprehensive laboratory workup including basic metabolic panel (BMP), complete blood count (CBC), urinalysis, and thyroid stimulating hormone (TSH), as well as specific tests such as plasma aldosterone concentration, plasma renin activity, 24-hour urine collection for metanephrines, and cortisol levels or dexamethasone suppression testing, as outlined in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

The BMP should assess electrolytes, kidney function (creatinine, BUN), and glucose levels. Additional specific tests include:

• Plasma aldosterone concentration and plasma renin activity to evaluate for primary aldosteronism, especially in patients with hypokalemia
• 24-hour urine collection for metanephrines, catecholamines, and vanillylmandelic acid (VMA) to screen for pheochromocytoma in patients with episodic hypertension
• Cortisol levels or dexamethasone suppression testing to evaluate for Cushing's syndrome
• Sleep study for patients with symptoms suggesting sleep apnea

These tests are crucial because identifying secondary causes can lead to specific treatments that may cure or better control hypertension. The timing of these tests is important - some medications can interfere with results, so coordination with a healthcare provider regarding medication adjustments before testing is essential for accurate results 1.

Some key points to consider when evaluating secondary causes of hypertension include:

• Resistant hypertension
• Sudden deterioration in BP control
• Hypertensive urgency and emergency
• High probability of secondary hypertension based on strong clinical clues
• Early onset hypertension (<30 years of age) in particular in the absence of hypertension risk factors

It is also important to consider referring patients with suspected secondary hypertension to a specialist center with access to appropriate expertise and resources 1.

The 2024 ESC guidelines provide a comprehensive outline of the tests that should be used to screen for secondary hypertension in the presence of suggestive signs, symptoms, or medical history, including:

• Primary aldosteronism: Aldosterone-to-renin ratio, prior potassium levels
• Renovascular hypertension: Renal doppler ultrasound, abdominal CT angiogram or MRI
• Phaeochromocytoma/paraganglioma: 24 h urinary and/or plasma metanephrine and normetanephrine
• Obstructive sleep apnoea syndrome: Overnight ambulatory polysomnography
• Renal parenchymal disease: Plasma creatinine, sodium, and potassium, eGFR, urine dipstick for blood and protein, urinary albumin-to-creatinine ratio, renal ultrasound
• Cushing’s syndrome: 24 h urinary free cortisol, low-dose dexamethasone suppression test
• Thyroid disease (hyper- or hypothyroidism): TSH
• Hyperparathyroidism: Parathyroid hormone, calcium and phosphate
• Coarctation of the aorta: Echocardiogram, aortic CT angiogram 1.

From the Research

Laboratory Tests for Secondary Causes of Hypertension

The following laboratory tests are recommended to evaluate secondary causes of hypertension:

• Electrolytes, urea, creatinine 2
• Aldosterone:renin ratio, which is best done before starting potentially interfering antihypertensive drugs 2
• Urinalysis and the urine albumin:creatinine ratio 2 These tests can help identify common causes of secondary hypertension, such as renal disease, primary aldosteronism, and obstructive sleep apnea.

Clinical Clues and Further Investigation

Abnormal results from the initial laboratory tests should prompt further investigation 2. Clinical clues obtained from a careful history, physical examination, and laboratory assessment guide the clinician through an appropriate evaluation for identifiable causes 3. A combination of the clinician's index of suspicion and interpretation of data provide guidance in the choice of diagnostic tests and therapies to target the mechanisms contributing to poor blood pressure control 3.

Specific Causes and Associations

The most common causes and associations of secondary hypertension include:

• Renal disease 2, 4, 3
• Primary aldosteronism 2, 4, 5
• Obstructive sleep apnea 2, 4, 5
• Drug-induced hypertension 5
• Endocrinopathies, such as pheochromocytoma or thyroid disease 3 These causes can be evaluated and managed with targeted therapies to supplement first-line antihypertensive agents 5.