What is the approach to managing secondary hypertension?

Approach to Secondary Hypertension

When to Screen for Secondary Hypertension

Screen for secondary hypertension in patients with early-onset hypertension (<30 years), resistant hypertension (uncontrolled on 3+ drugs including a diuretic), sudden deterioration in previously controlled BP, hypertensive urgency/emergency, or strong clinical clues suggesting a specific cause. 1, 2

Key Clinical Clues by Cause

• Primary aldosteronism: Unprovoked hypokalemia, muscle weakness/cramps, family history of early-onset hypertension, or resistant hypertension (affects 8-20% of resistant cases) 1, 2
• Renovascular disease: Abrupt onset or worsening hypertension, flash pulmonary edema, early-onset hypertension in women (suggests fibromuscular dysplasia), acute rise in creatinine >50% within one week of starting ACE inhibitor/ARB, unilateral small kidney or >1.5 cm size difference between kidneys 1, 2, 3
• Renal parenchymal disease: History of urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, or family history of polycystic kidney disease 2
• Obstructive sleep apnea: Snoring, daytime sleepiness, obesity, non-dipping or reverse-dipping pattern on 24-hour BP monitoring (present in 25-50% of resistant hypertension) 1, 2
• Pheochromocytoma: Episodic headaches, palpitations, sweating, labile hypertension 2

Initial Diagnostic Workup

Basic Screening (All Suspected Cases)

Before pursuing expensive imaging or specialized testing, complete basic laboratory screening 1, 2:

• Blood tests: Serum creatinine, sodium, potassium, eGFR, TSH, fasting glucose or HbA1c, lipid panel 1, 2
• Urine tests: Dipstick urinalysis for blood and protein, urinary albumin-to-creatinine ratio 1, 2
• 12-lead ECG 1, 2
• Thorough history and physical examination focusing on duration of hypertension, medication use (including NSAIDs, steroids, contraceptives), symptoms suggesting specific causes, and physical findings like abdominal bruits, delayed femoral pulses, or cushingoid features 1

Exclude Pseudoresistant Hypertension First

In patients with resistant hypertension, rule out poor adherence, white-coat effect, and drug/substance-induced hypertension before extensive workup for secondary causes 1, 2

Targeted Testing Based on Clinical Suspicion

Primary Aldosteronism

• Screening test: Plasma aldosterone-to-renin ratio (ARR) 1, 2
• Important: Review prior potassium levels (hypokalemia increases likelihood); discontinue interfering medications when possible (beta-blockers, ACE inhibitors, ARBs, potassium-sparing diuretics cause false negatives; alpha-2 agonists, NSAIDs cause false positives) 1
• Confirmatory testing: Intravenous saline suppression test 1, 2
• Imaging: Adrenal CT scan 1, 2
• Lateralization: Adrenal vein sampling to distinguish unilateral from bilateral disease 1, 2

Renovascular Disease

• Initial imaging: Renal Doppler ultrasound 1, 2
• Definitive imaging: CT angiography or MRI angiography of renal arteries (choice depends on renal function) 1, 2
• Monitor: Acute change in eGFR after starting RAS blocker, renin levels 1

Obstructive Sleep Apnea

• Screening: Validated questionnaires (though lack of symptoms doesn't rule out OSA) 1
• Diagnostic testing: Home sleep apnea testing (level 3 sleep study) or overnight polysomnography 1, 2
• Severity grading: Mild (AHI <15), moderate (AHI 15-30), severe (AHI >30) 1

Pheochromocytoma/Paraganglioma

• Screening test: 24-hour urinary metanephrines and normetanephrines, or plasma metanephrines 1, 2
• Imaging: Abdominal/pelvic CT or MRI if biochemical testing positive 1, 2

Other Causes

• Cushing syndrome: 24-hour urinary free cortisol, low-dose dexamethasone suppression test, followed by pituitary/abdominal imaging 1, 2
• Coarctation of aorta: Echocardiogram, CT angiography 1
• Hyperparathyroidism: Parathyroid hormone, calcium, phosphate 1

Treatment Approach by Specific Cause

Primary Aldosteronism

• Unilateral disease: Surgical adrenalectomy is treatment of choice 1, 2, 4
• Bilateral disease or non-surgical candidates: Mineralocorticoid receptor antagonists (spironolactone 50-100 mg daily or eplerenone) 1, 2, 4
• Spironolactone is FDA-approved for primary hyperaldosteronism and can be used for short-term preoperative treatment or long-term maintenance 4

Renovascular Disease

• Atherosclerotic disease: Medical therapy with optimal cardiovascular risk management is recommended 1, 2
• Fibromuscular dysplasia: Percutaneous transluminal renal angioplasty without stenting is treatment of choice 1, 2
• Atherosclerotic stenosis with specific indications: Consider renal angioplasty with stenting 1
• Monitor renal function carefully when using RAS blockers 2
• Note: Since fibromuscular dysplasia is systemic, CT or MRI angiography from head to pelvis is recommended 1

Obstructive Sleep Apnea

• Weight loss for obese patients 1, 2
• CPAP therapy for moderate-severe OSA 2
• Mandibular advancement devices as alternative 5

Renal Parenchymal Disease

• Address underlying renal disease with specific treatments 2
• Monitor renal function and adjust antihypertensive therapy accordingly 2

Management of Resistant Hypertension

When secondary causes are excluded or treated but hypertension persists 1, 2, 5:

1. Optimize lifestyle modifications: Sodium restriction, weight loss, limit alcohol 1, 2
2. Maximize diuretic therapy: Use thiazide-like diuretics (chlorthalidone, indapamide) rather than thiazides; switch to loop diuretics if eGFR <30 ml/min/1.73m² 2, 5
3. Add spironolactone as fourth-line agent if serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1, 2, 5, 4
4. Alternative agents if spironolactone contraindicated: Amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1
5. Consider renal denervation for resistant hypertension uncontrolled despite three-drug combination 2

Referral and Follow-up

• Refer to specialist centers with expertise in secondary hypertension for complex cases, resistant hypertension, or when specific interventions are needed 1, 2
• Regular monitoring of BP, renal function, and electrolytes is essential 2
• Lifelong treatment may be necessary even after addressing the underlying cause, as BP rarely returns completely to normal due to irreversible vascular remodeling 6

Critical Pitfalls to Avoid

• Delayed diagnosis leads to vascular remodeling affecting renal function and resulting in residual hypertension even after treating the underlying cause; early detection is crucial 2, 6
• Don't perform expensive imaging before completing basic laboratory screening 2
• Don't combine two RAS blockers (ACE inhibitor + ARB) 2
• Secondary hypertension is often underrecognized despite affecting 5-10% of hypertensive patients 1, 2, 7
• Consider medication-induced hypertension (NSAIDs, steroids, contraceptives) before extensive workup 1, 2