What are the diagnostic and treatment orders for a patient with secondary hypertension?

Diagnostic and Treatment Orders for Secondary Hypertension

Screen all patients with confirmed hypertension using plasma aldosterone-to-renin ratio (ARR), as this represents the most significant recent guideline change and primary aldosteronism is the most common treatable cause of resistant hypertension (8-20% of cases). 1, 2

Initial Screening Orders

Basic Laboratory Panel (Required for All Suspected Cases)

• Serum electrolytes (sodium, potassium) - hypokalemia strongly suggests primary aldosteronism 1, 2
• Serum creatinine and estimated glomerular filtration rate (eGFR) 1, 2
• Fasting blood glucose or HbA1c 1, 2
• Urinalysis with microscopy - looking for blood, protein, and casts suggesting renal parenchymal disease 1, 2
• Urinary albumin-to-creatinine ratio 2
• Thyroid-stimulating hormone (TSH) 2
• Fasting lipid panel 1
• 12-lead electrocardiogram - to assess for left ventricular hypertrophy and strain patterns 1, 2

Universal Endocrine Screening (New Recommendation)

• Plasma aldosterone-to-renin ratio (ARR) - the European Society of Cardiology 2024 guidelines now recommend this for ALL adults with confirmed hypertension (Class IIa recommendation), representing a major shift from selective screening 2
• Obtain morning sample with patient seated for 5-15 minutes 1
• Critical caveat: Withdraw mineralocorticoid receptor antagonists for 4-6 weeks before testing, as they falsely elevate aldosterone; beta-blockers and direct renin inhibitors lower renin and can cause false-positive results 2

Targeted Investigations Based on Clinical Clues

When to Order Renovascular Disease Workup

Order when patient presents with: 1, 2

• Abrupt onset or sudden worsening of previously controlled hypertension
• Flash pulmonary edema (especially recurrent)
• Serum creatinine increase ≥50% within one week of starting ACE inhibitor or ARB
• Severe hypertension with unilateral smaller kidney or kidney size difference >1.5 cm
• Abdominal systolic-diastolic bruit on examination

Initial test: Renal ultrasound with Duplex Doppler 1, 2 Confirmatory test: CT or MR renal angiography 1, 2 Gold standard: Bilateral selective renal intra-arterial angiography 1

When to Order Pheochromocytoma Workup

Order when patient presents with: 1, 2

• Episodic symptoms (headaches, palpitations, diaphoresis)
• Labile or paroxysmal hypertension
• Hypertensive crisis during anesthesia or surgery
• Family history of pheochromocytoma or multiple endocrine neoplasia

Screening test: 24-hour urinary metanephrines and catecholamines OR plasma metanephrines 1, 2 Localization: Abdominal/adrenal CT or MRI after biochemical confirmation 1

When to Order Sleep Apnea Evaluation

Order when patient presents with: 1, 2

• Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including diuretic)
• Snoring, witnessed apneas, daytime sleepiness
• Obesity (BMI >30) with Mallampati class III-IV airway
• Non-dipping nocturnal blood pressure pattern on ambulatory monitoring

Screening test: Home sleep apnea testing or polysomnography 2

When to Order Cushing Syndrome Workup

Order when patient presents with: 1, 2

• Central obesity with thin extremities
• Purple striae (>1 cm wide)
• Easy bruising, proximal muscle weakness
• Moon facies, buffalo hump, supraclavicular fat pads

Screening tests: 24-hour urinary free cortisol, late-night salivary cortisol, or 1-mg overnight dexamethasone suppression test 1

Confirmatory Testing for Primary Aldosteronism

When ARR is positive (ratio >20 with elevated aldosterone and suppressed renin): 1, 2

1. Confirmatory tests (choose one):

   • Oral sodium loading test with 24-hour urine aldosterone
   • IV saline infusion test with plasma aldosterone at 4 hours 1

2. Localization studies (after biochemical confirmation):

   • Adrenal CT scan (without and with contrast) 1
   • Adrenal vein sampling - mandatory before considering unilateral adrenalectomy to distinguish unilateral from bilateral disease 1, 2

Advanced Imaging Orders

Echocardiography

Order to assess: 1, 2

• Left ventricular hypertrophy (more sensitive than ECG)
• Left ventricular systolic and diastolic function
• Aortic coarctation (in young patients)
• Valvular abnormalities

Fundoscopy

Perform to evaluate for: 2

• Retinal arteriolar narrowing
• Arteriovenous nicking
• Hemorrhages, exudates, or papilledema (indicating hypertensive emergency)

Treatment Orders Based on Specific Diagnosis

Primary Aldosteronism

Unilateral disease (adenoma): 2, 3

• Unilateral laparoscopic adrenalectomy - curative in most cases
• Pre-operative preparation with spironolactone 25-50 mg daily for 4-6 weeks

Bilateral disease (hyperplasia): 2, 3

• Spironolactone 50-100 mg daily (most widely used mineralocorticoid receptor antagonist)
• Alternative: Eplerenone 50-100 mg daily (fewer side effects but more expensive)
• Target potassium 4.0-5.0 mmol/L

Renovascular Disease

Atherosclerotic renal artery stenosis: 2, 3

• Medical therapy is preferred - optimize cardiovascular risk management
• Statin therapy (high-intensity)
• Antiplatelet therapy (aspirin 81 mg daily)
• ACE inhibitor or ARB (monitor creatinine closely - acceptable increase up to 30%)
• Renal artery stenting - reserved only for flash pulmonary edema or rapidly declining renal function

Fibromuscular dysplasia: 2, 3

• Percutaneous transluminal renal angioplasty WITHOUT stenting - treatment of choice
• High cure rate in young patients

Obstructive Sleep Apnea

Moderate to severe OSA (AHI >15): 2, 3

• Continuous positive airway pressure (CPAP) therapy - first-line treatment
• Target weight loss if BMI >25 (5-10% reduction can significantly improve BP)
• Mandibular advancement devices for mild-moderate OSA or CPAP intolerance

Pheochromocytoma

Pre-operative preparation (essential to prevent hypertensive crisis): 1

• Alpha-blockade with phenoxybenzamine 10-20 mg twice daily, titrate up over 7-14 days
• Add beta-blockade ONLY AFTER adequate alpha-blockade (to prevent unopposed alpha stimulation)
• Surgical resection - laparoscopic adrenalectomy when feasible

Resistant Hypertension Protocol (After Excluding Secondary Causes)

When BP remains >140/90 mmHg despite optimal 3-drug regimen: 2, 3

1. Optimize current regimen:

   • Ensure maximum tolerated doses
   • Confirm medication adherence
   • Use thiazide-like diuretics (chlorthalidone 12.5-25 mg or indapamide 1.25-2.5 mg) rather than hydrochlorothiazide 2, 3
   • Switch to loop diuretic (furosemide 40-80 mg twice daily) if eGFR <30 mL/min/1.73m² 2, 3

2. Add fourth-line agent:

   • Spironolactone 25-50 mg daily - most effective fourth-line agent 2, 3
   • Prerequisites: Serum potassium <4.5 mmol/L AND eGFR >45 mL/min/1.73m² 2, 3
   • Monitor potassium and creatinine at 1 week, then monthly for 3 months

3. Alternative fourth-line agents (if spironolactone contraindicated):

   • Doxazosin 4-8 mg daily
   • Bisoprolol 5-10 mg daily (if not already on beta-blocker)

Critical Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB) - increases risk of hyperkalemia, hypotension, and acute kidney injury without additional benefit 2
• Do not perform expensive imaging (CT, MRI, angiography) before completing basic laboratory screening 2
• Avoid missing medication-induced hypertension - review all medications, supplements, and substances (NSAIDs, decongestants, oral contraceptives, licorice, cocaine, amphetamines) before extensive workup 2
• Do not delay diagnosis - vascular remodeling from prolonged hypertension can result in residual hypertension even after treating the underlying cause 2
• Recognize that 5-10% of all hypertensive patients have secondary causes, increasing to 10-20% in resistant cases - maintain high index of suspicion 4, 5

Indications for Specialist Referral

Refer to hypertension specialist or appropriate subspecialist when: 2, 4

• Positive screening for secondary hypertension requiring confirmatory testing
• Resistant hypertension uncontrolled despite optimal 4-drug regimen
• Suspected pheochromocytoma (refer to endocrinology)
• Confirmed primary aldosteronism requiring adrenal vein sampling (refer to endocrinology/interventional radiology)
• Renovascular disease requiring intervention (refer to vascular surgery/interventional radiology)
• Age <30 years with hypertension (higher likelihood of secondary cause)
• Hypertensive emergency with end-organ damage