In a 25‑year‑old patient on an angiotensin‑receptor blocker who experiences episodic severe hypertension (up to 170/140 mm Hg) and milder elevations (140/100 mm Hg), extreme fatigue, elevated C‑reactive protein (17.4 mg/L), normal adrenal MRI with contrast and normal cortisol, and has very high plasma renin activity with proportionally elevated aldosterone, what is the most likely diagnosis and recommended management?

Renovascular Hypertension (Fibromuscular Dysplasia) is the Most Likely Diagnosis

In this 25-year-old with episodic severe hypertension, elevated CRP, extreme fatigue, normal adrenal imaging, and very high plasma renin activity with proportionally elevated aldosterone (secondary aldosteronism), renovascular hypertension due to fibromuscular dysplasia is the most likely diagnosis, and you should proceed immediately with renal artery imaging (CT angiography or MRI angiography from head to pelvis) followed by referral to a hypertension specialist for potential revascularization. 1

Why This is NOT Primary Aldosteronism

The key distinguishing feature here is very high plasma renin activity with proportionally elevated aldosterone—this defines secondary aldosteronism, not primary aldosteronism. 1

• In primary aldosteronism, aldosterone is inappropriately high relative to suppressed renin—the hallmark is autonomous aldosterone production that suppresses the renin-angiotensin system. 1, 2
• When both renin and aldosterone are proportionally elevated together, the renin-angiotensin-aldosterone system is being appropriately activated by decreased renal perfusion. 1
• The aldosterone-to-renin ratio (ARR) would be normal or low in this scenario, ruling out primary aldosteronism. 2, 3

Why Renovascular Hypertension (Fibromuscular Dysplasia) Fits Perfectly

Demographics and Clinical Presentation

• Fibromuscular dysplasia (FMD) is the leading cause of renovascular hypertension in young women and patients under 30 years of age. 1
• The episodic nature of severe hypertension (170/140 during "major flares" and 140/100 during "mild flares") is characteristic of renovascular hypertension, where BP fluctuates with changes in renal perfusion pressure. 1
• Extreme fatigue and elevated CRP (17.4 mg/L) reflect the systemic inflammatory response and end-organ effects of severe, poorly controlled hypertension. 1

Laboratory Findings

• Very elevated renin levels are a classic (though not highly sensitive) clue to renovascular hypertension. 1
• When renal artery stenosis decreases perfusion pressure, the juxtaglomerular apparatus releases massive amounts of renin, which drives proportional aldosterone elevation—this is physiologic secondary aldosteronism. 1
• Normal adrenal imaging and normal cortisol exclude adrenal causes (pheochromocytoma, Cushing syndrome, primary aldosteronism). 1

Critical Caveat About ARB Use

• The patient is already on an angiotensin-receptor blocker (ARB), which normally raises renin levels. 4
• However, if renin remains very high despite ARB therapy, this suggests true pathologic renin hypersecretion from renal artery stenosis, not just drug effect. 5
• ARBs typically increase renin 2-3 fold; markedly elevated renin beyond this expected increase points to renovascular disease. 4

Recommended Diagnostic Workup

Immediate Imaging

Order renal artery imaging as the next diagnostic step: 1

• CT angiography of the abdomen (preferred for speed and availability) or MRI angiography to visualize renal artery stenosis. 1
• Look for the classic "string of beads" appearance of FMD on imaging. 1
• Renal artery Doppler ultrasound with bilateral assessment of renal arterial resistive index is an alternative if CT/MRI are contraindicated, though less sensitive. 1

Systemic FMD Evaluation

• Because fibromuscular dysplasia is a systemic vascular disease, CT or MRI angiography from head to pelvis is recommended to assess for involvement of carotid, vertebral, and other arteries. 1
• FMD can affect multiple vascular beds and increase stroke risk. 1

Rule Out "Bystander" Stenosis

• Not all renal artery stenosis causes renovascular hypertension—some patients have incidental stenosis without hemodynamically significant disease. 1
• The combination of very high renin, young age, severe episodic hypertension, and no other secondary cause makes true FMD-renovascular hypertension highly likely rather than bystander stenosis. 1

Recommended Management

Referral to Hypertension Specialist

• All patients with suspected renovascular hypertension should be referred to a hypertension specialist or vascular specialist for evaluation and treatment planning. 1
• Treatment decisions (medical management vs. revascularization) require specialized expertise. 1

Revascularization Considerations

• For hemodynamically significant FMD-renovascular hypertension in young patients, percutaneous transluminal angioplasty (without stenting) is the treatment of choice and can be curative. 1
• Success rates for BP improvement approach 80-90% in FMD when treated early. 1
• Continued ARB therapy is appropriate while awaiting imaging and specialist evaluation. 1

Blood Pressure Control in the Interim

• Continue the current ARB for BP control and renal protection. 1
• Add additional agents as needed (calcium channel blockers, alpha-blockers) to control severe hypertensive episodes. 1, 2
• Avoid abrupt discontinuation of antihypertensive therapy, as this can precipitate hypertensive crisis in renovascular disease. 1

Common Pitfalls to Avoid

• Do not assume primary aldosteronism based solely on elevated aldosterone—always check if renin is suppressed (primary) or elevated (secondary). 1, 2, 3
• Do not delay imaging in young patients with severe hypertension and very high renin—early diagnosis and treatment of FMD prevent irreversible renal damage and cardiovascular complications. 1
• Do not interpret high renin as "just ARB effect" when levels are markedly elevated beyond expected drug response—this suggests true pathology. 5, 4
• Do not forget to screen for systemic FMD involvement (carotid, vertebral arteries) once renal FMD is confirmed. 1