What is the most likely diagnosis and recommended management for a patient with severe hypertension, neurologic manifestations, elevated aldosterone and renin, and normal imaging of the kidneys, adrenal glands, and heart?

Likely Diagnosis: Primary Aldosteronism with Hypertensive Emergency

The most likely diagnosis is primary aldosteronism presenting as a hypertensive emergency with neurologic manifestations, despite the paradoxical finding of elevated renin. This presentation requires immediate ICU admission with IV antihypertensive therapy while simultaneously pursuing confirmatory testing for primary aldosteronism. 1

Understanding the Paradoxical Laboratory Pattern

Why Both Aldosterone AND Renin Are Elevated

• Severe hypertensive kidney damage can cause renin to "escape" suppression even in the presence of autonomous aldosterone production—this occurs when hypertensive arteriolosclerosis damages the kidneys sufficiently to trigger secondary renin release. 2

• The aldosterone-to-renin ratio (ARR) remains the key diagnostic parameter, not the absolute renin value; an elevated ARR with aldosterone ≥10–15 ng/dL still indicates primary aldosteronism even when renin is not fully suppressed. 3, 4

• In patients with severe, longstanding hypertension from primary aldosteronism, hypertensive nephropathy develops and the damaged kidneys begin secreting renin inappropriately, creating a mixed picture that mimics both primary and secondary hyperaldosteronism. 2

• This phenomenon is well-documented: three published cases showed primary aldosteronism patients with normal-to-high PRA due to hypertensive kidney damage, all with elevated serum creatinine and all responding to spironolactone (though with marked hyperkalemia and creatinine rise). 2

The Neurologic Symptoms Are the Critical Red Flag

• Neurologic symptoms combined with severe hypertension define this as a hypertensive emergency requiring immediate intervention, not simply resistant hypertension that can be worked up outpatient. 1, 5

• The neurologic manifestations likely represent hypertensive encephalopathy or posterior reversible encephalopathy syndrome (PRES), both of which occur in 10–15% of malignant hypertension cases and can progress to seizures, coma, and death without urgent treatment. 5

• Diplopia, headache, visual disturbances, altered mental status, or any focal neurologic finding in the setting of severe hypertension constitutes acute target-organ damage and mandates ICU admission with continuous arterial-line monitoring. 1, 5

Immediate Management Algorithm

Step 1: Confirm Hypertensive Emergency (First 15 Minutes)

• Perform rapid bedside assessment for acute target-organ damage: brief neurologic exam (mental status, visual changes, focal deficits), fundoscopy (look for bilateral retinal hemorrhages, cotton-wool spots, papilledema), cardiac exam (pulmonary edema, chest pain), and check for oliguria. 1

• Order stat labs: hemoglobin, platelets, creatinine, sodium, potassium, LDH, haptoglobin, urinalysis with microscopy, troponin, and ECG. 1, 5

• Obtain emergent brain MRI with contrast to exclude intracranial hemorrhage, acute stroke, or PRES; do not delay imaging while attempting BP reduction. 5

Step 2: ICU Admission and IV Antihypertensive Therapy (Within 30 Minutes)

• Admit to ICU immediately with continuous arterial-line BP monitoring (Class I recommendation). 1

• Initiate IV nicardipine as first-line agent: start 5 mg/h, titrate by 2.5 mg/h every 15 minutes to maximum 15 mg/h; nicardipine is preferred because it preserves cerebral blood flow without raising intracranial pressure. 1, 5

• Alternative: IV labetalol 10–20 mg bolus over 1–2 minutes, repeat or double every 10 minutes (max cumulative 300 mg), or continuous infusion 2–8 mg/min; labetalol is particularly useful if tachycardia is present. 1

• Target BP reduction: lower mean arterial pressure by 20–25% within the first hour, then to ≤160/100 mmHg over 2–6 hours if stable, then gradual normalization over 24–48 hours. 1, 5

• Avoid systolic drops >70 mmHg to prevent cerebral, renal, or coronary ischemia, especially in chronic hypertensives with altered autoregulation. 1

Step 3: Confirmatory Testing for Primary Aldosteronism (After Stabilization)

• Do NOT wait for BP normalization to pursue the diagnosis—primary aldosteronism screening and confirmatory testing can proceed once the patient is hemodynamically stable (typically 24–48 hours). 4

• Repeat ARR measurement after correcting hypokalemia (target K⁺ 4.0–5.0 mEq/L) and while on non-interfering antihypertensives (nicardipine and labetalol minimally affect ARR). 4

• Proceed directly to confirmatory testing if ARR remains elevated (≥20–30 with aldosterone ≥10–15 ng/dL): options include IV saline suppression test (2L NS over 4 hours, failure to suppress aldosterone <5 ng/dL confirms diagnosis) or oral sodium loading with 24-hour urine aldosterone. 3, 4

• Critical point: In patients with renal impairment (elevated creatinine), use the oral sodium loading test rather than IV saline to avoid volume overload; collect 24-hour urine for aldosterone while patient consumes high-salt diet (>200 mEq/day sodium). 4

Step 4: Subtype Determination (Before Definitive Treatment)

• Obtain non-contrast CT of adrenal glands as initial imaging to identify unilateral adenoma versus bilateral hyperplasia. 4

• Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease—up to 25% of patients would undergo unnecessary surgery based on CT findings alone. 4

• Exception: AVS may be omitted in patients <40 years with unilateral adenoma on CT and markedly elevated aldosterone, as bilateral hyperplasia is rare in this population. 4

Why This Is NOT Renovascular Hypertension

• Renovascular hypertension causes HIGH renin with NORMAL or LOW aldosterone (secondary hyperaldosteronism), the opposite of this patient's pattern. 3

• Both aldosterone AND renin are elevated here, which is atypical for either pure primary aldosteronism or pure renovascular disease—this suggests primary aldosteronism with superimposed hypertensive nephropathy. 2

• Renal artery stenosis should still be excluded as part of the secondary hypertension workup, but it would not explain the elevated aldosterone. 3

Why This Is NOT Pheochromocytoma

• Pheochromocytoma causes episodic hypertension with paroxysmal symptoms (palpitations, diaphoresis, headache), not sustained severe hypertension with elevated aldosterone. 3

• Pheochromocytoma does not cause elevated aldosterone or suppressed/elevated renin—it causes catecholamine excess. 3

• Screen for pheochromocytoma anyway (24-hour urine or plasma metanephrines) because 20–40% of malignant hypertension cases have identifiable secondary causes, and multiple etiologies can coexist. 1, 4

Definitive Treatment Based on Subtype

If Unilateral Disease (Adenoma or Unilateral Hyperplasia)

• Laparoscopic unilateral adrenalectomy is the treatment of choice—it improves BP in virtually 100% of patients and cures hypertension in approximately 50%. 4

• Hypertension cure rates are higher with early diagnosis; delayed treatment allows irreversible vascular remodeling that persists even after removing the aldosterone source. 4

If Bilateral Disease (Bilateral Hyperplasia)

• Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of lifelong treatment—spironolactone 50–100 mg once daily, titrated up to 300–400 mg daily if needed. 4

• Eplerenone is an alternative with fewer anti-androgenic side effects but requires twice-daily dosing and is less potent than spironolactone. 4

• Monitor potassium closely when starting MRAs in patients with renal impairment—these patients are at high risk for severe hyperkalemia, especially if already on ACE inhibitors or ARBs. 4, 2

Critical Pitfalls to Avoid

• Do not dismiss the elevated renin as excluding primary aldosteronism—hypertensive kidney damage can cause renin to escape suppression while aldosterone remains autonomously elevated. 2

• Do not delay ICU admission and IV therapy while pursuing the endocrine workup—the neurologic symptoms indicate acute target-organ damage requiring immediate intervention. 1, 5

• Do not rely on hypokalemia to make or exclude the diagnosis—approximately 50% of primary aldosteronism cases are normokalemic. 4, 6

• Do not proceed to adrenalectomy based on CT findings alone—AVS is mandatory to prevent unnecessary surgery in patients with bilateral disease and incidental adrenal nodules. 4

• Do not use ACE inhibitors or ARBs during the acute phase in patients with elevated creatinine—they can cause precipitous renal function decline in volume-depleted states. 1

• Do not assume normal imaging excludes primary aldosteronism—bilateral micronodular hyperplasia and aldosterone-producing microadenomas can be invisible on CT. 7

Prognosis and Long-Term Considerations

• Untreated hypertensive emergencies carry >79% one-year mortality with median survival of only 10.4 months. 1

• Primary aldosteronism causes dramatically worse cardiovascular outcomes than essential hypertension at equivalent BP levels: 3.7-fold increase in heart failure, 4.2-fold increase in stroke, 6.5-fold increase in MI, and 12.1-fold increase in atrial fibrillation. 4

• Even after successful treatment, some patients have residual hypertension due to irreversible vascular remodeling from delayed diagnosis—emphasizing the importance of early detection and treatment. 4

• Schedule monthly follow-up until target BP <130/80 mmHg is achieved and organ-damage findings regress. 1