In a patient with migraines, hypertension, elevated plasma renin activity and hyperaldosteronism, what is the most likely cause and how should it be evaluated and managed?

Hyperaldosteronism with High Renin in a Patient with Migraines and Hypertension

Most Likely Diagnosis

This presentation represents secondary hyperaldosteronism driven by an underlying condition that is stimulating both renin and aldosterone production, most likely renovascular disease (renal artery stenosis) or severe hypertensive kidney damage. 1 The combination of elevated renin and elevated aldosterone distinguishes this from typical primary aldosteronism, where renin is suppressed. 1

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Understanding the Pathophysiology

The key to this case is recognizing that high renin with high aldosterone indicates the renin-angiotensin-aldosterone system is being appropriately activated by a stimulus such as:

• Renal artery stenosis (most common in patients >60 years with resistant hypertension) 2
• Hypertensive kidney damage causing renin escape from suppression 1
• Pheochromocytoma (rare but can cause hyperreninemia with secondary hyperaldosteronism) 3

In contrast, primary aldosteronism typically shows suppressed renin due to aldosterone-mediated volume expansion. 4, 1 However, severe hypertensive kidney damage from longstanding primary aldosteronism can cause renin to "escape" suppression, creating this atypical pattern. 1

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Diagnostic Evaluation Algorithm

Step 1: Rule Out Renovascular Disease First

Order renal Doppler ultrasound as the initial imaging test for renal artery stenosis. 5 This is the most common surgically correctable cause in this presentation.

• If Doppler is inconclusive or clinical suspicion remains high, proceed to CT angiography or MRI of the renal arteries. 5
• Clinical clues favoring renal artery stenosis include: age >60 years, acute change in blood pressure control, flash pulmonary edema, or age <40 years (suggesting fibromuscular dysplasia). 5

Step 2: Assess for Pheochromocytoma

Check 24-hour urinary or plasma metanephrines if the patient has paroxysmal symptoms (episodic headaches, palpitations, sweating, pallor). 5 Pheochromocytoma can cause hyperreninemia with secondary hyperaldosteronism. 3

• The migraines mentioned in this case warrant consideration of pheochromocytoma, especially if they are episodic and associated with hypertensive crises.

Step 3: Evaluate Renal Function

Check plasma creatinine, eGFR, and urinalysis to assess for renal parenchymal disease. 5 Hypertensive kidney damage can cause renin to escape suppression even in the setting of hyperaldosteronism. 1

• Patients with severe hypertension and elevated creatinine may have developed secondary renal damage that is driving renin production. 1

Step 4: Consider Atypical Primary Aldosteronism

If renovascular disease and pheochromocytoma are excluded, this may represent primary aldosteronism with renin escape due to hypertensive kidney damage. 1

• Confirmatory testing is still warranted despite the elevated renin, using oral salt-loading test with 24-hour urine aldosterone measurement or IV saline suppression test. 6
• Ensure the patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 5, 6
• The aldosterone-to-renin ratio may be less reliable in this scenario, but an elevated ratio with disproportionately high aldosterone still suggests autonomous aldosterone production. 1

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Management Strategy

If Renovascular Disease is Confirmed:

Medical therapy is first-line treatment for atherosclerotic renal artery stenosis, with revascularization (angioplasty ± stenting) reserved for medical management failure or fibromuscular dysplasia. 5

• Use angiotensin receptor blockers (ARBs) or ACE inhibitors as first-line agents for high-renin hypertension with secondary hyperaldosteronism. 7
• Alternative: Aliskiren (direct renin inhibitor) if ARBs/ACE inhibitors are not tolerated. 7

If Pheochromocytoma is Confirmed:

Refer to surgery for adrenalectomy after appropriate alpha-blockade preparation. 2

If Atypical Primary Aldosteronism is Confirmed:

Start spironolactone 50-100 mg daily as first-line medical therapy. 5, 1

• Monitor serum creatinine and potassium closely within 1 week of initiation, as patients with renal impairment may develop significant hyperkalemia and creatinine elevation. 1
• If unilateral disease is confirmed by adrenal venous sampling, laparoscopic adrenalectomy can be curative, though hypertension may persist if hypertensive kidney damage has already occurred. 1

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Critical Pitfalls to Avoid

• Do not dismiss primary aldosteronism solely because renin is elevated. Severe hypertensive kidney damage can cause renin to escape suppression. 1
• Do not start spironolactone without close monitoring in patients with elevated creatinine, as they are at high risk for severe hyperkalemia and further creatinine elevation. 1
• Do not rely on the aldosterone-to-renin ratio alone when renin is elevated; confirmatory testing is essential. 6
• Do not assume all cases require surgery. Treatment should be guided by identifying the underlying cause (renovascular vs. primary aldosteronism with renin escape). 1

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Addressing the Migraines

The migraines in this patient may be:

• Related to pheochromocytoma if they are episodic and associated with hypertensive crises (check metanephrines). 3
• Secondary to severe hypertension itself, which should improve with blood pressure control regardless of the underlying cause.
• Unrelated to the hypertension, though less likely given the constellation of findings.