What is the best management plan for a patient with high‑renin, sodium‑sensitive hypertension due to aldosterone excess who also has a mood disorder, ensuring that both antihypertensive and psychiatric medications do not worsen blood pressure or sodium balance?

Management of High-Renin, Sodium-Sensitive Hypertension with Aldosterone Excess and Comorbid Mood Disorder

For a patient with high-renin, aldosterone-excess hypertension who also has a mood disorder, initiate spironolactone 25 mg daily as first-line therapy while avoiding beta-blockers and calcium channel blockers for blood pressure control, and coordinate psychiatric medication selection to favor angiotensin-converting enzyme inhibitors or angiotensin receptor blockers if additional antihypertensive agents are needed. 1, 2, 3

Understanding the Unusual Presentation

This clinical scenario represents an atypical form of primary aldosteronism where renin is not suppressed despite aldosterone excess. 4

• High renin with high aldosterone suggests secondary hypertensive kidney damage has developed, causing renin to "escape" from the usual aldosterone-mediated suppression. 4
• The aldosterone-to-renin ratio (ARR) may still be elevated due to disproportionately high aldosterone levels relative to renin, even when renin is not frankly suppressed. 4
• This pattern occurs in patients with severe, longstanding hypertension who have developed hypertensive nephrosclerosis or renal arteriolosclerosis. 4

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis:

• Calculate the ARR—even with elevated renin, if aldosterone is disproportionately high (ARR ≥20-30 with plasma aldosterone ≥10-15 ng/dL), primary aldosteronism remains likely. 1, 2
• Check serum creatinine and estimated glomerular filtration rate (eGFR), as these patients typically have high-normal or elevated creatinine reflecting hypertensive kidney damage. 4
• Ensure potassium is repleted to 4.0-5.0 mEq/L before confirmatory testing, though hypokalemia may be absent in 50% of cases. 1, 2
• Proceed with confirmatory testing (oral sodium loading with 24-hour urine aldosterone or IV saline suppression test) to demonstrate autonomous aldosterone secretion. 1, 2

First-Line Antihypertensive Treatment

Spironolactone is the cornerstone of therapy for this condition. 1, 5

Dosing Strategy

• Start spironolactone 25 mg once daily in patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m². 5
• If eGFR is 30-50 mL/min/1.73 m², initiate at 25 mg every other day due to hyperkalemia risk. 5
• Titrate to 50-100 mg daily as needed for blood pressure control, with maximum doses up to 100-400 mg daily for confirmed primary aldosteronism. 5, 6
• For resistant hypertension with aldosterone excess, spironolactone provides an additional 25/12 mmHg blood pressure reduction when added to existing regimens. 2

Critical Monitoring Requirements

• Check serum potassium and creatinine within 1 week of initiation, then regularly thereafter. 1, 2
• Expect serum creatinine to rise when starting spironolactone in patients with pre-existing kidney damage—this reflects decreased glomerular hyperfiltration and reduced mineralocorticoid-driven sodium reabsorption, not acute kidney injury. 4
• Watch for hyperkalemia, especially with concurrent ACE inhibitor or ARB use, diabetes, chronic kidney disease, or advanced age. 1, 2
• If hyperkalemia develops on 25 mg daily, reduce to 25 mg every other day. 5

Psychiatric Medication Considerations

The choice of antihypertensive agents significantly impacts mood disorder risk. 3

Antihypertensives to Favor

• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are associated with the lowest risk of mood disorder hospitalizations and should be the preferred additional agents if spironolactone alone does not achieve blood pressure control. 3
• These agents also provide renal protection in the setting of hypertensive kidney damage. 1

Antihypertensives to Avoid

• Beta-blockers carry a 2.11-fold increased hazard ratio for mood disorder admissions compared to ACE inhibitors/ARBs and should be avoided in patients with existing mood disorders. 3
• Calcium channel blockers (CCBs) carry a 2.28-fold increased hazard ratio for mood disorder admissions and should similarly be avoided as first-line agents. 3
• Nondihydropyridine CCBs (verapamil, diltiazem) are contraindicated in heart failure and should be avoided regardless. 1

Building the Antihypertensive Regimen

If spironolactone plus an ACE inhibitor or ARB does not achieve target blood pressure (<130/80 mmHg): 1

• Add a thiazide or thiazide-type diuretic for additional blood pressure reduction and sodium excretion. 1
• If eGFR <30 mL/min/1.73 m², substitute a loop diuretic for volume control (though less effective for blood pressure lowering than thiazides). 1
• Consider amiloride or triamterene (potassium-sparing diuretics) as alternatives if spironolactone side effects are intolerable. 6
• Hydralazine can be added if additional vasodilation is needed, particularly in African American patients. 1

Sodium Restriction is Essential

• Strict dietary sodium restriction (<2 grams/day) is mandatory to reduce aldosterone-mediated sodium retention and volume expansion. 1
• Sodium sensitivity is a hallmark of aldosterone excess, and dietary sodium directly worsens hypertension in this population. 1

Subtype Determination and Definitive Treatment

Once the diagnosis is confirmed and blood pressure is stabilized:

• Obtain a non-contrast CT scan of the adrenal glands to identify unilateral adenoma versus bilateral hyperplasia. 2
• Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, as CT findings alone lead to unnecessary surgery in up to 25% of cases. 2
• If unilateral disease is confirmed, laparoscopic unilateral adrenalectomy is curative, improving blood pressure in 100% and achieving complete cure in approximately 50% of patients. 2, 7, 6
• If bilateral disease is confirmed, continue lifelong mineralocorticoid receptor antagonist therapy with spironolactone or eplerenone. 2, 7, 6

Common Pitfalls to Avoid

• Do not dismiss primary aldosteronism because renin is not suppressed—hypertensive kidney damage can cause renin to escape suppression while aldosterone remains inappropriately elevated. 4
• Do not withhold spironolactone due to fear of hyperkalemia or rising creatinine in patients with mild-to-moderate renal impairment—start at lower doses (25 mg every other day) and monitor closely. 5, 4
• Do not use beta-blockers or calcium channel blockers as first-line agents in patients with mood disorders, as they significantly increase the risk of mood disorder hospitalizations. 3
• Do not rely on hypokalemia to diagnose aldosterone excess—it is absent in 50% of cases. 1, 2
• Do not proceed to adrenalectomy based on CT findings alone—adrenal venous sampling is required to confirm lateralization. 2

Monitoring for Treatment Response

• Reassess blood pressure, serum potassium, and creatinine at 1 week, then every 2-4 weeks during dose titration. 1, 2
• Target blood pressure is <130/80 mmHg in most patients, though <140/80 mmHg is acceptable in elderly patients. 1
• Monitor for spironolactone side effects including gynecomastia, breast tenderness, and menstrual irregularities; if intolerable, switch to eplerenone 50-100 mg twice daily. 6
• Assess mood stability regularly and coordinate with psychiatry to optimize psychiatric medication management. 3