Korlym Withdrawal and Hypertension: Mechanisms and Management
Abrupt withdrawal of Korlym (mifepristone) can lead to rebound hypertension and hypokalemia due to sudden loss of glucocorticoid receptor blockade, allowing unopposed cortisol effects on mineralocorticoid receptors and vascular tone. 1
Mechanism of Hypertension During Korlym Withdrawal
Why Blood Pressure Increases
Loss of glucocorticoid receptor antagonism: Mifepristone blocks cortisol's effects at the receptor level. When withdrawn, endogenous cortisol suddenly regains full activity, leading to increased vascular tone and sodium retention 1
Mineralocorticoid receptor activation: High cortisol levels can activate mineralocorticoid receptors, causing sodium retention, volume expansion, and potassium wasting—all contributing to hypertension 1
Sympathetic nervous system reactivation: Similar to other antihypertensive withdrawal syndromes, abrupt cessation can trigger sympathetic overactivity with increased catecholamine release 2, 3
Clinical Presentation
Hypertension during mifepristone withdrawal manifests with:
- Rapid blood pressure elevation (often within days to weeks) 1
- Moderate to severe hypokalemia (observed in 55% of patients on mifepristone) 1
- Potential signs of adrenal insufficiency paradoxically coexisting with hypertension 1
- Absence of typical withdrawal symptoms like palpitations or tremor in most cases 4
Management Strategy
Immediate Monitoring Requirements
Close surveillance is mandatory during and after Korlym withdrawal:
- Daily blood pressure monitoring for the first week, then every 2-3 days for 2-4 weeks 1
- Serum potassium levels checked every 2-3 days initially, as severe hypokalemia can develop rapidly 1
- Assessment for clinical signs of adrenal insufficiency (fatigue, nausea, hypotension) 1
Pharmacological Management
For hypertension control during withdrawal:
Mineralocorticoid receptor antagonists are first-line: Add spironolactone 25-50 mg daily or eplerenone to counteract mineralocorticoid effects and manage both hypertension and hypokalemia 5
Potassium supplementation: Aggressive potassium replacement is often necessary, as hypokalemia can be severe and refractory 1
Standard antihypertensive agents: If additional blood pressure control is needed, use calcium channel blockers or ACE inhibitors/ARBs as per resistant hypertension guidelines 5
Avoid abrupt cessation: When possible, taper mifepristone gradually rather than stopping abruptly, though specific tapering protocols are not well-established 2
Pitfalls and Caveats
Critical considerations to avoid complications:
Do not confuse hypertension with adrenal insufficiency: Patients may paradoxically have both elevated blood pressure (from mineralocorticoid effects) and signs of glucocorticoid deficiency 1
Hypokalemia requires aggressive management: Standard potassium supplementation may be insufficient; mineralocorticoid receptor antagonists are more effective 1
Monitor for rebound Cushing's symptoms: Clinical signs of hypercortisolism may worsen temporarily as receptor blockade is removed 1
Blood pressure may not exhibit classic "rebound": Unlike beta-blocker withdrawal, mifepristone cessation typically returns blood pressure toward pretreatment levels rather than overshooting, but this depends on the underlying cortisol excess 4
Duration of Monitoring
Extended surveillance is necessary:
- Blood pressure monitoring should continue for at least 4 weeks post-withdrawal 4
- Potassium levels require monitoring until stable for 2 consecutive weeks 1
- Consider that full equilibration may take 2-4 weeks as mifepristone has a long half-life 1
When to Seek Specialist Input
Referral to endocrinology or hypertension specialist is warranted when: