Should a patient with hypercortisolism be prescribed antihypertensive medication for elevated blood pressure?

Antihypertensive Treatment in Patients with Hypercortisolism

Yes, patients with hypercortisolism should be prescribed antihypertensive medication for elevated blood pressure, with mineralocorticoid receptor antagonists (particularly spironolactone) as the first-line treatment option. 1

Pathophysiology and Prevalence

Hypertension is one of the most distinguishing features of hypercortisolism (Cushing's syndrome), present in approximately 80% of adult patients 2. This high prevalence results from multiple pathophysiological mechanisms:

• Intrinsic mineralocorticoid activity of excess cortisol
• Activation of the renin-angiotensin system
• Enhancement of vasoactive substances
• Suppression of vasodilatory systems
• Central nervous system effects via glucocorticoid and mineralocorticoid receptors

Hypercortisolism significantly increases cardiovascular morbidity and mortality, with hypertension being a major contributing factor 3.

First-Line Antihypertensive Treatment

Mineralocorticoid Receptor Antagonists

• Spironolactone is the preferred first-line agent for hypertension in hypercortisolism 1, 2
• Eplerenone can be considered as an alternative if spironolactone is not tolerated 1

These agents directly counteract the mineralocorticoid effects of excess cortisol, addressing a key pathophysiological mechanism of hypertension in these patients.

Second-Line Options

If blood pressure remains uncontrolled on mineralocorticoid receptor antagonists, consider adding:

1. Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril) 4, 2
2. Angiotensin II receptor blockers (ARBs) 2
3. Calcium channel blockers 1

Medications to Avoid or Use with Caution

• Thiazide and loop diuretics should generally be avoided as first-line agents 2
• Beta-blockers and calcium channel blockers alone are often ineffective as monotherapy 2

Blood Pressure Targets

According to the 2024 ESC guidelines and 2017 ACC/AHA guidelines:

• Target blood pressure should be <130/80 mmHg 1
• This target is associated with reduced cardiovascular morbidity and mortality 1

Monitoring and Follow-up

• Monitor electrolytes, particularly potassium, when using mineralocorticoid receptor antagonists 1, 5
• Check renal function within 1-2 weeks of starting new antihypertensive agents 5
• Assess for orthostatic changes by measuring blood pressure in both sitting and standing positions 5

Special Considerations

• Combination therapy is often required to achieve blood pressure targets in hypercortisolism 1
• Fixed-dose combinations may improve adherence 5
• Definitive treatment of hypercortisolism (surgical or medical) should be pursued concurrently, as hypertension often resolves with correction of the underlying hypercortisolism 1, 2
• Consider medical therapy targeting hypercortisolism (e.g., metyrapone, ketoconazole) in patients who are not surgical candidates 6

Pitfalls to Avoid

1. Delaying antihypertensive treatment while awaiting definitive treatment of hypercortisolism can lead to increased cardiovascular risk
2. Inadequate monitoring of electrolytes, especially when using mineralocorticoid receptor antagonists
3. Failure to recognize resistant hypertension, which is common in hypercortisolism and may require multiple agents
4. Overlooking other cardiovascular risk factors that commonly coexist with hypercortisolism (diabetes, dyslipidemia, obesity)

By addressing hypertension aggressively in patients with hypercortisolism, you can significantly reduce their cardiovascular morbidity and mortality while definitive treatment of the underlying condition is being pursued.