Hypertension in Cushing’s Syndrome: Mechanisms and Implications

Cushing’s syndrome, a disorder caused by chronic exposure to high cortisol levels, is frequently associated with hypertension. Approximately 80% of patients with Cushing’s syndrome develop high blood pressure, underscoring its clinical significance. The pathogenesis of hypertension in this context is multifaceted, driven by cortisol’s diverse effects on fluid balance, vascular tone, and hormonal systems.

One critical factor is cortisol’s mineralocorticoid activity. While primarily involved in stress response and metabolism, cortisol can bind to mineralocorticoid receptors, mimicking aldosterone. This leads to increased sodium retention and water reabsorption in the kidneys, expanding blood volume and elevating blood pressure. Normally, cortisol’s effect is limited by the enzyme 11β-hydroxysteroid dehydrogenase type 2, which inactivates it. However, in Cushing’s syndrome, excessive cortisol overwhelms this system, amplifying its mineralocorticoid action.

Additionally, cortisol heightens vascular sensitivity to vasoconstrictors like catecholamines and angiotensin II. This results in pronounced vasoconstriction, raising peripheral vascular resistance. Simultaneously, cortisol inhibits vasodilators such as nitric oxide and prostacyclin, which ordinarily help maintain vascular relaxation. The diminished presence of these substances tips the balance further towards vasoconstriction, compounding the hypertensive effects.

Cortisol also activates the renin-angiotensin-aldosterone system (RAAS), a critical regulator of blood pressure. Through increased angiotensin II and aldosterone, the RAAS enhances vasoconstriction and promotes further sodium and water retention. Notably, even when plasma renin levels are suppressed in Cushing’s syndrome, cortisol's direct stimulation of aldosterone release sustains the hypertensive drive.

Recent studies emphasize the role of endothelial dysfunction in Cushing’s-related hypertension. Chronic exposure to high cortisol disrupts endothelial cell function, exacerbating vascular rigidity and resistance. Furthermore, the syndrome is associated with metabolic derangements, including hyperglycemia and dyslipidemia, which independently contribute to cardiovascular risk.

In conclusion, hypertension in Cushing’s syndrome arises from a complex interplay of mechanisms, including cortisol’s mineralocorticoid-like effects, vascular hyperreactivity, suppression of vasodilators, and RAAS activation. Understanding these pathways is crucial for effective management, as persistent hypertension significantly elevates the risk of cardiovascular complications in these patients.
Hypertension in Cushing’s Syndrome: Mechanisms and Implications