Hypercortisolism Can Promote Hyperaldosteronism Through Multiple Mechanisms
Hypercortisolism can contribute to hyperaldosteronism through mineralocorticoid receptor activation and other pathways, though true concurrent primary aldosteronism is rare. 1
Mechanisms by which hypercortisolism affects aldosterone pathways:
- Excess cortisol can activate mineralocorticoid receptors, mimicking aldosterone's effects on renal sodium absorption and potassium excretion 1
- Hypercortisolism can promote hypertension through activating the renin-angiotensin system, which may indirectly stimulate aldosterone production 1
- Cortisol excess sensitizes the vasculature to catecholamines and impairs endothelial nitric oxide bioavailability, further contributing to hypertension 1
- Metyrapone, a medication that inhibits cortisol production, can also suppress aldosterone biosynthesis, indicating shared pathways in steroid hormone production 2
Clinical presentations of overlap syndromes:
- Patients with Cushing syndrome commonly present with hypertension (prevalence >80%) that mimics features of hyperaldosteronism 1
- The blocking of mineralocorticoid actions with spironolactone or eplerenone is often effective in managing hypertension in Cushing syndrome patients 1
- True concurrent primary aldosteronism and subclinical cortisol hypersecretion is rare but has been documented in case studies 3, 4
- Bilateral adrenocortical masses can independently produce both aldosterone and cortisol, requiring careful diagnostic workup 4
Diagnostic considerations:
- In patients with suspected hypercortisolism, measuring plasma aldosterone and renin activity is important to evaluate for concomitant hyperaldosteronism 1, 5
- An aldosterone-to-renin ratio >30 is suggestive of primary aldosteronism 5
- Hypokalaemic hypertension with low plasma renin activity is typical of both primary aldosteronism and cortisol-induced mineralocorticoid hypertension 6
- Adrenal vein sampling is crucial for distinguishing the source of hormone excess in patients with bilateral adrenal masses 1, 4
Treatment implications:
- Treating the underlying hypercortisolism often improves mineralocorticoid-related symptoms 1
- In cases of adrenal adenomas producing both hormones, adrenalectomy may normalize both cortisol and aldosterone levels 4
- Medical management with mineralocorticoid receptor antagonists (spironolactone or eplerenone) is effective for managing the mineralocorticoid effects of cortisol excess 1
- Diuretic therapy is often a cornerstone of managing hypertension in Cushing syndrome due to the prominent role of mineralocorticoid receptor activation 1
Important clinical caveat:
- While hypercortisolism can cause symptoms similar to hyperaldosteronism, true concurrent primary aldosteronism (Conn syndrome) and Cushing syndrome is uncommon 3
- Cortisol excess appears to have an additional impact on cardiac remodeling in patients with primary aldosteronism, with treatment improving left ventricular hypertrophy 7
- Careful hormonal evaluation is needed to distinguish between primary aldosteronism, hypercortisolism, and rare cases of concurrent hormone excess 6, 3