Unraveling hypertension through mineralocorticoid receptor activation in Cushing's syndrome: A case report.

Abstract

Background: Cushing's syndrome is a rare cause of secondary hypertension. There are several mechanisms reported as contributing factors for blood pressure elevation in hypercortisolism patients. This case highlights the central role of mineralocorticoid receptors' activation by the excess cortisol in the development of hypertension.

Case presentation: A 45-year-old male presented with several months of cushingoid features and refractory hypertension on maximum doses of five antihypertensive drugs, not including a mineralocorticoid receptor blocker. Workup for other causes of secondary hypertension revealed sleep apnea but was otherwise negative. Further evaluation revealed a carcinoid lung tumor as the cause of Cushing's syndrome with its ectopic production of adrenocorticotropic hormone (ACTH). Prior to the resection of this tumor, the addition of eplerenone, a mineralocorticoid receptor blocker, resulted in significant improvement in blood pressure within 4 weeks, highlighting that cortisol activation of mineralocorticoid receptors is one of the main mechanisms of hypertension in this patient with hypercortisolism.

Conclusion: In hypercortisolism patients, some excess cortisol escapes deactivation by the 11β-hydroxysteroid dehydrogenase 2 enzyme in the kidney and directly activates mineralocorticoid receptors. Recent literature suggests that specific patient populations have subtle elevations in cortisol levels, and cortisol's effect on end-organ damage follows a spectrum from high-normal cortisol to overt hypercortisolism. Other data suggest a decline in 11β-hydroxysteroid dehydrogenase 2 enzyme activity with age. Additional research is needed to further define the role of cortisol- mineralocorticoid receptor interaction in hypertension among patients without overt hypercortisolism but with high-normal cortisol or low 11β-hydroxysteroid dehydrogenase 2 enzymatic activity.