Hypertension in Patients with Cushing’s Syndrome

Abstract

Hypertension in patients with Cushing’s syndrome (CS) occurs in up to 95% of adult and in half of pediatric cases. It represents a major cardiovascular risk and mortality factor in such patients. Its pathogenesis is incompletely understood and includes an imbalance of factors involved in vasodilation and vasoconstriction. Amongst these are upregulation of the renin–angiotensin system activity, salt and water retention, increased peripheral resistance, increase in production/activity of endothelin-1 and vasopressin, increased reactivity to catecholamines, as well as decline in antioxidants, nitric oxide synthase, and others. Patients with ectopic CS usually have more pronounced hypercortisolism and hypertension than patients with CS of other etiologies. This might in part be caused by a functional state of mineralocorticoid excess due to oversaturation of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme. In patients with exogenous CS, the prevalence of hypertension is dose-dependent and lower (about 20%) than in those with endogenous CS. The aim of therapy is to normalize blood pressure and to remove the source of glucocorticoid excess with subsequent resolution of hypertension after surgical cure which will occur in almost all children and adolescents, but only in two-thirds of adults. This resolution depends on the age of onset, duration, and degree of glucocorticoid excess, as well as other underlying hypertension risk factors such as obesity, sleep apnea, and insulin resistance. Treatment should include ACE inhibitors and angiotensin II ­receptor blockers, as well as eplerenone in selected patients (especially those with ectopic CS). Glucocorticoid excess and its effects should be controlled, if necessary with careful use of drugs such as steroidogenesis inhibitors or type II glucocorticoid receptor antagonists.KeywordsCushing’s syndromeGlucocorticoidsHypertensionEctopic ACTH11-βHSD systemEndothelins