Hypertension is one of the most distinguishing features of endogenous
Cushing's syndrome (CS), as it is present in about 80% of adult patients whereas in children its prevalence is about 47%.
Hypertension in CS is significantly correlated with the duration of
hypercortisolism and results from the interplay between several pathophysiological mechanisms regulating plasma volume, peripheral vascular resistance and cardiac output, all of which are increased in this state.
Glucocorticoids cause
hypertension through several mechanisms: their intrinsic
mineralocorticoid activity; through activation of the renin-angiotensin system; by enhancement of vasoactive substances, and by causing suppression of the vasodilatory systems. In addition,
glucocorticoids may exert some hypertensive effects on cardiovascular regulation through the CNS via both
glucocorticoid and
mineralocorticoid receptors.
Hypertension in CS usually resolves with surgical removal of the
tumor, but some patients require pharmacological
antihypertensive treatment both pre- and postoperatively.
Thiazides and
furosemide should be avoided, while
adrenergic blockade and
calcium channel antagonists are usually ineffective.
Mineralocorticoid receptor antagonists, Ang II blockers and
ACE inhibitors are good
anti-hypertensive options;
PPAR-γ agonists may help in many aspects of the
insulin resistance syndrome. The relatively selective
glucocorticoid receptor antagonist
Mifepristone (
RU 486) could reduce blood pressure in patients with CS. Neuromodulatory agents such as the
serotonin inhibitors
cyproheptadine and
ritanserin, valproid
acid,
dopamine agonists,
somatostatin analogs may occasionally be effective, as well as drugs acting directly at the adrenal levels, such as
Ketoconazole and aminoglutetimide or even opDDD. Treating
hypertension in CS remains a difficult task and a big challenge, in order to decrease the morbidity and mortality associated with the disease.