Management of dyslipidemia in Cushing's syndrome.

Cardiovascular risk factors such as hypertension, hyperlipidemia and glucose intolerance are highly prevalent in Cushing's syndrome. Lipid abnormalities have been reported in 40-70% of patients, including those with 'subclinical' disease. Surgical cure is associated with significant amelioration of lipid profile in the majority of patients. Treatment of persistent hyperlipidemia should be conducted according to the accepted general principles in use for other medical conditions. Nevertheless, patients requiring medical treatment for persistent hypercortisolism present specific challenges, according to the selected therapeutic agent. For example, treatment with the adrenolytic drug o,p'DDD is associated with a prominent increase in cholesterol levels that necessitates intensive use of lipid lowering agents. The use of ketoconazole, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), may significantly increase plasma concentrations of certain statins (such as simvastatin and atorvastatin) that undergo metabolism by the same pathway, thus increasing the risk of complications and side effects. Therefore, preference should be given to HMG-CoA inhibitors that are metabolized by different pathways, such as pravastatin. In summary, hyperlipidemia should be aggressively treated in patients with Cushing's syndrome in view of the increased cardiovascular morbidity and mortality associated with this disorder.