Metabolic Syndrome in Cushing’s Syndrome

Although the concept of metabolic syndrome (MetS) as a disease entity continues to be debated, it provides a means by which patients at risk for diabetes and cardiovascular disease can be identified and categorized with routinely available criteria. Insulin resistance plays a central role in these abnormalities. Risk factors include central obesity, elevated fasting glucose, hypertension, elevated serum triglycerides, and low high-density-lipoprotein cholesterol. Various definitions of MetS have been proposed since 1998. Recently, a joint statement by several major organizations concluded that three abnormal values in a series of five criteria determined whether a person had MetS, and that elevated waist circumference was not an obligatory feature. A single set of cutoff points was proposed, except for waist circumference, which should be defined according to population and ethnic group. Cushing's syndrome (CS) represents an archetype of MetS. High glucocorticoid levels lead to muscle, liver and adipocyte insulin resistance. Almost all patients with CS are obese or overweight, and have abdominal visceral adiposity. Many also have glucose metabolism abnormalities (21-60% and 20-47% of the patients have impaired glucose tolerance and diabetes, respectively), hypertension (more than 70% of the patients), and elevated triglyceride levels (20% of the patients). Almost two thirds of CS patients fulfill at least three criteria for MetS. The elevated incidence of diabetes and premature atherosclerosis (directly related to the length of exposure to hypercortisolism), and the increased mortality (particularly cardiovascular mortality) relative to the general population (2 to 4 times higher) show that the predictive value of MetS is also valid in CS. Effective treatment of hypercortisolism improves each of the five MetS components, but MetS and carotid atherosclerosis persist in most patients, and the cardiovascular risk therefore remains elevated. This calls for aggressive treatment of comorbidities and for very long-term follow-up.