Dr Rosario Pivonello, University of Naples Federico II, Italy

Uncontrolled Cushing's disease is associated with an increased mortality rate of up to four times higher than the normal population and, in the absence of adequate treatment, is a fatal condition. This mortality is directly related to elevated cortisol levels.

Diagnosis of Cushing's disease takes up to around 4 years after the onset of hypercortisolism, and in some cases as long as 12 years. This delay in diagnosis has serious implications, with duration of hypercortisolism an important predictor of poor outcome in these patients, and may contribute to the high morbidity burden, higher mortality and decreased health related patient quality of life.

Chronic hypercortisolism is associated with multi-organ abnormalities and many comorbidities. Metabolic comorbidities are prevalent and include central obesity, impairment of glucose tolerance, diabetes mellitus and hyperlidaemia. Cardiovascular risk in these patients is directly related to metabolic syndrome. Cardiovascular comorbidities include hypertension, coagulopathy and hypercoagulopathy, all of which predispose patients to thromboembolic events. Insulin resistance represents the main pathogenic factor of metabolic syndrome in Cushing's disease and leads to diabetes mellitus and impaired glucose tolerance. It is possible that a subgroup of diabetes mellitus patients are undiagnosed Cushing's disease patients. Hypertension is one of the most common complications associated with Cushing's disease.

Other serious comorbidities include osteoporosis and fractures, renal disease, major depression and cognitive impairment. All of these have a significant impact on health related patient quality of life.

Achievement of biochemical remission in order to reduce the excess morbidity and mortality risk of Cushing's disease is the ultimate goal in its treatment.