Overview and Initial Management of Cushing Syndrome

Cushing syndrome is characterized by chronic exposure to supra-physiologic glucocorticoid levels, which may be exogenous or endogenous, manifesting as a constellation of clinical symptoms and signs that vary with the severity and duration of glucocorticoid excess. When hypercortisolism is severe, it reveals itself quite distinctively. However, the pathognomonic signs and symptoms of Cushing syndrome are not always present in every individual. The clinical phenotype ranges from changes in body habitus, moon facies, central obesity, a dorsocervical fat pad, proximal muscle weakness, and easy bruising, to frank diabetes, hypertension, and dyslipidemia. Cushing syndrome may additionally disturb the reproductive system (causing amenorrhea, hypogonadism, and erectile dysfunction) and may be associated with mood lability, anxiety, depression, and cognitive decline. In children, glucocorticoid excess may result in statural growth failure in the setting of weight gain. The wide spectrum of manifestations can make the diagnosis particularly challenging. Available screening tests also have their caveats, which makes it fundamental to individualize diagnostic testing, depending upon each patient’s situation, including their lifestyle. It is crucial to clearly demonstrate cortisol excess before pursuing evaluation of the etiology of Cushing syndrome. Prompt diagnosis enables clinicians to tailor the management plan to the individual and to optimize therapy while preventing comorbidities that significantly impair quality of life and increase mortality.