Detecting Mild Autonomous Cortisol Secretion in Patients With Adrenal Incidentaloma

Mild Autonomous cortisol secretion (MACS) is defined as the hypersecretion of cortisol by the adrenal glands, independent of Adrenocorticotropic Hormone (ACTH) regulation. MACS can be a challenging diagnosis for clinicians to make. It is commonly associated with adrenal incidentalomas (AI), the incidental finding of adrenal gland masses on cross-sectional imaging. There are a variety of adverse clinical conditions associated with MACS, including central obesity, hypertension, impaired fasting glucose due to insulin resistance, and dyslipidemia, which together comprise the "metabolic syndrome," as well as type 2 diabetes mellitus, cardiovascular disease, osteoporosis with vertebral fractures, and early mortality. Androulakis et al. concluded that patients with AI, even without hypertension, diabetes, and/or dyslipidemia, may still have adverse cardiovascular outcomes, possibly due to increased insulin resistance and endothelial dysfunction linked to subtle cortisol excess. There is also a reported association of non-alcoholic fatty liver disease (NAFLD), an increasingly significant cause of morbidity and mortality, with the metabolic syndrome and diabetes, as well as hypercortisolism. However, the link between MACS and NAFLD has not been well delineated, nor has the effect of treatment with MACS on NAFLD been explored.

Given the findings cited above, there may be benefit in treating patients with AI and MACS with medical therapy. Therefore, identifying those individuals who have the metabolic syndrome or its components, bone disease, NAFLD, or increased cardiovascular risk related to excess cortisol secretion is essential but difficult.

Inclusion criteria

• Patients ages 18 years and older.
• Presence of adrenal incidentaloma by cat scan (CT) or magnetic resonance imaging (MRI) examination.
• 1-mg Dexamethasone suppression test cortisol ≤ 5 μg/dL with adequate dexamethasone level.

Exclusion criteria

• 1-mg Dexamethasone suppression test cortisol > 5 μg/dL with adequate dexamethasone level. Patients who fail to suppress below this level will be considered to have Cushing's syndrome and will be referred for appropriate treatment.
• Current or recent (3 months) history of use of glucocorticoid medication (including joint injections of steroids).
• History of uncontrolled hypertension or history of hypertension with more than 2 medications.
• History of uncontrolled type 2 Diabetes Mellitus or history of diabetes mellitus with A1c>7.5.
• Known History of osteoporosis
• Documented Clinical Cushing's disease.
• Clinical suspicion of adrenal carcinoma.
• History of alcohol abuse/dependence.
• History of cirrhosis of liver.
• History of hepatitis B or C infection regardless of treatment.
• History of type 1 diabetes.
• History of hemochromatosis.
• History of autoimmune hepatitis.
• History of Wilson's disease.