Hypercortisolism in Difficult-To-Control Type II Diabetes

Cortisol can induce insulin resistance³ and, in high doses, can cause glucose intolerance. Studies have shown that chronic administration of glucocorticoids, such as cortisol, can lead to the development of diabetes by promoting insulin resistance and impaired insulin secretion.² Glucocorticoids inhibit the cellular uptake of glucose and induce lipolysis, which increases glucose and free fatty acid levels in the serum. As elevated cortisol levels drive insulin resistance, this creates a positive feedback loop within the hypothalamic-pituitary axis (HPA) that continues to disturb glucose homeostasis, which can contribute to the progression of type 2 diabetes mellitus (T2DM) and metabolic syndrome.⁴

While it has been appreciated for quite some time that patients with Cushing syndrome have an increased risk for cardiometabolic disorders and T2DM, it has only recently been appreciated that in patients diagnosed with T2DM, elevated cortisol may be driving pathogenesis.²

Hypercortisolism is diagnosed with a dexamethasone suppression test (test code 6921). Patients are prescribed 1 mg of dexamethasone to be taken at 11:00 PM the night before an 8:00 AM blood draw to test for cortisol. If cortisol levels are not suppressed (≥1.8 µg/dL) and dexamethasone concentrations are adequate, such testing is consistent with hypercortisolism and the patient should be referred to an endocrinologist for further diagnostic assessment.⁵ 

The ability to identify hypercortisolism in patients with difficult-to-control diabetes is beneficial in that potential adrenal tumor sources of cortisol can be identified and removed and/or patients can be treated with glucocorticoid antagonists.⁶

The recent Catalyst study showed that mifepristone treatment lowered HbA1c values with consequential improvements in weight and reductions in the use of glucose-lowering medication in patients with difficult-to-control diabetes.⁶