Medical Science Liaison Corcept Therapeutics Brighton, Michigan, United States
Introduction : Hypercortisolism, a detrimental and often overlooked condition, has an impact on an estimated 5–10% of individuals with type 2 diabetes (T2D). When diabetes remains unresponsive or only partially responsive to known effective medications, it is crucial to consider hypercortisolism as an underlying driver of T2D and initiate treatment.
Case(s) Description : A 71-year-old man with long-standing (40+ years) difficult-to-control T2D (continuous glucose monitoring [CGM] time-in-range [TIR] 41%, HbA1c 8%, average glucose 196 mg/dL) despite receiving multiple antihyperglycemic drugs (including U500 insulin, metformin, and GLP1 agonists) also had multiple comorbidities, including resistant hypertension (on 7 antihypertensive medications) and morbid obesity (post gastric sleeve). His biochemical evaluation confirmed hypercortisolism with elevated serum cortisol (2.3 and 2.4 μg/dL) post-1-mg dexamethasone suppression test, and computed tomography imaging revealed a stable sub-centimeter adrenal adenoma. He was treated with mifepristone 300 mg/day for 4 months, during which he experienced substantial improvement in glucose control (CGM TIR 91%, HbA1c 6.6%, average glucose 136 mg/dL), insulin reduction (U500 to U100), weight loss of 34 lbs (310.4 lbs to 276 lbs), and discontinuation of 4 antihypertensive medications. After 4 months of treatment, the patient experienced unrelated orthostatic hypotension, and mifepristone was discontinued per his cardiologist’s recommendation. Upon discontinuation, the patient's glycemic control quickly deteriorated (CGM TIR 3%, HbA1c 10.2%, average glucose 286 mg/dL), with increased insulin use, weight gain, and reintroduction of 2 antihyperglycemic medications and 2 antihypertensive medications.
Discussion : This case presents a patient with difficult-to-control T2D and additional comorbidities that could not be effectively managed despite long-term, extensive medical interventions. This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic derangements. Failure to do so resulted in a worsening clinical picture for this patient, which was ameliorated with the administration of mifepristone to address the underlying hypercortisolism.
