Osilodrostat for Cyclic Cushing Disease

Cyclic Cushing syndrome is a rare subtype of Cushing syndrome with episodes of hypercortisolism, followed by spontaneous remission.

Our patient was a 68-year-old man who presented with his third cycle of cyclic Cushing disease with facial swelling, buffalo hump, fatigue, proximal muscle weakness, and lower extremity edema. Laboratory tests showed the following: (1) 24-hour urine free cortisol level, 12 030.3 mcg/d (normal, ≤60.0 mcg/d); (2) morning adrenocorticotropic hormone level, 464 pg/mL (normal, 6-59 pg/mL); (3) morning serum cortisol level, 91 mcg/dL (normal, 8-25 mcg/dL); and (4) potassium level, 3.3 mmol/L (normal, 3.6-5.3 mmol/L). Magnetic resonance imaging of the pituitary without/with contrast showed a partially empty sella. Prior inferior petrosal sinus sampling during the second cycle indicated a potential pituitary source of increased adrenocorticotropic hormone production, localized or draining to the right side. The patient was treated with osilodrostat with improvement in laboratory values and clinical symptoms by 2 to 3 weeks. After development of adrenal insufficiency, osilodrostat was rapidly titrated off by 2 months of treatment. Subsequently, laboratory findings after 8 days off osilodrostat confirmed clinical remission and reversibility of medication-induced adrenal insufficiency.

Because hypercortisolism is associated with mortality risk and comorbidities, timely management is a priority. If a surgical cure is not possible, a medication that treats hypercortisolism with rapid onset, reversible inhibition, and minimal side effects would be ideal to address the cyclicity.

Our case is the first to our knowledge demonstrating osilodrostat's use for native cyclic Cushing syndrome treatment and highlighted its reversibility and ability to preserve normal adrenal function.