Osilodrostat for Cyclic Cushing Disease.

Background/Objective: Cyclic Cushing syndrome is a rare subtype of Cushing syndrome with episodes of hypercortisolism, followed by spontaneous remission. Case Report: 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. Discussion: 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. Conclusion: 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.