Case Report: Continuous block-and-replace strategy with osilodrostat in a patient with cyclic Cushing's syndrome.

Evidence on cyclic Cushing's syndrome (cCS) is limited. Due to its rarity and diagnostic challenges, some patients remain undiagnosed and experience life-threatening episodes of hyper- and hypocortisolemia. We present a case of a 68-year-old male with a 5-year history of recurrent hospitalizations due to infections, sepsis, and episodes of blood pressure and glycemic instabilities, who was admitted to the Endocrinology Department for evaluation of bilateral adrenal incidentalomas. Physical examination revealed cushingoid features, and biochemical tests confirmed ACTH-dependent CS, with dynamic tests suggesting ectopic origin. Retrospective review showed several peaks of hypercortisolemia separated by spontaneous remissions. These fluctuations correlated with severe infections, hypertension, and hyperglycemia, followed by hypotension and improved metabolic control. Medical therapy with steroidogenesis inhibitors in a block-and-replace regimen resulted in sustained biochemical and clinical stabilization. Imaging failed to identify the ACTH source; therefore inferior petrosal sinus sampling is planned to definitively establish the etiology of CS. This case illustrates the unpredictable nature of cCS and the considerable challenges it poses for both diagnosis and management, emphasizing the need for individualized therapeutic strategies.