De Novo Development Of A Cortisol-Producing Adrenocortical Carcinoma In A Patient With Primary Adrenal Insufficiency

Objective: This case report describes the unusual transition from primary adrenal insufficiency to adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) associated with adrenocortical carcinoma (ACC). Methods: We report the clinical, laboratory, imaging, and pathological findings from a 57-year-old man with a history of primary adrenal insufficiency (Addison disease) who subsequently developed endogenous ACTH-independent CS associated with ACC. Results: Eight years after the patient was diagnosed with Addison disease, he developed features of CS, which led to cessation of the steroid replacement therapy he had been taking for his adrenal insufficiency. Hormonal tests, performed while the patient was not receiving corticosteroids, revealed elevated 24-hour urinary free cortisol (458 μg/24 h) and suppressed plasma ACTH. Computed tomography of the abdomen revealed a 10-cm heterogeneous right adrenal mass that did not exist on imaging studies performed 8 years earlier. The patient underwent open resection with pathological confirmation of ACC (Weiss score of 8 and Ki-67 labeling index of 19%). After surgery, the patient's CS resolved, and adjuvant mitotane therapy was initiated. Conclusions: We describe a unique case of transition from Addison disease without an adrenal mass to CS associated with ACC. This case illustrates the de novo development of ACC rather than ACC developing from a pre-existing adrenal mass. The molecular changes leading to de novo ACC development were not examined in this report and warrant further research.