P30 - Successful non-surgical treatment of bilateral macronodular adrenocortical disease with osilodrostat

Bilateral Macronodular Adrenocortical Disease (BMAD) is a rare cause of endogenous Cushing’s syndrome (CS). Untreated CS contributes to various comorbidities and is independently associated with increased mortality. The primary treatment for BMAD is bilateral or unilateral adrenalectomy. In patients who are not candidates for surgery, pharmacological therapy with steroidogenesis inhibitors remains the primary treatment option. Osilodrostat is a potent inhibitor of 11β-hydroxylase, a key enzyme involved in the final steps of cortisol biosynthesis. Data on osilodrostat use in patients with ACTH-independent CS are limited, even more so for BMAD. We present the case of a 67-year-old woman diagnosed with BMAD and ACTH- independent CS, along with multiple comorbidities, including uncontrolled diabetes mellitus (HbA1c% 9.5%) requiring complex pharmacological management with metformin, dapagliflozin, semaglutide, and insulin therapy in basal/bolus regimen. Due to the comorbid conditions, the patient was deemed ineligible for surgical intervention. Treatment with osilodrostat was initiated at a starting dose of 2 mg twice a day. During the initial phase of dosage titration (up to a maximum dose of 7 mg/day), the main complication was a pronounced effect of elevated concentrations of mineralocorticoid precursors (serum 11-deoxycorticosterone concentration: 377.0 ng/100 mL 15x ULN), which manifested as marked worsening of hypertension control and hypokalemia; however effectively managed with spironolactone and potassium supplementation. The maintenance dose of osilodrostat was 1 mg in the evening. The therapy resulted in effective biochemical control of hypercortisolemia and led to marked clinical improvement in CS manifestations, including resolution of proximal myopathy symptoms and enhanced physical capacity. Additionally, glycemic control improved substantially (HbA1c 5.8%), enabling insulin therapy discontinuation and continuation of diabetes management with oral antidiabetic agents. This case highlights the efficacy and safety of osilodrostat in the management of BMAD and demonstrates its role as a viable therapeutic alternative when surgical treatment is not feasible.