SAT-414 - The Increased Use of Neoadjuvant Anticorticosteroid Therapy in Adrenal Hypercortisolism Prior to Adrenalectomy

Background:
Cortisol-modulating drugs (e.g., osilodrostat, levoketoconazole, mifepristone) may be used to optimize patients with adrenal hypercortisolism (AHC) prior to adrenalectomy, particularly in those with metabolic derangements or obesity. However, their role and indications as neoadjuvant therapy are poorly defined. We evaluated utilization trends and perioperative outcomes associated with preoperative medical therapy.

Methods:
We analyzed 1,965 consecutive adrenalectomies performed at the Carling Adrenal Center between 01/01/2022-12/31/2025. A total of 816 patients (41.6%) demonstrated biochemically unequivocal AHC, classified (grade 1-3) by low-dose dexamethasone suppression test as mild (1.8–5.0 µg/dL; 79.6%), moderate (5.0–10 µg/dL; 11.7%), or severe (≥10 µg/dL and/or overt Cushing syndrome; 8.7%). Twenty-two patients (2.9%) underwent neoadjuvant cortisol-modulating therapy. In this group, median age was 65.5 years (IQR 10), BMI 27 kg/m² (IQR 8), and tumor size 2.8 cm (IQR 2.1). Outcomes were compared between medicated and non-medicated groups, and included baseline characteristics, pathology and postoperative day 1 cosyntropin stimulation test (CST). Personalized, uni- or staged (≥6 weeks apart) partial bilateral mini back scope adrenalectomy was used in 99.4% of cases to preserve adrenocortical function. Postoperative hypocortisolism (PHC, adrenal insufficiency; AI) and need for glucocorticoid replacement (GR) was determined based on published institutional protocols.

Results:
Baseline biochemical values, age, sex, and tumor size did not differ between groups. The pathological results in non-medicated patients included cortisol-producing adenoma (CPA, 71.9%), bilateral macronodular disease (BMAD, 17.9%), bilateral micronodular disease (BMiNAD, 9.5%), and adrenocortical carcinoma (ACC, 0.8%); corresponding frequencies in medicated patients were 68.2%, 27.3%, 4.5%, and 0%. Disease severity differed significantly, with a higher proportion of grade 3 AHC in the medicated group (40.0% vs. 7.9%, p< 0.00001). Preoperative therapy use increased over time (0% in 2022 to 4.9% in 2025; p< 0.001). Such therapy was not associated with increased PHC, although a trend was observed (p=0.08). Following CST, PHC occurred in 35.7% of CPA, 26.1% of BMAD, 9.6% of BMiNAD, and 33.6% of ACC patients in the non-medicated group, and in 23.1% of CPA patients in the medicated group.

Conclusion:
Neoadjuvant anticorticosteroid therapy is increasingly used to manage AHC, particularly in patients with more severe disease. Pre-treated patients demonstrated similar pathology and postoperative adrenal function, without differences in PHC or need for GR. These findings support the perioperative safety of medical therapy as a bridge to adrenalectomy and justify further studies evaluating metabolic and long-term outcomes of neoadjuvant therapy of AHC.

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