MON-107 A Novel Approach to Corticotroph Adenoma Localization: 11C Methionine PET/CT Following Osilodrostat Therapy

Abstract Disclosure: Z. Htut: None. J. MacFarlane: None. R. Nair: None. D.A. Papadopoulou: None. N.M. Martin: None. K. Meeran: None. D. Gillett: None. M. Gurnell: None. F. Wernig: None. Background: Optimal long-term outcomes in Cushing’s disease (CD) depend on precise localization and complete resection of the ACTH-secreting adenoma while preserving normal pituitary function. However, adenomas may evade detection on conventional MRI. 11C-methionine PET/CT (11C-MET PET/CT) offers an alternative imaging modality that may enhance visualization of these elusive tumors. We hypothesized that preoperative cortisol-lowering therapy would lead to increased ACTH levels, heightened tumor metabolic activity and improved 11C-MET PET signal intensity. Osilodrostat, a potent 11-β-hydroxylase inhibitor, has demonstrated superior efficacy and tolerability compared to traditional steroidogenesis inhibitors such as ketoconazole and metyrapone. Case: A 28-year-old man with a history of juvenile arthritis, total hip replacement, and post-operative pulmonary embolism presented with uncontrolled hypertension, centripetal obesity, purple striae, and significant weight gain, suggestive of Cushing’s syndrome (CS). Laboratory investigations confirmed ACTH-dependent hypercortisolism, with markedly elevated post-1 mg dexamethasone cortisol of 807 nmol/L (<50 nmol/L), ACTH of 56.7 ng/L (10-30 ng/L), and 24-hour urinary free cortisol (UFC) of 774 nmol/24h (0-164 nmol/24h). Salivary cortisol and cortisone levels were 13.5 nmol/L (< 2.6 nmol/L) and 42.7 nmol/L (<18 nmol/L) respectively.Inferior petrosal sinus sampling (IPSS) excluded an ectopic source of ACTH secretion, yet MRI failed to identify a discrete pituitary adenoma. Functional imaging with 11C-MET PET/CT showed equivocal tracer uptake near the left cavernous sinus, but without definitive adenoma localization. Given persistent hypercortisolism, the patient was initially treated with metyrapone but experienced intolerance, prompting a switch to osilodrostat (2 mg twice daily titrated gradually to achieve eucortisolaemia). With cortisol normalization, ACTH levels tripled suggesting increased tumor metabolic activity. After three months of sustained eucortisolaemia, repeat 11C-MET PET/CT revealed strikingly increased focal tracer avidity near the left cavernous sinus, providing a precise target for transsphenoidal surgery. Conclusion: This case illustrates a novel preoperative strategy for improving adenoma detection in CD. Cortisol-lowering therapy may enhance functional imaging sensitivity, enabling more accurate tumor localization and optimizing surgical outcomes. If validated in larger cohorts, this approach has the potential to significantly improve surgical cure rates while preserving normal pituitary function. Presentation: Monday, July 14, 2025