MON-022 - Osilodrostat Therapy and 11C-Methionine PET to Improve Corticotroph Pituitary Adenoma Detection and Localisation in Patients with Cushing Disease (OPTIMAL); Study Design and Rationale

Background:
Approximately one-third of ACTH-secreting pituitary adenomas are not detectable on conventional MRI. In patients with negative or indeterminate MRI findings, functional imaging with ¹¹C-methionine PET/CT has been shown to improve localisation of corticotroph adenomas. Osilodrostat, a selective 11β-hydroxylase inhibitor, suppresses cortisol synthesis and may lead to secondary elevation in ACTH through attenuation of negative feedback, thereby potentially enhancing corticotroph adenoma metabolic activity and radiotracer uptake.

Objective:
To evaluate whether short-term pre-operative osilodrostat improves the detectability of corticotroph adenomas on 11C-methionine PET/CT and enhances lesion visibility on conventional pituitary MRI in patients with Cushing disease.

Methods:
This is a single-arm, prospective observational study enrolling 15 adults with biochemically confirmed Cushing disease and absent or equivocal pituitary lesions on MRI. Participants undergo baseline ¹¹C-methionine PET/CT co-registered with pituitary MRI, followed by initiation of osilodrostat therapy. Osilodrostat dosing is titrated over 3–4 months to achieve and maintain eucortisolaemia, guided by serial biochemical monitoring. After a sustained period of biochemical control, PET/CT and MRI are repeated.
The primary endpoint is the within-patient change in adenoma maximum standardised uptake value (SUVmax) between baseline and post-treatment PET/CT, with a >20% increase predefined as clinically meaningful.
The secondary endpoint is the within-patient change in adenoma visibility and conspicuity on pituitary MRI.
Exploratory endpoints include changes in biochemical markers of bone turnover and hypercoagulability, as well as clinical outcomes and quality-of-life measures.
PET and MRI scans will be independently reviewed by two expert radiologists, with adjudication by a third-reader in cases of disagreement. When imaging identifies a definitive surgical target, transsphenoidal surgery will be offered following multidisciplinary team consensus. Safety and tolerability of osilodrostat will be assessed throughout the study.
Expected impact:
If pharmacological priming with osilodrostat enhances ¹¹C-methionine PET/CT signal intensity and improves MRI conspicuity of corticotroph adenomas, this strategy may facilitate more accurate surgical localisation and targeting in patients with MRI-negative or equivocal Cushing disease.

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