Osilodrostat therapy and 11C-methionine PET to IMprove corticotroph pituitary Adenoma detection and Localisation in patients with Cushing

Zin Htut; James MacFarlane; Heok Cheow; Debbie Papadopoulou; Waiel Bashari; Daniel Gillett; Mark Gurnell; Florian Wernig

doi:10.1530/endoabs.117.P171

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Endocrine Abstracts (2026) 117 P171 | DOI: 10.1530/endoabs.117.P171

SFEBES2026 Poster Presentations Neuroendocrinology and Pituitary (40 abstracts)

Osilodrostat therapy and 11C-methionine PET to IMprove corticotroph pituitary Adenoma detection and Localisation in patients with Cushing's disease (OPTIMAL); study design and rationale

Zin Htut ¹ , James MacFarlane ^2,3 , Heok Cheow ³ , Debbie Papadopoulou ⁴ , Waiel Bashari ³ , Daniel Gillett ³ , Mark Gurnell ^2,3 & Florian Wernig ^1,4

Author affiliations

¹Imperial College London, London, United Kingdom; ²University of Cambridge, Cambridge, United Kingdom; ³Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ⁴Imperial College Healthcare NHS Trust, London, United Kingdom

Background: Up to one-third of ACTH-secreting pituitary adenomas are occult on standard MRI. Functional imaging with ¹¹C-methionine PET/CT can improve adenoma localisation in MRI-negative or equivocal cases. Osilodrostat, a potent 11β-hydroxylase inhibitor, lowers cortisol and may raise ACTH via reduced negative feedback, potentially increasing adenoma metabolic activity and tracer uptake.

Objective: To determine whether short-term pre-operative osilodrostat enhances detectability of corticotroph adenomas on ¹¹C-methionine PET/CT and increases conspicuity on conventional MRI.

Methods: Single-arm, prospective observational study (n = 15 adults) with confirmed Cushing’s disease and absent/equivocal pituitary lesion on MRI. Participants undergo baseline ¹¹C-methionine PET/CT co-registered with MRI, then commence osilodrostat with titration to achieve eucortisolaemia over a period of 3–4 months, guided by biochemical monitoring including free cortisol measurements (urine and saliva). After a sustained period of eucortisolaemia, imaging is repeated. Primary endpoint: within–patient change in adenoma SUVmax values pre- vs post-treatment; a >20% increase is predefined as clinically meaningful. Secondary endpoint: within–patient change in MRI adenoma visibility/conspicuity. Exploratory endpoints: markers of bone turnover and hypercoagulability, plus clinical and quality-of-life measures. PET and MRI will be independently read by two experts radiologists with third-reader adjudication as required. Where imaging reveals a definitive surgical target, transsphenoidal surgery will be offered per MDT consensus; safety/tolerability of osilodrostat will be recorded.

Expected impact: If pharmacological optimisation with osilodrostat augments ¹¹C-methionine PET/CT signal and MRI conspicuity of corticotroph adenomas, this priming strategy could improve surgical targeting in MRI-negative or equivocal Cushing’s disease.