Use of [18F]FET PET-MRI to Improve Detection of Pituitary Adenomas in Cushing's Disease

In ACTH-dependent hypercortisolism it is important to distinguish between Cushing's disease (CD), with ACTH production by a pituitary neuroendocrine tumour (PitNET) and Cushing's syndrome (CS), with ectopic ACTH production. Bilateral inferior petrosal sinus sampling (IPSS) is the gold standard for this distinction, with a diagnostic accuracy of 98%. However, IPSS is an invasive procedure and an indi-rect diagnostic method, rarely providing reliable data on the exact location of the PitNET. This has a major impact on the therapeutic approach, short and long-term remission rates, and other outcomes. Hybrid Positron-emission tomography-Magnetic Resonance Imaging (PET-MRI) using O-(2-\[18F\]-fluo-roethyl)-L-tyrosine (\[18F\]FET) is promising in this respect. Recent data published by our research group demonstrate a a sensitivity of 100% a high accuracy in in the precise localization of ACTH-secreting PitNETs. We hypothesize that \[18F\]FET PET-MRI could become the new non-invasive diagnostic stand-ard, but data regarding a direct comparison between the diagnostic impact of \[18F\]FET PET-MRI versus IPSS in the differentiation between CD and ectopic CS are lacking. In addition, there are currently no other reliable biomarkers to distinguish the two disorders. The investigators hypothesize that the ACTH-dependent biomarker copeptin could be a valuable addition in this regard. The aim of this prospective diagnostic study is to compare the diagnostic accuracy of \[18F\]FET-PET-MRI and IPSS in differentiating CD from ectopic CS in patients with ACTH-dependent hypercortisolism.

Inclusion Criteria: * Age ≥18 years * Biochemically confirmed ACTH-dependent hypercortisolism, defined as: * Non-suppressed ACTH levels plus minimal 2 of the following: * Overnight 1mg dexamethasone suppression test \> 50 nmol/L * Elevated late night salivary cortisol (min. 2/3 measurements) * Elevated 24-hours urinary free cortisol (min. 2 measurements) * Pituitary microadenoma (\< 10mm) OR negative / inconclusive findings on standard MRI of the pituitary sella-region. * Indication for further evaluation with IPSS Exclusion Criteria: * Non-ACTH dependent hypercortisolism * Pituitary macroadenoma (≥ 10mm) * Suspicion of Pseudo-Cushing's disease (e.g. due to alcohol use disorder, PCO's, obesity, de-pression) according to standard work up / guidelines * use of glucocorticosteroids * Impaired renal function, defined as eGFR (MDRD) \