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

NCT07108244 | Enrolling By Invitation

• 1 other identifier: FIND study
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Cushing Disease

Outcome Measures

Primary Outcomes (1)

• Comparison of the proportion of correct distinctions between CD and ectopic CS in patients with ACTH-dependent hypercortisolism using [18F]FET PET-MRI versus IPSS

  The difference in the proportion of correct distinction between CD and ectopic CS in patients with ACTH-dependent hypercortisolism using \[18F\]FET PET-MRI versus IPSS

  Patients will receive standard surgical or radiotherapeutic treatment. The study will collect follow-up data 3-6 months post-treatment without influencing clinical management or requiring study-specific visits.

Secondary Outcomes (6)

• Copeptin values during IPSS

  During the IPSS

• ACTH values during IPSS

  During the IPSS

• Comparison of the diagnostic accuracy between [18F]FET PET-MRI and IPSS for differentiating between CD and ectopic CS in patients with ACTH-dependent hy-percortisolism

  Follow-up data 3-6 months post-treatment

• Exact localization of small functional PitNETs in patients with CD using the [18F]FET PET-MRI

  perioperative

• Exact localization of small functional PitNETs in patients with CD using the inferior petrosal sinus sampling (IPSS)

  perioperative

Study Arms (1)

[18F]FET-PET-MRI vs IPSS for diagnosing CD vs ectopic CS in ACTH-dependent cases

OTHER

Participants will undergo both \[18F\]FET-PET-MRI and inferior petrosal sinus sampling (IPSS) to evaluate their diagnostic performance in differentiating Cushing's disease from ectopic ACTH secretion. Results of both procedures will be made available to the treating medical team and participants as they become available.

Diagnostic Test: [18F]FET PET-MRI

Interventions

[18F]FET PET-MRI DIAGNOSTIC_TEST

All participants will undergo both \[18F\]fluoroethyltyrosine positron emission tomography-magnetic resonance imaging (\[18F\]FET-PET-MRI) and inferior petrosal sinus sampling (IPSS) as part of the diagnostic work-up for ACTH-dependent hypercortisolism. The purpose is to compare the diagnostic accuracy of these two modalities in distinguishing Cushing's disease from ectopic ACTH secretion. The results from both diagnostic tests will be communicated to the treating medical team and the participant to guide further clinical management.

[18F]FET-PET-MRI vs IPSS for diagnosing CD vs ectopic CS in ACTH-dependent cases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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) \<30ml/min/1,73 m2. An exception can be made in consultation with the treating physician.
• Impaired Liver function
• Pregnancy/breastfeeding. For the latter, temporary discontinuation may be considered.
• Known allergic reaction to therapeutic radiopharmaceuticals.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Erasmus Medical Center: collaborator

Study Sites (2)

Erasmus University Medical Centre

Rotterdam, South Holland, 3015, Netherlands

Location

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 6, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): July 30, 2029
• Study Completion (Estimated): July 30, 2029
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); NL (1)