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Enrolling by Invitation

NCT Number: NCT07108244

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.

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Key information

Conditions

Cushing Disease Brain Diseases Central Nervous System Diseases Endocrine System Diseases Hyperpituitarism Hypothalamic Diseases Nervous System Diseases Pituitary ACTH Hypersecretion Pituitary Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Erasmus University Medical Centre, Rotterdam, South Holland, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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) <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.

Treatment and study plan

[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.

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

    Time frame: 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.

    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

Secondary outcomes

  1. Copeptin values during IPSS

    Time frame: During the IPSS

    Best fit of diagnostic copeptin values for differentiation between CD and ectopic CS with the inferior petrosal sinus sampling (IPSS) after desmopressin injection,

  2. ACTH values during IPSS

    Time frame: During the IPSS

    Best fit of diagnostic ACTH values for differentiation between CD and ectopic CS with the inferior petrosal sinus sampling (IPSS) after desmopressin injection

  3. 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

    Time frame: Follow-up data 3-6 months post-treatment

    ROC AUC of the [18F]FET PET-MRI and IPSS in differentiating CD from ectopic CS Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the [18F]FET PET-MRI and IPSS for differentiation between CD and ectopic CS

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

    Time frame: perioperative

    Stated as left, central or right side, assessed by an experienced nuclear medicine physician and neuroradiologist Sensitivity, specificity, PPV and NPV of the [18F]FET PET-MRI for the exact localization of small functional PitNETs in patients with CD

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

    Time frame: perioperative

    Sensitivity, specificity, PPV and NPV of the IPSS for the exact localization of small functional PitNETs in patients with CD

  6. Exact localization of small functional PitNETs in patients with CD using the structural MRI

    Time frame: perioperative

    Sensitivity, specificity, PPV and NPV of the structural MRI for the exact localization of small functional PitNETs in patients with CD

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

  • Erasmus Medical Center

Registry information

Official study title

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

Acronym: FIND

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Aug 6, 2025
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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