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

Официальное название

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

Обзор

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.

Вмешательства

• Диагностический тест [18F]FET PET-MRI
  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 participan

Первичные конечные точки

• 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 [Срок оценки: 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.]

Вторичные конечные точки (6)

• Copeptin values during IPSS [Срок оценки: During the IPSS]
• ACTH values during IPSS [Срок оценки: 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 [Срок оценки: Follow-up data 3-6 months post-treatment]
• Exact localization of small functional PitNETs in patients with CD using the [18F]FET PET-MRI [Срок оценки: perioperative]
• Exact localization of small functional PitNETs in patients with CD using the inferior petrosal sinus sampling (IPSS) [Срок оценки: perioperative]
• Exact localization of small functional PitNETs in patients with CD using the structural MRI [Срок оценки: perioperative]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Нидерланды · 1 центр

• Erasmus University Medical Centre — Rotterdam

Швейцария · 1 центр

• University Hospital Basel — Basel

Идентификаторы

NCT: NCT07108244 · FIND study

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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