Impact of [11C]-Methionine PET/MRI in the Detection of Pituitary Adenomas Secreting ACTH and Causing Cushing's Disease (IMPEC)

Cushing's disease is characterized by the existence of a benign pituitary tumor developed from corticotropic cells responsible for excessive ACTH secretion. This results in hypercorticism causing high morbidity and mortality and severely impairing quality of life. The etiological diagnosis is based on Magnetic Resonance Imaging (MRI). However, pituitary MRI revealed a pituitary tumor in only 60% of patients. The diagnostic procedure is complicated by the existence of extra pituitary tumors responsible for ACTH ectopic secretion. This rare etiology imposes, in the absence of typical pituitary image, the realization of catheterization of the lower petrosal sinuses. Treatment of Cushing's disease is based on transsphenoidal surgical management, even in the absence of a formal MRI image, if pituitary origin is confirmed by the catheterization. Although pituitary surgery without identified target is part of French recommendations, this surgery is associated with a high risk of failure and morbidity. Optimization of the management of patients' with Cushing's disease thus requires the improvement of the diagnostic methods.

Hypothesis of our study is that [11C] MET MRI-PET may be performed as a first-line MRI for suspected Cushing's disease and may limit indications for catheterization of lower petrosal sinuses. Its localizing value should also make it possible to improve the surgical results with a better identification of the adenoma

Study Overview

• Status: Completed
• Conditions: Cushing's Disease
• Intervention / Treatment: Other: [11C]-Methionine PET/MRI

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Service de Médecine Nucléaire - Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years old or over
• Patient with a diagnosed Cushing's disease according to the French "protocole national de diagnostic et de soins (PNDS)"
• Patient who underwent a MRI pituitary for diagnostic purposes
• Patient who have undergone catheterization of the lower petrosal sinuses (if MRI does not detect pituitary adenoma) and have a result in favor of a central secretion of ACTH
• Patient having an indication of surgical excision of the adenoma
• Patient with a micro-adenoma (less than 1 cm in diameter) if the tumor is visualized on MRI
• Patient for which informed and written consent to participate has been obtained.

Exclusion Criteria:

• - Patient participating in another study
• Patient with a pituitary macro-adenoma with visual impairment
• Patient with ACTH-dependent Cushing's syndrome secondary to ectopic ACTH secretion
• Patient with recurrence and / or history of pituitary adenoma excision
• Patient with a contraindication to pituitary surgery or general anesthesia
• Pregnant woman, breastfeeding or old enough to have children but without effective recognized contraception
• Contra-indication to the realization of an MRI: permanently fixed metal parts (pacemaker, cerebral clip, cephalic end piercing, cochlear implant, pin or screw for recent bone fracture, dental equipment, metal splinters), claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Cushing's disease; Implementation of [11C]-Methionine PET/MRI	Other: [11C]-Methionine PET/MRI; Implementation [11C]-Methionine PET/MRI performed for each patient in one place (department of nuclear medicine of the Hospices Civils de Lyon). The [11C]-Methionine PET/MRI will be performed after a pituitary MRI and before a transsphenoidal surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of [11C]-Methionine PET/MRI	Sensitivity of [11C]-Methionine PET/MRI to correctly localizes the pituitary corticotropic adenoma in comparison with the sensitivity of the pituitary MRI. The gold standard being the localization defined by anatomopathological analysis on operative resection.	Within 3 months and 3 weeks after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
False negatives and false positives description	Description of false negatives and false positives [11C]-Methionine PET/MRI to identify and localize the microadenoma. Characteristics of unidentified adenomas will be described using: volume, localization, type of fixation	Within 3 months and 3 weeks after inclusion
Description of identified microadenomas	Proportion of microadenomas identified by the [11C]-Methionine PET/MRI as a function of the degree of aggressiveness of the adenoma, evaluated by the number of mitoses, the level of expression of Ki67 and p53.	Within 3 months and 3 weeks months after inclusion
Comparison of [11C]-Methionine PET/MRI and pituitary MRI	Study of the concordance between the results of [11C]-Methionine PET/MRI and pituitary MRI	Within 3 months and 3 weeks months after inclusion

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Study Director: BOURNAUD Claire, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2017
• Primary Completion (Actual): June 11, 2019
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: November 15, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: : Cushing's disease, [11C]-Methionine PET/MRI, Sensitivity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
• Other Study ID Numbers: 69HCL17_0167; 2017-002721-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No