Adrenal Vein Sampling as a Tool to Identify Biomarkers That Aid the Diagnosis of Adrenocortical Carcinoma

Study Overview
=================
Brief Summary
-----------------
The goal of this observational pilot study is to explore whether we can identify biomarkers predictive for the diagnosis of adrenocortical carcinoma in blood. Five participants who are suspected to have adrenocortical carcinoma will undergo an adrenal vein sampling in order to obtain a blood sample from the adrenal vein. This blood sample will be analyzed and compared to blood samples taken from the adrenal vein of 20 control patients, which are patients who do not have adrenocortical carcinoma. The blood samples of the control patients will be drawn during routine medical care.

Official Title
-----------------
Adrenal Vein Sampling as a Tool to Identify Biomarkers That Aid the Diagnosis of Adrenocortical Carcinoma

Conditions
-----------------
Adrenocortical Carcinoma

Intervention / Treatment
-----------------
* Other: Blood sampling.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In order to be eligible to participate in the study group, a subject must meet all of the following criteria: Patient age ≥18 years High clinical suspicion of adrenocortical carcinoma, based on clinical signs (due to hormonal overproduction), steroid hormone profile and radiological features (e.g. tumor size ≥4cm, inhomogenous aspect and tumor attenuation of HU ≥10) Able to provide signed informed consent In order to be eligible to participate in the control group, a subject must meet all of the following criteria: Patient age ≥18 years Routine diagnostic process includes AVS No suspicion of malignancy Able to provide signed informed consent Exclusion Criteria: Patients are not able to participate if: They have a known allergy to (iodinated) contrast fluid They use vitamin K antagonizing anticoagulants or DOAC's, except for when on the day of the adrenal vein sampling the anticoagulants are already stopped for the following adrenal surgery, and in case of using vitamin K antagonizing anticoagulants the INR is <3 The platelet count is below 20 Anatomy of the adrenal vein is not suitable for performing the AVS procedure, based on the judgement of an experienced interventional radiologist Contraindications for use of Synacthen They have a known hypersensitivity to any of the substances of Synacthen They are pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Five patients with strong clinical suspicion of adrenocortical carcinoma | Other: Blood sampling.<br>* Blood samples from both study groups, taken during an adrenal vein sampling, will be compared across the groups.<br>|
| Control group<br>Twenty patients without suspicion of adrenal malignancy. These patients should undergo an adrenal vein sampling as part of their routine diagnostics. | Other: Blood sampling.<br>* Blood samples from both study groups, taken during an adrenal vein sampling, will be compared across the groups.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MicroRNA profile | miRNAs with a log2Fold change > |1| difference in expression in patient compared to control samples. | Analyses will be done at the end of inclusion of all patients, this will be after 2 years. Blood drawn before surgery/treatment will be analysed. | 
| Presence of mutations in ctDNA | Presence of mutations will be assessed in patient samples and compared to control samples | Analyses will be done at the end of inclusion of all patients, this will be after 2 years. Blood drawn before surgery/treatment will be analysed | 
| ctDNA methylation pattern | Differentially methylated probes and differentially methylated regions will be assessed as those with a beta >0.8 and <0.2 | Analyses will be done at the end of inclusion of all patients, this will be after 2 years. Blood drawn before surgery/treatment will be analysed | 
| Steroid profile | Laboratory values will be compared using Mann-Whitney-U tests | Analyses will be done at the end of inclusion of all patients, this will be after 2 years. Blood drawn before surgery/treatment will be analysed |