Evaluating the Functional Status of the Adrenal Glands With [68Ga]Ga-PentixaFor in Hyperaldosteronism and Hypercortisolism

Background: The adrenal glands are 2 small organs that sit on top of each kidney. They release hormones; these are chemicals that control how the body works. Tumors on or outside the adrenal glands are called functional if they release hormones; they are called nonfunctional if they do not. Doctors who treat adrenal tumors need to know which type a person has. Researchers want to find better ways to learn whether an adrenal tumor is functional. Objective: To see if a new radioactive tracer (\[68Ga\]Ga-PentixaFor) can make it easier to identify functional adrenal tumors with positron emission tomography (PET) scans. Eligibility: People aged 18 years and older with 1 or more adrenal tumors. They must have increased levels of the hormones aldosterone or cortisol. They must also be enrolled in at least 1 other related NIH study (protocols 19-DK-0066, 18-CH-0031, or 09-C-0242). Design: Participants will be screened. They may have imaging scans. Their ability to perform normal activities will be reviewed. Participants will have one PET scan with the study tracer. The tracer will be given through a tube attached to a needle inserted into a vein. Participants will receive the tracer 1 hour before the scan. They will lie still on a bed while a machine captures images of the inside of their body. The scan will take 45 to 90 minutes. Participants heart rate, blood pressure, and rate of breathing will be checked before, during, and after the scan. Participants will have a follow-up visit 3 days after their scan. This visit can be by phone, email, or in person.

Background: * \[68Ga\]Ga-PentixaFor is a PET agent targeting the C-X-C chemokine receptor type 4 (CXCR4) with promising applications in oncology, cardiology, and infectious disease. * CXCR4 has also been noted to show high expression in many aldosterone-producing adenomas (APA) and some cortisol-producing adenomas (CPA) but not usually in nonfunctioning adenomas. * \[68Ga\]Ga-PentixaFor may be useful in the evaluation of adrenal adenomas in the setting of Conn's or Cushing's syndrome. Localizing functional adenomas is important for managing treatment options but current imaging modalities are either too invasive or insufficiently able to differentiate adrenal conditions. Objective: -To estimate the percent concordance of \[68Ga\]Ga-PentixaFor imaging with clinical diagnosis in identifying functional adrenal or extra-adrenal adenomas in hyperaldosteronism and hypercortisolism Eligibility: * Must have any of the following: * one or more adrenal masses on CT and/or MRI and biochemical evidence of excess aldosterone or * ACTH-independent hypercortisolism with or without adrenal masses on CT and/or MRI or * history of ACTH-dependent hypercortisolism (with or without adrenal enlargement) * Age \>= 18 years * ECOG performance status \<= 2 Design: * This is a Phase II, single site study where participants from three cohorts are enrolled into one arm according to their probable disease: primary aldosteronism (Cohort 1), ACTHindependent Cushing's syndrome (Cohort 2), or ACTH-dependent Cushing's syndrome (Cohort 3). * All participants will undergo a \[68Ga\]Ga-PentixaFor PET/CT or \[68Ga\]Ga-PentixaFor PET/MR. * A safety visit will be performed 3 days following the \[68Ga\]Ga-PentixaFor imaging. * Participants will remain on-study for up to 1 year to allow the collection of samples for correlative analysis from the parent protocol (adrenal venous sampling, imaging assessments, laboratory evaluations, and/or tissue samples).