DDAVP‑stimulated FDG PET to find hidden pituitary microadenomas

Desmopressin (DDAVP) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing's Disease

This study will try using a DDAVP injection followed by a high-resolution FDG PET scan to find small pituitary tumors in people with Cushing's disease whose MRIs don't show a clear tumor.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 8 Years to 99 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04569591 on ClinicalTrials.gov

What this trial studies

This single-center trial gives DDAVP and then, about four hours later, intravenous 18F-FDG followed by high-resolution PET imaging to detect MRI-negative pituitary microadenomas in patients with Cushing's disease. Participants with PET imaging will proceed to surgical resection within 24 weeks, and the surgical and histopathologic findings will serve as the reference standard for tumor location. All PET images will be read independently by neuroradiologists blinded to clinical and pathology outcomes, and PET localization will be compared directly with histopathology. The protocol uses clinically validated preoperative tools to improve localization of small corticotropinomas that are occult on MRI.

Who should consider this trial

Good fit: Ideal candidates are people aged 8 or older with biochemical confirmation of Cushing's disease, a negative or equivocal pituitary MRI, and who are surgical candidates able to undergo PET without general anesthesia.

Not a fit: Patients unlikely to benefit include those with a clearly visible pituitary tumor on MRI, those who are not surgical candidates, those who cannot tolerate PET imaging, or those whose tumors do not take up FDG.

Why it matters

Potential benefit: If successful, this approach could help surgeons find and remove tiny pituitary tumors more reliably, improving cure rates and reducing the need for repeat operations.

How similar studies have performed: Previous work has used DDAVP and other stimulation tests for ACTH localization and FDG PET in small series, but combining DDAVP stimulation with high-resolution FDG PET for MRI-negative corticotropinomas is relatively novel with limited prior data.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Subjects aged 8 or older with biochemical evidence of Cushing s disease and a clinical MRI pituitary neuroradiology result of negative or possible adenoma (e.g. "no tumor" or "possible tumor")
2. MRI of the pituitary gland with and without contrast obtained within 9 months of screening
3. For newly diagnosed Cushing s disease cases, IPSS is required.
4. Ability to undergo PET-imaging without general anesthesia
5. Ability to provide informed consent for study participation (parents or guardians in the case of minors)
6. Clinical diagnosis of Cushing s disease based on documented medical records
7. Surgical candidate for and subject agrees to resection of ACTH producing pituitary adenoma within 24 weeks of PET-imaging
8. Normal liver function as evidenced by liver enzyme tests completed within 14 days before injection of radiopharmaceutical: SGOT, SGPT \<= 5 x upper limit of normal; bilirubin \<= 2 x upper limit of normal
9. Tolerance of a previous infusion of DDAVP, including as part of workup and diagnosis of Cushing's disease

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Current pregnancy or lactation
2. Glomerular filtration rate \< 50 mL/min/1.73 m\^2, hepatorenal syndrome, history of urinary retention or post-liver or kidney transplantation.
3. Hyponatremia (serum sodium below 135 mmol/L)
4. Current diagnosis of angina, significant coronary artery disease, congestive heart failure, or SIADH due to risk of fluid overload and/or hyponatremia.
5. Uncontrolled hypertension (blood pressure \>150/95 mmHg) due to risk of further increase if fluid overload occurs.
6. Uncontrolled, severe hypotension (sustained blood pressure \<90/60), or symptomatic hypotension.
7. Current use of any of the following medications:

   * Vasopressors: phenylephrine, dopamine and vasopressin
   * Drugs that can worsen hyponatremia: non-steroidal anti-inflammatory drugs (NSAIDs) within 4 days of testing, loop diuretics (bumetanide, ethacrynic acid, furosemide, torsemide), chlorpromazine, chlorpropamide, cisplatin, opiate agonists within 48 hours of testing, and/or vincristine.
   * Drugs that interfere with DDAVP duration of action or potency: carbamazepine, lamotrigine, and/or tolvaptan
8. Habitual or psychogenic polydipsia, due to increased risk of hyponatremia
9. History of Type IIB von Willebrand s disease due to risk for thrombosis.
10. Elevated blood glucose level above 200 mg/dL on the day of the scan prior to FDG administration.
11. Known intolerance to DDAVP

INCLUSION OF VULNERABLE PARTICIPANTS:

* Children: Children age 8 and older are included in this protocol. More than half of the subjects with CD requiring transsphenoidal surgery at the NIH are children. The knowledge gained by the use of DDAVP PET imaging in children with MR-invisible tumors will provide generalizable knowledge in the treatment of CD in this population. Children under the age of 8 usually require anesthesia for a PET scan, which involves greater risk. Therefore, children under the age of 8 will be excluded from participation.
* Pregnant or lactating women: Pregnant and lactating women will be excluded from participation. The PET radiopharmaceutical used in this study can be harmful to a developing fetus. Therefore women who are able to become pregnant will have a pregnancy test performed within 24 hours before PET imaging. Individuals will not be able to participate in PET scanning if the pregnancy test results positive.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Prashant Chittiboina, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
• Study coordinator: Christina P Hayes, C.R.N.P.

Conditions: Cushing's Disease, Pituitary Adenoma, Corticotropinoma, Pituitary Microadenoma, Acthrel