CRH stimulation improves 18F-FDG-PET detection of pituitary adenomas in Cushing's disease

Endocrine. 2019 Jul;65(1):155-165. doi: 10.1007/s12020-019-01944-7. Epub 2019 May 6.


Objective: In MRI-negative cases Cushing's disease (CD), surgeons perform a more extensive exploration of the pituitary gland, with fewer instances of hormonal remission. 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) has a limited role in detecting adenomas that cause CD (corticotropinomas). Our previous work demonstrated corticotropin-releasing hormone (CRH) stimulation leads to delayed, selective glucose uptake in corticotropinomas. Here, we prospectively evaluated the utility of CRH stimulation in improving 18F-FDG-PET detection of adenomas in CD.

Methods: Subjects with a likely diagnosis of CD (n = 27, 20 females) each underwent two 18F-FDG-PET studies [without and with ovine-CRH (oCRH) stimulation] on a high-resolution PET platform. Standardized-uptake-values (SUV) in the sella were calculated. Two blinded neuroradiologists independently read 18F-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins.

Results: The mean-SUV of adenomas was significantly increased from baseline (3.6 ± 1.5) with oCRH administration (3.9 ± 1.7; one-tailed p = 0.003). Neuroradiologists agreed that adenomas were visible on 21 scans, not visible on 26 scans (disagreed about 7, kappa = 0.7). oCRH-stimulation led to the detection of additional adenomas (n = 6) not visible on baseline-PET study. Of the MRI-negative adenomas (n = 5), two were detected on PET imaging (one only after oCRH-stimulation). USP8 mutations or glycolytic pathway proteins were not associated with SUV in corticotropinomas.

Conclusions: The results of the current study suggest that oCRH-stimulation may lead to increased 18F-FDG uptake, and increased rate of detection of corticotropinomas in CD. These results also suggest that some MRI invisible adenomas may be detectable by oCRH-stimulated FDG-PET imaging.

Clinical trial information: 18F-FDG-PET imaging with and without CRH stimulation was performed under the clinical trial NIH ID 12-N-0007 ( identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 ( identifier NCT00060541).

Keywords: CRH; Cushing’s disease; PET imaging; Pituitary adenoma; Secretagogue; Transsphenoidal surgery.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / diagnosis*
  • ACTH-Secreting Pituitary Adenoma / metabolism
  • ACTH-Secreting Pituitary Adenoma / pathology
  • Adenoma / diagnosis*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Child
  • Corticotropin-Releasing Hormone / metabolism*
  • Diagnosis, Differential
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / metabolism
  • Pituitary ACTH Hypersecretion / pathology
  • Positron-Emission Tomography / methods*
  • Sensitivity and Specificity
  • Young Adult


  • Fluorodeoxyglucose F18
  • Corticotropin-Releasing Hormone

Associated data