Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm

J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1816-e1826. doi: 10.1210/clinem/dgaa755.


Background: Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information.

Methods: Subjects with ACTH-dependent Cushing's syndrome (CS) (n = 27, 24 with Cushing's disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings.

Findings: 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production.

Conclusion: 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS.

Funding: None.

Keywords: 68Ga CRH PET-CT; BIPSS; Cushing’s; MRI; diagnostic imaging.

Publication types

  • Clinical Trial

MeSH terms

  • ACTH Syndrome, Ectopic / diagnosis
  • ACTH Syndrome, Ectopic / metabolism
  • ACTH-Secreting Pituitary Adenoma / diagnosis*
  • ACTH-Secreting Pituitary Adenoma / metabolism
  • ACTH-Secreting Pituitary Adenoma / pathology
  • Adenoma / diagnosis*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adolescent
  • Adrenocorticotropic Hormone / analysis
  • Adrenocorticotropic Hormone / metabolism
  • Adult
  • Cushing Syndrome / diagnosis
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / pathology
  • Diagnosis, Differential
  • Female
  • Gallium Radioisotopes
  • Humans
  • India
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Molecular Imaging / methods*
  • Petrosal Sinus Sampling
  • Receptors, Corticotropin-Releasing Hormone / analysis
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Young Adult


  • Gallium Radioisotopes
  • Receptors, Corticotropin-Releasing Hormone
  • Adrenocorticotropic Hormone