Rama Walia, Rahul Gupta, Anil Bhansali, Rosario Pivonello, Rajender Kumar, Harmandeep Singh, Chirag Ahuja, Rajesh Chhabra, Apinderpreet Singh, Sivashanmugam Dhandapani, Sushant Sahoo, Nivedita Rana, Rakhee Vatsa, Pinaki Dutta, Sanjay Kumar Bhadada, Naresh Sachdeva, B R Mittal, Uma Nahar, Jaya Shukla
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 4, April 2021, Pages e1816–e1826
https://doi.org/10.1210/clinem/dgaa755
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.
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.
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.
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.
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