New types of localization methods for adrenocorticotropic hormone-dependent Cushing's syndrome

The management of endogenous Cushing's syndrome (CS) typically involves two key steps: (i) confirmation of autonomous hypercortisolism and (ii) localization of the cause to guide treatment. Adrenocorticotropic hormone (ACTH)-dependent CS is most commonly due to a pituitary corticotrope tumor which may be so small as to evade detection on conventional magnetic resonance imaging (MRI). Although biochemical testing (e.g., corticotropin stimulation; dexamethasone suppression) can provide an indication of the likely origin of ACTH excess, bilateral inferior petrosal sinus catheterization offers greater accuracy to distinguish pituitary-driven CS [Cushing's Disease (CD)] from the ectopic ACTH syndrome [EAS, e.g., due to a bronchial or pancreatic neuroendocrine tumor (NET)]. In patients with CD, 40-50% may not have a pituitary adenoma (PA) readily visualized on standard clinical MRI. In these subjects, alternative MR sequences (e.g., dynamic, volumetric, fluid attenuation inversion recovery) and higher magnetic field strength (7T > 3T > 1.5T) may aid tumor localization but carry a risk of identifying coincidental (non-causative) pituitary lesions. Molecular imaging is therefore increasingly being deployed to detect small ACTH-secreting PA, with hybrid imaging [e.g., positron emission tomography (PET) combined with MRI] allowing precise anatomical localization of sites of radiotracer (e.g., C-11-methionine) uptake. Similarly, small ACTH-secreting NETs, missed on initial cross-sectional imaging, may be detected using PET tracers targeting abnormal glucose metabolism (e.g., F-18- fluorodeoxyglucose), somatostatin receptor (SSTR) expression (e.g., Ga-68- DOTATATE), amine precursor (e.g., F-18-DOPA) or amino acid (e.g., C-11-methionine) uptake. Therefore, modern management of ACTH-dependent CS should ideally be undertaken in specialist centers which have an array of cross-sectional and functional imaging techniques at their disposal. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The management of endogenous Cushing's syndrome involves confirming autonomous hypercortisolism and localizing the cause, typically a pituitary corticotrope tumor or an ectopic ACTH syndrome due to a neuroendocrine tumor. Advanced imaging techniques such as MRI with higher field strength and molecular imaging like PET are becoming increasingly important in accurately identifying small tumors that may not be visualized on standard MRI. Specialized centers with a range of imaging techniques are ideal for managing ACTH-dependent CS effectively.