Reversibility of cerebral blood flow in patients with Cushing's disease after surgery treatment

Background and objectives: Cushing's disease (CD) patients have metabolic abnormalities in the brain caused by excessive exposure to endogenous cortisol. However, the reversibility of brain metabolism of CD patients after treatment remains largely unknown. Methods: This study recruited 50 CD patients seeking treatment and 34 matched normal controls (NCs). The patients were treated with Transsphenoidal Adenomectomy (TSA) and reexamined 3 months later. Cerebral blood flow (CBF) of the patients was assessed using 3D pseudo-continuous arterial spin labelling (PCASL) imaging before the treatment and at the 3-month follow-up and were compared with CBF measure of the NCs using a whole-brain voxelwise group comparison method. For remitted patients, their CBF measures and hormone level measures, including adrenocorticotropic hormone (ACTH), 24-hour urinary free cortisol (24hUFC) and serum cortisol, were compared before and after the treatment Finally, a correlation analysis was carried out to explore the relationship between changes of CBF and hormone level measures of the remitted CD patients. Results: After the treatment, 45 patients reached remission. Compared with the NCs, the CD patients before the treatment exhibited significantly reduced CBF in cortical regions, induding occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, midd lelposterior cingulate gyms, and rolandic open alum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyms, hippocampus, thalamus, and amygdala (p < 0.01, false discovery rale corrected). For the remitted patients, the change in CBF before and after the treatment displayed a spatial pattern similar to the difference between the NCs and the CD patients before the treatment, and no significant difference in CBF was observed between the NCs and the remitted CD patients after the treatment. The changes of 24hUFC were significantly correlated with the changes of averaged CBF within the subcortical region in the remitted patients (p = 0.01). Conclusions: Our findings demonstrate that the brain metabolic abnormalities of CD patients are reversible when their hormone level changes towards normal after surgery treatment. (C) 2019 Elsevier Inc. All rights reserved.