Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing's Disease after Surgery Treatment: A Longitudinal Study.

INTRODUCTION: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing's disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. METHODS: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. RESULTS: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. CONCLUSION: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment.

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, including occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, middle/posterior cingulate gyrus, and rolandic operculum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyrus, hippocampus, thalamus, and amygdala (p < 0.01, false discovery rate 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.