Abstract
Long-term remitted Cushing’s disease (LTRCD) patients commonly continue to present persistent psychological and cognitive deficits, and alterations in brain function and structure. Although previous studies have conducted gray matter volume analyses, assessing cortical thickness and surface area of LTRCD patients may offer further insight into the neuroanatomical substrates of Cushing’s disease. Structural 3T magnetic resonance images were obtained from 25 LTRCD patients, and 25 age-, gender-, and education-matched healthy controls (HCs). T1-weighted images were segmented using FreeSurfer software to extract mean cortical thickness and surface area values of 68 cortical gray matter regions and two whole hemispheres. Paired sample t tests explored differences between the anterior cingulate cortex (ACC; region of interest), and the whole brain. Validated scales assessed psychiatric symptomatology, self-reported cognitive functioning, and disease severity. After correction for multiple comparisons, ROI analyses indicated that LTRCD-patients showed reduced cortical thickness of the left caudal ACC and the right rostral ACC compared to HCs. Whole-brain analyses indicated thinner cortices of the left caudal ACC, left cuneus, left posterior cingulate cortex, right rostral ACC, and bilateral precuneus compared to HCs. No cortical surface area differences were identified. Cortical thickness of the left caudal ACC and left cuneus were inversely associated with anxiety symptoms, depressive symptoms, and disease duration, although certain associations did not persist after correction for multiple testing. In six of 68 regions examined, LTRCD patients had reduced cortical thickness in comparison to HCs. Cortical thickness of the left caudal ACC was inversely associated with disease duration. This suggests that prolonged and excessive exposure to glucocorticoids may be related to cortical thinning of brain structures involved in emotional and cognitive processing.
Highlights
Cushing’s disease (CD), a rare endocrine disorder that is caused by an adrenocorticotropic hormone (ACTH) producing pituitary adenoma, is the most common etiology of endogenous Cushing’s syndrome (CS1)
Within the Long-term remitted Cushing’s disease (LTRCD)-patient group, we investigated whether cortical thickness and surface area measures of regions that showed significant differences in the regions of interest (ROI) and whole-brain analyses correlated with measures of
We found smaller cortical thickness in several key regions for emotional and cognitive processing: the left caudal and right rostral anterior cingulate cortex (ACC), the left cuneus, left posterior cingulate cortex, and bilateral precuneus in LTRCD patients compared with controls, while no significant differences in surface area between the groups were observed
Summary
Cushing’s disease (CD), a rare endocrine disorder that is caused by an adrenocorticotropic hormone (ACTH) producing pituitary adenoma, is the most common etiology of endogenous Cushing’s syndrome (CS1). GC exposure can cause psychiatric symptomology (e.g., Bauduin et al Translational Psychiatry (2020)10:293 an anxiodepressive-like phenotype in animals10,11), which has been linked to structural and functional changes of certain limbic structures, such as the hippocampus and the anterior cingulate cortex (ACC12). In line with these preclinical study findings, long-term exposure to high levels of cortisol in (remitted) CD patients has been associated with functional and structural alterations in similar limbic areas[13].
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