MON-021 - Brain Evaluation in Cushing Disease: A Longitudinal Pilot Study

Introduction
Impairments in cognition, mood, and quality of life (QoL) may persist after treatment for Cushing disease (CD) and are important symptoms to patients. Prospective studies incorporating structural and perfusion MRI evaluation at defined pre- and postoperative intervals are lacking and may help delineate neuropsychiatric recovery.

Hypothesis
Cognition, self-reported outcomes, cerebral hemodynamics, and clinical variables influence the residual neuropsychiatric burden.

Methods
We conducted a preliminary analysis of an ongoing longitudinal study of patients with CD enrolled before and followed up to 2 years after surgery for CD. Patients underwent assessment of quality of life (Cushing QoL, SF-36), mood (PROMIS anxiety, depression, sleep surveys), muscle strength (hand grip), and cognition (validated neuropsychological testing). We performed Arterial Spin Labeling MRI to measure cerebral blood flow (CBF) and arterial transit time (ATT), alongside the volumetric analysis on structural MRI. We calculated hypercortisolism clinical severity score (CSS) based on comorbidities and physical exam features (PMID 37327378).

Results
A total of 8 subjects (7 female/1 male, mean age 46.5 +/- 11.1 years) completed the baseline (BL) visit and the first post-operative visit 3-4 months after pituitary surgery. Following surgery, 5 patients became hypocortisolemic and 1 normocortisolemic. Of the 2 hypercortisolemic patients, 1 received medical treatment for CD. Compared to BL, mean weight decreased from 95.3 +/- 8.9 to 90.5 +/- 8.1 kg (P=0.018). Hand grip strength declined from 30.3 +/- 7.2 to 27.5 +/- 8.6 (P=0.028). Mean anxiety scores improved from 57.5 +/- 11.2 to 52.1 +/- 10.3 (P=0.043). A linear regression model including BL anxiety and CSS predicted anxiety post-surgery (P=0.042), with BL anxiety, but not CSS, as an independent predictor. Depression and sleep scores post-surgery were similar to BL. SF-36 mental component summary improved from 36.9 +/- 14.2 to 42.2 +/-11.5 (P=0.048), but physical component summary did not change. Mean Cushing QoL score improved from 35.4 +/- 21.8 to 54.2 +/- 16.5 (P=0.036). Post-surgery, cognitive measures did not differ from BL, while imaging comparisons revealed increased CBF and decreased ATT along major brain networks and increased regional brain volumes and cortical thickness.

Conclusion
At 3 months post-surgery for CD, improvement in anxiety, quality of life (mental health component), and structural brain parameters were observed compared to BL, while cognitive function was unchanged. Our findings highlight differences in timeline of recovery and the importance of multidisciplinary care to address neuropsychiatric symptoms. Our results require confirmation with larger samples and repeated evaluation during longer follow-up period.

Funding: This project was supported by an investigator-initiated grant from Recordati.

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