White matter alterations in the brains of patients with active, remitted, and cured cushing syndrome: a DTI study.
OBJECTIVE
Cushing syndrome appears after chronic exposure to elevated glucocorticoid levels. Cortisol excess may alter white matter microstructure. Our purpose was to study WM changes in patients with Cushing syndrome compared with controls by using DTI and the influence of hypercortisolism.


METHODS
Thirty-five patients with Cushing syndrome and 35 healthy controls, matched for age, education, and sex, were analyzed through DTI (tract-based spatial statistics) for fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity (general linear model, family-wise error, and threshold-free cluster enhancement corrections, P < .05). Furthermore, the influence of hypercortisolism on WM DTI changes was studied by comparing 4 subgroups: 8 patients with Cushing syndrome with active hypercortisolism, 7 with Cushing syndrome with medication-remitted cortisol, 20 surgically cured, and 35 controls. Cardiovascular risk factors were used as covariates. In addition, correlations were analyzed among DTI values, concomitant 24-hour urinary free cortisol levels, and disease duration.


RESULTS
There were widespread alterations (reduced fractional anisotropy, and increased mean diffusivity, axial diffusivity, and radial diffusivity values; P < .05) in patients with Cushing syndrome compared with controls, independent of the cardiovascular risk factors present. Both active and cured Cushing syndrome subgroups showed similar changes compared with controls. Patients with medically remitted Cushing syndrome also had reduced fractional anisotropy and increased mean diffusivity and radial diffusivity values, compared with controls. No correlations were found between DTI maps and 24-hour urinary free cortisol levels or with disease duration.


CONCLUSIONS
Diffuse WM alterations in patients with Cushing syndrome suggest underlying loss of WM integrity and demyelination. Once present, they seem to be independent of concomitant hypercortisolism, persisting after remission/cure.
From the Asociación para la Innovación en Análisis, Gestión y Procesamiento de Datos Científicos y Tecnológicos (P.P., Y.V.-G.), Barcelona, Spain Departments of Endocrinology/Medicine (P.P., A.S., S.M.W., E.R., I.C.), Hospital Sant Pau, IIB-Sant Pau, Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona, Barcelona, Spain.
P
P
Pires
Departments of Endocrinology/Medicine (P.P., A.S., S.M.W., E.R., I.C.), Hospital Sant Pau, IIB-Sant Pau, Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona, Barcelona, Spain.
A
A
Santos
From the Asociación para la Innovación en Análisis, Gestión y Procesamiento de Datos Científicos y Tecnológicos (P.P., Y.V.-G.), Barcelona, Spain Port d'Informació Científica (Y.V.-G., A.S.-R.), Bellaterra, Barcelona, Spain.
Y
Y
Vives-Gilabert
Departments of Endocrinology/Medicine (P.P., A.S., S.M.W., E.R., I.C.), Hospital Sant Pau, IIB-Sant Pau, Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona, Barcelona, Spain.
S M
SM
Webb
Port d'Informació Científica (Y.V.-G., A.S.-R.), Bellaterra, Barcelona, Spain Institut de Fisica d'Altes Energies (A.S.-R.), Barcelona, Spain.
A
A
Sainz-Ruiz
Departments of Endocrinology/Medicine (P.P., A.S., S.M.W., E.R., I.C.), Hospital Sant Pau, IIB-Sant Pau, Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona, Barcelona, Spain.
E
E
Resmini
Departments of Endocrinology/Medicine (P.P., A.S., S.M.W., E.R., I.C.), Hospital Sant Pau, IIB-Sant Pau, Instituto de Salud Carlos III, and Universitat Autònoma de Barcelona, Barcelona, Spain.
I
I
Crespo
Neuroradiology Unit (M.d.J.-D., B.G.-A.), Hospital Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
M
M
de Juan-Delago
Neuroradiology Unit (M.d.J.-D., B.G.-A.), Hospital Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. BGomezA@santpau.cat.
B
B
Gómez-Anson
D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D003480:Cushing Syndrome / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D066127:White Matter / Q000473:pathology*