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Hippocampal dysfunction in cured Cushing's syndrome patients, detected by (1) H-MR-spectroscopy.

Abstract：

BACKGROUND:Proton magnetic resonance spectroscopy ((1) H-MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushing's syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure. OBJECTIVE:To investigate metabolites in the hippocampi of CS patients and controls, using (1) H-MRS. PATIENTS AND METHODS:Eighteen right-handed cured CS patients (age 44·8 ± 12·5 years, 12·6 ± 3·8 years of education) and 18 right-handed healthy controls, matched for age (40·0 ± 11·9) and years of education (14·4 ± 3·8), underwent 3-Tesla magnetic resonance imaging (3T MRI) and (1) H-MRS including the head of each hippocampus. Concentrations of Glu (Glutamate), Glx (Glutamate + Glutamine), NAA (N-Acetyl-aspartate), total NAA (N-Acetyl-aspartate + N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes (mm(3) ) were additionally calculated using an automated procedure (FreeSurfer). RESULTS:CS patients had lower NAA than controls in the left and right hippocampus (5·2 ± 1·0 vs 6·1 ± 0·7, P < 0·05; 4·9 ± 0·8 vs 6·1 ± 0·6, P < 0·001, respectively), and lower total NAA on the right side (5·7 ± 0·9 vs 6·3 ± 0·9, P < 0·05), suggesting neuronal dysfunction/loss. CS patients had higher Glx than controls in both hippocampi (10·4 ± 1·9 vs 8·6 ± 1·4, P < 0·01; 9·9 ± 1·6 vs 8·9 ± 1·3, P < 0·05, respectively), suggesting glial proliferation, as a repair mechanism after neuronal dysfunction. No differences were found in the other brain metabolites, and there were no differences in left (3815·78 ± 502·96) and right (3980·75 ± 369·44) total hippocampal volumes between CS patients and controls (3945·08 ± 408·90 and 4108·39 ± 365·11, respectively). CONCLUSION:Persistently abnormal metabolites are evidenced in the hippocampi of CS patients despite endocrine cure. These functional alterations could be early markers of glucocorticoid neurotoxicity, preceding hippocampal volume reduction.

journal_name

Clin Endocrinol (Oxf)

journal_title

Clinical endocrinology

authors

Resmini E,Santos A,Gómez-Anson B,López-Mourelo O,Pires P,Vives-Gilabert Y,Crespo I,Portella MJ,de Juan-Delago M,Webb SM

doi

10.1111/cen.12224

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

700-7

issue

eissn

0300-0664

issn

1365-2265

journal_volume

pub_type

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Hippocampal dysfunction in cured Cushing's syndrome patients, detected by (1) H-MR-spectroscopy.