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

Authors

  • Eugenia Resmini,

    Corresponding author
    • Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
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  • Alicia Santos,

    1. Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
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  • Beatriz Gómez-Anson,

    1. Neuroradiology Unit, Hospital Sant Pau and IIB-Sant Pau, UAB, Barcelona, Spain
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  • Olga López-Mourelo,

    1. Port d'Informació Científica (PIC) and Institut de Fisica d'Altes Energies (IFAE), UAB, Bellaterra, Barcelona, Spain
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  • Patricia Pires,

    1. Port d'Informació Científica (PIC) and Institut de Fisica d'Altes Energies (IFAE), UAB, Bellaterra, Barcelona, Spain
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  • Yolanda Vives-Gilabert,

    1. Port d'Informació Científica (PIC) and Institut de Fisica d'Altes Energies (IFAE), UAB, Bellaterra, Barcelona, Spain
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  • Iris Crespo,

    1. Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
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  • Maria J. Portella,

    1. Department of Psychiatry, Hospital Sant Pau, UAB, Barcelona, Spain
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  • Manel de Juan-Delago,

    1. Neuroradiology Unit, Hospital Sant Pau and IIB-Sant Pau, UAB, Barcelona, Spain
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  • Susan M. Webb

    1. Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
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Correspondence: Eugenia Resmini, Department of Endocrinology, Hospital de Sant Pau, C. S. Antoni Maria Claret n.167, 08025 Barcelona, Spain. Tel.: +34 935 537 917; Fax: +91 44 42197754; E-mail: eresmini@santpau.cat

Summary

Background

Proton magnetic resonance spectroscopy (1H-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 1H-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 1H-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 (mm3) 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.

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