Interactive reportRecovery of the brain choline level in treated Cushing’s patients as monitored by proton magnetic resonance spectroscopy☆
Introduction
Cushing’s syndrome (CS) is caused by excessive glucocorticoid levels from endogenous or exogenous sources. Endogenous CS is due to the presence of glucocorticoid-producing tumors on the pituitary or adrenal glands and approximately 80–85% of endogenous CS cases are ACTH-dependent [27]. Exogenous CS results from the chronic administration of supraphysiological amounts of glucocorticoids to treat different diseases. CS affects brain functions as assessed by different measurements such as a reduction of the number of cholinergic neurons in the medial area of the septum [37], neuronal necrosis in the neocortex area [34], localized [35] or diffuse [28] cerebral atrophy, cognitive dysfunctions and psychological disturbances [8], [24], [27], [35], [36].
In a recent article, we reported a proton magnetic resonance spectroscopy (1H MRS) study of different cerebral areas of patients with endogenous CS before treatment, comparing them to normal control subjects [18]. Quantification of the signals of the main observable brain metabolites was performed in three areas: frontal lobe, thalamus and temporal lobe. The metabolites were: (a) N-acetyl groups mostly from N-acetylaspartate (NAA, 2.0 ppm), which is known as a neuronal marker, (b) creatine and phosphocreatine (Cr, 3.0 ppm), which play an important role in energy metabolism, (c) choline and choline-containing molecules (Cho, 3.2 ppm), arising mostly from the degradation products of cell membrane phosphatidylcholine and (d) myo-inositol (mI, 3.5 ppm) whose biological function is less understood but which is implicated in the biosynthesis of second messengers. Quantification of metabolites was performed by calculating ratios relative to Cr since the signal of Cr is relatively stable in human brain and has been the most widely used quantification method. Our data clearly showed a decrease of the Cho/Cr ratios in both the frontal and thalamic areas for CS patients relative to normal subjects. No variation could be measured for the Cho/Cr ratios in the temporal area and for the other metabolite ratios (NAA/Cr, mI/Cr).
In this follow-up study, we compared the metabolite levels for CS patients before and after the correction of hypercortisolism. Comparisons are also made with normal control subjects. Metabolite ratios are calculated relative to total H2O in the voxel Which allows to monitor the variation of the Cr metabolite and provides an absolute quantification without the assumptions necessary to determine concentrations in mM units [14]. Our data demonstrate a practically complete recovery of the Cho in the frontal and thalamic areas for treated patients 6 months after cortisol has returned to normal levels.
Section snippets
Patients and normal subjects
Three groups are compared in this study: normal subjects, untreated CS patients and treated CS patients. Data for normal subjects and untreated CS patients were partially reported previously [18]. Forty normal subjects were used as controls (age range=19–64 years; mean age=38.5 years; 23 males and 17 females). The CS patients groups comprise ten female patients with endogenous Cushing’s syndrome (CS) secondary either to a pituitary corticotroph adenoma (five patients) or to primary adrenal
Results
Fig. 2 displays examples of 1H magnetic resonance spectra obtained in the thalamus region of a normal subject (Fig. 2A) and from a patient with a pituitary Cushing’s syndrome before treatment (Fig. 2B) and 6 months after correction of hypercortisolism (Fig. 2C). As compared to the normal subject, the intensity of the Cho signal is seen to be reduced before treatment and to recover after treatment. Such is not the case for the other metabolites, NAA, Cr and mI, whose signal intensities remain
Discussion
Data presented in Table 1 are metabolite ratios calculated relative to total H2O. In recent years, efforts have been made to obtain absolute concentrations from spectroscopic measurements [21], [30] in order to avoid possible errors caused by variations in the Cr concentration, the most common ratio denominator. Although metabolite concentrations in mM would be desirable, their calculations require an accurate knowledge of the relaxation times (and other parameters) which is difficult to obtain
Acknowledgements
The authors would like to thank Mrs. Ann Anderson for the recruitment of patients, Mr. Claude Bureau and Mrs. Paule Samson, radiology technologists, for performing the MRS data acquisition and Mr. Robert Boileau for his help with biostatistical analyses. They are grateful to the Fonds de la recherche en santé du Québec (FRSQ) for financial support.
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2010, Journal of Psychiatric ResearchCitation Excerpt :Brown et al. explain these contradictory findings with different concentration reference methods used by their group (metabolite/creatine ratio) and the group of Khiat et al. (water peak reference in the 2001 study) arguing that water concentration would decrease at corticosteroid exposure and, therefore, would not be an appropriate reference. However, in their first two studies (studying endogenous Cushing’s syndrome) Khiat et al. (1999, 2000) also used Cre as a reference and report a Cho resonance reduction. In fact, a decrease in water concentration would explain a general metabolite increase but not a selective Cho reduction, so that these issues remain obscure.
Cognitive function and cerebral assessment in patients who have Cushing's syndrome
2005, Endocrinology and Metabolism Clinics of North America
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Published on the World Wide Web on 6 March 2000.