Introduction: Proton magnetic resonance spectroscopy (1H-MRS) is a sensitive, non-invasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushings 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), 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 (NAcetyl-aspartate), total-NAA (NAcetyl-aspartate+N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes 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 in the right (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 mm3) and right (3980.75±369.44 mm3) total hippocampal volumes between CS patients and controls (3945.08±408.90 and 4108.39±365.11 mm3, respectively).
Conclusion: Persistently abnormal metabolites are evidenced in the hippocampi of CS patients despite endocrine cure. These functional alterations could be early markers of glucocorticoids neurotoxicity and would precede hippocampal volume reduction.
27 Apr - 01 May 2013
European Society of Endocrinology