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Reduced Parietooccipital White Matter Glutamine Measured by Proton Magnetic Resonance Spectroscopy in Treated Graves’ Disease Patients

Department of Radiology (E.R.D., C.T.), Memory Disorders Research Group (T.V.E., J.D., G.W., M.H.), Medical Endocrinology Rigshospitalet (Å.K.R., U.F.-R.), and Department of Endocrinology Bispebjerg Hospital (H.P.), University of Copenhagen, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: E. R. Danielsen, Ph.D., Department of Radiology, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: else.rubaek.danielsen{at}rh.regionh.dk.

Context: Graves’ disease is an autoimmune disease of the thyroid gland. Patients often have affective and cognitive complaints, whether these disappear after treatment remains disputed.

Objective: Our objective was to evaluate cerebral biochemistry in acute and treated Graves’ disease.

Design: We conducted a prospective study, investigating volunteers once and patients before and 1 yr after treatment.

Setting: The study was performed at a radiology department, a memory disorder clinic, and two endocrinology clinics.

Patients and Other Participants: Of 53 consecutively referred, newly diagnosed, and untreated patients with Graves’ thyrotoxicosis, 27 patients (34 ± 8 yr) and 33 matched volunteers were included.

Interventions: Patients were treated with thionamide.

Main Outcome Measures: We assessed brain metabolite concentrations.

Methods: Proton magnetic resonance spectroscopy of the brain and a battery of biochemical, affective, and cognitive tests were used.

Results: Previously reported findings of reduced choline and myo-inositol in acute Graves’ disease were confirmed and reversibility was demonstrated. Parieto-occipital white matter glutamine was and remained significantly reduced (P < 0.01). Acute phase parieto-occipital white matter total choline correlated significantly (r = –0.57; P < 0.01) with impaired thyroid function. Pretreatment total T₃ predicted posttreatment occipital gray matter glutamine (r = –0.52; P < 0.01). Occipital gray matter total choline (r = –0.53; P < 0.01) and parietooccipital white matter glutamate (r = –0.54; P < 0.01) correlated with initial values of selected attention and concentration cognitive scores and predicted them at follow-up.

Conclusions: The persistent reduction of glutamine in white matter, the decreasing glutamate in occipital gray matter, and the correlation with severity of the initial disease as well as with attention and concentration cognitive scores indicated that there was a persistent and possibly progressive disturbance of the glutamate glutamine cycling in Graves’ disease.