Outcome of Graves disease
Abstract
Graves' disease (GD) is an autoimmune condition with elevated thyroid hormone levels and symptoms suggesting an affected brain. These symptoms often resolve with treatment but, for some patients, GD results in a long period of reduced well-being. The overall aim of this thesis is to characterize the consequences of GD with a special focus on the brain. Three studies were conducted with data from questionnaires and clinical assessments of patients with GD in both the hyperthyroid and the euthyroid phase.
Paper I was a longitudinal cohort study that assessed long-term treatment results 6–10 years after the onset of GD. Among 1186 included patients, the 774 who were initially treated with antithyroid drugs had a 40% chance of being euthyroid without thyroid medication at follow-up. One in four patients did not feel fully recovered.
Paper II was a longitudinal case-control study designed to characterize affective and cognitive symptoms in 65 premenopausal women with newly diagnosed untreated GD. At onset of GD, the patients were significantly more affected with depression, anxiety, and mental fatigue compared to controls. At follow-up after 15 months, these symptoms remained in a significant proportion of patients. Patients with eye symptoms or a history of psychiatric conditions were more likely to be affected with brain-related symptoms.
Paper III was a longitudinal case-control study of 65 premenopausal women with newly diagnosed untreated GD designed to investigate the effect of GD on hippocampal volumes. At onset of GD, hippocampus and amygdala volumes of the patients were smaller compared to controls. These brain structures became larger with treatment and, after 15 months, only the left amygdala remained smaller than in controls. At inclusion, there was an inverse correlation between thyroid-stimulating hormone receptor antibody (TRAb) and the volumes of both amygdalae and the right hippocampus. There were also inverse correlations between TRAb and free triiodothyronine recovery and the recovery of most of the four assessed brain volumes.
GD is a condition where a minority of patients can hope for a long-lasting restored thyroid function. A large proportion of GD patients do not feel recovered after 8 years. Mental fatigue is an important concept for understanding the brain-derived symptoms in GD. In summary, the studies demonstrate that Graves' hyperthyroidism has unexpected long-term consequences for many patients, provide extensive new data on the serious and chronic nature of GD, and show for the first time that GD is accompanied by reversible brain changes.
Parts of work
I. Sjölin G*, Holmberg M*, Törring O, Byström K, Khamisi S, de Laval D, Abraham-Nordling M, Calissendorff J, Lantz M, Hallengren B, Filipsson Nyström H, Wallin G. The long-term outcome of treatment for Graves' hyperthyroidism. Published in Thyroid 2019; nov 29(11):1545-1557.
*Gabriel Sjölin and M Holmberg have contributed equally
::doi::10.1089/thy.2019.0085 II. Holmberg M, Malmgren H, Berglund PF, Johansson B, Klasson N, Skau S, Filipsson Nyström H. Predictors for mental symptoms in Graves' disease. Manuscript III. Holmberg M, Malmgren H, Berglund PF, Heckemann RA, Johansson B, Klasson N, Olsson E, Skau S, Starck G, Filipsson Nyström H. A longitudinal study of medial temporal lobe volumes in Graves' disease. Manuscript
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Inst of Medicine. Department of Internal Medicine and Clinical Nutrition
Disputation
Fredagen den 21 februari 2020, kl. 9.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborg
Date of defence
2020-02-21
mats@xnet.se
Date
2020-02-05Author
Holmberg, Mats
Keywords
Graves disease
Mental fatigue
Depression
Anxiety
Magnetic resonance volumetry
Hippocampus
Volumetry
Quality of life
Publication type
Doctoral thesis
ISBN
978-91-7833-773-6 (Pdf)
978-91-7833-772-9 (Print)
Language
eng