The Long-Term Outcome of Treatment for Graves' Hyperthyroidism

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 wellbeing. 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.

Should radioiodine now be first line treatment for Graves’ disease?

“…A study of Swedish Graves' disease patients randomised to treatment with thionamides, radioiodine, or surgery, showed no difference in treatment satisfaction [29] or long-term quality of life between the treatment arms [30]. However, a more recent study, also from Sweden, in which Graves' disease patients were followed up for 6-10 years after primary therapy, showed that the proportion of patients who felt fully recovered was significantly lower amongst those receiving levothyroxine compared to those not on levothyroxine [3].…”

“…Three well established therapies, namely antithyroid drugs, radioiodine, and thyroidectomy have been available for decades, and their efficacy and limitations are well recognised (Table 1) [1,2]. Thionamide drugs offer the prospect of remission without the need for lifelong thyroid hormone replacement but only about 45% of patients achieve long-term remission [3]. Ablative treatment with radioiodine or thyroidectomy result in better cure rates and overcome the risk of non-compliance with thionamides, but both treatments incur the need for permanent levothyroxine therapy [1,2].…”

Hyperthyreose – Fokus Immunthyreopathie Basedow

“…Daten einer longitudinalen Studie an 1186 Basedow-Patien-tInnen beleuchten jedoch die mögliche Problematik einer Langzeit-Thyreostatika-Therapie. Die Autoren konnten zeigen, dass ein Patient mit Immunthyreopathie Basedow, der sich für eine thyreostatische Therapie entscheidet, nur eine Chance von 50,3 % hat, eine ablative Therapie zu vermeiden, und nur eine Chance von 40 %, eine Euthyreose ohne medikamentöse Therapie zu erreichen [54]. Zudem fühlten sich 25,3 % der Patien-tInnen nach 6-10 Jahren nicht vollständig genesen [54].…”

“…Die Autoren konnten zeigen, dass ein Patient mit Immunthyreopathie Basedow, der sich für eine thyreostatische Therapie entscheidet, nur eine Chance von 50,3 % hat, eine ablative Therapie zu vermeiden, und nur eine Chance von 40 %, eine Euthyreose ohne medikamentöse Therapie zu erreichen [54]. Zudem fühlten sich 25,3 % der Patien-tInnen nach 6-10 Jahren nicht vollständig genesen [54]. Das Problem an dieser Situation ist, dass PatientInnen somit den Risiken mehrerer Therapiemodalitäten ausgesetzt werden.…”

Prediction of Relapse After Antithyroid Drugs Withdrawal: A Narrative Review

“…discontinuation of ATDs (5). Relapse following treatment occurs approximately 30% -40% in the first year and 50% -60% in the long term (6)(7)(8)(9)(10)(11). An autoimmune disease should theoretically be viewed as a recurring disease.…”