Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy

Ann-Elin Meling Stokland, Marie Austdal, Bjørn Gunnar Nedrebø, Siri Carlsen, Hanne Brit Hetland, Lars Breivik, Hans Olav Ueland, Torquil Watt, Per Karkov Cramon, Kristian Løvås, Eystein Sverre Husebye*, Grethe Åstrøm Ueland

*Corresponding author for this work


CONTEXT: Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing.

OBJECTIVE: This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life.

METHODS: A retrospective follow-up was conducted of GD patients that participated in a randomized trial from 1997 to 2001. Demographic and clinical data were obtained from medical records and questionnaires. Biobank samples were analyzed for inflammatory biomarkers and compared with age- and sex-matched healthy individuals.

RESULTS: We included 83% (182/218) of the patients from the original study. At the end of follow-up, normal thyroid function was achieved in 34%. The remaining had either active disease (1%), spontaneous hypothyroidism (13%), or had undergone ablative treatment with radioiodine (40%) or thyroidectomy (13%). Age younger than or equal to 40 years, thyroid eye disease (TED), smoking, and elevated levels of interleukin 6 and tumor necrosis factor receptor superfamily member 9 (TNFRS9) increased the risk of relapsing disease (odds ratio 3.22; 2.26; 2.21; 1.99; 2.36). At the end of treatment, CD40 was lower in patients who maintained normal thyroid function (P = .04). At the end of follow-up, 47% had one or more autoimmune diseases, including vitamin B12 deficiency (26%) and rheumatoid arthritis (5%). GD patients who developed hypothyroidism had reduced quality of life.

CONCLUSION: Careful lifelong monitoring is indicated to detect recurrence, hypothyroidism, and other autoimmune diseases. Long-term ATD treatment emerges as a beneficial first-line treatment option, especially in patients with young age at onset or presence of TED.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number3
Pages (from-to)827-836
Number of pages10
Publication statusPublished - 20 Feb 2024


  • Antithyroid Agents/adverse effects
  • Graves Disease/pathology
  • Graves Ophthalmopathy/drug therapy
  • Humans
  • Hypothyroidism/drug therapy
  • Iodine Radioisotopes/therapeutic use
  • Quality of Life
  • Recurrence
  • Retrospective Studies


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