Among patients over age 40, Graves hyperthyroidism is associated with increased mortality (primarily cardiovascular) when biochemical control of Graves hyperthyroidism may be suboptimal (i.e., during active treatment with antithyroid drugs, or after radioiodine but before achieving a hypothyroid state).[154]Boelaert K, Maisonneuve P, Torlinska B, et al. Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine. J Clin Endocrinol Metab. 2013 May;98(5):1869-82.
http://www.ncbi.nlm.nih.gov/pubmed/23543662?tool=bestpractice.com
Prompt treatment of hyperthyroidism, irrespective of modality used, reduces long-term cardiovascular complications.[84]Okosieme OE, Taylor PN, Evans C, et al. Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study. Lancet Diabetes Endocrinol. 2019 Feb 28;7(4):278-87.
http://www.ncbi.nlm.nih.gov/pubmed/30827829?tool=bestpractice.com
Prognosis of hyperthyroidism is excellent following therapy with antithyroid medications for control of hyperthyroidism.
There is, however, a high degree of relapse. Remission rates of 45.3%, 81.5%, and 96.3% have been reported for first-line therapy with antithyroid drugs, 131-I, and surgery, respectively.[98]Sjölin G, Holmberg M, Törring O, et al. The long-term outcome of treatment for Graves' hyperthyroidism. Thyroid. 2019 Nov;29(11):1545-57.
http://www.ncbi.nlm.nih.gov/pubmed/31482765?tool=bestpractice.com
About 50% of patients achieve remission after an initial course of antithyroid drugs, with most relapses occurring within 4 years.[155]Wiersinga WM. Graves' disease: can it be cured? Endocrinol Metab (Seoul). 2019 Mar;34(1):29-38.
https://e-enm.org/journal/view.php?doi=10.3803/EnM.2019.34.1.29
http://www.ncbi.nlm.nih.gov/pubmed/30912336?tool=bestpractice.com
At 10 years, the remission rate is about 30% to 40%. Approximately 27% are estimated to achieve permanent remission.[155]Wiersinga WM. Graves' disease: can it be cured? Endocrinol Metab (Seoul). 2019 Mar;34(1):29-38.
https://e-enm.org/journal/view.php?doi=10.3803/EnM.2019.34.1.29
http://www.ncbi.nlm.nih.gov/pubmed/30912336?tool=bestpractice.com
Risk factors for relapse
Several risk factors appear to be associated with relapse in Graves disease patients treated with antithyroid drugs:[156]Struja T, Fehlberg H, Kutz A, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017 Jan;176(1):87-97.
http://www.eje-online.org/content/176/1/87.long
http://www.ncbi.nlm.nih.gov/pubmed/27780830?tool=bestpractice.com
[157]Shi H, Sheng R, Hu Y, et al. Risk factors for the relapse of Graves' disease treated with antithyroid drugs: a systematic review and meta-analysis. Clin Ther. 2020 Apr;42(4):662-75.e4.
https://www.doi.org/10.1016/j.clinthera.2020.01.022
http://www.ncbi.nlm.nih.gov/pubmed/32139177?tool=bestpractice.com
Thyroid-stimulating hormone (TSH) receptor antibody levels are less useful in predicting relapse risk in older patients with Graves disease.[54]Bano A, Gan E, Addison C, et al. Age may influence the impact of TRAbs on thyroid function and relapse-risk in patients with Graves disease. J Clin Endocrinol Metab. 2019 May 1;104(5):1378-85.
http://www.ncbi.nlm.nih.gov/pubmed/30517711?tool=bestpractice.com
When radioactive iodine is used and an appropriate dose is given, 90% of patients develop hypothyroidism within 3-6 months and need levothyroxine therapy.
Patients with orbitopathy and/or atrial fibrillation
Mild cases of Graves orbitopathy often settle down spontaneously. A significant proportion of patients with moderate-to-severe orbitopathy require immunosuppressive treatment and rehabilitative surgeries. Sight-threatening orbitopathy is an emergency, but the prognosis is excellent provided it is treated promptly by an experienced team.[60]Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67.
https://www.doi.org/10.1530/EJE-21-0479
http://www.ncbi.nlm.nih.gov/pubmed/34297684?tool=bestpractice.com
If the patient has atrial fibrillation, anticoagulant therapy may be required due to risk of thromboembolism. There is a lack of studies comparing anticoagulants in thyrotoxic atrial fibrillation. Direct oral anticoagulants (DOACs) may be associated with fewer bleeding events.[158]Tng EL, Tiong YS, Aung AT, et al. Efficacy and safety of anticoagulation in thyrotoxic atrial fibrillation: a systematic review and meta-analysis. Endocr Connect. 2022 May 23;11(5):e220166.
https://ec.bioscientifica.com/view/journals/ec/11/5/EC-22-0166.xml
http://www.ncbi.nlm.nih.gov/pubmed/35521808?tool=bestpractice.com