BACKGROUND: Graves' disease is routinely treated with antithyroid drugs (ATD), radioactive-iodine (RAI), or surgery but it is uncertain whether the choice of initial therapy influences long-term outcomes. We evaluated cardiovascular morbidity and mortality according to the modality and effectiveness of primary therapy in Graves' disease. METHODS: The study was conducted through linked datasets within the All-Wales Secure Anonymised Information Linkage (SAIL) Databank. Graves' disease patients were identified from a regional TSH-receptor-antibody test register, (n=4,189, female 82%, 1998-2013) and matched by age and sex to a control population in SAIL (n=16,756). Patients were grouped by treatment within one-year of diagnosis as: (1) ATD (n=3587), (2) RAI with resolved hyperthyroidism (RAI-Group-A, n=250), and (3) RAI with unresolved hyperthyroidism (RAI-Group-B, n=182). One-year landmark Kaplan-Meier and Cox regression models were used to analyse the association of treatment with all-cause mortality and major adverse cardiovascular events (MACE, myocardial infarction, heart failure, ischaemic stroke, or death). The relationship between FT4 concentration and outcomes was analysed using restricted cubicspline regression models. FINDINGS: Overall, patients had increased mortality compared to controls (HR 1•23, 95%CI 1•06, 1•42). Compared to ATD-treated patients, mortality was reduced in RAI-Group-A (HR 0•50, 95%CI 0•29, 0•85) but not RAI-Group-B (HR 1•51, 95%CI 0•96, 2•37). Persistently low-TSH at 1-year was associated with increased mortality independent of treatment modality (HR 1•55, 95%CI 1•08-2•24). Spline-regressions demonstrated a positive non-linear relationship between 1-year-FT4 and outcomes.
Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.