Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study

Published on Apr 1, 2019in The Lancet Diabetes & Endocrinology 19.31
· DOI :10.1016/s2213-8587(19)30059-2
Onyebuchi E. Okosieme16
Estimated H-index: 16
(Cardiff University),
Peter N. Taylor12
Estimated H-index: 12
(Cardiff University)
+ 11 AuthorsColin Mark Dayan42
Estimated H-index: 42
(Cardiff University)
Summary Background Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. Methods In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. Findings We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05–1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29–0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96–2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08–2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. Interpretation Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. Funding National Institute for Social Care and Health Research, Wales.
  • References (32)
  • Citations (1)
Published on May 1, 1988in American Journal of Epidemiology 4.32
Marlene B. Goldman29
Estimated H-index: 29
(Harvard University),
Farahe Maloof37
Estimated H-index: 37
+ 3 AuthorsE. Chester Ridgway46
Estimated H-index: 46
A follow-up study of 1762 hyperthyroid women who were treated at the Massachusetts General Hospital Thyroid Unit between 1946 and 1964 was conducted. The average length of follow-up was 17.2 years. A 1978 mailing address or a death certificate was located for 92% of the women, and 88% of 1058 living patients responded to a mail questionnaire. The standardized mortality ratio (SMR) for all causes of death was 1.3 (95% confidence interval (CI) 1.2-1.4). The standardized mortality ratios for all ma...
75 Citations Source Cite
Published on Apr 1, 2013in Thyroid 7.56
Frans Brandt8
Estimated H-index: 8
Marianne Thvilum8
Estimated H-index: 8
+ 4 AuthorsThomas Heiberg Brix31
Estimated H-index: 31
Background: Hyperthyroidism has been associated with increased all-cause mortality. Whether the underlying cause of hyperthyroidism influences this association is unclear. Our objectives were to explore whether mortality risk and cause of death differ between Graves' disease (GD) and toxic nodular goiter (TNG). Methods: This is an observational cohort study, using record-linkage data from nationwide Danish health registers. A total of 1291 subjects with GD and 861 with TNG, treated in a hospital...
33 Citations Source Cite
Published on Apr 1, 2007in The American Journal of Medicine 5.12
D. C. Bauer90
Estimated H-index: 90
(University of California, San Francisco),
Nicolas Rodondi43
Estimated H-index: 43
(University of Lausanne)
+ 1 AuthorsTeresa A. Hillier46
Estimated H-index: 46
(Kaiser Permanente)
Abstract Purpose Thyroid dysfunction is common, particularly among older women. The safety of thyroid hormone use and long-term prognosis of hyperthyroidism remain controversial. We performed a prospective cohort study to examine the relationship among thyroid hormone use, previous hyperthyroidism, abnormal thyroid function, and mortality. Methods We studied 9449 community-dwelling white women aged ≥65 years followed for 12 years. For analyses of thyroid function, we performed a nested case-coho...
54 Citations Source Cite
Published on Jul 1, 2005in Thyroid 7.56
Moffat Nyirenda19
Estimated H-index: 19
David N. Clark1
Estimated H-index: 1
+ 5 AuthorsAnthony Toft18
Estimated H-index: 18
The effects of thyroid dysfunction are thought to be reversible on restoration of euthyroidism, but postmortem and epidemiologic data suggest that subclinical or treated thyroid disease is associated with increased vascular risk. In order to determine the extent of this risk, and to explore whether the nature and/or treatment of thyroid disease are critical in this relationship, we used medical record linkage to match patients with treated thyroid disease of various etiologies with routinely col...
54 Citations Source Cite
Kristien Boelaert30
Estimated H-index: 30
(University of Birmingham),
Patrick Maisonneuve Eng98
Estimated H-index: 98
(European Institute of Oncology)
+ 1 AuthorsJayne A. Franklyn62
Estimated H-index: 62
(University of Birmingham)
Context: Hyperthyroidism is common, but opinions regarding optimal therapy with antithyroid drugs or radioiodine (131-I) differ. There are no randomized trials comparing these options in terms of mortality. Objective: The aim of the study was to determine whether mortality associated with hyperthyroidism varies with treatment administered or other factors. Design, Setting, and Patients: We conducted a prospective observational population-based study of 1036 subjects aged ≥ 40 years presenting to...
30 Citations Source Cite
Published on Jul 6, 2005in JAMA 47.66
Jayne A. Franklyn62
Estimated H-index: 62
(University of Birmingham),
Michael C. Sheppard60
Estimated H-index: 60
Patrick Maisonneuve Eng98
Estimated H-index: 98
ContextHyperthyroidism has been reported to cause excess all-cause and circulatory mortality. Whether this can be reversed is unknown, as is the influence of mild persisting thyroid dysfunction and treatment-induced hypothyroidism.ObjectivesTo determine whether radioiodine treatment is associated with increased mortality and to determine the influences of mild thyroid dysfunction and the development of overt hypothyroidism treated with thyroxine (T4).Design, Setting, and ParticipantsA population...
111 Citations Source Cite
Published on Dec 1, 2009in BMC Medical Informatics and Decision Making 2.13
Ronan Lyons50
Estimated H-index: 50
(Swansea University),
Kerina H. Jones15
Estimated H-index: 15
(Swansea University)
+ 5 AuthorsKen Leake2
Estimated H-index: 2
(Cardiff University)
Background Vast amounts of data are collected about patients and service users in the course of health and social care service delivery. Electronic data systems for patient records have the potential to revolutionise service delivery and research. But in order to achieve this, it is essential that the ability to link the data at the individual record level be retained whilst adhering to the principles of information governance. The SAIL (Secure Anonymised Information Linkage) databank has been e...
162 Citations Source Cite
Published on Mar 12, 1998in The New England Journal of Medicine 79.26
Jayne A. Franklyn62
Estimated H-index: 62
Patrick Maisonneuve Eng98
Estimated H-index: 98
+ 2 AuthorsPeter Boyle101
Estimated H-index: 101
Background Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. Methods We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had ...
225 Citations Source Cite
Published on May 1, 2013in Clinical Endocrinology 3.08
Helena Filipsson Nyström10
Estimated H-index: 10
(University of Gothenburg),
Svante Jansson31
Estimated H-index: 31
(Sahlgrenska University Hospital),
Gertrud Berg18
Estimated H-index: 18
(Sahlgrenska University Hospital)
SummaryObjectives To study hyperthyroidism in long-term iodine sufficiency (IS), as iodine supply affects its occurrence. Design Prospective descriptive study. Patients In 2003–2005, all referred cases of subclinical (SH) and overt hyperthyroidism (OH) were registered at diagnosis from a population (n = 631 239) in Gothenburg, Sweden. Measurements Information on age, gender, smoking, thyroid associated ophthalmopathy (TAO), thyroid hormones and TSH receptor antibodies (TRab) was collected. Incid...
25 Citations Source Cite
Published on Jan 1, 2016in Clinical Endocrinology 3.08
L. Bartelena57
Estimated H-index: 57
(University of Insubria),
H.B. Burch1
Estimated H-index: 1
(Walter Reed National Military Medical Center)
+ 1 AuthorsGeorge J. Kahaly43
Estimated H-index: 43
(University of Mainz)
SummaryObjective Management of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey. Design Members of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey. Results A total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would r...
39 Citations Source Cite