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

Published on Apr 1, 2019in The Lancet Diabetes & Endocrinology 24.54
· DOI :10.1016/S2213-8587(19)30059-2
Onyebuchi E. Okosieme16
Estimated H-index: 16
(Cardiff University),
Peter N. Taylor13
Estimated H-index: 13
(Cardiff University)
+ 11 AuthorsColin Mark Dayan42
Estimated H-index: 42
(Cardiff University)
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Abstract
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.
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References32
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Published on Sep 1, 2018in Thyroid 7.79
Essi Ryödi3
Estimated H-index: 3
,
Saara Metso11
Estimated H-index: 11
+ 3 AuthorsPia Jaatinen20
Estimated H-index: 20
ABSTRACT BACKGROUND Hyperthyroid patients remain at an increased risk of cardiovascular diseases (CVDs) after restoring euthyroidism. The impact of the different treatment modalities of hyperthyroidism on future CVD risk remains unclear. The aim of this paper is to assess cardiovascular morbidity and mortality in hyperthyroidism before and after the treatment, and to compare the effects of two different treatment modalities, radioactive iodine (RAI) and thyroid surgery. METHODS A comparative coh...
1 Citations Source Cite
Published on May 1, 2018in Thyroid 7.79
Mads Lillevang-Johansen3
Estimated H-index: 3
,
Bo Abrahamsen43
Estimated H-index: 43
+ 2 AuthorsLaszlo Hegedüs59
Estimated H-index: 59
Objective To investigate the association between hypothyroidism and mortality in both treated and untreated hypothyroid patients, and the consequences of over- and undertreatment with respect to mortality. Patients and methods Register-based cohort study of 235 168 individuals who had at least one serum TSH during 1995 to 2011 (median follow-up, 7.2 years). Hypothyroidism was defined as at least two measurements of TSH>4.0 mIU/L within a half year spaced by at least 14 days, or one measurement o...
6 Citations Source Cite
Published on May 1, 2018in Nature Reviews Endocrinology 24.65
Peter N. Taylor13
Estimated H-index: 13
,
Diana Albrecht1
Estimated H-index: 1
+ 4 AuthorsOnyebuchi E. Okosieme16
Estimated H-index: 16
Iodine nutrition is a key determinant of thyroid disease risk, and continued vigilance against iodine deficiency remains essential. Here, Peter Taylor and colleagues review the global incidence and prevalence of thyroid disease, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data.
24 Citations Source Cite
Published on Feb 1, 2018in British Journal of Surgery 5.59
P. Giesecke1
Estimated H-index: 1
(KI: Karolinska Institutet),
Viveka Frykman11
Estimated H-index: 11
(KI: Karolinska Institutet)
+ 4 AuthorsMårten Rosenqvist49
Estimated H-index: 49
(KI: Karolinska Institutet)
Background Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women. Methods Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery b...
1 Citations Source Cite
Published on Jan 1, 2018in Annals of Clinical Biochemistry 1.89
Chiara Autilio3
Estimated H-index: 3
(CUA: The Catholic University of America),
Renato Morelli4
Estimated H-index: 4
(CUA: The Catholic University of America)
+ 3 AuthorsCinzia Carrozza12
Estimated H-index: 12
(CUA: The Catholic University of America)
BackgroundThyroid-stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAbs) are a heterogeneous group of antibodies (Abs) with different functionalities. Among all TRAbs, only the stimulating ones (S-TRAbs) are considered as the pathogenetic marker of Graves’ disease (GD). To date, the methods available for TRAbs testing are based on immunoassays (IMAs) which detect total serum TRAbs or bioassays which are not suitable in clinical practice, even though they discern Abs functionality. The ...
3 Citations Source Cite
Published on Jan 1, 2018in European thyroid journal
George J. Kahaly43
Estimated H-index: 43
(University of Mainz),
L. Bartelena56
Estimated H-index: 56
+ 3 AuthorsSimon S.H. Pearce1
Estimated H-index: 1
(Newcastle University)
11 Citations Source Cite
Published on Jul 1, 2017in The Journal of Clinical Endocrinology and Metabolism 5.61
Mads Lillevang-Johansen3
Estimated H-index: 3
(University of Southern Denmark),
Bo Abrahamsen43
Estimated H-index: 43
(University of Southern Denmark)
+ 2 AuthorsLaszlo Hegedüs59
Estimated H-index: 59
(OUH: Odense University Hospital)
8 Citations Source Cite
Published on Jul 1, 2017in Thyroid 7.79
Peter Giesecke1
Estimated H-index: 1
,
Mårten Rosenqvist49
Estimated H-index: 49
+ 5 AuthorsOve Tørring24
Estimated H-index: 24
Background: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data t...
6 Citations Source Cite
Published on Oct 1, 2016in Thyroid 7.79
Douglas S. Ross41
Estimated H-index: 41
(Harvard University),
Henry B. Burch3
Estimated H-index: 3
(WRAIR: Walter Reed Army Institute of Research)
+ 8 AuthorsMarius N. Stan15
Estimated H-index: 15
(Mayo Clinic)
Background: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods: The American Thyroid Association (ATA) previously c...
232 Citations Source Cite