Resistance to thyroid hormone β is one of those subjects that keeps cropping up - but all too rarely seems to move forward meaningfully. This appears to be a very interesting study. And so good to see it come from Cardiff, Merthyr Tydfil, Cambridge and Dublin.
Cardiovascular morbidity and mortality in patients in Wales, UK with resistance to thyroid hormone β (RTHβ): a linked-record cohort study
Onyebuchi E Okosieme, Danyal Usman, Peter N Taylor, Colin M Dayan, Greta Lyons, Carla Moran, Krishna Chatterjee, Dafydd Aled Rees
a Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK
b Diabetes and Endocrinology Department, Prince Charles Hospital, Cwm Taf Morgannwg Health Board, Merthyr Tydfil, UK
c Wellcome Trust-MRC Institute of Medical Science, University of Cambridge, Cambridge, UK
d Endocrine Section, Beacon Hospital, Dublin, Ireland
e Endocrine Department, St Vincent's University Hospital, Dublin, Ireland
f School of Medicine, University College Dublin, Dublin, Ireland
g Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, UK
Summary
Background
Individuals with resistance to thyroid hormone owing to mutations in the thyroid hormone receptor β gene (RTHβ) exhibit impaired tissue sensitivity to thyroid hormones, but retain sensitivity in cardiac tissue. Long-term health and survival outcomes in this rare disorder have not been evaluated. We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTHβ, followed-up in UK endocrine clinics.
Methods
In a retrospective cohort design, we linked genetically confirmed patients with RTHβ and age-matched and sex-matched population controls to outcomes in datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank. Kaplan-Meier and Cox regression models analysed associations of RTHβ with all-cause mortality and cardiovascular events.
Findings
We identified 61 patients with a genetic diagnosis of RTHβ between Jan 1, 1997, and Dec 31, 2019, and matched them with 2750 controls. Compared with controls, patients exhibited increased risks for all-cause mortality (hazard ratio [HR] 2·84, 95% CI 1·59–5·08), atrial fibrillation (10·56, 4·72–23·63), heart failure (HR 6·35, 95% CI 2·26–17·86), and major adverse cardiovascular events (MACE), comprising cardiovascular death, acute myocardial infarction, heart failure, or strokes (HR 3·49, 95% CI 2·04–5·99). The median age of first occurrence of any adverse event was 11 years earlier in patients (56 years, 95% CI 44–65) compared with controls (67 years, 65–70). Cubic spline analyses showed positive associations between FT4 concentrations at diagnosis and mortality or MACE, with FT4 concentration of 30 pmol/L or greater conferring increased risk. Compared with no intervention, treatment with antithyroid drugs, surgery or radioiodine gland ablation, or thyroxine did not control thyroid hormone excess.
Interpretation
We have documented reduced survival and increased cardiovascular morbidity in a cohort of patients with RTHβ for the first time. These outcomes might be driven by lifelong cardiac exposure to thyroid hormone excess; and effective therapies, targeting hormone resistant pathways, could potentially curtail this risk.
Full paper including PDF openly accessible here:
