Context Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. Objective To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. Design Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). Setting University hospital setting in The Netherlands. Patients Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. Main outcome measures HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). Results During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P < 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P < 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. Conclusion During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.
Thyroid hormone stimulates cardiac inotropy and chronotropy via direct genomic and non-genomic mechanisms. Hyperthyroidism magnifies these effects, resulting in an increase in heart rate, ejection fraction and blood volume. Hyperthyroidism also affects thrombogenesis and this may be linked to a probable tendency towards thrombosis in patients with hyperthyroidism. Patients with hyperthyroidism are therefore at higher risk for atrial fibrillation, heart failure and cardiovascular mortality. Similarly, TSH suppressive therapy for differentiated thyroid cancer is associated with increased cardiovascular risk. In this review, we present the latest insights on the cardiac effects of thyroid suppression therapy for the treatment of thyroid cancer. Finally, we will show new clinical data on how to implement this knowledge into the clinical practice of preventive medicine.
Although cancer in general is a strong risk factor for developing venous thromboembolism (VTE), the risk factors for venous thromboembolic events in patients with differentiated thyroid carcinoma (DTC) have never been assessed. This is remarkable, as several parts of the treatment comprise a hypercoagulable state that could in subgroups of DTC patients lead to an increased risk of VTE. The aim of this study was to assess which risk factors could cause DTC patients to develop VTE. We performed a nested case-control study, involving cases of DTC patients treated between 1980 and 2014 with confirmed VTE after diagnosis of DTC. Controls were defined as DTC patients without VTE. In all subjects, we collected information about thyroid cancer characteristics, treatment characteristics, traditional risk factors for VTE and additional clinical data, and we performed univariable and multivariable regression analyses. We included 28 cases and 56 controls matched for age at DTC diagnosis, sex and date of DTC diagnosis. In the univariable regression analysis, histology, distant metastases, DTC risk classification, recent surgery and other active malignancy were associated with VTE. In the multivariable analysis, distant metastases (odds ratio 7.9) and recent surgery (odds ratio 6.1) were independently associated with VTE. In conclusion, surgery and presence of distant metastases are independent risk factors for developing VTE in DTC patients. The risk factors identified in this study could be considered when making decisions regarding thromboprophylaxis for patients with thyroid cancer.
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