To investigate the effect of resistance to thyroid hormone (RTH) due to a TRβ mutation on coagulation and fibrinolysis
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Thyroid gland disorders
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following groups of lab markers will be tested: labmarkers: thyroid
function and SHBG, coagulation markers and fibrinolysis markers.
Secondary outcome
not applicable
Background summary
Recent interest has focused on the association between thyroid dysfunction and
venous thromboembolism (VTE). Hyperthyroidism is associated with a
hypercoagulable state (1-3). Several coagulation and fibrinolytic parameters
appear to be affected by thyrotoxicosis; elevated plasma levels of factor VIII
(FVIII), factor IX (FIX), von Willebrand factor (VWF), and fibrinogen, and a
reduced fibrinolytic activity due to increased levels of plasminogen activator
inhibitor-1 (PAI-1) have been reported in both hyperthyroid patients and
healthy subjects after taking thyroid hormones (1, 4-10).
A retrospective cohort study was done to determine the risk of VTE in all
patients with overt hyperthyroidism and to compare this to the risk of VTE in
the general population (11). The incidence rate of VTE in patients with
hyperthyroidism appeared to be high.
The exact mechanism of hyperthyroidism leading to affected coagulation and
fibrinolytic parameters and thus the hypercoagulable state is unknown. It was
shown that in cultured endothelial cells triiodothyronine (T3) induces
upregulation of mRNA expression and protein synthesis of VWF, fibronectin (FN)
and endothelin-1 (ET-1) (12). The effect of T3 treatment on target gene
regulation was investigated in a thyroid hormone receptor (TR)-overexpressing
hepatoma cell line by performing cDNA microarrays (13). Thrombin for example,
was multiplied 8-fold by T3 induction and coagulation factor X (FX) 4.9-fold.
We hypothesize that the hypercoagulable state in hyperthyroidism is mediated by
the thyroid hormone receptor (TR). Patients with a mutation in the thyroid
hormone receptor beta (TRβ) gene have elevated plasma T3 and T4. Therefore,
patients with a TRβ mutation can serve as the optimal clinical model to
investigate the role of TRβ in the hypercoagulable state seen in patients with
hyperthyroidism.
Study objective
To investigate the effect of resistance to thyroid hormone (RTH) due to a TRβ
mutation on coagulation and fibrinolysis
Study design
cross-sectional study
Study burden and risks
Blood will be drawn once. Participation in the study will not influence the
treatment of the patients.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Patients with thyroid hormone resistance due to a mutation in the thyroid hormone receptor beta gene
- Elevated T3 and/or T4 according to the local reference ranges;For the control groups:
a) hyperthyroid patients with elevated serum T4 and/or T3 according to the local reference ranges
b) euthyroid controls with general good health, both matched for age (± 5 years) and gender
Exclusion criteria
- No informed consent
- Oral anticoagulant therapy (warfarin, vitamin K antagonists)
- Hemophilia or von Willebrand's disease
- Oral corticosteroid therapy
- Previous VTE within the last 6 months
- Previous thyroid surgery or radio-iodine treatment
- Current anti-thyroid drugs
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL46481.018.13 |