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Determinants of changes in plasma homocysteine in hyperthyroidism and hypothyroidism
M J Diekman1, N M van der Put, H J Blom
1Department of Endocrinology & Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. m.j.diekmann@amc.uva.nl
Insights
Plasma total homocysteine (tHCys) levels are altered in thyroid dysfunction, increasing in hypothyroidism and decreasing in hyperthyroidism. Free thyroxine (fT4) is a key determinant of these changes.
Area of Science:
- Endocrinology
- Vascular Medicine
- Clinical Chemistry
Background:
- Hyperhomocysteinemia is a known risk factor for atherosclerotic vascular disease and venous thrombosis.
- Thyroid hormones play a crucial role in regulating various metabolic processes, potentially influencing homocysteine levels.
Purpose of the Study:
- To investigate plasma total homocysteine (tHCys) concentrations in hypothyroid and hyperthyroid patients.
- To assess changes in tHCys levels before and after treatment to restore euthyroidism.
- To identify determinants of plasma tHCys levels in thyroid dysfunction.
Main Methods:
- Prospective follow-up study involving 50 hypothyroid and 46 hyperthyroid patients.
- Measurement of plasma tHCys and potential determinants including free thyroxine (fT4), folate, vitamin B12, renal function, and MTHFR genotype.
- Analysis of tHCys levels and their relationship with fT4, folate, creatinine, and age before and after treatment.
Main Results:
- Plasma tHCys levels increased in hypothyroid patients and decreased in hyperthyroid patients after treatment.
- Free thyroxine (fT4) was identified as an independent determinant of tHCys concentrations.
- Changes in folate and creatinine clearance partially explained the observed alterations in tHCys.
Conclusions:
- Thyroid status significantly impacts plasma tHCys concentrations, with opposite effects in hypo- and hyperthyroidism.
- Plasma fT4 levels are a critical independent factor influencing tHCys levels.
- While folate and renal function contribute, fT4 is the primary driver of tHCys variability in thyroid dysfunction.
Objective:
Hyperhomocysteinaemia is a risk factor for premature atherosclerotic vascular disease and venous thrombosis. The aim of the present study was to assess plasma total homocysteine (tHCys) concentrations in hypo- as well as hyperthyroid patients before and after treatment, and to evaluate the role of potential determinants of plasma tHCys levels in these patients.
Design:
Prospective follow up study.
Patients:
Fifty hypothyroid and 46 hyperthyroid patients were studied in the untreated state and again after restoration of euthyroidism.
Measurements:
Fasting plasma levels of tHCys and its putative determinants (plasma levels of free thyroxine (fT4), folate, vitamin B(12), renal function, sex, age, smoking status and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene were measured before and after treatment.
Results:
Restoration of the euthyroid state decreased both tHCys (17.6 +/- 10.2-13.0 +/- 4.7 micromol/l; P < 0.005) and creatinine (83.9 +/- 22.0-69.8 +/- 14.2 micromol/l; P < 0.005) in hypothyroid patients and increased both tHCys (10.7 +/- 2.5-13.4 +/- 3.3 micromol/l; P < 0.005) and creatinine (49.0 +/- 15.4-66.5 +/- 15.0 micromol/l; P < 0.005) in hyperthyroid patients (values as mean +/- SD). Folate levels were lower in the hypothyroid group compared to the hyperthyroid group (11.7 +/- 6.4 and 15.1 +/- 7.6 nmol/l; P < 0.05). Pretreatment tHCys levels correlated with log fT(4) (r = - 0.47), folate (r = - 0.21), plasma creatinine (r = 0.45) and age (r = 0.35) but not with C677T genotype. Multivariate analysis indicated that pretreatment log(fT(4)) levels and age accounted for 28% the variability of pre-treatment tHCys (tHCys = 14.2-5.50 log(fT(4)) + 0.14 age). After treatment the logarithm of the change (Delta) in fT(4) (expressed as the post-treatment fT(4)/pre-treatment fT(4) ratio) accounted for 45% of the variability in change of tHCys ( tHCys = - 0.07-4.94 log ( fT(4))); there was no independent contribution of changes in creatinine which was, however, strongly related to changes in tHCys (r = 0.61).
Conclusions:
Plasma tHCys concentrations increased in hypothyroidism and decreased in hyperthyroidism. Plasma fT(4) is an independent determinant of tHCys concentrations. Lower folate levels and a lower creatinine clearance in hypo-thyroidism, and a higher creatinine clearance in hyperthyroidism only partially explain the changes in tHCys.