A Comparative Study of Homocysteine, Cyanocobalamine, Folate, Lipid Profile and Serum Creatinine Level in Hypothyroid Subjects before and During Treatment

Introduction: Hyperhomocystenemia is a disease involving abnormal homocysteine metabolism and is characterized by increased level of total homocysteine concentration (normal 5-15 μmol/L). Many factors like dietary folate, cyanocobalamine deficiency or thyroid disorder are the most common causes for increased homocysteine level. This present study was planned to delineate the usefulness of levothyroxin, supplementation of folate and cyanocobalamine in patients of hypothyroidism to evaluate change in homocysteine level before and during treatment. Also to find out correlation between levothyroxin, cyanocobalamine and folate with homocysteine. Material and Method: The present study was conducted on 75 pateints of hypothyroidism of either sex in department of biochemistry, J.L.N. medical college and hospitals, Ajmer. Serum homocysteine, cyanocobalamine, folate level was measured by ELISA while thyroid function test were evaluated by RIA method. Result and discussion: There was highly significant change in homocysteine, cyanocobalamine, folate, total cholesterol, HDL, VLDL and LDL in hypothyroid subjects before and during treatment (P<0.0001). This emerging evidence suggest that these parameters are influenced by levothyroxine used in treatment of hypothyroid disorder and usefulness of supplementation of cyanocobalamine and folate for significant improvement of serum lipid profile. Conclusion: It is concluded that supplementation of levothyroxin, cyanocobalamine and folate in hypothyroid patients can cause significant decrease in level of homocysteine and significant improvement of serum lipid profile, which decreases risk of coronary heart disease in hypothyroid patients.


Introduction
Thyroid disorders are most common endocrine abnormalities encounter in clinical practices. Thyroid function affects the activity of MTHER gene, its activity reduced in person with underactive thyroid. Hypothyrosis can also disturb the conversion of riboflavin to FAD, which can equally affects the activity of MTHER gene. Even other enzyme such as cystathionine ß synthase or methionine synthase, a vitamin B12 dependent enzyme may be affected. Furthermore, a change of kidney functions may have an effect; lower glomerular function rate (GFR) is found in patients of hypothyroidism, with increase serum creatinine level.
Homocysteine is metabolite of amino acid methionine. Hyperhomocysteinemia is a disease involving abnormal homocysteine metabolism, is characterized by increased total homocysteine concentration (normal 5-15 µmol/L). This can be result of a dietary folate or cobalamine deficiency and thyroid dysfunction. Several studies have concluded that moderate hyperhomocystenemia is powerful independent factor for arterioscelerosis.

Aims and objectives:
To estimate plasma homocysteine, serum cyanocobalamine, folate, lipid profile and serum creatinine in control and hypothyroid subjects before treatment and in hypothyroid patients during treatment to find out correlation between thyroxin and cyanocobalamine, folate with homocysteine, lipid profile and serum creatinine in hypothyroid patients.

Material and method
The present study will comprise of 75 diagnosed patients of thyroid dysfunction (hypothyroidism) attending OPD of Medicine / Surgery of J.L.N. Medical College and Hospital, Ajmer. Diagnosis would be finalised after thyroid profile estimation.
Seventy five healthy subjects of either sex of similar age group will be included in the study, as the control group.
Blood samples will be collected by venipuncture by aseptic technique, Serum / plasma will be subjected to following estimations: 1) Plasma homocysteine -By ELISA method. 2) Serum cobalamin -By ELISA method.

Discussion
Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic change in lipid profile. Because hypothyroidism decreases hepatic level of enzyme involved in the remethylation pathway of homocysteine, we evaluated fasting t-Hcy in patients before and after recovery of euthyroidism. In univeriate analysis, fasting Hcy was positively related to thyrotropin(TSH) and inversely related to folates, as thyroid hormone affects riboflavin metabolism and mainly by stimulating flavokinase and thereby synthesis of FMN and FAD which serve as cofactor for enzyme involve in metabolism of cobalamine, folate. MTHER is FAD dependent enzyme is possible mediator of change in t-Hcy level according to riboflavin status.
Dyslipidemia is common finding in hypothyroid patients, explained by influences all aspect of lipid metabolism including synthesis, mobilization and degradation.

Conclusion
Hyper-homocysteinimia is a modifiable risk factor of arterosclerosis and can be prevented and treated by vitamin B12 and folic acid supplementation.
There is strong correlation of supplementation of thyroxin to patients of hypothyroidism which causes significantly decrease level of serum homocysteine and significant improvement of serum lipid profile which decreases relative risk of coronary artery disease in hypothyroid patients.