Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Completed

CT.gov ID

NCT02467244

Collaborator

(none)

120

Enrollment

Location

22.9

Actual Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters. The study may explore the lacunae in present treatment protocol and can suggest the possibilities of add-on therapies for a better management.

Condition or Disease	Intervention/Treatment	Phase
Hypothyroidism	Drug: Levothyroxine

Detailed Description

Hypothyroidism is associated with premature atherosclerosis and increased prevalence of coronary artery diseases. Long-term hypothyroidism is associated with severe cardiovascular manifestations including reduced intravascular volume, increased systemic vascular resistance, and hypertension. Hypothyroidism is one of the main causes of secondary dyslipidemia. The classic manifestations of hypothyroidism are raised VLDL, LDL and apo A. The increase in cardiovascular risk is not only due to dyslipidemia, but also to hemodynamic changes, endothelial dysfunction, hormonal and metabolic changes. Insulin resistance and the metabolic syndrome are important cardiovascular risk factors as insulin-resistant individuals with raised TSH have higher LDL concentrations.

Among the various markers associated with obesity and insulin resistance, of particular importance is adiponectin which is inversely related to the degree of adiposity, increases insulin sensitivity, and has antiatherogenic and anti-inflammatory properties, hence may be cardioprotective. Hypoadiponectinaemia is associated with obesity, insulin resistance and type II diabetes, as well as atherosclerosis, hypertension and coronary artery disease.

Treating hypothyroidism with levothyroxine has an antioxidant and cholesterol reducing effect, and thus already has proven beneficial impact on cardiovascular function, blood pressure and lipid profile. But the association of adiponectin and insulin resistance in hypothyroid state and future cardiovascular risk is still not clear because there are few published studies in this domain and result of some the studies are contradictory. The aim of this study is to evaluate plasma adiponectin level, insulin resistance, cardiovascular risk and their correlation (if any) in patients with hypothyroidism and also to investigate the effect of levothyroxine on these parameters.

Study Design

Study Type:

Observational

Actual Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism

Actual Study Start Date :

Feb 1, 2017

Actual Primary Completion Date :

Sep 30, 2018

Actual Study Completion Date :

Dec 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Euthyroid group Fifty (50) age and sex matched euthyroid subjects will serve as the control group. Control euthyroid subjects will be evaluated once at baseline and after 12 weeks.
Hypothyroid group Fifty (50) hypothyroid patients attending the outpatient department of General Medicine, AIIMS, Bhubaneswar, will be recruited for the present study following inclusion and exclusion criteria.	Drug: Levothyroxine At first visit, after taking detailed history including baseline symptomatology, clinical evaluation, and laboratory investigation, treatment will be started with levothyroxine (50 microgram/day). The dosage of levothyroxine (LT4) will be adjusted (at 4th and 8th week) in an attempt to keep the serum FT4 and TSH concentrations within the normal range. After 12 weeks, all the patients will be followed up, clinical and laboratory tests will be repeated.

Arm

Intervention/Treatment

Euthyroid group

Fifty (50) age and sex matched euthyroid subjects will serve as the control group. Control euthyroid subjects will be evaluated once at baseline and after 12 weeks.

Hypothyroid group

Fifty (50) hypothyroid patients attending the outpatient department of General Medicine, AIIMS, Bhubaneswar, will be recruited for the present study following inclusion and exclusion criteria.

Drug: Levothyroxine

At first visit, after taking detailed history including baseline symptomatology, clinical evaluation, and laboratory investigation, treatment will be started with levothyroxine (50 microgram/day). The dosage of levothyroxine (LT4) will be adjusted (at 4th and 8th week) in an attempt to keep the serum FT4 and TSH concentrations within the normal range. After 12 weeks, all the patients will be followed up, clinical and laboratory tests will be repeated.

Outcome Measures

Primary Outcome Measures

Change of Serum Adiponectin from baseline [At baseline and after 12 weeks at follow up]
Method: ELISA
Change of hsCRP from baseline [At baseline and after 12 weeks at follow up]
Method: ELISA
Change in Insulin resistance from baseline by Homeostatic Model Assessment (HOMA-IR) [At baseline and after 12 weeks at follow up]

Secondary Outcome Measures

Serum Insulin [At baseline and after 12 weeks at follow up]
Method: ELISA
Lipid profile (Total cholesterol) [At baseline and after 12 weeks at follow up]
Lipid profile (LDL-C) [At baseline and after 12 weeks at follow up]
Lipid profile (HDL-C) [At baseline and after 12 weeks at follow up]
Lipid profile (Triglyceride) [At baseline and after 12 weeks at follow up]
Long term glycemic status by Glycosylated hemoglobin (HbA1c%) [At baseline and after 12 weeks at follow up]
Change in Insulin resistance from baseline by Quantitative Insulin Sensitivity Check Index (QUICKI) [At baseline and after 12 weeks at follow up]
Change in Cardiovascular risk assessment scoring (Framingham scoring) from baseline [At baseline and after 12 weeks at follow up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients of either sex, aged 18 years or above suffering from hypothyroidism (hypothyroidism was defined as serum TSH level > 5μIU/ml, serum FT3 level < 1.57 pg/ml, serum FT4 level < 0.7 ng/dL. Subclinical hypothyroidism was defined as an elevated TSH level and a normal serum FT3 and FT4 level) and need treatment (treatment is indicated in patients with TSH levels >10 µIU/mL or in patients with TSH levels between 5 and 10 µIU/mL in conjunction with goiter or positive anti-thyroid peroxidase antibodies (or both).
Patients not having hepatic/renal dysfunction, Diabetes mellitus, and chronic inflammatory diseases and not taking any medications for thyroid disease.
Euthyroid subjects not having any significant medical disease.

Exclusion Criteria:

Patients with other comorbidites which can interfere the outcome measures.
Patients who are already on levothyroxine therapy or taking other medications.
Patients with subacute thyroiditis were excluded from the study since acute inflammation could influence the measurements.
Pregnant and lactating mothers.