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

Completed

• Conditions: Hypothyroidism
• Interventions: Drug: Levothyroxine

• Registration Number: NCT02467244
• Lead Sponsor: All India Institute of Medical Sciences, Bhubaneswar

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.

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 Timeline

• Study First Submitted: 2015-06-04
• Study First Submitted QC: 2015-06-05
• Study First Posted: 2015-06-10
• Study Start: 2017-02-01
• Primary Completion: 2018-09-30
• Study Completion: 2018-12-30
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-27
• Last Update Posted: 2019-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hypothyroid group	Levothyroxine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

AIIMS, Bhubaneswar; 🇮🇳 Bhubaneshwar, Odisha, India