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

Hypothyroidism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02467244
• Other study ID #: T/EM-F/Pharm/14/03
• Status: Completed
• Start date: February 1, 2017
• Est. completion date: December 30, 2018

Study information

• Verified date: September 2019
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 30, 2018
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypothyroidism
• Insulin Resistance

Intervention

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.

Locations

Country	Name	City	State
India	AIIMS, Bhubaneswar	Bhubaneshwar	Odisha

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (7)

Altinova AE, Törüner FB, Aktürk M, Bukan N, Cakir N, Ayvaz G, Arslan M. Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism. Clin Endocrinol (Oxf). 2006 Oct;65(4):530-5. — View Citation

Benvenga S, Robbins J. Lipoprotein-thyroid hormone interactions. Trends Endocrinol Metab. 1993 Aug;4(6):194-8. — View Citation

Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2004;59:31-50. Review. — View Citation

Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. Review. — View Citation

Kowalska I, Borawski J, Nikolajuk A, Budlewski T, Otziomek E, Górska M, Straczkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011 Aug; — View Citation

Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010 Jan 15;314(1):1-16. doi: 10.1016/j.mce.2009.07.031. Epub 2009 Aug 12. Review. — View Citation

Robinson K, Prins J, Venkatesh B. Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care. 2011 Apr 20;15(2):221. doi: 10.1186/cc10021. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Serum Adiponectin from baseline	Method: ELISA	At baseline and after 12 weeks at follow up
Primary	Change of hsCRP from baseline	Method: ELISA	At baseline and after 12 weeks at follow up
Primary	Change in Insulin resistance from baseline by Homeostatic Model Assessment (HOMA-IR)		At baseline and after 12 weeks at follow up
Secondary	Serum Insulin	Method: ELISA	At baseline and after 12 weeks at follow up
Secondary	Lipid profile (Total cholesterol)		At baseline and after 12 weeks at follow up
Secondary	Lipid profile (LDL-C)		At baseline and after 12 weeks at follow up
Secondary	Lipid profile (HDL-C)		At baseline and after 12 weeks at follow up
Secondary	Lipid profile (Triglyceride)		At baseline and after 12 weeks at follow up
Secondary	Long term glycemic status by Glycosylated hemoglobin (HbA1c%)		At baseline and after 12 weeks at follow up
Secondary	Change in Insulin resistance from baseline by Quantitative Insulin Sensitivity Check Index (QUICKI)		At baseline and after 12 weeks at follow up
Secondary	Change in Cardiovascular risk assessment scoring (Framingham scoring) from baseline		At baseline and after 12 weeks at follow up