Clinical trial NCT02467244: Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism
Official title: Effect of Levothyroxine on Serum Adiponectin, Insulin Resistance and Cardiovascular Risk in Patients With Hypothyroidism
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypothyroidism
Keywords: Hypothyroidism
Serum adiponectin
hsCRP
Homeostatic Model Assessment (HOMA-IR)
Quantitative Insulin Sensitivity Check Index (QUICKI)
Cardiovascular risk assessment scoring (Framingham scoring)
Levothyroxin
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2015-06-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will be conducted on 50 patients of hypothyroidism attending the outpatient department of General Medicine, All India Institute of Medical Sciences, Bhubaneswar. Another 50 euthyroid, age-, sex-matched subjects will be recruited as control.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of Serum Adiponectin from baseline
timeFrame: At baseline and after 12 weeks at follow up
measure: Change of hsCRP from baseline
timeFrame: At baseline and after 12 weeks at follow up
measure: Change in Insulin resistance from baseline by Homeostatic Model Assessment (HOMA-IR)
timeFrame: At baseline and after 12 weeks at follow up
Secondary outcomes:
measure: Serum Insulin
timeFrame: At baseline and after 12 weeks at follow up
measure: Lipid profile (Total cholesterol)
timeFrame: At baseline and after 12 weeks at follow up
measure: Lipid profile (LDL-C)
timeFrame: At baseline and after 12 weeks at follow up
measure: Lipid profile (HDL-C)
timeFrame: At baseline and after 12 weeks at follow up
measure: Lipid profile (Triglyceride)
timeFrame: At baseline and after 12 weeks at follow up
measure: Long term glycemic status by Glycosylated hemoglobin (HbA1c%)
timeFrame: At baseline and after 12 weeks at follow up
measure: Change in Insulin resistance from baseline by Quantitative Insulin Sensitivity Check Index (QUICKI)
timeFrame: At baseline and after 12 weeks at follow up
measure: Change in Cardiovascular risk assessment scoring (Framingham scoring) from baseline
timeFrame: At baseline and after 12 weeks at follow up
Other outcomes:
Locations:
city: Bhubaneshwar
country: India
facility: AIIMS, Bhubaneswar
state: Odisha
Study officials:
affiliation: AIIMS, Bhubaneswar
name: DEBASISH HOTA, MD, DM
role: STUDY_DIRECTOR
References:
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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. doi: 10.1210/rp.59.1.31.
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.
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.
citation: Altinova AE, Toruner FB, Akturk 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. doi: 10.1111/j.1365-2265.2006.02628.x.
citation: Kowalska I, Borawski J, Nikolajuk A, Budlewski T, Otziomek E, Gorska M, Straczkowski M. Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy. Endocrine. 2011 Aug;40(1):95-101. doi: 10.1007/s12020-011-9446-5. Epub 2011 Mar 18.