Can Levothyroxine Treatment Reduce the Development of Cardio-metabolic Disorder in Subclinical Hypothyroidism?

Phase 1

• Conditions: Subclinical hypothyroïdism
• Interventions: Drug: Levothyroxine

• Registration Number: NCT04178928
• Lead Sponsor: Ain Shams University

Brief Summary

2. Aim/ Objectives The aim of this study is to evaluate the clinical, laboratory and echocardiographic findings in children with SCH.

To investigate the effect of replacement therapy with levothyroxine on cardiovascular risk factors in children with SCH.

Detailed Description

Sub-clinical hypothyroidism (SCH) is a form of thyroid dysfunction in which the thyroid-stimulating hormone (TSH) level is high, while serum total/free thyroxine (T4/fT4) is within the normal reference range . SCH is mostly detected accidentally as most of the patients manifest few or no signs of thyroid dysfunction.

The most common causative factor for SCH is chronic autoimmune thyroiditis characterized by high titers of thyroid peroxidase antibodies, thyroglobulin antibodies and rarely TSH receptor blocking antibodies. However, mutations in several proteins involving in TSH action including TSH receptor gene and mutations of dual oxidase 2 (DUOX2), phosphodiesterase 8B and thyroid peroxidase have also been demonstrated as causes of TSH elevation .

SCH might be associated with endothelial dysfunction due to early changes in proatherogenic profiles as there is elevation in plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in SCH patients , also there is increased risk of hypertension in SCH patients than in euthyroid .

Many studies found that homocysteine concentration appears to be increased in hypothyroidism and decreased in hyperthyroidism, and there is relationship between hyperhomocysteinemia and cardiovascular disease, including increased platelet aggregation, increased coagulation or reduced thrombolysis and endothelial dysfunction .

The acute-phase reactant hs-CRP is known to be a sensitive and non-specific marker for inflammation, tissue damage and infection . Serum hs-CRP measurements are used to determine cardiovascular risk. hs-CRP is regarded as a predictive marker for myocardial infarction, stroke, peripheral artery disease and sudden cardiac death .

The treatment of children with SCH is controversial; and there is not enough evidence that treatment can prevent the risk of developing cardiovascular and metabolic disorders in SCH.

Study Timeline

• Status Verified: 2019-11
• Study First Submitted: 2019-11-25
• Study First Submitted QC: 2019-11-25
• Study First Posted: 2019-11-26
• Last Update Submitted: 2019-11-26
• Last Update Posted: 2019-11-29
• Study Start: 2020-01
• Primary Completion: 2021-01
• Study Completion: 2021-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 1. Patients aged from 5-15 years diagnosed with SH (patients with elevated TSH and normal Ft4 on two different measurements 4-6 weeks apart).

Exclusion Criteria

• 1. Patients with acute or chronic disorders (anemia, infection, diabetes mellitus, malignancy, liver and renal disorder).

  2. Patients with a history of medication that affect thyroid function tests as glucocorticoids, dopamine or dobutamine, amiodarone, lithium, interferons, alemtuzumab.

  3. Patients with BMI>95 percentile.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group A	Levothyroxine	patiWill receive L-T4 treatment at a dose 1 µg/kg/day for 12 weeks. And the dose will be titrated every 4 weeksents with SCH will be subjected to clinical, laboratory and imaging assessment and

Primary Outcome Measures

Name	Time	Method
: Normalization of TSH.	12 week	Normalization of TSH by receive L-T4 treatment at a dose 1 µg/kg/day for 12 weeks. And the dose will be titrated every 4 weeks then check differences in results between baseline assessment and12 weeks after intervention.