Insulin Resistance and Metformin Use on Volume of Benign Thyroid Nodules

Study Overview
=================
Brief Summary
-----------------
It has been shown that insulin might be involved in the pathogenesis of thyroid growth. Objective To evaluate the impact of IR and metformin use on the volume of benign thyroid nodules (TNs). Methods A randomized clinical trial to placebo (P) or MTF use. Previous fine needle aspiration confirming the diagnosis is necessary to inclusion. Patients will receive similar tablets of MTF and placebo and instruct to take 3 tablets/day of MTF (500mg/tablet). Thyroid volume, as TN volume, will be assess by ultrasound, both in the beginning, six months and one year after randomization, by the same researcher blinded regarding location group. Blood samples to measure: TSH, FT4, TPO-Ab, lipid profile, glucose and insulin were done after 8h fasting.

Detailed Description
-----------------
It has been shown that insulin might be involved in the pathogenesis of thyroid growth. Previous studies suggest that metformin (MTF) therapy decreased thyroid volume and nodule size in subjects with insulin resistance (IR). Objectives To evaluate the impact of IR and metformin use on the volume of benign thyroid nodules (TNs). Methods A randomized clinical trial to placebo (P) or MTF use. Previous fine needle aspiration confirming the diagnosis is necessary to inclusion. Exclusion criteria were: nodules with a predominantly cystic pattern, pregnancy, diabetes, acromegaly, previous use of MTF, levothyroxine, corticoid or any weight loss medication in the past six months, hepatic or cardiac insufficiency, creatinine levels > 1.4 mg/dL and MTF intolerance doses >1.0 gram/day. Patients will receive similar tablets of MTF and placebo and will be instructed to take 3 tablets/day of MTF (500mg/tablet). Thyroid volume, as TN volume, will be accessed by ultrasound, both in the beginning, six months and one year after randomization, by the same researcher blinded regarding location group. Blood samples to measure: TSH, FT4, TPO-Ab, lipid profile, glucose and insulin were done after 8h fasting.

Official Title
-----------------
The Role of Insulin Resistance and the Effect of Metformin Use on Volume of Benign Thyroid Nodules

Conditions
-----------------
Thyroid Nodule, Insulin Resistance

Intervention / Treatment
-----------------
* Drug: Metformin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with benign nodules diagnosed by fine needle aspiration biopsy (FNAB) Exclusion Criteria: Nodules with a predominantly cystic pattern Eggshell calcification Coalescent thyroid nodules (not suitable for size analysis) Pregnancy Diabetes Acromegaly Previous use of MTF, levothyroxine, corticoid or any weight loss medication in the past six months Hepatic or cardiac insufficiency Creatinine levels > 1.4 mg/dL MTF intolerance doses < 1.0 gram/day

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized clinical trial with two groups: to use placebo or Metformine
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>patients randomized to Metformin group | Drug: Metformin<br>* 500 mg metformin three times daily<br>* Other names: MTF;|
| Placebo Comparator: Placebo<br>patients randomized to placebo group | Drug: Placebo<br>* 500 mg placebo three times daily<br>* Other names: PLC;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in nodule volume from baseline after metformin use | the impact of metformin on the volume of thyroid nodules | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in nodule volume from baseline and changes in homa-ir | the impact of insulin resistance in volume of thyroid nodules | one year | 
| changes in TSH levels from baseline after metformin use | the impact of metformin use in TSH levels | one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thyroid volume, thyroid, insulin, thyroid nodule, insulin resistance, metformin