Total Thyroidectomy Versus Thionamides in Patients With Moderate-to-Severe Graves' Ophthalmopathy

Study Overview
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Brief Summary
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Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO. Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months. Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

Detailed Description
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Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO. Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months. Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

Official Title
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Prospective Randomized Clinical Trial of Total Thyroidectomy (Tx) Versus Thionamides (Anti-Thyroid Drugs) in Patients With Moderate-to-Severe Graves' Ophthalmopathy - a 1-year Follow-up

Conditions
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Graves Disease, Graves Ophthalmopathy, Graves' Ophthalmopathy Worsened

Intervention / Treatment
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* Drug: Antithyroid Drug
* Procedure: Total thyroidectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GD and GO onset < 12 months no previous GD treatment other than antithyroid drugs (ATD) first relapse after decrease of antithyroid medication within 4-6 months GO treatment with glucocorticoids based on the Kahaly scheme patients under ATD with normal thyroid function or subclinical hyperthyroid function and moderate-to-severe GO clinically active inflammation according to CAScore (>3/7) informed consent Exclusion Criteria: GD and GO onset > 12 months more than one relapse of GO longer than 6 months from diagnosis previous GD treatment by RAI or surgery SNI greater than 7.0 urgent orbital decompression surgery loss of vision loss of visual field loss of color vision patients not receiving glucocorticoids for GO cytological findings of postsurgical histopathological results suspicious for malignancy pregnancy or breast-feeding contraindication to GC halt of GC therapy Patients with diabetes mellitus age below 18 years no informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thyroidectomy<br>Total thyroidectomy | Drug: Antithyroid Drug<br>* Antithyroid drug<br>* Other names: Propylthiouracil;|
| Active Comparator: Antithyroid drug<br>Thiamazol, Propylthiouracil | Procedure: Total thyroidectomy<br>* Operation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle index (MI) from ultrasound measurements | Muscle index (MI) from ultrasound measurements | 12 months | 
| Thyroid antibodies | Thyroid antibodies | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAScore/NOSPECS score | CAScore/NOSPECS score | 12 months | 
| Superonasal index measurements via ultrasound | Superonasal index measurements via ultrasound | 12 months | 
| Quality of life score | Quality of life score | 12 months |