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

Medical University of Vienna

Status and phase: Unknown; Phase 3

Conditions: Graves' Ophthalmopathy Worsened; Graves Ophthalmopathy; Graves Disease

Treatments: Drug: Antithyroid Drug; Procedure: Total thyroidectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT03066076

1839/2015

2015-003515-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. GD and GO onset < 12 months
2. no previous GD treatment other than antithyroid drugs (ATD)
3. first relapse after decrease of antithyroid medication within 4-6 months
4. GO treatment with glucocorticoids based on the Kahaly scheme
5. patients under ATD with normal thyroid function or subclinical hyperthyroid function and moderate-to-severe GO
6. clinically active inflammation according to CAScore (>3/7)
7. informed consent

Exclusion criteria

1. GD and GO onset > 12 months
2. more than one relapse of GO longer than 6 months from diagnosis
3. previous GD treatment by RAI or surgery
4. SNI greater than 7.0
5. urgent orbital decompression surgery
6. loss of vision
7. loss of visual field
8. loss of color vision
9. patients not receiving glucocorticoids for GO
10. cytological findings of postsurgical histopathological results suspicious for malignancy
11. pregnancy or breast-feeding
12. contraindication to GC
13. halt of GC therapy
14. Patients with diabetes mellitus
15. age below 18 years
16. no informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 2 patient groups

Thyroidectomy

Active Comparator group

Description:

Total thyroidectomy

Treatment:

Drug: Antithyroid Drug

Antithyroid drug

Active Comparator group

Description:

Thiamazol, Propylthiouracil

Treatment:

Procedure: Total thyroidectomy