Low-dose Radioiodine Ablation in Graves' Disease (LORIGRAVES)

Use of Low-dose Radioiodine for Ablation of Thyroid Remnants in Patients With Graves' Disease Following Thyroidectomy

Graves' orbitopathy (GO) is an autoimmune condition almost always associated with autoimmune thyroid disease, especially Graves' disease (GD). According to the most widely accepted model, the autoantigen/s responsible for GO would include molecules expressed by thyroid epithelial cells that are present also in orbital tissues. The high likelihood that the etiologies of GO and of the underlying autoimmune thyroid diseases are somehow linked is confirmed by the very close relationship between GO, the onset and the course of Graves' diseases, the size of the thyroid gland, and most importantly, thyroid function and thyroid treatment. Based on these considerations, it has been proposed that complete removal of thyroid antigens and of thyroid infiltrating lymphocytes, the so called total thyroid ablation (TTA), may be followed by an attenuation of the immune reaction against orbital antigens, and ultimately by an amelioration of GO. The possibility that TTA, achieved by near total thyroidectomy followed by radioiodine, may be beneficial for GO was initially suggested by two retrospective studies and more recently by two prospective, randomized clinical trials conducted in patients with moderate GO treated with intravenous glucocorticoids. Although there seemed to be no difference in the long term, compared with near total thyroidectomy alone TTA was associated with a shorter time required for GO to improve, or anyway to reach its best possible outcome, and with a lesser requirement for additional treatments in order for GO to improve.

TTA is usually performed with a radioiodine dose of 30 millicurie (mCi), administered after 2 injections of recombinant human thyrotropin TSH (rhTSH), the latter in order to induce radioiodine uptake by thyroid remnants. According to the Italian legislation the administration of such a dose of radioiodine must be followed by a 24 hours protected hospitalization. Clearly, this necessity implies a remarkable increase of the waiting list, due to the limited number of radiation-isolated beds available and, concerning GO patients, to the competition with patients with thyroid cancer. In contrast, a radioiodine dose of 15 mCi can be performed in out-patients without hospitalization and with much lower costs. Concerning GD patients, they usually have serum TSH-receptor stimulating antibodies that ay persist after thyroidectomy and that may increase radioiodine uptake along with rhTSH, possibly resulting in the need for a lower dose of radioiodine to ablate thyroid remnants. In order to investigate whether this is the case, the present study was designed in patients with GD. The study design was to include patients scheduled to radioiodine treatment with 30 or 15 mCi after administration of rhTSH, being the primary outcome the values of serum thyroglobulin at peak after administration of rhTSH 6 months after radioiodine, as a measure of the presence of residual thyroid tissue.

Study Overview

• Status: Completed
• Conditions: Thyroid Diseases
• Intervention / Treatment: Radiation: Radioiodine

• Study Type: Observational
• Enrollment (Actual): 12

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Thyroidectomized patients with Graves' hyperthyroidism and GO undergoing radioiodine ablation with either 15 or 30 mCi of 131I

Description

Inclusion Criteria:

• Graves' disease at histology
• Thyroid cancer at histology
• Undetectable serum anti-thyroglobulin autoantibodies
• Informed consent

Exclusion Criteria:

• Detectable serum anti-thyroglobulin autoantibodies
• lack of informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
15 mCi radioiodine; 6 patients with low risk differentiated thyroid cancer, as determined by histology	Radiation: Radioiodine; Administration of radioiodine; Other Names: 131-Iodine
30 mCi radioiodine; 6 patients with low risk differentiated thyroid cancer, as determined by histology	Radiation: Radioiodine; Administration of radioiodine; Other Names: 131-Iodine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rhTSH-stimulated serum thyroglobulin (Tg) at 6 months	Measurement of Tg after 2 injections of rhTSH	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Tg	Measurement of Tg prior to injections of rhTSH	6 months

Collaborators and Investigators

• Sponsor: University of Pisa

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): March 28, 2017
• Study Completion (ACTUAL): March 28, 2017

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (ACTUAL): April 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2017
• Last Update Submitted That Met QC Criteria: April 5, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Endocrine System Diseases; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Graves Disease
• Other Study ID Numbers: LORIGRAVES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No