Serum Thyrotropin Receptor Antibodies Concentrations in Patients with Graves' Disease Before, at the End of Methimazole Treatment, and After Drug Withdrawal: Evidence That the Activity of Thyrotropin Receptor Antibody and/or Thyroid Response Modify During the Observation Period
Abstract
AIM AND METHODS: We performed a quantitative retrospective analysis of serum thyrotropin receptor antibody (TRAb) concentrations measured by a second-generation radioreceptor assay in 58 patients with Graves' disease (GD) at the onset of the disease, at the end of 18 month methimazole (MMI) treatment, and after MMI withdrawal in order to evaluate the correlation between the presence of these antibodies and the relapse of hyperthyroidism. Sixty healthy subjects were enrolled as a control group. RESULTS: Before MMI treatment the best cutoff TRAb value for identifying patients with GD was 1.45 UI/L (specificity, 100%; sensitivity, 98.3%). At the end of MMI treatment, serum TRAb concentrations were significantly lower (p < 0.001) than those measured at baseline, but they were still significantly higher (p < 0.001) than those found in the control subjects. At the end of MMI treatment, 44 patients (75.9%) had positive TRAb values (>1.45 UI/L). After MMI withdrawal (median, 15 months), 34 patients (58.6%) became hyperthyroid, 4 patients (6.9%) became hypothyroid, and 20 patients (34.5%) remained euthyroid. There was a significant correlation between serum TRAb concentrations at the end of MMI treatment and the percentage of patients who became hyperthyroid (r: 0.56; p < 0.001) and the time of appearance of hyperthyroidism (r: -0.38; p = 0.03). All 4 patients with TRAb values below 0.9 UI/L at the end of MMI treatment remained euthyroid throughout the follow-up period. Among the 27 patients who had serum TRAb values higher than 4.4 UI/L, 23 developed hyperthyroidism and 4 hypothyroidism. The TRAb values between 0.9 and 4.4 UI/L did not discriminate between the 27 patients (46.6%) who remained euthyroid from those who had relapse of hyperthyroidism. Thus a different TRAb end of treatment cutoff was calculated to identify patients who became again hyperthyroid. This TRAb cutoff value was 3.85 UI/L (sensitivity, 85.3%; specificity, 96.5%). All but 1 patient who had serum TRAb values above 3.85 UI/L became hyperthyroid after MMI was withdrawn (positive predictive value, 96.7%). In these patients, relapse of hyperthyroidism was independent of the changes in serum TRAb concentrations (r: 0.27; p = 0.15) and occurred after a median period of 8 weeks (range, 4-48). Hyperthyroidism also developed in 5 of 24 patients who had serum TRAb concentrations lower than 3.85 UI/L at the end of MMI treatment. In these 5 patients the relapse of hyperthyroidism occurred after a median period of 56 weeks (range, 24-120) and was always accompanied by an increase in serum TRAb concentrations. CONCLUSIONS: TRAb persist in the blood of most patients with GD after 18 months of MMI treatment. Both the frequency and the time of appearance of hyperthyroidism are closely correlated with serum TRAb concentrations at the end of MMI treatment. Our data would suggest that TRAb maintain stimulating activity after a full course of MMI treatment in the large majority of patients with GD. However, it is likely that the potency of these antibodies and/or the thyroid response to them change during treatment, as suggested by the different values measured in euthyroid control subjects and in euthyroid patients after MMI treatment.
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In the group with elevated TRAb, relapse rates approach 80%-100%, while in the group with low or undetectable TRAb, relapse rates are in the 20%-30% range.
“In the group with elevated TRAb, relapse rates approach 80%-100%, while in the latter group, relapse rates are in the 20%-30% range (171,172).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [171]
TRAb assessment at the end of the course of ATD therapy is a useful method of dividing patients into two groups: one with persistent elevations who are unlikely to be in remission, and another group with low or undetectable TRAb, who have a higher probability of permanent remission.
“TRAb assessment at the end of the course of ATD therapy is a useful method of dividing patients into two groups: one with persistent elevations who are unlikely to be in remission, and another group with low or undetectable TRAb, who have a higher probability of permanent remission (171,172).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [171]
In patients who remain euthyroid for more than 1 year (in remission), relapses can occur years later, and some patients eventually become hypothyroid.
“If the patient remains euthyroid for more than 1 year (i.e., they are in remission), thyroid function should be monitored at least annually because relapses can occur years later (171), and some patients eventually become hypothyroid (179).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [171]
In patients with negative TRAb, relapses tend to occur relatively later than those that develop in patients whose MMI is stopped when TRAb is still positive, although 5% occurred within the first 2 months in one study.
“In patients with negative TRAb, relapses tend to occur relatively later than those that develop in patients whose MMI is stopped when TRAb is still positive (171,176), although 5% occurred within the first 2 months in one study (167).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [171]
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“TRAb assessment at the end of the course of ATD therapy is a useful method of dividing patients into two groups: one with persistent elevations who are unlikely to be in remission, and another group with low or undetectable TRAb, who have a higher probability of permanent remission (171,172).”
BackgroundMethodInfluentialDe Leo, S., Lee, S. Y., & Braverman, L. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00278-6 · Cited by 883 · see citing works
Self-citationClinical Utility of TSH Receptor Antibodies
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- Authors
- Carella, C., Mazziotti, G., Sorvillo, F., Piscopo, M., Cioffi, M., Pilla, P., Nersita, R., Iorio, S., Amato, G., Braverman, L. E., & Roti, E.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Boston University (US)
- University of Milan (IT)
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2006-03
- Volume
- 16
- Issue
- 3
- Pages
- 295-302
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2085313965
- Cited by
- 119
- References
- 60
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 1 · 2013: 6 · 2012: 3
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- Graves' disease, TSH receptor antibodies, TRAb, methimazole, antithyroid drug withdrawal, hyperthyroidism relapse, hypothyroidism, radioreceptor assay, disease activity markers, treatment response prediction, prognostic factors
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Female, Graves Disease, Humans, Male, Methimazole, Middle Aged, Predictive Value of Tests, Receptors, Thyrotropin, Recurrence, Retrospective Studies, Sensitivity and Specificity, Substance Withdrawal Syndrome
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