Long-term remission following antithyroid drug withdrawal in patients with Graves’ hyperthyroidism: parameters with prognostic value

García‐Mayor, Ricardo V.; Álvarez-Vázquez, Paula; Fluiters, Enrique; Valverde, Diana; Andrade, Amalia

doi:10.1007/s12020-018-1785-z

Cited by 17 publications

(14 citation statements)

References 45 publications

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“…In our series, other risk factors for GD relapse such as high TRAbs concentrations, large goiter size were not significantly different between relapsed and not relapsed patients and were not included in multivariate analysis. In contrast to other studies (30) we found no association between GO and an increased risk of hyperthyroidism recurrence. In any case, we found that in young GO patients, that in some studies are considered at higher risk of recurrent hyperthyroidism, MPDS treatment reduced the relapse rate to levels lower than those in patients without GO.…”

Section: Discussioncontrasting

confidence: 99%

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Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism

et al. 2020

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Background: A course of anti-thyroid drugs (ATD) is the most common first line treatment for Graves' hyperthyroidism. However, hyperthyroidism relapse is frequent (30-70%). Due to the autoimmune nature of Graves' disease, the immunosuppressive treatment used for active Graves' orbitopathy (GO) may reduce the relapses after ATD discontinuation. Objective: To evaluate the recurrence rate in Graves' patients who, in addition to standard ATD, were treated or not treated with parenteral methylprednisolone (MPDS) for GO. Methods: Single-center retrospective study in a continuous series of 162 newly diagnosed Graves' patients, with or without GO, all gone into remission and followed-up until hyperthyroidism recurrence or at least 4 years after ATD discontinuation. Patients with moderate-severe active GO underwent middle dose MPDS treatment according to the EuGoGo guidelines. Cox proportional-hazard model was used to comparatively evaluate the risk of recurrence and the predictive factors in patients treated or not treated with MPDS pulse therapy. Results: MPDS treatment was the most significant factor that independently correlated with a reduced risk of hyperthyroidism relapse (HR = 0.53, 95% C.I. = 0.31-0.89). FT3 and female sex were also independent protective factors, while age almost reached the significance level, p = 0.062. The efficacy of MPDS was very high in patients aged <40 years (42.1% decrease in relapses, p < 0.01) but it was not significant in older patients. Discussion: Our study found that after ATD discontinuation the frequency of Graves' hyperthyroidism relapse was reduced in patients treated with MPDS pulse therapy for GO. This effect was more marked in young patients.

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Section: Discussioncontrasting

confidence: 99%

“…Our study has some limitations inherent to retrospective studies and lacks familial and genetic characteristics of the studied patients (11,16,30).…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism

et al. 2020

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“…Its accuracy might possibly be enhanced by replacing TBII by an assay which more specifically measures TSH receptor stimulating antibodies [2627]. It is also foreseen that the predictive value of the GREAT + score (which incorporates genotyping) could be enhanced by adding more genotypes related to Graves' disease (like CTLA-4 G/G and TSHR ) [2829].…”

Section: Antithyroid Drugsmentioning

confidence: 99%

Graves' Disease: Can It Be Cured?

Wiersinga

2019

Endocrinol Metab

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Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 131I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.

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“…A study conducted in Japan also found that remission of GD was associated with the A/G polymorphism at position 49 in exon 1 of CTLA4 by analyzing the time of TRAb disappearance after the start of ATD treatment (66). More recently, the CTLA-4 A/G genotype has been demonstrated as an independent predictor of long-term remission following a first course of ATD in a Spanish population (67). However, Kim et al (68) did not find an association between GD relapse and the risk alleles of CTLA-4 and CD40 genes.…”

Section: The Costimulatory Genesmentioning

confidence: 93%

Prediction of Relapse After Antithyroid Drugs Withdrawal: A Narrative Review

Wang

2020

Int J Endocrinol Metab

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Context: Antithyroid drugs (ATD) are the first-line treatment for Graves’ disease (GD); however, relapse following treatment is approximately 30% - 40% in the first year, and 50% - 60% in the long term. Identification of risk factors that predict relapse, after discontinuing ATD, plays an important role in guiding therapeutic options. Evidence Acquisition: PubMed was used to search for studies published in English between 1995 and 2019. The following search terms were used: Graves’ disease, antithyroid drugs, relapse, recurrence, and outcome. The reference lists from review articles were also included in the search in order to find older journals. Results: Factors associated with a high recurrence rate, as reported in most studies, were divided into phenotype and genotype predictors. Phenotype factors included large goiter size, persistence of high TSH receptor antibody (TRAb), severe hyperthyroidism, smoking, younger age, male sex, and prior history of recurrence. Genotype factors included human leukocyte antigen (HLA), CD40, CTLA-4, PTPN22, Tg, and TSHR genes. In a subgroup analysis by age, genetic factors were better predictors in the younger group, while clinical signs were more useful in the older group. The reliability of using individual baseline risk factors to predict subsequent relapse is poor; however, predictive scores calculated by grouping single risk factors might help to predict future outcomes. Conclusions: Longer normalization time of TRAb, the persistence of a palpable goiter, and harboring genetic risk factors in younger patients are associated with high recurrence rate of GD. Multi-marker prediction models have been proposed and validated to improve the predictive value of relapse after ATD withdrawal.

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Long-term remission following antithyroid drug withdrawal in patients with Graves’ hyperthyroidism: parameters with prognostic value

Cited by 17 publications

References 45 publications

Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism

Corticosteroid Pulse Therapy for Graves' Ophthalmopathy Reduces the Relapse Rate of Graves' Hyperthyroidism

Graves' Disease: Can It Be Cured?

Prediction of Relapse After Antithyroid Drugs Withdrawal: A Narrative Review

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