Graves’ disease (GD) is an auto-immune disease and the most common cause of hyperthyroidism in iodine-sufficient areas with a prevalence of 0.5–2% [1]. GD is characterized by the presence of autoantibodies that are directed against the thyroid-stimulating hormone (TSH) receptor (TRAb) and thereby able to activate this receptor. This leads to increased free thyroxine (fT4) and free triiodothyronine (fT3) concentrations and suppressed TSH concentrations. TRAbs are often measured to differentiate between GD and other causes of hyperthyroidism, where positive TRAb results (above a pre-defined cut-off value) guide towards GD [2, 3]. Furthermore, TRAbs are measured for follow-up GD treatment [3]. First-line treatment of GD often involves a 12–18 months course of antithyroid drugs (ATD) in the form of ATD titration therapy or combined with levothyroxine (LT4) (block-and-replace therapy). After discontinuation of ATD, GD relapses in approximately 50% of the patients [4, 5]. After a relapse, patients can also choose a more definite form of treatment including radioiodine (RAI) treatment or (total) thyroidectomy, after which life-long LT4 treatment is necessary.

In 2016, the ‘Graves recurrent event after therapy’ (GREAT) and GREAT+ score were developed in the Department of Endocrinology of Amsterdam UMC to improve the prediction of relapse after discontinuation of ATD already at the start of the first-line treatment [6]. These scores were based on four clinical markers: age, fT4 concentration, TRAb concentration, and goiter size. The GREAT + score included the genetic markers tyrosine-protein phosphatase non-receptor type 22 (PTPN22) C/T polymorphism and HLA subtypes DQB1*02, DQA1*05 and DRB*03 (Table 1). The GREAT score allocates patients in three different categories corresponding with a relapse chance of 16%, 44% and 68%. The GREAT+ score uses four categories corresponding with a relapse chance of 4%, 21%, 49% and 84% (Table 1). Scores to predict relapse after ATD discontinuation are currently limited to the GREAT( +) score and the clinical severity score (CSS). The CSS score was developed by Bartalena et al. [7] and incorporated fT4 concentration, thyroid volume and the presence of Graves orbitopathy [7].

The GREAT score has been validated in three independent cohorts [8,9,10], but the GREAT+ score has not been validated yet. Nevertheless, the addition of a fourth category seems extremely valuable in distinguishing relapse chances, especially in the lowest and the highest categories. Before starting an external validation of the GREAT+ score, we aimed to investigate the need for implementation of the GREAT+ score among patients treated for GD and physicians treating GD.

The need for the GREAT+ score was assessed by a questionnaire for current and past GD patients and physicians treating GD patients in the Netherlands. The questionnaire was distributed and completed between June 2022 and August 2023 and supported by the Dutch Thyroid Organization (Schildklier Organisatie Nederland; SON), Dutch Thyroid Research Foundation and the Dutch Society for Endocrinology (NVE) by posting the link to the questionnaire on either their website, social media account, or newsletter. Respondents were not approached personally and could anonymously and voluntarily complete the questionnaire. Therefore, no informed consent from each subject was necessary. Furthermore, the study was not subject to the Medical Research Involving Human Subjects Act since it does not impose any act or mode of behavior on the subjects.

The patient questionnaire consisted of three sections (Supplementary Table 1). The first section concerned questions on age, sex, and medication (except thyroid medication). The second section concerned 14 questions and dealt with patients’ experience with GD. Before the third section, information regarding the GREAT+ score was provided. After taking note of this information, nine specific questions regarding the GREAT+ score were asked. Closed questions were often followed by open questions.

The physician questionnaire consisted of two sections (Supplementary Table 2). The first section included four questions regarding experience as a GD treating physician. Before the second section, information regarding the GREAT+ score was provided. After taking note of this information, 14 questions regarding the GREAT+  score were asked. Closed questions were followed by open questions.

The results of both questionnaires were fully anonymous. Questions that subsequently proved redundant were excluded from the analysis. Since most questions were closed, results were merely depicted as a percentage of the total respondents. IBM SPSS Statistics 28.0 (Chicago, IL, USA) and GraphPad Prism 9.3.1 Software were used to analyze the results. Answers from the open questions were used to get insight into the rationale of answers from closed questions, but were not statistically assessed.