Wilmar M. Wiersinga
Antithyroid drugs (ATD) are nowadays the preferred treatment modality of Graves’ hyperthyroidism, but recurrent hyperthyroidism after a course of ATD is a major drawback. To predict recurrences from baseline data, a prospective study was done in 178 consecutive patients with first episode of Graves’ hyperthyroidism treated for one year with ATD (Vos et al. JCEM 2016; 101: 1381). Independent risk factors for recurrences were age <40 yr (assign 1 point), FT4 ≥40 pmol/l (1 point), TBII 6-<20 U/L (1 point) ≥20 U/L (2 points), goitre size grade II-III (2 points), summarized in the GREAT score (Graves’ Recurrent Events After Therapy): recurrence rates are 16% in class I (score 0-1), 44% in class II (score 2-3), 68% in class III (score 4-6). ATD are a reasonable option in class I (34% of all patients) but not in class III (11% of all patients). In class II (55% of all patients) genotyping may be helpful. The presence of PTPN22 SNP C/T (1 point) or HLA DRB1-03, DQA1-05, DQB1-02 (2 points for 2 and 3 points for 3 polymorphisms) are added giving rise to the GREAT+ score: recurrence rates are now 4% in GREAT+ class I (score 0-2), 21% in class II (score 3-4), 49% in class III (score 5-6), and 84% in class IV (score 7-10). Applying the GREAT+ score in patients with GREAT score class II, recurrence risk remains the same in 62% (GREAT+ class III) but decreases in 33% (GREAT+ class I, II) and increases in 5% (GREAT+ class IV). The predictive GREAT scores are useful in delivering personalised treatment of Graves’ hyperthyroidism. Future improvement might be derived from next generation assays of TSH receptor antibodies and from more extensive genotyping. The external validity of the GREAT score has been ascertained in three retrospective studies from Switzerland, Italy and Turkey. New interest emerges in the possibility of very long-term treatment with ATD.