Prediction of recurrent hyperthyroidism after a course of antithyroid drugs

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.

Cushings Disease

Lynnette Niemann

EASD/ADA Guidelines

David Matthews

The EASD and the ADA have worked over many years to produce joint guidelines and statements about the treatment of type 2 diabetes. Additionally the ADA publishes its ‘Standards of Care’ annually. All these documents are opinion pieces put together on the basis of evidence, experience and accepted practice. They are helpful, have a wide readership and are useful for clinicians, health-care workers, payers, hospitals, clinics and sometimes lawyers!

Nevertheless, it is worth asking ‘how do we know what we know?’. Indeed that question forms a significant branch of philosophy called ‘epistemology’.  In diabetes we know much from trials and meta-analyses, from physiology and diagnostic techniques and clinical measurements. But how ‘true’ are the trials?

All major studies have had flaws – can we extract the truths?

Most of the science of how we treat diabetes comes from the building together of a coherent edifice of science. This edifice has some important corner-stones – the UKPDS (with coherent resonances from the DCCT), ADVANCE, ACCORD and the VADT. Beyond these generic trials we have drug-specific trials including RECORD (rosiglitazone), LEADER (liraglutide), and CANVAS (canagliflozin), and subsets of these trials examining specifics including SUSTAIN (once-weekly GLP1), PIONEER (oral semaglutide) and CREDENCE (renal protection of SGLT2s).  Each of these trials gives a differing insight into our care of type 2 diabetes and none alone can inform us of the best course of action. Nevertheless, over the years we move towards a consensus, hoping that we also learn the wisdom of when to deviate from the strictures of dogma.