Letter to the Editor from Valdes-Socin et al: “Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves’ Disease and Hashimoto’s Hypothyroidism”

Abstract

We read with interest the study by Zhang and colleagues (1) that suggests, after identifying several susceptibility genes in a Chinese Han population, that the pathogenesis of Hashimoto thyroiditis (HT) and Graves disease (GD) is different. Importantly, in the “Introduction,” the authors remind the readers that thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) are present in some GD patients. Furthermore, because HT and GD both have thyroiditis with immune infiltration, these entities must be closely related, as stated by the authors. Conversion of HT to Grave disease is still an underestimated clinical feature for most clinicians. In our series of nearly 2000 HT patients (2), we identified 24 patients (1.2%) who developed GD after a mean follow-up of 38 months. Interestingly, the conversion from HT to GD has been described as prevalent (25.7% of cases) in a controlled series of 35 children with either Down or Turner syndrome (3). Several mechanisms have been postulated behind the conversion from HT to GD. One of them is the presence of different autoantibodies that include thyroid-stimulating antibodies (TSAbs) and thyroid-blocking antibodies. Another possible explanation for this transition is that the autoimmune tissue damage, initially severe enough to cause thyroid hypofunction, recovers sufficiently to allow subsequent stimulation by TSAbs (2, 3). Zhang et al recruited patients with HT and GD using distinct diagnostic criteria. Importantly, the HT patient had only TPOAb or TgAb measurements, whereas thyrotropin receptor autoantibodies and thyroid I131 iodine uptake were determined only in GD patients. After inclusion, there was no long-term follow-up of patients. Consequently, these could be considered potential limitations to their genetic study, because at the moment of inclusion, some GD patients could have previously started as HT, and conversely, some HT patients will further develop a GD phenotype. Interestingly, some single-nucleotide polymorphism genes (SLAMF6 and HLA-B) were found both in the HT and GD groups. More extensive cohort, immunological and genetic studies are necessary to gain insight into these interesting observations. Financial Support: The authors received no financial support for the research, authorship, and/or publication of this article. Disclosure Summary: The authors have nothing to disclose.