The association of TSH-receptor antibody with the clinical and laboratory parameters in patients with newly diagnosed Graves’ hyperthyroidism: experience from a tertiary referral center including a large number of patients with TSH-receptor antibody-negative patients with Graves’ hyperthyroidism

Abstract

Introduction: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves' disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients. Material and methods: This study included 440 patients [326 (74%) female, 114 (26%) make]. All patients were classified according to gender, age, smoking habit, and TRAb level. Results: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goitre size, male gender, cigarette smoking, Graves' orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAbnegative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD. Conclusions: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.

Asymmetrical Graves’ disease in children: potential usefulness of potassium iodide monotherapy

“…In the study by Mukuta et al 14 untreated patients with TRAb-negative GD (determined using the less sensitive first generation TRAb assay) had lower levels of serum thyroid hormones, less radioiodine thyroidal uptake and smaller thyroid volumes than patients with TRAb-positive GD. In a large-scale study by Zuhur et al, 15 patients with TRAb-negative GD also had lower FT3, FT4 and antithyroid peroxidase antibody levels as well as smaller goitre size. Furthermore, Vos et al 16 reported that none of the patients with TRAb-negative GD had Graves’ orbitopathy or anterior tibial myxoedema.…”

TSH Receptor Antibodies (TRAb) Assay: An Underutilized Test in India

“…[ 8 ] However, issues related to assay performance at these cut-offs leading to misclassification of patients were reported from the United Kingdom, Turkey, Italy, Switzerland, and the Netherlands subsequently. [ 9 10 11 12 ] The current paper in this issue is a step in defining more country-specific cut-offs, which, in turn, might lead to better utilization of TRAb assays in our country.…”

IgG4 as a Biomarker in Graves’ Orbitopathy

“…The TSH receptor antibodies (TRAb) play a key role in GD and GO pathogenesis. Elevated TRAb serum concentrations are associated with the development of GO as well as the activity and severity of the disease [69][70][71]. The effects of the autoimmunity directed against TSH-R in orbital cells are mediated through the phosphoinositide 3-kinase/Akt, adenylyl cyclase/cAMP signaling cascades, and other signaling pathways [72].…”