Influence of Rapid Urbanization on Thyroid Autoimmune Disease in China

Background. The prevalence of autoimmune thyroid diseases (AITDs), especially Hashimoto’s thyroiditis (HT), has increased dramatically in China. Moreover, China is experiencing the largest scale of urbanization in the world. We intended to explore the relationship between rapid urbanization and HT. Methods. A total of 2946 subjects in Zhejiang Shangyu (SY) (n = 1546) and Jiangsu Nanjing (NJ) (n = 1400) were enrolled in this study. Serum TPOAb, TGAb, and thyrotropin (TSH) were measured, and ultrasonography of the thyroid was performed in all subjects. DNA was extracted from all subjects, and four SNPs were selected for genotyping. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction between genetic factors and environment factors. Results. TPOAb and TGAb concentrations were higher in NJ than in SY (34.60 vs. 14.00 IU/ml and 21.05 vs. 7.50 IU/ml). People in NJ also had higher TPOAb and TGAb positivity rates than those in SY (7.8% vs. 12.7% and 8.7% vs. 16.3%). Logistic regression analysis indicated that rapid urbanization was an independent risk factor for TPOAb (OR = 1.473) and TGAb (OR = 1.689). Genotype TT in rs11675434 was associated with an increased risk of TPOAb positivity both in SY (OR = 2.955) and in NJ (OR = 1.819). GMDR analysis showed a two-locus model (SNP2 × urbanization) and a three-locus model (SNP2 × SNP3 × urbanization), which had testing accuracies of 56.88% and 57.25%, respectively ( P values were 0.001 and 0.001). Conclusion. Rapid urbanization influences the incidence of TPOAb and TGAb positivity. We should pay more attention to thyroid autoimmune disease in areas of China experiencing rapid urbanization.

Autoimmune polyendocrine syndrome type II: After adrenal crisis

Autoimmune Polyendocrine Syndromes (APS) are rare autoimmune endocrinopathies, characterized by the association of two or more organ-specific disorders. Type II Autoimmune Polyendocrine Syndromes (APS II) comprises the association of Addison’s disease with thyroid autoimmune disease and/or type 1 diabetes mellitus. Although the classic presentation is symptomatic hypotension, it can manifest as an adrenal crisis - a life-threatening condition. We report a case of a 41-year-old woman with prolonged asthenia, cutaneous hyperpigmentation and symptomatic hypotension refractory to intravenous fluids. APS II was diagnosed with a presentation of an Addisonian crisis, resolved after the onset of hydrocortisone.

Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease

Thyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as Graves’ disease and Hashimoto’s thyroiditis. Here we report the biophysical and structural characterisation of two novel TPO constructs containing only the ectodomain of TPO and lacking the propeptide. Both constructs were enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultra-centrifugation data suggests that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional and antigenic characteristics of TPO, a molecule behind some of the most common autoimmune diseases.

Thrombocytopaenia and thyroiditis: coincidence?

Thrombocytopaenia can be associated with an autoimmune mechanism. Immune thrombocytopaenia can be associated with thyroid autoimmune disease. The authors present a case of a teenager with a history of thrombocytopaenia who complained of tiredness. Laboratory investigation showed thyroid autoantibodies. The co-existence of thrombocytopaenia and thyroiditis lead to further investigation and antibodies against platelet glycoprotein IIbIIIa were found. This case illustrates the association of the overlap aspects between thyroid and platelet autoimmunity.

DIAGNOSIS OF ENDOCRINE DISEASE: IgG4-related thyroid autoimmune disease

IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100 000, but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria. Indeed, high concentrations of IgG4 in tissue and serum are not a reliable diagnostic marker. The spectrum of IgG4-RD also includes well-known thyroid diseases including Riedel’s thyroiditis, Hashimoto’s thyroiditis and its fibrotic variant, Graves’ disease and Graves’ orbitopathy. Results from clinical studies indicate that a small subset of patients with the above-mentioned thyroid conditions present some features suggestive for IgG4-RD. However, according to more recent views, the use of the term thyroid disease with an elevation of IgG4 rather than IgG4-related thyroid diseases would appear more appropriate. Nevertheless, the occurrence of high IgG4 levels in patients with thyroid disease is relevant due to peculiarities of their clinical course.