Pragmatic Use of Thyroid Autoantibodies in Clinical Practice: An Update

A utoimmune thyroid diseases, encompassing Hashimoto's thyroiditis and Graves' disease, are driven by immune-mediated targeting of thyroid antigens.Central to their diagnosis and management is the detection of circulating thyroid autoantibodies (TAbs), particularly those against thyroid peroxidase (TPO), thyroglobulin (Tg) and the thyrotropin receptor (TR).These antibodies have traditionally served as disease markers, but emerging evidence underscores their functional roles in pathogenesis, prognostication and therapeutic decision-making.For example, TR antibodies not only confirm the diagnosis of Graves' disease but also help assess disease activity, predict treatment response and evaluate foetal risk during pregnancy.Similarly, TPO and Tg antibodies contribute to the identification of subclinical thyroid dysfunction and have implications for reproductive health and immune-related adverse events from biologic therapies.Newly identified antibodies targeting molecules, such as pendrin, sodium-iodide symporter and megalin, suggest a broader autoimmune footprint than previously recognized.However, their clinical relevance remains to be fully elucidated.The interpretation of TAb is further complicated by assay variability, dynamic antibody titres and their presence in euthyroid individuals, particularly in special populations such as pregnant women, children and those with other autoimmune disorders.This article synthesizes current insights into the immunological basis, diagnostic performance and clinical applications of TAb.It emphasizes the need for a pragmatic, context-specific approach to testing, advocating for a more tailored integration of antibody data into clinical decision-making.By aligning immunologic knowledge with real-world practice, this article aims to refine the utility of TAb in contemporary endocrine care. Highlights• Autoantibodies refine autoimmune thyroid disorder diagnosis and risk.• Thyroid-stimulating hormone receptor antibody predicts relapse, severity and foetal impact.• Thyroid peroxidase antibody and thyroglobulin antibody linked to fertility outcomes.• Novel antibodies expand thyroid autoimmunity scope.The interplay between immunology and endocrinology is vividly exemplified in autoimmune thyroid disorders (AITDs), where immune dysregulation targets the thyroid gland through both cellular and humoral mechanisms.Hashimoto's thyroiditis (HT) and Graves' disease (GD) represent the predominant phenotypes of these conditions, marked by distinct patterns of thyroid dysfunction: hypothyroidism and hyperthyroidism, respectively.1-3 A central and defining feature of AITD is the generation of thyroid autoantibodies (TAbs), which are circulating autoantibodies against key thyroid antigens, most notably thyroid peroxidase (TPO), thyroglobulin (Tg) and the thyrotropin receptor (TR).While these autoantibodies have long served as serological markers for diagnosis, mounting evidence supports their active role in disease pathogenesis, prognosis and treatment stratification.4,5 Over recent decades, advances in molecular immunology have expanded the understanding of these autoantibodies beyond their diagnostic value.For example, TR antibodies not only confirm the diagnosis of GD but also predict the risk of relapse after treatment, influence ophthalmopathy severity and guide decisions in pregnancy.6,7 Similarly, TPO antibodies (TPOAbs) and Tg antibodies (TgAbs) have implications extending beyond the thyroid axis, including associations with reproductive failure, postpartum thyroiditis and responses to immunomodulatory therapies.8,9 The discovery of antibodies targeting lesser known antigens, such as pendrin, sodium-iodide symporter (NIS) and megalin, adds further depth to the evolving landscape of thyroid autoimmunity, though their clinical utility remains less established.10,11 Despite this wealth of information, the clinical use of TAb often lacks consistency and nuance.In some settings, serological testing is overutilized without clear clinical indication, while in others, potentially informative antibody data are underused or misinterpreted.Moreover, the significance of antibody positivity in asymptomatic or euthyroid individuals, such as pregnant women, children