Conceptual comorbidity networks in autoimmune thyroid disease: A PRISMA-guided review of clinical patterns, immunological links, and emerging disease clusters.

Autoimmune thyroid disease (AITDs), including Hashimoto's thyroiditis and Graves' disease, are among the most prevalent organ-specific autoimmune disorders and are increasingly recognized as components of broader multimorbidity patterns rather than isolated endocrine conditions. While previous studies have largely examined individual comorbid associations or disease-pair relationships, a comprehensive synthesis that conceptualizes AITDs within an integrated disease-clustering and network-based framework remains limited. This review presents a semi-systematic literature synthesis informed by PRISMA reporting principles to enhance transparency in literature identification and study selection, drawing on approximately 60 studies published between 2010 and 2024. The evidence is systematically organized into endocrine autoimmune, non-endocrine autoimmune, dermatological, gastrointestinal, and non-autoimmune comorbidity domains. Beyond descriptive aggregation, this review critically examines consistencies, contradictions, and variations across studies and links observed clustering patterns to shared genetic susceptibility, convergent immunological pathways, and environmental and hormonal modulators. A central contribution of this work is the development of a conceptual disease-clustering framework that positions AITDs as dynamic hub conditions within interconnected comorbidity networks, moving beyond traditional disease-pair models toward a systems-level understanding of multimorbidity. This framework integrates clinical observations with biological mechanisms and highlights potential pathways for disease progression and risk amplification. The principal contribution of this review is the development of a qualitative conceptual disease-clustering framework that synthesizes evidence across endocrine, autoimmune, dermatological, gastrointestinal, and systemic comorbidity domains. Rather than performing a quantitative graph-theoretical network analysis, this review adopts a network medicine perspective to integrate published evidence on shared biological mechanisms, disease co-occurrence patterns, and potential mechanistic bridges linking autoimmune thyroid disease with associated disorders. This conceptual synthesis provides a systems-oriented interpretation of multimorbidity, highlights clinically relevant disease clusters, and identifies opportunities for future studies employing formal network analytics and multi-omics approaches.