TY - JOUR T1 - A 50-year Revisit of the Initiation and Associations of Hashimoto’s Disease: Might Findings Conform to a Concept of Multifactorial Physiopathologic Transitions? JF - The Journal of Rheumatology JO - J Rheumatol SP - 1475 LP - 1478 DO - 10.3899/jrheum.121166 VL - 40 IS - 9 AU - ALFONSE T. MASI Y1 - 2013/09/01 UR - http://www.jrheum.org/content/40/9/1475.abstract N2 - Tagoe, et al have comprehensively reviewed rheumatic disorders associated with autoimmune thyroid disease (AITD) in The Journal1. The spectrum of AITD was defined as including Graves’ disease and chronic (nonfocal) lymphocytic thyroiditis, which incorporates Hashimoto’s disease (HD)2. The review1 rekindled long-past memories, and this commentary offers a personal historical perspective on some complex research questions and challenges persisting in HD and its associated conditions. Such issues had been posed some 2 generations ago2,3,4,5,6,7,8,9,10 (Table 1), but have not yet been adequately resolved.View this table:In this windowIn a new windowTable 1. The 1912 report of Hakaru Hashimoto (1881–1934) and mid-20th century articles on this disease*.Basic questions remain in interpreting the root of AITD. First, is a primary immunological dysregulation from genetic predisposition or environmentally related processes the cause of the observed antibodies and thyroid pathology as well as associated hyperthyroidism or hypothyroidism? Alternatively, is a primary thyroid cellular dysfunction from as-yet undiscovered physiological insufficiencies the cause of increased or modified cellular antigenic release, leading to secondary autoimmune serological and tissue reactions? Likely, the primary and secondary biological mechanisms are integrated in a complex way and are not clearly separated from each other. Nevertheless, evidence for the alternative initiation pathways can be investigated by their sequences of events, like genetic predisposition, initiation following triggering mechanisms, or whether particular early alterations (mild thyroid dysfunction vs minor elevated antibodies) are necessary in the beginning process or must progress for the disease to become manifest.In the course of disease development, function may become disturbed before evidence of serological abnormalities or tissue pathological changes are manifest. A physiopathologic interpretation of disease focuses upon altered body function as related to the course of pathological alterations and mechanisms. In multifactorial … Address correspondence to Dr. Masi; E-mail: amasi{at}uic.edu ER -