Evidence of anti-corticotroph autoantibodies in Down syndrome with isolated adrenocorticotropic hormone deficiency: findings from a single case.

purposeDown syndrome (DS) is associated with immune dysregulation and a broad spectrum of autoimmune diseases; however, autoimmune involvement of the pituitary gland remains poorly characterized. Isolated adrenocorticotropic hormone deficiency (IAD) is a rare cause of secondary adrenal insufficiency, and its relationship to DS-related autoimmunity has not yet been elucidated. We encountered a single case of DS that was complicated by IAD. We describe the clinical course in detail and present immunological findings suggestive of an autoimmune basis for IAD in the context of DS. METHODS AND

resultsTo experimentally evaluate pituitary-directed autoimmunity, circulating antibodies were analyzed using immunofluorescence staining of mouse pituitary tissue. Immunoglobulin G derived from an individual with DS and IAD specifically showed reactivity toward corticotrophs, as demonstrated by colocalization with ACTH immunostaining. HLA genotyping did not identify alleles previously associated with idiopathic IAD, suggesting a disease mechanism distinct from established genetic susceptibility.

conclusionThe identification of anti-corticotroph antibodies in DS provides the first immunological evidence linking IAD to DS-related autoimmunity. These findings suggest that autoimmune IAD may represent a previously unrecognized component of endocrine polyautoimmunity in DS and underscore the importance of considering pituitary autoimmunity in the endocrine assessment of this population. However, considering that the present findings are derived from a single case, further studies are warranted to confirm their broader applicability.