SAT-LB079 Clinical Heterogeneity of Acquired Idiopathic ACTH Deficiency: A New Classification Based on the Clinical Characteristics and Autoantibodies

[Background] In acquired idiopathic isolated ACTH deficiency (IAD), anti-pituitary antibodies are reportedly detected in a part of the patients; however, the significance of the antibodies remains unclarified. [Subjects and methods] Forty-six patients with IAD who diagnosed between 1992 and 2018 were retrospectively analyzed. Serum anti-corticotroph and anti-follicular stellate cell (FSC) antibody were analyzed using immunofluorescence staining in 33 patients, whose serum was available. We performed principle component and cluster analysis for the clarification of pathophysiology of IAD based on the clinical characteristics and autoantibodies. [Results] Among 46 patients, male was predominant (63%). The average age of the onset of IAD was 58.1 ± 12.3 years and that in male was significantly older (male vs. female: 62.8 ± 9.3 vs. 50.1 ± 13.0 years, P < 0.01). Forty-one % of the patients exhibited other autoimmune diseases including chronic thyroiditis. Interestingly, 58% of the patients exhibited anti-corticotroph antibody and 6% exhibited anti-FSC antibody in the serum. Principle component analysis demonstrated that 69.6% of the patients were explained by following 3 components; 1) age and gender, 2) the presence of antibody against corticotroph or FSC and the serum ACTH level, 3) the presence of other autoimmune disease. Cluster analysis demonstrated that the patients can be divided into 3 groups; A) middle-aged male (60.9 ± 10.3 years) with low ACTH values at the onset (2.2 ± 5.6 pg/mL) and positive for the anti-coricotroph antibody (73.3%), B) elderly male (72.8 ± 3.8 years) with relatively high ACTH values (21.1 ± 10.3 pg/mL), including positive for the anti-FSC antibody (50%), C) middle-aged female (45.3 ± 11.2 years) with low ACTH values at the onset (3.8 ± 5.8 pg/mL), and positive for the anti-corticotroph antibody (60%). [Discussion] These data clearly showed the clinical heterogeneity of IAD and suggested a presence of different pathogenesis. Group A and C were characterized by a high prevalence of anti-corticotroph antibody and low levels of serum ACTH, suggesting a presence of specific autoimmunity against corticotroph resulting in a severe injury of corticotrophs. Interestingly, group B was characterized by the most elderly male with relatively high ACTH levels and half of the patients exhibited anti-FSC antibody. It is suggested that anti-FSC antibody is a novel marker for IAD especially in elderly male patients. In this group, it is speculated that the corticotroph function was indirectly impaired because of the injury of FSCs. Although further investigations are necessary, our data enabled a useful classification of IAD especially for the clarification of the pathogenesis. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.