Clinical Heterogeneity of Acquired Idiopathic Isolated Adrenocorticotropic Hormone Deficiency

• Published in: Frontiers in endocrinology (Lausanne) 2021-02, Vol.12, p.578802-578802
• Main Authors: Fujita, Yasunori, Bando, Hironori, Iguchi, Genzo, Iida, Keiji, Nishizawa, Hitoshi, Kanie, Keitaro, Yoshida, Kenichi, Matsumoto, Ryusaku, Suda, Kentaro, Fukuoka, Hidenori, Ogawa, Wataru, Takahashi, Yutaka
• Format: Article
• Language: English
• Subjects: Adrenal Insufficiency - blood; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - epidemiology; Adrenocorticotropic Hormone - blood; Adrenocorticotropic Hormone - deficiency; Adult; Aged; Animals; anti-corticotroph antibody; anti-follicular stellate cell antibody; anti-pituitary antibody; Autoantibodies - blood; Case-Control Studies; classification; Cluster Analysis; Endocrine System Diseases - blood; Endocrine System Diseases - diagnosis; Endocrine System Diseases - epidemiology; Endocrinology; Female; Genetic Diseases, Inborn - blood; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - epidemiology; Humans; Hypoglycemia - blood; Hypoglycemia - diagnosis; Hypoglycemia - epidemiology; hypopituitarism; isolated ACTH deficiency; Japan - epidemiology; Male; Mice; Mice, Inbred C57BL; Middle Aged; Principal Component Analysis; Retrospective Studies
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2021.578802

Heterogeneous clinical characteristics are observed in acquired isolated adrenocorticotropic hormone (ACTH) deficiency (IAD); however, its classification remains to be established because of its largely unknown pathophysiology. In IAD, anti-pituitary antibodies have been detected in some patients, although their significance remains unclear. Therefore, this study aimed to classify patients with IAD and to clarify the significance of anti-pituitary antibodies. We analyzed 46 consecutive patients with IAD. Serum anti-pituitary antibodies were analyzed immunofluorescence staining using a mouse pituitary tissue. Principal component and cluster analyses were performed to classify IAD patients based on clinical characteristics and autoantibodies. Immunofluorescence analysis using the sera revealed that 58% of patients showed anti-corticotroph antibodies and 6% of patients showed anti-follicular stellate cell (FSC) antibodies. Principal component analysis demonstrated that three parameters could explain 70% of the patients. Hierarchical cluster analysis showed three clusters: Groups A and B comprised patients who were positive for anti-corticotroph antibodies, and plasma ACTH levels were extremely low. Groups A and B comprised middle-aged or elderly men and middle-aged women, respectively. Group C comprised patients who were positive for the anti-FSC antibody and elderly men; plasma ACTH levels were relatively high. Patients with IAD were classified into three groups based on clinical characteristics and autoantibodies. The presence of anti-corticotroph antibody suggested severe injury to corticotrophs. This new classification clearly demonstrated the heterogeneity in the pathogenesis of IAD.