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. 2021 Feb 19:12:578802.
doi: 10.3389/fendo.2021.578802. eCollection 2021.

Clinical Heterogeneity of Acquired Idiopathic Isolated Adrenocorticotropic Hormone Deficiency

Yasunori Fujita  1 , Hironori Bando  1 , Genzo Iguchi  1   2   3 , Keiji Iida  4 , Hitoshi Nishizawa  1 , Keitaro Kanie  1 , Kenichi Yoshida  1 , Ryusaku Matsumoto  1 , Kentaro Suda  1 , Hidenori Fukuoka  1 , Wataru Ogawa  1 , Yutaka Takahashi  1   5
Affiliations

Clinical Heterogeneity of Acquired Idiopathic Isolated Adrenocorticotropic Hormone Deficiency

Yasunori Fujita et al. Front Endocrinol (Lausanne). .

Abstract

Objective: 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.

Design and methods: We analyzed 46 consecutive patients with IAD. Serum anti-pituitary antibodies were analyzed via immunofluorescence staining using a mouse pituitary tissue. Principal component and cluster analyses were performed to classify IAD patients based on clinical characteristics and autoantibodies.

Results: 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.

Conclusions: 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.

Keywords: anti-corticotroph antibody; anti-follicular stellate cell antibody; anti-pituitary antibody; classification; cluster analyses; hypopituitarism; isolated ACTH deficiency; principal component analyses.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immunofluorescence analysis using mouse pituitary tissue. (A) Patient’s serum recognized ACTH-positive cells. (B) Control serum showed negative staining. (C) Patient’s serum recognized ACTH-negative cells. (D) Patient’s serum recognized S100b-positive cells.
Figure 2
Figure 2
Hierarchical cluster and principal component analysis. (A) Hierarchical cluster analysis classified patients into 3 groups: Groups A, B, and C. (B) The constellation plots based on the principal component analysis. Three components were clearly discriminated into 3 groups, which were comparable with groups categorized using cluster analysis.
Figure 3
Figure 3
Three-dimensional scatter plot based on PCA and cluster analysis. Three-dimensional scatter plot shows clear discrimination among the 3 groups.
See this image and copyright information in PMC

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