TY - JOUR
T1 - Identification of clinical factors related to antibody-mediated immune response to the subfornical organ
AU - Nakamura-Utsunomiya, Akari
AU - Goda, Satoshi
AU - Hayakawa, Seiichi
AU - Sonoko, Sakata
AU - Hoorn, Ewout J.
AU - Blanchard, Anne
AU - Saito-Hakoda, Akiko
AU - Kakimoto, Haruna
AU - Hachiya, Rumi
AU - Kamimura, Miki
AU - Kawakita, Rie
AU - Higuchi, Shinji
AU - Fujimaru, Rika
AU - Shirai, Yoko
AU - Miyaoka, Daichi
AU - Nagata, Yuki
AU - Kishi, Yutaro
AU - Wada, Aya
AU - Mitsuboshi, Akari
AU - Ozaki, Kayo
AU - Komatsu, Nagisa
AU - Niizuma, Hidetaka
AU - Kanno, Junko
AU - Fujiwara, Ikuma
AU - Hasegawa, Yukihiro
AU - Yorifuji, Tohru
AU - Brickman, Wendy
AU - Vantyghem, Marie Christine
AU - Yamaguchi, Kei
AU - Goshima, Naoki
AU - Hiyama, Takeshi Y.
N1 - Funding Information:
We thank Drs. J. Caccia, N. Yamaguchi, K. Tamai, N. Ohmori, and H. Kadowaki, for their collaboration in this study. We also thank Prof. M. Noda for procuring participants in this study. This work was supported by MEXT/JSPS KAKENHI (Grant number 21K15894 to ANU), by Forum on Growth Hormone research grant in 2017 (to ANU), and by the Japanese Society for Pediatric Endocrinology (Future Development Grant in 2015 to ANU and 2019 to SS), which was sponsored by Novo Nordisk Pharma Ltd.
Publisher Copyright:
© 2022 John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.
AB - Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.
KW - adipsic hypernatremia
KW - dysnatremia
KW - hypothalamus dysfunction
KW - Na channel
KW - ROHHAD syndrome
KW - sensory circumventricular organ
KW - subfornical organ
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U2 - 10.1111/cen.14737
DO - 10.1111/cen.14737
M3 - Article
C2 - 35419873
AN - SCOPUS:85128996561
SN - 0300-0664
JO - Clinical Endocrinology
JF - Clinical Endocrinology
ER -
