title: Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ.
abstract: Adipsic (or essential) hypernatremia is a rare hypernatremia caused by a deficiency in thirst regulation and vasopressin release. In 2010, we reported a case in which autoantibodies targeting the sensory circumventricular organs (sCVOs) caused adipsic hypernatremia without hypothalamic structural lesions demonstrable by magnetic resonance imaging (MRI); sCVOs include the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which are centers for the monitoring of body-fluid conditions and the control of water and salt intakes, and harbor neurons innervating hypothalamic nuclei for vasopressin release. We herein report three newly identified patients (3- to 8-year-old girls on the first visit) with similar symptoms. The common features of the patients were extensive hypernatremia without any sensation of thirst and defects in vasopressin response to serum hypertonicity. Despite these features, we could not detect any hypothalamic structural lesions by MRI. Immunohistochemical analyses using the sera of the three patients revealed that antibodies specifically reactive to the mouse SFO were present in the sera of all cases; in one case, the antibodies also reacted with the mouse OVLT. The immunoglobulin (Ig) fraction of serum obtained from one patient was intravenously injected into wild-type mice to determine whether the mice developed similar symptoms. Mice injected with a patient's Ig showed abnormalities in water/salt intake, vasopressin release, and diuresis, which resultantly developed hypernatremia. Prominent cell death and infiltration of reactive microglia was observed in the SFO of these mice. Thus, autoimmune destruction of the SFO may be the cause of the adipsic hypernatremia. This study provides a possible explanation for the pathogenesis of adipsic hypernatremia without demonstrable hypothalamus-pituitary lesions.
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, 444-8787, Japan.|School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8787, Japan.
authors.forename: Takeshi Y
authors.initials: TY
authors.lastname: Hiyama
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Hiroshima, 734-8551, Japan.
authors.forename: Akari N
authors.initials: AN
authors.lastname: Utsunomiya
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, 444-8787, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, 444-8787, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujikawa
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, 444-8787, Japan.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, National Hospital Organization Kure Medical Center, Kure, Hiroshima, 737-0023, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Hiroshima, 734-8551, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kagawa
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Hiroshima, 734-8551, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Hiroshima, 734-8551, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Kawasaki Municipal Hospital, Kawasaki, Kanagawa, 210-0013, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Pediatrics, Kawasaki Municipal Hospital, Kawasaki, Kanagawa, 210-0013, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Anzo
authors.affiliation: Department of Pediatrics, Kawasaki Municipal Hospital, Kawasaki, Kanagawa, 210-0013, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takayasu
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nigawara
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.affiliation: Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), Okazaki, Aichi, 444-8787, Japan.|School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8787, Japan.
authors.forename: Masaharu
authors.identifier: 0000-0002-3796-524X
authors.initials: M
authors.lastname: Noda
mesh_terms: D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001921:Brain / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006955:Hypernatremia / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000473:pathology; D013356:Subfornical Organ / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies
keywords: adipsic hypernatremia; autoimmune disease; essential hypernatremia; sensory circumventricular organs