Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ

Takeshi Y. Hiyama, Akari N. Utsunomiya, Masahito Matsumoto, Akihiro Fujikawa, Chia Hao Lin, Keiichi Hara, Reiko Kagawa, Satoshi Okada, Masao Kobayashi, Mayumi Ishikawa, Makoto Anzo, Hideo Cho, Shinobu Takayasu, Takeshi Nigawara, Makoto Daimon, Tomohiko Sato, Kiminori Terui, Etsuro Ito, Masaharu Noda

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)323-331
Number of pages9
JournalBrain Pathology
Volume27
Issue number3
DOIs
Publication statusPublished - May 2017
Externally publishedYes

Fingerprint

Subfornical Organ
Hypernatremia
Autoantibodies
Vasopressins
Thirst
Serum
Drinking
Immunoglobulins
Salts
Magnetic Resonance Imaging
Antibodies
Diuresis
Microglia
Body Fluids
Hypothalamus
Cell Death
Neurons

Keywords

  • adipsic hypernatremia
  • autoimmune disease
  • essential hypernatremia
  • sensory circumventricular organs

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

Hiyama, T. Y., Utsunomiya, A. N., Matsumoto, M., Fujikawa, A., Lin, C. H., Hara, K., ... Noda, M. (2017). Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ. Brain Pathology, 27(3), 323-331. https://doi.org/10.1111/bpa.12409

Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ. / Hiyama, Takeshi Y.; Utsunomiya, Akari N.; Matsumoto, Masahito; Fujikawa, Akihiro; Lin, Chia Hao; Hara, Keiichi; Kagawa, Reiko; Okada, Satoshi; Kobayashi, Masao; Ishikawa, Mayumi; Anzo, Makoto; Cho, Hideo; Takayasu, Shinobu; Nigawara, Takeshi; Daimon, Makoto; Sato, Tomohiko; Terui, Kiminori; Ito, Etsuro; Noda, Masaharu.

In: Brain Pathology, Vol. 27, No. 3, 05.2017, p. 323-331.

Research output: Contribution to journalArticle

Hiyama, TY, Utsunomiya, AN, Matsumoto, M, Fujikawa, A, Lin, CH, Hara, K, Kagawa, R, Okada, S, Kobayashi, M, Ishikawa, M, Anzo, M, Cho, H, Takayasu, S, Nigawara, T, Daimon, M, Sato, T, Terui, K, Ito, E & Noda, M 2017, 'Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ', Brain Pathology, vol. 27, no. 3, pp. 323-331. https://doi.org/10.1111/bpa.12409
Hiyama, Takeshi Y. ; Utsunomiya, Akari N. ; Matsumoto, Masahito ; Fujikawa, Akihiro ; Lin, Chia Hao ; Hara, Keiichi ; Kagawa, Reiko ; Okada, Satoshi ; Kobayashi, Masao ; Ishikawa, Mayumi ; Anzo, Makoto ; Cho, Hideo ; Takayasu, Shinobu ; Nigawara, Takeshi ; Daimon, Makoto ; Sato, Tomohiko ; Terui, Kiminori ; Ito, Etsuro ; Noda, Masaharu. / Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ. In: Brain Pathology. 2017 ; Vol. 27, No. 3. pp. 323-331.
@article{dad72e4f32ae4ec189de3e6a22e2a859,
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.",
keywords = "adipsic hypernatremia, autoimmune disease, essential hypernatremia, sensory circumventricular organs",
author = "Hiyama, {Takeshi Y.} and Utsunomiya, {Akari N.} and Masahito Matsumoto and Akihiro Fujikawa and Lin, {Chia Hao} and Keiichi Hara and Reiko Kagawa and Satoshi Okada and Masao Kobayashi and Mayumi Ishikawa and Makoto Anzo and Hideo Cho and Shinobu Takayasu and Takeshi Nigawara and Makoto Daimon and Tomohiko Sato and Kiminori Terui and Etsuro Ito and Masaharu Noda",
year = "2017",
month = "5",
doi = "10.1111/bpa.12409",
language = "English",
volume = "27",
pages = "323--331",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Adipsic hypernatremia without hypothalamic lesions accompanied by autoantibodies to subfornical organ

AU - Hiyama, Takeshi Y.

AU - Utsunomiya, Akari N.

AU - Matsumoto, Masahito

AU - Fujikawa, Akihiro

AU - Lin, Chia Hao

AU - Hara, Keiichi

AU - Kagawa, Reiko

AU - Okada, Satoshi

AU - Kobayashi, Masao

AU - Ishikawa, Mayumi

AU - Anzo, Makoto

AU - Cho, Hideo

AU - Takayasu, Shinobu

AU - Nigawara, Takeshi

AU - Daimon, Makoto

AU - Sato, Tomohiko

AU - Terui, Kiminori

AU - Ito, Etsuro

AU - Noda, Masaharu

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

KW - adipsic hypernatremia

KW - autoimmune disease

KW - essential hypernatremia

KW - sensory circumventricular organs

UR - http://www.scopus.com/inward/record.url?scp=84980023239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84980023239&partnerID=8YFLogxK

U2 - 10.1111/bpa.12409

DO - 10.1111/bpa.12409

M3 - Article

C2 - 27338632

AN - SCOPUS:84980023239

VL - 27

SP - 323

EP - 331

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 3

ER -