今日の臨床サポート

多飲

著者: 村島美穂 名古屋市立大学腎臓内科学講座

監修: 大滝純司 東京医科大学 医学教育学 総合診療科

著者校正/監修レビュー済:2020/04/22
参考ガイドライン:
  1. 厚生労働科学研究費補助金難治性疾患等製作研究事業「間脳下垂体機能障害に関する調査研究」班、日本内分泌学会間脳下垂体機能障害の診断と治療の手引き(平成30年度改訂)
患者向け説明資料

概要・推奨   

  1. 尿崩症と心因性多飲の鑑別のためには、高張食塩水負荷試験あるいは水制限試験を行い、そのあと、バソプレシン負荷試験にて中枢性および腎性の尿崩症の鑑別を行う。水制限試験は尿崩症患者に行うと著しい脱水の危険があるため、通常、高張食塩水負荷試験が推奨されている(推奨度2)。
  1. 中枢性尿崩症の治療においては、脱水を避けるために十分な水分をとることが重要である。また、塩分制限と蛋白制限が推奨されている(推奨度2)。
  1. 腎性尿崩症の治療として、塩分制限と蛋白制限が推奨されている(推奨度2)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
村島美穂 : 特に申告事項無し[2021年]
監修:大滝純司 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、高張食塩水負荷試験について加筆修正を行った。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 1日尿量3L以上を一般的に多尿と呼び、飲水量が多くて多尿を来す状態を多飲としている。したがって、1日何L以上飲めば多飲、という定義はない[1][2]
 
  1. 多飲は精神疾患患者でよくみられる。精神科長期入院病棟での多飲の頻度は3~21%であると報告がある。
  1. 多飲は精神疾患患者でよくみられる。
  1. ある総説では、1979年から1992年に行われた9つの疫学研究から、精神科長期入院病棟での多飲の頻度は3~17%であると報告しているが[3]、これらの疫学研究は、カルテのレビューや病棟スタッフへのアンケートに基づいた頻度であり、実際の頻度を過少評価している可能性が高い。ある研究では多飲を日中の体重増加が4%以上であること、早朝尿が低張尿であるというより精度の高い基準で判断した[4]。この研究では精神科で長期入院を要する精神疾患患者61人を対象に多飲の頻度を調査した。43%が精神分裂病、12%が躁うつ病であった。多飲は13/61(21%)の患者でみられ、特に精神分裂病患者では8/32(25%)と割合が高かった。低Na血症は7/61(11%)の患者でみられた。
  1. 心因性多飲は精神疾患患者では非常によくみられるものである。
問診・診察のポイント  
  1. 多飲を来す疾患、病態の代表例は以下の通りであり、それぞれの可能性をふまえて問診を行う。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

著者: Y Oiso
雑誌名: Nihon Naika Gakkai Zasshi. 1998 Jun 10;87(6):1002-7.
Abstract/Text
PMID 9702009  Nihon Naika Gakkai Zasshi. 1998 Jun 10;87(6):1002-7.
著者: Amgad N Makaryus, Samy I McFarlane
雑誌名: Cleve Clin J Med. 2006 Jan;73(1):65-71.
Abstract/Text Diabetes insipidus, characterized by excretion of copious volumes of dilute urine, can be life-threatening if not properly diagnosed and managed. It can be caused by two fundamentally different defects: inadequate or impaired secretion of antidiuretic hormone (ADH) from the posterior pituitary gland (neurogenic or central diabetes insipidus) or impaired or insufficient renal response to ADH (nephrogenic diabetes insipidus). The distinction is essential for effective treatment.

PMID 16444918  Cleve Clin J Med. 2006 Jan;73(1):65-71.
著者: J de Leon, C Verghese, J I Tracy, R C Josiassen, G M Simpson
雑誌名: Biol Psychiatry. 1994 Mar 15;35(6):408-19.
Abstract/Text Polydipsia among chronic psychiatric patients is poorly understood and underdiagnosed. It may have three stages: simple polydipsia, polydipsia with water intoxication, and physical complications. Epidemiological surveys have used staff reports and polyuria measures to identify polydipsic patients. Water intoxication has been screened by chart review, weight, or serum sodium data. According to these surveys, polydipsia, not explained by medically induced polyuria, may be present in more than 20% of chronic inpatients. Up to 5% of chronic inpatients had episodes of water intoxication although mild cases may have been missed. Single time point surveys show that 29% of polydipsic patients had presented water intoxication. Methodologically limited clinical studies suggest that polydipsia with water intoxication rather than simple polydipsia may be associated with poor prognosis in schizophrenia. Epidemiological surveys found polydipsia with water intoxication to be associated with chronicity, schizophrenia, smoking, some medications, male gender, and white race. New pathophysiological models need to elucidate these findings.

PMID 8018788  Biol Psychiatry. 1994 Mar 15;35(6):408-19.
著者: Jose de Leon
雑誌名: Eur Arch Psychiatry Clin Neurosci. 2003 Feb;253(1):37-9. doi: 10.1007/s00406-003-0403-z.
Abstract/Text This is a retrospective review of the author's experience with polydipsia in a long-term unit for treatment refractory patients at a US psychiatric state hospital during a 5-year period [1996-2000]. Sixty-one patients were admitted to this long-term unit, comprising approximately 1 % of the hospital admissions. Polydipsic patients were followed with diurnal weight changes and other biological measures. This longitudinal study of 61 chronic inpatients suggests that polydipsia is no doubt present in at least 20 % of chronic psychiatric inpatients and hyponatremia in more than 10 %. Two polydipsic patients worsened when switched from clozapine to other atypical antipsychotics. Polydipsia in severe mentally ill patients continues to be a neglected subject and a challenge for psychiatrists. Polydipsic patients should not be switched to other atypical antipsychotics, unless new prospective studies prove that they are as effective as clozapine for polydipsia.

PMID 12664312  Eur Arch Psychiatry Clin Neurosci. 2003 Feb;253(1):37-9・・・
著者: Yoshiaki Kondo
雑誌名: Nihon Jinzo Gakkai Shi. 2011;53(2):177-80.
Abstract/Text
PMID 21516703  Nihon Jinzo Gakkai Shi. 2011;53(2):177-80.
著者: Gabor Szinnai, Nils G Morgenthaler, Kaspar Berneis, Joachim Struck, Beat Müller, Ulrich Keller, Mirjam Christ-Crain
雑誌名: J Clin Endocrinol Metab. 2007 Oct;92(10):3973-8. doi: 10.1210/jc.2007-0232. Epub 2007 Jul 17.
Abstract/Text CONTEXT: The measurement of arginine vasopressin (AVP) is often cumbersome because it is unstable with a short half-life time. AVP is derived from a larger precursor peptide along with the more stable peptide copeptin. Copeptin is the C-terminal part of provasopressin and has been shown to be a useful tool to indicate AVP concentration in critically ill patients.
OBJECTIVE: The objective of the study was to evaluate the clinical usefulness of copeptin as a new marker in disordered states of blood volume and plasma osmolality.
DESIGN AND SETTING: This was a prospective observational study in a university hospital.
PARTICIPANTS AND MAIN OUTCOME MEASURES: Three techniques with respective control studies were used in 24 healthy adults to produce changes in plasma osmolality and/or volume: 1) a 28-h water deprivation, 2) a 17-h hypertonic saline infusion combined with thirsting, and 3) a hypotonic saline infusion with iv desmopressin administration during free water intake.
RESULTS: Water deprivation produced a weight loss of 1.7 kg, an increase in plasma osmolality to 294.8 +/- 4.3 mosmol/kg, and an increase of copeptin from 4.6 +/- 1.7 pmol/liter to 9.2 +/- 5.2 pmol/liter (P < 0.0001). During hypertonic saline infusion and thirsting with a raise of plasma osmolality to 296.1 +/- 3.4 mosmol/kg, copeptin increased from 4.9 +/- 3.0 pmol/liter to 19.9 +/- 4.8 pmol/liter (P < 0.0001). Conversely, during hypotonic saline infusion, plasma osmolality decreased to 271.3 +/- 4.1 mosmol/kg, and copeptin decreased from 6.2 +/- 2.4 pmol/liter to 2.4 +/- 2.1 pmol/liter (P < 0.01).
CONCLUSION: Copeptin shows identical changes during disordered water states as previously shown for AVP. It might be a reliable marker of AVP secretion and substitute for the measurement of circulating AVP levels in clinical routine.

PMID 17635944  J Clin Endocrinol Metab. 2007 Oct;92(10):3973-8. doi: 1・・・
著者: Jeff M Sands, Daniel G Bichet, American College of Physicians, American Physiological Society
雑誌名: Ann Intern Med. 2006 Feb 7;144(3):186-94.
Abstract/Text
PMID 16461963  Ann Intern Med. 2006 Feb 7;144(3):186-94.
著者: Mirjam Christ-Crain
雑誌名: Eur J Endocrinol. 2019 Jul;181(1):R11-R21. doi: 10.1530/EJE-19-0163.
Abstract/Text Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a 'revival' of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.

PMID 31067508  Eur J Endocrinol. 2019 Jul;181(1):R11-R21. doi: 10.1530・・・
著者: Mirjam Christ-Crain
雑誌名: Neuroendocrinology. 2020 Jan 2;. doi: 10.1159/000505548. Epub 2020 Jan 2.
Abstract/Text Diabetes insipidus, be it from central or from nephrogenic origin, has to be differentiated from primary polydipsia. This differentiation is crucial since wrong treatment can have dangerous consequences. For decades, the "gold standard" for differential diagnosis has been the standard water deprivation test. However, this test has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 hours and is cumbersome for patients. Also clinical signs and symptoms and MRI characteristics overlap between patients with diabetes insipidus and primary polydipsia. Direct measurement of AVP upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay. Copeptin is secreted in equimolar ratio to AVP, mirroring AVP concentrations in the circulation. We have shown that copeptin, without prior fluid deprivation, identifies patients with nephrogenic diabetes insipidus. For the more difficult differentiation between central diabetes insipidus and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these two entities with a high diagnostic accuracy, and is superior to the water deprivation test. However, it is important to note that close and regular sodium monitoring every 30 minutes during the hypertonic saline test is a prerequisite, which is not possible in all hospitals. Furthermore, side effects are common. Therefore, a nonosmotic stimulation test would be advantageous. Arginine significantly stimulates copeptin and therefore is a novel, so far unknown stimulus of this peptide. Consequently, infusion of arginine with subsequent copeptin measurement was shown to be an even simpler and better tolerated test, but head to head comparison is still lacking.

© 2020 S. Karger AG, Basel.
PMID 31986514  Neuroendocrinology. 2020 Jan 2;. doi: 10.1159/000505548・・・
著者: Wiebke Fenske, Julie Refardt, Irina Chifu, Ingeborg Schnyder, Bettina Winzeler, Juliana Drummond, Antônio Ribeiro-Oliveira, Tilman Drescher, Stefan Bilz, Deborah R Vogt, Uwe Malzahn, Matthias Kroiss, Emanuel Christ, Christoph Henzen, Stefan Fischli, Anke Tönjes, Beat Mueller, Jochen Schopohl, Jörg Flitsch, Georg Brabant, Martin Fassnacht, Mirjam Christ-Crain
雑誌名: N Engl J Med. 2018 Aug 2;379(5):428-439. doi: 10.1056/NEJMoa1803760.
Abstract/Text BACKGROUND: The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.
METHODS: From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.
RESULTS: A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.
CONCLUSIONS: The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).

PMID 30067922  N Engl J Med. 2018 Aug 2;379(5):428-439. doi: 10.1056/N・・・
著者: Bettina Winzeler, Nicole Cesana-Nigro, Julie Refardt, Deborah R Vogt, Cornelia Imber, Benedict Morin, Milica Popovic, Michelle Steinmetz, Clara O Sailer, Gabor Szinnai, Irina Chifu, Martin Fassnacht, Mirjam Christ-Crain
雑誌名: Lancet. 2019 Aug 17;394(10198):587-595. doi: 10.1016/S0140-6736(19)31255-3. Epub 2019 Jul 11.
Abstract/Text BACKGROUND: Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test.
METHODS: In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Würzburg, Würzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or primary polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and primary polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276.
FINDINGS: Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with primary polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with primary polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3-10·9] to a maximum of 9·8 pM [6·4-19·6]) and in participants with primary polydipsia (from 3·6 pM [IQR 2·4-5·7] to a maximum of 7·9 pM [5·1-11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9-2·7] to a maximum of 2·5 pM [1·9-3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84-98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73-94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86-97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86-98; specificity 92%, 95% CI 84-100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2-4) in patients with diabetes insipidus, 3 (2-4) in those with primary polydipsia, 1 (1-3) in healthy adults, and 1 (0-5) in healthy children in the pooled participant dataset.
INTERPRETATION: Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice.
FUNDING: Swiss National Science Foundation and University Hospital Basel.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 31303316  Lancet. 2019 Aug 17;394(10198):587-595. doi: 10.1016/S0・・・
著者: S M Lauriat, T Berl
雑誌名: J Am Soc Nephrol. 1997 Oct;8(10):1599-607.
Abstract/Text
PMID 9335390  J Am Soc Nephrol. 1997 Oct;8(10):1599-607.
著者: Richard H Sterns, Sagar U Nigwekar, John Kevin Hix
雑誌名: Semin Nephrol. 2009 May;29(3):282-99. doi: 10.1016/j.semnephrol.2009.03.002.
Abstract/Text Virtually all investigators now agree that self-induced water intoxication, symptomatic hospital-acquired hyponatremia, and hyponatremia associated with intracranial pathology are true emergencies that demand prompt and definitive intervention with hypertonic saline. A 4- to 6-mmol/L increase in serum sodium concentration is adequate in the most seriously ill patients and this is best achieved with bolus infusions of 3% saline. Virtually all investigators now agree that overcorrection of hyponatremia (which we define as 10 mmol/L in 24 hours, 18 mmol/L in 48 hours, and 20 mmol/L in 72 hours) risks iatrogenic brain damage. Appropriate therapy should keep the patient safe from serious complications of hyponatremia while staying well clear of correction rates that risk iatrogenic injury. Accordingly, we suggest therapeutic goals of 6 to 8 mmol/L in 24 hours, 12 to 14 mmol/L in 48 hours, and 14 to 16 mmol/L in 72 hours. Inadvertent overcorrection owing to a water diuresis may complicate any form of therapy, including the newly available vasopressin antagonists. Frequent monitoring of the serum sodium concentration and urine output are mandatory. Administration of desmopressin to terminate an unwanted water diuresis is an effective strategy to avoid or reverse overcorrection.

PMID 19523575  Semin Nephrol. 2009 May;29(3):282-99. doi: 10.1016/j.se・・・
著者: J C Cheng, D Zikos, H A Skopicki, D R Peterson, K A Fisher
雑誌名: Am J Med. 1990 Jun;88(6):561-6.
Abstract/Text PURPOSE: The purpose of our study was to ascertain the safety of rapidly correcting acute symptomatic hyponatremia in psychogenic water drinkers, particularly in regard to any delayed adverse neurologic sequelae.
PATIENTS AND METHODS: We reviewed the medical records of all known psychogenic water drinkers (34) in our hospital from 1977 to 1989. Using seizure as a marker of severity, we identified 13 patients having a total of 27 episodes associated with severe hyponatremia. We evaluated the charts of those patients in detail to assess the mode of treatment, rate of correction, and long-term neurologic outcome. None of the patients experienced respiratory arrest before treatment, which was initiated within 2 hours of seizure.
RESULTS: For all 27 episodes, the initial serum sodium level (mean +/- SE) was 110.9 +/- 1.2 mmol/L, and the rate of correction (mean +/- SE) was 1.65 +/- 0.2 mmol/L/hour. All but one episode were corrected "rapidly" (initial correction rate of 0.7 or more mmol/L/hour) to 120 to 130 mmol/L within 12 hours. The absolute change in the serum sodium level was 15.1 +/- 1.2 mmol/L in 12 hours, 21.6 +/- 1.4 mmol/L in 24 hours, and 25.9 +/- 1.4 mmol/L in 48 hours. In no instance did therapy induce hypernatremia. All patients recovered immediately after treatment. There was no clinical or radiologic evidence of adverse neurologic sequelae immediately after treatment or after 6 years of follow-up.
CONCLUSION: In this series of male psychogenic water drinkers, early "rapid" correction of acute symptomatic hyponatremia by raising the serum sodium level 15 mmol/L in 12 hours while maintaining an absolute change in the serum sodium level of 26 mmol/L within 48 hours produced no long-term neurologic sequelae.

PMID 2189300  Am J Med. 1990 Jun;88(6):561-6.
著者: R S Tanneau, A Henry, F Rouhart, B Bourbigot, B Garo, Y Mocquard, J Y Goas
雑誌名: J Clin Psychiatry. 1994 Aug;55(8):349-54.
Abstract/Text BACKGROUND: Patients with self-induced water intoxication usually tolerate a large, rapid increase in plasma sodium without developing osmotically induced central pontine myelinolysis. However, we have previously reported a case of clinically suspected pontine myelinolysis in a patient with self-induced water intoxication. The purpose of our study was to investigate if a subgroup of these patients may also be vulnerable to neurologic complications of hyponatremia therapy.
METHOD: Over a 10-year period, we identified retrospectively 12 polydipsic patients having a total of 24 episodes of symptomatic hyponatremia with plasma sodium < or = 115 mmol/L. The mode of treatment, the kinetics of correction, and the neurologic outcome were recorded. The presence of alcoholism was noted.
RESULTS: Seven patients recovered uneventfully from 19 episodes of symptomatic hyponatremia. Five patients had delayed neurologic complications. Late therapy and/or respiratory arrest might have been associated with the complications for 2 patients. The other 3 patients experienced clinical features of central pontine myelinolysis leading to death in 1. Patients with neurologic complications had a higher maximal 24-hour increase in plasma sodium concentration (21.8 +/- 3.9 vs. 15.5 +/- 5.1 mmol/L, p < .02), and a higher incidence of both overcorrection to hypernatremia and chronic alcoholism, often associated with poor nutrition. All 5 patients became water intoxicated at home, and 2 patients with pontine dysfunction had subacute rather than acute hyponatremia.
CONCLUSION: A large rapid increase in plasma sodium may also be detrimental in patients with self-induced water intoxication when they are alcoholic, malnourished, and have nonacute hyponatremia.

PMID 8071304  J Clin Psychiatry. 1994 Aug;55(8):349-54.
著者: Y Ueta, S Taniguchi, A Yoshida, I Murakami, Y Mitani, I Hisatome, I Manabe, R Sato, M Tsuboi, A Ohtahara, E Nanba, C Shigemasa
雑誌名: J Clin Endocrinol Metab. 1996 May;81(5):1787-90.
Abstract/Text We studied the genetic basis of familial neurohypophyseal diabetes insipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplified exons of the AVP-neurophysin-II gene were subcloned and sequenced. Exons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 was substituted with Thymine (T), which induced a substitution of glycine (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them induced a new endonuclease restriction site in the PCR fragments from normal, and the other induced a new endonuclease restriction site from patients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, indicating that the mutation was heterozygous. We concluded that this mutation caused neurohypophyseal diabetes insipidus in this family.

PMID 8626836  J Clin Endocrinol Metab. 1996 May;81(5):1787-90.
著者: F Rauch, C Lenzner, P Nürnberg, C Frömmel, U Vetter
雑誌名: Clin Endocrinol (Oxf). 1996 Jan;44(1):45-51.
Abstract/Text OBJECTIVE: Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare cause of diabetes insipidus, in which AVP serum levels are insufficient. AVP is synthesized along with neurophysin-II (NPII) as an AVP-NPII precursor polypeptide in the hypothalamus. After proteolytic cleavage during axonal transport, AVP and NPII are reassembled and stored loosely bound to each other in the posterior pituitary until both are released into the circulation. In this study, we investigated the genetic basis of ADNDI in a German kindred with 10 affected members spanning three generations.
DESIGN: Genomic DNA was isolated from peripheral blood leucocytes. The entire coding region of the AVP-NPII gene of one of the affected persons was amplified by polymerase chain reaction (PCR) and subjected to nucleotide sequence analysis. Sequencing results were confirmed by restriction enzyme analysis of PCR products.
PATIENTS: Six affected and two unaffected members of a family with ADNDI and 54 unrelated healthy control subjects were studied.
RESULTS: The index patient was found by direct sequencing to be heterozygous for a G to T transversion at nucleotide position 1884 (exon 2) of the AVP-NPII gene. This mutation introduced a new recognition site for the restriction enzyme Ava II, which was used to test for the presence of the mutation in other family members and in control subjects. The mutation was detected in all family members with ADNDI, but was not found in unaffected family members or in control subjects. The mutation encodes a valine in place of the normal glycine at amino acid 65 of NPII, which is known to be highly conserved during evolution.
CONCLUSIONS: In this family, the autosomal dominant neurohypophyseal diabetes insipidus phenotype cosegregates with a point mutation in a region of the AVP-neurophysin-II gene which codes for the carboxy-terminal domain of neurophysin-II. Although the altered amino acid is not directly involved in AVP binding, the mutation might lead to conformational changes that impair the dimerization of neurophysin-II molecules. This could in turn affect the AVP binding affinity of neurophysin-II or might interfere with the transport of the AVP-neurophysin-II precursor in the AVP-producing cells of the hypothalamus.

PMID 8706292  Clin Endocrinol (Oxf). 1996 Jan;44(1):45-51.
著者: D R Repaske, R Medlej, E K Gültekin, M R Krishnamani, G Halaby, J W Findling, J A Phillips
雑誌名: J Clin Endocrinol Metab. 1997 Jan;82(1):51-6.
Abstract/Text Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form of diabetes insipidus due to progressive vasopressin deficiency with onset typically at 1-6 yr of age. Affected individuals demonstrate specific degeneration of the vasopressinergic magnocellular neurons in the hypothalamic supraoptic and paraventricular nuclei and loss of the posterior pituitary bright spot on magnetic resonance imaging. The genetic locus of ADNDI is the arginine vasopressin-neurophysin II (AVP-NPII) gene. Mutations that cause ADNDI have been found to occur both within the signal peptide of the prepro-AVP-NPII precursor and within the coding sequence for neurophysin II, but not within the coding sequence for AVP itself. We evaluated the AVP-NPII genes in two independent families with ADNDI and identified a mutation (C280-->T) in the coding sequence for the signal peptide of the prepro-AVP-NPII precursor in both families. This mutation encodes an Ala-->Val substitution at the C-terminus of the signal peptide (-1 amino acid). This mutation predicts the complete inability of signal peptidase to cleave the signal peptide from the preproprecursor and supports the hypothesis that the progressive neural degeneration that underlies ADNDI is caused by accumulation of malprocessed precursor. However, considerable heterogeneity in the age of onset (1-28 yr of age) and the severity of diabetes insipidus among affected members of these two families suggests that additional factors modulate the rate and extent of progression of the neurodegeneration that results from this one specific ADNDI mutation.

PMID 8989232  J Clin Endocrinol Metab. 1997 Jan;82(1):51-6.
著者: J Seckl, D Dunger
雑誌名: BMJ. 1989 Jan 7;298(6665):2-3.
Abstract/Text
PMID 2492841  BMJ. 1989 Jan 7;298(6665):2-3.
著者: Edward C Nemergut, Zhiyi Zuo, John A Jane, Edward R Laws
雑誌名: J Neurosurg. 2005 Sep;103(3):448-54. doi: 10.3171/jns.2005.103.3.0448.
Abstract/Text OBJECT: Diabetes insipidus (DI) is a common complication of transsphenoidal surgery. The purpose of this study was to elucidate patient- and surgery-specific risk factors for DI.
METHODS: The perioperative records of 881 patients who had undergone transsphenoidal microsurgery at the authors' institution between January 1995 and June 2001 were reviewed. Among 857 patients without preoperative DI, the overall incidence of immediate postoperative DI was 18.3%, with 12.4% of patients requiring treatment with desmopressin at some point during their hospitalization. Persistent DI requiring long-term treatment with desmopressin was noted in 2% of all patients. An observable intraoperative cerebrospinal fluid (CSF) leak was strongly associated with an increased incidence of both transient (33.3%) and persistent (4.4%) DI. Craniopharyngioma and Rathke cleft cyst (RCC) were also associated with an increased incidence of transient and persistent DI, whereas repeated operation was not. Among patients with pituitary adenomas, those with Cushing's disease had an increased risk of transient (22.2%), but not persistent, DI. Patients with a microadenoma were more likely to suffer transient DI than those harboring a macroadenoma (21.6 compared with 14.3%) but were not more likely to experience persistent DI.
CONCLUSIONS: Diabetes insipidus remains a common complication of transsphenoidal surgery; however, it is most frequently transient in nature. Patients with an intraoperative CSF leak, a microadenoma, a craniopharyngioma, or an RCC appear to have an increased risk of transient DI. Risk factors for persistent DI include an intraoperative CSF leak, a craniopharyngioma, or an RCC.

PMID 16235676  J Neurosurg. 2005 Sep;103(3):448-54. doi: 10.3171/jns.2・・・
著者: Stefano Ghirardello, Neil Hopper, Assunta Albanese, Mohamad Maghnie
雑誌名: J Pediatr Endocrinol Metab. 2006 Apr;19 Suppl 1:413-21.
Abstract/Text Pre-operative central diabetes insipidus has been reported in 8-35% of patients affected with craniopharyngioma, and in 70-90% after surgery. The management of postoperative polyuria and polydipsia can be challenging and fluid balance needs to be closely monitored. The classical triphasic pattern of endogenous vasopressin secretion--an initial phase of symptomatic diabetes insipidus occurring 24 hours after surgery; a second phase of inappropriate vasopressin secretion potentially causing hyponatraemia; and a third phase with a return to diabetes insipidus occurring up to 2 weeks later--is often complicated by cerebral salt wasting and thirst disorders. Inadequate adrenal replacement therapy and anticonvulsant agent treatment may increase the risk of life-threatening hyponatraemia in the course of desmopressin (DDAVP) treatment. Appropriate management, in order to avoid life-threatening or disabling electrolyte disturbances, requires a good grasp of the relevant pathophysiology. We review here the pathophysiology and management of the multiple fluid disorders encountered following surgery for craniopharyngiomas.

PMID 16700319  J Pediatr Endocrinol Metab. 2006 Apr;19 Suppl 1:413-21.・・・
著者: Pantelis Hadjizacharia, Elizabeth O Beale, Kenji Inaba, Linda S Chan, Demetrios Demetriades
雑誌名: J Am Coll Surg. 2008 Oct;207(4):477-84. doi: 10.1016/j.jamcollsurg.2008.04.017. Epub 2008 Jun 2.
Abstract/Text BACKGROUND: The incidence and risk factors for acute diabetes insipidus after severe head injury and the effect of this complication on outcomes have not been evaluated in any large prospective studies.
STUDY DESIGN: We conducted a prospective study of all patients admitted to the surgical ICU of a Level I trauma center with severe head injury (head Abbreviated Injury Score [AIS] >or= 3). The following potential risk factors with p < 0.2 on bivariate analysis were included in a stepwise logistic regression to identify independent risk factors for diabetes insipidus and its association with mortality: age, mechanism of injury (blunt or penetrating), blood pressure, Glasgow Coma Scale, Injury Severity Score, head and other body area AIS, skull fracture, cerebral edema and shift, intracranial hemorrhage, and pneumocephaly.
RESULTS: There were 436 patients (blunt injuries, 392; penetrating injuries, 44); 387 patients had isolated head injury. Diabetes insipidus occurred in 15.4% of all patients (blunt, 12.5%; penetrating, 40.9%; p < 0.0001) and in 14.7% of patients with isolated head injury (blunt, 11.8%; penetrating, 39.5%; p < 0.0001). The presence of major extracranial injuries did not influence the incidence of diabetes insipidus. Independent risk factors for diabetes insipidus in isolated head injury were Glasgow Coma Scale3. Diabetes insipidus was an independent risk factor for death (adjusted odds ratio, 3.96; 95% CI [1.65, 9.72]; adjusted p value = 0.002).
CONCLUSIONS: The incidence of acute diabetes insipidus in severe head injury is high, especially in penetrating injuries. Independent risk factors for diabetes insipidus include a Glasgow Coma Scale3. Acute diabetes insipidus was associated with significantly increased mortality.

PMID 18926448  J Am Coll Surg. 2008 Oct;207(4):477-84. doi: 10.1016/j.・・・
著者: J R Seckl, D B Dunger, J S Bevan, Y Nakasu, C Chowdrey, C W Burke, S L Lightman
雑誌名: Lancet. 1990 Jun 9;335(8702):1353-6.
Abstract/Text 23 patients without diabetes insipidus before transfrontal (hypothalamic) or trans-sphenoidal (pituitary) surgery were studied prospectively to investigate the pathogenesis of early postoperative diabetes insipidus. 12 patients who underwent trans-sphenoidal surgery and who did not develop diabetes insipidus were used as controls. All received prophylactic corticosteroid replacement. Blood samples were obtained immediately after operation, at the onset of diabetes insipidus, and 24 h later. Immediately after trans-sphenoidal pituitary surgery, plasma vasopressin (AVP) was raised but had fallen to subnormal concentrations by the onset of diabetes insipidus. After transfrontal hypothalamic surgery diabetes insipidus occurred sooner and was associated with high plasma AVP immunoreactivity--but the plasma showed no antidiuretic bioactivity and greatly attenuated the antidiuretic response to standard AVP. Early diabetes insipidus after hypothalamic surgery is associated with release of a substance, presumably an analogue, from the damaged hypothalamo-neurohypophyseal system, which acts as an antagonist to normal AVP activity; after trans-sphenoidal operations diabetes insipidus seems to be caused by failure of AVP release.

PMID 1971658  Lancet. 1990 Jun 9;335(8702):1353-6.
著者: Dimitri G Sigounas, Julie L Sharpless, D Ming L Cheng, Tiffany G Johnson, Brent A Senior, Matthew G Ewend
雑誌名: Neurosurgery. 2008 Jan;62(1):71-8; discussion 78-9. doi: 10.1227/01.NEU.0000311063.10745.D8.
Abstract/Text OBJECTIVE: With the advent of minimally invasive endoscopic pituitary surgery, there has been concern that the technique may be associated with higher rates of complications such as diabetes insipidus (DI) than traditional approaches, particularly early in a center's experience. We report the incidence and predictors of diabetes insipidus in patients after endoscopic transnasal resection (minimally invasive pituitary surgery) of pituitary lesions.
METHODS: Data were collected from hospital and clinic records on the first 119 consecutive patients undergoing endoscopic pituitary surgery at our center.
RESULTS: The rate of postoperative diabetes insipidus is low in patients undergoing minimally invasive pituitary surgery (permanent, 2.7%; transient, 13.6%). Factors associated with development of DI after minimally invasive pituitary surgery include Rathke's cleft cyst histology, intraoperative cerebrospinal fluid leak, and previous nonendoscopic lesion resection. Elevated serum sodium (>145 mmol/L) within the first 5 days postoperatively has a high sensitivity (87.5%), specificity (83.5%), and negative predictive value (99.5%) for permanent postoperative DI development.
CONCLUSION: Transitioning from microscopic to endoscopic pituitary surgery can be achieved with a low incidence of DI. An elevated serum sodium level in the first 5 postoperative days using standard monitoring can predict the chance of developing permanent DI. Patients having no elevated serum sodium measurements, defined as >145 mmol/L, in the first 5 days postoperatively will rarely, if ever, develop permanent DI, thereby validating short postoperative inpatient stays with minimal risk of readmission for DI management. Those with a single serum sodium measurement greater than 145 mmol/L have a 15% risk of developing permanent DI.

PMID 18300893  Neurosurgery. 2008 Jan;62(1):71-8; discussion 78-9. doi・・・
著者: Scott A Rivkees, Nancy Dunbar, Thomas A Wilson
雑誌名: J Pediatr Endocrinol Metab. 2007 Apr;20(4):459-69.
Abstract/Text Infants consume most of their calories as formula. Because of this large fluid intake, infants normally produce dilute urine, not far off from that seen in individuals with diabetes insipidus (DI). Infants with DI are therefore prone to water intoxication if fixed antidiuresis is achieved using the long-acting vasopressin analog desmopressin (DDAVP), which induces a state of high urine concentration. DI treatment approaches applied to older children and adults, who consume the their calories as solids, are difficult to apply to infants with DI. When used in infants, oral and intranasal DDAVP can be associated with wide swings in serum sodium concentration (SNA). In comparison, precisely administered subcutaneous doses of DDAVP can be successfully used in infants with DI, and appear to be superior to oral or intranasal DDAVP therapy. Alternatively, consistent eunatremia can be simply achieved in infantile DI using low renal solute load (RSL) formula and thiazide diuretics. Low RSL formula reduces obligatory urinary water losses, and thiazide diuretics concentrate the urine to levels seen in normal formula-fed infants. This report addresses treatment options of DI in infancy and the delicate management issues involved.

PMID 17550208  J Pediatr Endocrinol Metab. 2007 Apr;20(4):459-69.
著者: J D CRAWFORD, G C KENNEDY, L E HILL
雑誌名: N Engl J Med. 1960 Apr 14;262:737-43. doi: 10.1056/NEJM196004142621501.
Abstract/Text
PMID 13812709  N Engl J Med. 1960 Apr 14;262:737-43. doi: 10.1056/NEJM・・・
著者: L E Earley, J Orloff
雑誌名: J Clin Invest. 1962 Nov;41(11):1988-97. doi: 10.1172/JCI104657.
Abstract/Text
PMID 16695887  J Clin Invest. 1962 Nov;41(11):1988-97. doi: 10.1172/JC・・・
著者: S Libber, H Harrison, D Spector
雑誌名: J Pediatr. 1986 Feb;108(2):305-11.
Abstract/Text The antidiuretic effect of two prostaglandin synthetase inhibitors, ibuprofen (25 mg/kg/day) and indomethacin (2 mg/kg/day), was studied in patients aged 8 to 18 years with hereditary nephrogenic diabetes insipidus. Ibuprofen (studied in five patients) did not have demonstrable effects on urine volume, free water clearance, or osmolar clearance, but fractional excretion of sodium decreased from a mean of 0.38% to 0.19% (P less than 0.05). In contrast, indomethacin (studied in three patients) was associated with a decrease in mean urine volume from 5.8 to 2.8 mL/min and a decrease in mean free water clearance from 3.1 to 1.1 mL/min (both P less than 0.05). Fractional excretion of sodium decreased from 0.77% to 0.27% (P less than 0.01) and was accompanied by an increase in serum urea nitrogen level (P less than 0.01) and a decrease in urea nitrogen clearance (P less than 0.025). Thus, prostaglandin synthetase inhibitors are not uniformly effective in treatment of nephrogenic diabetes insipidus. The inhibitory effect of indomethacin on urine volume and free water clearance in our patients may have been mediated by an enhancement of antidiuretic hormone (ADH)-stimulated cyclic adenosine monophosphate generation, or by increased ADH-independent water reabsorption resulting from an increase in solute reabsorption and consequent medullary hypertonicity.

PMID 3080575  J Pediatr. 1986 Feb;108(2):305-11.
著者: L Monnens, A Jonkman, C Thomas
雑誌名: Clin Sci (Lond). 1984 Jun;66(6):709-15.
Abstract/Text Four boys with classical nephrogenic diabetes insipidus have been treated by indomethacin, by hydrochlorothiazide, and by the combination of indomethacin and hydrochlorothiazide. Hydrochlorothiazide treatment was slightly more effective than indomethacin treatment in reducing the urine volume and increasing the urine osmolality. The combination of indomethacin and hydrochlorothiazide appeared to be additive and especially helpful in infants and young children before the autonomy of drinking.

PMID 6723207  Clin Sci (Lond). 1984 Jun;66(6):709-15.
著者: R Boton, M Gaviria, D C Batlle
雑誌名: Am J Kidney Dis. 1987 Nov;10(5):329-45.
Abstract/Text From the analysis of several studies published from 1979 to 1986 comprising 1,172 patients, we estimated that glomerular filtration rate (GFR) was normal in 85% of unselected patients on chronic lithium therapy. The remaining 15% of patients displayed only mild reduction in GFR, clustering at approximately 60 mL/min. Thus, the data available to date do not support earlier concerns that long-term lithium therapy could eventuate into renal insufficiency. The most prevalent renal effect of lithium is impairment of concentrating ability, which we estimated to be present in at least 54% of 1,105 unselected patients on chronic lithium therapy. This defect translated into overt polyuria in only 19% of unselected cases. A renal lesion confined to the collecting tubule has been described in humans who have taken lithium for short periods of time. This lesion may represent the collecting tubule's response to the intracellular accumulation of lithium, which interferes with cAMP formation and results in an early and probably reversible inhibition of antidiuretic hormone (ADH)-mediated water transport. However, long-term lithium therapy may induce a progressive and partly irreversible defect in concentrating ability. The potential risk for dehydration associated with lithium-induced polyuria, as well as the discomfort inherent to this side effect, deserves evaluation and consideration for therapeutic intervention. Amiloride has additional advantages over conventional treatment of nephrogenic diabetes insipidus using thiazide diuretics. The action of amiloride on ADH-mediated water transport seems specific in as much as it is capable of preventing the uptake of lithium in high resistance epithelia and thereby prevents the inhibitory effect of intracellular lithium on water transport. Unlike thiazides, amiloride has a weak natriuretic effect and is less likely to increase plasma lithium levels by causing volume contraction. In addition, amiloride, by conserving potassium, obviates the need for potassium supplementation that is usually required to prevent hypokalemia when thiazides are used to treat lithium-induced polyuria. Since amiloride may prevent chronic intracellular lithium accumulation in the collecting tubule, future studies should elucidate whether amiloride also has a role in preventing lithium-induced chronic tubulo-interstitial damage.

PMID 3314489  Am J Kidney Dis. 1987 Nov;10(5):329-45.

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