中枢性尿崩症50例病因及治疗分析

目的　探讨小儿中枢性尿崩症的病因及治疗措施。方法　对中枢性尿崩症 5 0例患儿临床资料、实验室检查结果、病因及治疗方法进行总结。结果　 1.病因 :以特发性居多 ,继发性中以肿瘤为最多见 ,遗传性仅 1例。 2 .治疗 :肿瘤以手术及放疗为主 ,其他以补充激素为主。结论　对中枢性特发性尿崩症患儿应询问家族史 ,其中有些病例可能属遗传性中枢性尿崩症 ,因抗利尿激素基因突变所致。MRI对早期诊断及追踪治疗有重要意义。弥凝替代治疗安全有效     

Acquired central diabetes insipidus in children: a 12-year Brisbane experience

OBJECTIVE: To study the clinical, endocrine and radiological features and progress of children presenting with acquired diabetes insipidus (CDI). METHODOLOGY: Chart review of children presenting because of CDI to Brisbane paediatric endocrine clinics between 1987 and 1999. RESULTS: Thirty-nine children (female/male ratio 21/18) aged 0.1-15.4 years (mean age 6.7 years) were identified. Aetiologies were head trauma or familial in eight cases (20.5%) each, central nervous system (CNS) tumours in five cases (12.8%), CNS malformations in four cases (10.2%), histiocytosis in three cases (7%) and hypoxia and infection in two cases (5.1%) each. Seven cases (17.9%) remain undiagnosed. Of the 32 (82%) cases with isolated anti-diuretic hormone deficiency at presentation, 24 cases (61.5%) experienced no further endocrine deficit. Additional endocrine deficits occurred mainly in the tumour or undiagnosed groups. On follow-up brain magnetic resonance imaging (MRI) scans in the seven undiagnosed cases, six patients had mild or no change and one patient had marked improvement of MRI findings. These changes occurred 10-48 months (mean 18 months) after presentation. CONCLUSIONS: Children without an aetiological diagnosis for the uncommon condition of acquired CDI require careful follow-up. More intensive investigation at presentation (e.g. estimation of cerebrospinal fluid human chorionic gonadotrophin) promises to lessen the number of such cases. Pituitary stalk biopsies should be reserved for those patients with progressive MRI changes. If these changes do not occur early, our experience suggests that follow-up MRI scans may need to be performed only yearly.     

Rapid differential diagnosis of diabetes insipidus in a 7-month-old infant: The copeptin approach

Introduction

Diabetes insipidus is characterized by hypoosmotic polyuria related to deficiency of arginine–vasopressin (AVP) secretion (central diabetes insipidus, CDI) or renal insensitivity to AVP (nephrogenic diabetes insipidus, NDI). The water deprivation test with assessment of AVP activity is currently the gold standard for differential diagnosis in patients presenting polyuria–polydipsia syndrome. Nevertheless, it can be dangerous without proper surveillance and its interpretation may be challenging. Other markers have been suggested. Direct quantification of circulating AVP is not sufficient for diagnosis: vasopressin is unstable, analysis is complex. AVP comes from prohormone preprovasopressin with concomitant release of copeptin (C-terminal moiety) in the equimolar ratio. Copeptin is stable in vitro, with easy and rapid measurement (< 4 h). Past studies have shown greater sensitivity and specificity of copeptin versus AVP to discriminate etiologies of polyuria in adults, but its value has not been demonstrated in infants yet.

Oral desmopressin treatment of central diabetes insipidus in children

To assess the efficacy of treatment with oral desmopressin (DDAVP), 20 patients, aged 5–20 y, with central diabetes insipidus were studied during 3 d of hospitalization and for 3 months at the outpatient clinic. At baseline the median rate of diuresis was 12. 7 ml kg^-1 h^-1. Urinary output decreased significantly under treatment with an increase in urinary osmolality, normalization of plasma osmolality and absence of nocturia. Patients were discharged from hospital with a median dose of 500μg d^-1 (100–1200μg d^-1). An adjustment in dosage was necessary in seven patients during follow-up, resulting in a final dose of 600μg d^-1. Body weight and DDAVP doses ( r = 0. 75, p = 0. 001) and body surface and DDAVP doses ( r = 0. 72, p < 0. 001) were significantly correlated. The average dosage was 474 ± 222μg m^-2 d^-1 (mean ± SD). The oral DDAVP treatment remained effective during the 3 months of follow-up. This therapy offers an alternative for the treatment of central diabetes insipidus in children.     

急性中枢性尿崩症临床经过和治疗评估

目的　 调查分析急性中枢性尿崩症的临床过程和疗效。 方法 　回顾性总结 1997年 5月～ 1999年 12月住我院PICU的 16例急性中枢性尿崩症患儿临床资料。 结果 　所有病例均继发于脑损伤和应用垂体加压素治疗 ,其剂量为 0 0 0 0 3～0 0 0 65U/(kg·min) ,治疗时间为 5小时～ 18天 ,平匀 2 8 5小时。治疗目标达到 :尿量 2～ 3ml/(kg·h) ,尿比重 1 0 10～ 1 0 2 0 ,血钠 14 0～ 14 5mmol/L。存活 3例 ( 19% ) ,死亡 13例 ( 81% )。 结论 　垂体加压素治疗急性中枢性尿崩症对于减少尿量和纠正高钠血症有显著效果。     

Treatment of pitressin sensitive diabetes insipidus in children with clofibrate and carbamazepine

Four children with pitressin sensitive diabetes insipidus were treated with clofibrate and carbamazepine. Both substances significantly reduced daily urine volumes, clofibrate by 40–83%, carbamazepine by 50–70%. The combination of both substances led to a significant further reduction. Long term clinical control of diabetes insipidus was achieved with clofibrate 25–30 mg/kg/day in 2 cases, and by clofibrate 45 mg/kg/day and carbamazepine 6 mg/kg/day in one child. No side effects of the treatment were observed. In healthy adult volunteers, clofibrate inhibited diuresis effectively after acute hydration.This study was partly supported by the Deutsche Forschungsgemeinschaft (Scha 169/3) and by Fa. Rheinpharma, Heidelberg.     

小儿脑死亡并中枢性尿崩症

目的了解小儿脑死亡合并中枢性尿崩症(DI)的临床特点。 方法对北京儿童医院PIC17例脑死亡患儿的临床资料进行分析。 结果本组DI脑死亡儿发生率为59％(10／17),原发病以颅内感染为主。DI多在脑死亡前24h内出现,其发生与年龄、心肺复苏无明显相关性。垂体加压素可使DI患儿尿量明显减少。 结论DI是小儿脑死亡较常见的特殊临床表现之一,但并非脑死亡的必备特征。     

Central diabetes insipidus in a newborn with deletion of chromosome 7q

Abstract: We report an infant with midline craniofacial defects and holoprosencephaly due to chromosome 46, XY, del (7) (pter →q34) who presented at 1 week of age with central diabetes insipidus. The importance of hypothalamic-pituitary endocrine investigation in patients with this syndrome, and more generally, in patients with midline craniofacial malformation or holoprosencephaly is emphasized. As infants with chromosome 7q deletion bear close phenotypic resemblance to infants of Trisomy 13, chromosomal confirmation and karyotype banding is mandatory to establish an accurate diagnosis and for genetic counselling of their parents.     

Idiopathic central diabetes insipidus in an extreme premature infant: A case report

Context

Central diabetes insipidus (CDI) is a rare disease during the neonatal period, making it diagnosis difficult and delaying medical treatment.

Risk factors for diabetes insipidus in langerhans cell histiocytosis

BACKGROUND: Diabetes insipidus (DI) is the most frequent central nervous system (CNS)-related permanent consequence in Langerhans cell histiocytosis (LCH), which mostly requires life-long hormone replacement therapy. In an attempt to define the population at risk for DI, 1,741 patients with LCH registered on the trials DALHX 83 and DALHX 90, LCH I and LCH II were studied. RESULTS: Overall 212 of 1,741 patients (12%) was reported to have DI. In 102 of 1,741 patients (6%) DI was present at diagnosis of LCH. One thousand one hundred eighty three of 1,539 patients without DI at diagnosis had follow up information. One hundred ten of these (9%) later developed DI. The risk of developing DI was 20% at 15 years after diagnosis. Multisystem disease patients at diagnosis carried a 4.6-fold risk for DI compared to single system patients. Craniofacial lesions, in particular in the "ear," "eye," and oral region were associated with a significantly increased risk for DI (relative hazard rate, RHR 1.7), independent of the extent of disease. No influence of the duration of therapy could be determined, but the duration of initial disease activity (RHR 1.5) and the occurrence of reactivations (RHR 3.5) significantly increased the risk for DI. CONCLUSIONS: Patients with multisystem disease and craniofacial involvement at diagnosis, in particular of the "ear," "eye," and the oral region carry a significantly increased risk to develop DI during their course. This risk is augmented when the disease remains active for a longer period or reactivates.     

Clinical,hormonal and imaging findings in 27 children with central diabetes insipidus

Clinical, auxological, biological and neuroradiological characteristics of 27 children with central diabetes insipidus (CDI) were retrospectively analysed. Median age at diagnosis was 8.6 years (range: 0.3–16.1 years). Final aetiologies were postsurgical infundibulo-hypophyseal impairment (n=7), cerebral tumour (n=8), Langerhans cell histiocytosis (n=3), septo-optic dysplasia (n=1), ectrodactyly ectodermal dysplasia clefting syndrome (n=1), and idiopathic (n=7). In the non-postsurgical CDI patients, major cumulative and often subtle presenting manifestations were: polyuria (n=20), polydipsia (n=19), fatigue (n=11), nycturia (n=10), growth retardation (n=9), and headache (n=9). An associated antehypophyseal insufficiency, mainly somatotropic, was documented in 11 children. All patients except one who initially had a cerebral tomography, underwent magnetic resonance imaging revealing the lack of the physiological posterior pituitary hyperintense signal. One third of the idiopathic patients initially had a thickened pituitary stalk. All patients with idiopathic CDI were intensively followed up with 3-monthly physical examination, antehypophyseal evaluation, search for tumour markers, and cerebral MRI every 6 months. In one of them the pituitary stalk had normalized after 4.3 years. In one patient Langerhans cell histiocytosis was diagnosed after 7 months of follow-up, and in another patient a malignant teratoma was found after 2.4 years of follow-up. Conclusion: CDI may be the early sign of an evolving cerebral process. The association of polyuria-polydipsia should incite a complete endocrine evaluation and a meticulous MRI evaluation of the hypothalamo-hypophyseal region. A rigorous clinical and neuroradiologic follow-up is mandatory to rule out an evolving cerebral process and to detect associated antehypophyseal insufficiencies.     

A Novel Mutation of the Arginine Vasopressin Receptor 2 Gene in a Patient with Congenital Nephrogenic Diabetes Insipidus

We have identified a novel mutation of the arginine vasopressin receptor 2 (AVPR2) gene in a case of congenital X-linked nephrogenic diabetes insipidus (NDI). The patient was a 2-mo-old Japanese boy with persistent fever and failure to thrive. He was diagnosed as having congenital NDI by clinical and laboratory findings. Molecular analysis demonstrated that he was hemizygous for a G to C transversion in exon 2 of the AVPR2 gene which resulted in a glycine to arginine substitution (G107R) at the 107th codon of the first extracellular loop. His mother was heterozygous for the same mutation. We speculated that the G107R mutation would interfere with the binding capacity of the AVPR2, since G107R is located near F105 and R106, both of which are crucial for ligand binding. In cases of X-linked NDI, mutations in the AVPR2 gene are distributed widely. Thus, DNA analysis throughout the gene is of clinical value for the identification of female carriers, and it also gives precise information for genetic counseling.     

A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction

A case of a 6 year old boy with Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction is reported. Magnetic resonance imaging revealed abnormal findings of the pituitary gland and stalk. Good catch-up growth was obtained by treatment with growth hormone. These findings suggest that hypothalamic-pituitary dysfunction might be involved in Kabuki make-up syndrome.     

Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus

Jakobsson B, Berg U. Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus. Acta Pædiatr 1994;83:522–5. Stockholm. ISSN 0803–5253
The purpose of this study was to investigate the effects of treatment with hydrochlorothiazide and hydrochlorothiazide and indomethacin combined on renal function in four boys, two with nephrogenic diabetes insipidus and two with partial nephrogenic diabetes insipidus using the clearances of inulin and para-aminohippuric acid under water diuresis and lithium clearance. Hydrochlorothiazide reduced urine flow and lithium clearance. These effects were further potentiated by addition of indomethacin. No consistent effects on renal plasma flow or glomerular filtration rate were found. It is concluded that treatment with hydrochlorothiazide alone and hydrochlorothiazide and indomethacin combined reduces urine flow in nephrogenic diabetes insipidus by increasing proximal tubular reabsorption of sodium.