Central Diabetes Insipidus In Children Research Articles

Central Diabetes Insipidus in Children as a Diagnostic Challenge.

Central diabetes insipidus (CDI) is a disorder in the pediatric population resulting from antidiuretic hormone deficiency. The excessive production of dilute urine characterizes it and manifests with polyuria, nocturia, and polydipsia. The diagnostics of CDI is often challenging, especially concerning the underlying condition of the disease. This article highlights the diverse clinical presentation of children with CDI and diagnostic difficulties among patients with polyuria and polydipsia. The article also reviews the etiology, symptoms, diagnostic workup, and management of CDI. We present 4 pediatric patients (aged 3-13.5 years) diagnosed with CDI of different etiology: 1 due to septo-optic dysplasia/optic nerve hypoplasia and 3 due to acquired processes such as Langerhans cell histiocytosis and germ cell tumor in 2 patients. Central diabetes insipidus was the first manifestation of a tumor or granuloma in all presented patients with acquired pathology. The patients sometimes need long-term follow-up to establish the proper final diagnosis.

Arginine-Stimulated Copeptin-Based Diagnosis of Central Diabetes Insipidus in Children and Adolescents

Introduction: Diagnosis of central diabetes insipidus (CDI) remains challenging. Water deprivation testing and hypertonic saline infusion, as established diagnostic tests, are mentally and physically demanding for patients. Arginine-stimulated copeptin has been shown as a putative parameter for the differential diagnosis of CDI in adults. Methods: In this single-centre retrospective study, we identified paediatric patients with suspected pituitary disorders who underwent standard arginine testing. Patients with CDI, matched controls, and primary polydipsia (PP) were identified. Diagnoses were confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in samples stored for a median of 4.6 years (1.3–10.84) and collected before and 60 min after arginine infusion. Cut-off analyses were performed using ROC curves. Results: Serum samples from 32 patients with CDI, 32 matched controls, and 5 patients with PP (n = 69; 51 males, 18 females) were available for analysis. Median copeptin concentrations increased from 4.47 pmol/L (interquartile range [IQR]: 3.47–8.36) to 6.96 pmol/L (IQR: 4.51–12.89; p < 0.001) in controls, from 1.46 pmol/L (IQR: 1.21–2.12) to 1.44 (IQR: 1.10–1.87; p = 0.645, ns) in CDI, and from 4.40 pmol/L (3.95–6.33) to 9.58 pmol/L (8.19–11.42; p < 0.001) in PP. The published cut-off value of 3.8 pmol/L revealed a sensitivity of 100% and a specificity of 86.5% in confirming CDI. Conclusion: Our results suggest that arginine-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for CDI in paediatric patients, which may replace and simplify the conventional diagnostic pathway of water deprivation testing and hypertonic saline infusion.

Central Diabetes Insipidus in Children and Adolescents: Twenty-Six Year Experience from a Single Centre.

Introduction Paediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalence for different causes of CDI. The objective of this study was to determine the causes of CDI and long-term outcome in children and adolescents from a Tertiary Paediatric Endocrinology unit. Methods The clinic database was searched to identify patients with CDI managed between 1993 and 2019. Relevant clinical information was collected from patient records. Results A total of 138 CDI patients, median age 6 years (range <1–18) at presentation, were identified. Principal CDI aetiologies were craniopharyngioma (n = 44), acute central nervous system (CNS) insult (n = 33), germinoma (n = 15), postneurosurgery (indication other than craniopharyngioma and germinoma, n = 20), midline CNS malformation (n = 14), Langerhans cell histiocytosis (n = 5), and familial (n = 2). Idiopathic CDI in this cohort was infrequent (n = 5). Patients with CNS malformations/infections presented with CDI at a younger age compared to patients with CNS tumours (p < 0.0001). Five patients, initially presenting as idiopathic CDI, were subsequently diagnosed with germinoma after a median interval of 3.3 years. All patients with CDI related to craniopharyngioma and nearly all (87%) patients with CDI related to germinoma had concomitant GH, ACTH, and TSH deficiency. The majority of patients who manifested CDI due to acute CNS insult either deceased (30%) or had transient CDI (33.3%). Conclusion Surgery for craniopharyngioma was the most common underlying aetiology of CDI with ubiquitous occurrence of panhypopituitarism in these patients. Manifestation of CDI in patients with acute CNS insult carries poor prognosis. We affirm that neuroimaging assessment in idiopathic CDI should be continued beyond 3 years from diagnosis as a significant number of patients exhibited progression of infundibular thickening 3 years post-CDI diagnosis.

Causes of central diabetes insipidus in children: a single-centre experience

Causes of central diabetes insipidus in children: a single-centre experience

Central diabetes insipidus in children: difficulties of etiological diagnosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Langerhans cell histiocytosis presenting as isolated central diabetes insipidus in a 2-year-old child: a rare manifestation of rare disease

Central diabetes insipidus, though uncommon in children, has varied causes, the commonest ones being genetic mutations, infiltrative disorders, infections. Isolated central diabetes insipidus is not one of the often encountered conditions in the pediatric practice. Here we report a case of 2 ½ years old female child who presented to us following history of polyuria for 2 months, who was confirmed to have central diabetes insipidus which was later evaluated to be secondary to Langerhans cell histiocytosis. Magnetic resonance imaging (MRI) and histopathological studies further helped in confirmation of the diagnosis. Langerhans cell histiocytosis is a rare, multifarious, and underdiagnosed hematologic disease in which isolated diabetes insipidus can be the sole presenting feature before other manifestations. Hence, this diagnosis could strongly be considered in the work up of central diabetes insipidus in children.

Causes and Follow-Up of Central Diabetes Insipidus in Children.

Objective To identify the causes of central diabetes insipidus (CDI) by evaluating the values of magnetic resonance imaging (MRI) in the diagnosis of pediatric CDI, providing evidence for the clinical diagnosis and treatment of CDI. Methods Seventy-nine patients with CDI (CDI group) hospitalized from July 2012 to March 2017 and 43 healthy children (control group) were enrolled in this study. All cases underwent MRI examination including T1-weighted three-dimensional magnetization-prepared rapid gradient-echo (T1WI-3D-MP RAGE) imaging sequences. The pituitary volume, the signal intensity of posterior pituitary, and the morphology of pituitary stalk were measured between two groups. The medical history, urine testing, imaging of hypothalamic-pituitary region, and hormone levels were also recorded. Results Age and gender were matched between the CDI and control groups. The height and BMI in the CDI group were less and the urine volume in 24 h was higher than those in the control group. The signal intensity of the posterior pituitary was higher in the control group, whereas the pituitary volume was smaller in the CDI group. In the CDI group, 44 cases presented with morphological changes of the pituitary stalk. Clinical symptoms mainly included polydipsia, polyuria, short stature, and vomiting. All patients were confirmed by water deprivation vasopressin test. Forty-four CDI children were associated with hypopituitarism, including 33 cases of PSIS with multiple pituitary hormone deficiencies (MPHD) and 11 cases of growth hormone deficiency (IGHD). The pituitary volume in the cases of pituitary stalk interruption syndrome (PSIS) with MPHD was smaller than that in the IGHD patients. Conclusions The signal intensity ratio of the posterior lobe, pituitary volume, and the morphology of pituitary stalk on T1WI-3D-MP RAGE image contribute to the diagnosis of CDI.

Central diabetes insipidus in children: about eight cases

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Incidence of Central Diabetes Insipidus in Children Presenting with Polydipsia and Polyuria

Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made. The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period. The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality. The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT. BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.

Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience

Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience

Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience.

BackgroundCentral diabetes insipidus (CDI) results from a number of conditions affecting the hypothalamic-neurohypophyseal system to cause vasopressin deficiency. Diagnosis of CDI is challenging, and clinical data and guidelines for management are lacking. We aim to characterize clinical and radiological characteristics of a cohort of pediatric patients with CDI.MethodsA chart review of 35 patients with CDI followed at North Carolina Children’s Hospital from 2000 to 2015 was undertaken. The frequencies of specific etiologies of CDI and characteristic magnetic resonance imaging (MRI) findings were determined. The presence of additional hormone deficiencies at diagnosis and later in the disease course was ascertained. Patient characteristics and management strategies were evaluated.ResultsThe cohort included 14 female and 21 male patients with a median age of 4.7 years (range, less than 1 month to 16 years) at diagnosis. Median duration of follow-up was 5 years (range, 2 months to 16 years). The cause of CDI was intracranial mass in 13 patients (37.2 %), septo-optic dysplasia in 9 patients (25.7 %), holoprosencephaly in 5 patients (14.2 %), Langerhans cell histiocytosis in 3 patients (8.6 %), isolated pituitary hypoplasia in 2 patients (5.7 %), and encephalocele in 1 patient (2.9 %). Patients were symptomatic for a mean of 6.3 months (range, less than 1 month to 36 months) prior to diagnosis of CDI. Growth hormone (GH), thyrotropin (TSH), adrenocorticotropic hormone (ACTH), and gonadotropin deficiencies were present at diagnosis in 34, 23, 23, and 6 % of patients, respectively. GH, TSH, ACTH, and gonadotropin deficiencies were diagnosed during follow-up in 23, 40, 37, and 14 % of patients, respectively. In patients with structural CNS abnormalities, development of additional hormone deficiencies occurred anywhere from 2 months to 13 years after the time of initial presentation.ConclusionsAll patients in our cohort had an underlying organic etiology for CDI, with intracranial masses and CNS malformations being most common. Therefore, MRI of the brain is indicated in all pediatric patients with CDI. Other pituitary hormone deficiencies should be investigated at diagnosis as well as during follow-up.

Etiologies of Central Diabetes Insipidus in Children

Background Central diabetes insipidus is a heterogeneous disease mainly due to lesions of hypothalamic nuclei or pituitary stalk caused by tumors of the suprasellar region or infiltrative diseases such as Langerhans cells histiocytosis or sarcoidosis. Objective: The aim of our study was to analyze the etiologies of central diabetes insipidus in children. Methods: Medical records of 31 children (mean age of 7 years) were reviewed. Results Craniopharyngioma was the main etiology found in 71%, in 3.2% diabetes insipidus was secondary to autoimmune hypophysitis, in 3.2% it appears after radiotherapy for a germinoma of the pineal region, finally, in 22.6% it was considered as idiopathic.

PO-0059 Central Diabetes Insipidus In Children: Clinical Profile And Etiologies Monocentric Experience (about 10 Cases)

Introduction Central diabetes insipidus (CDI) or neurohypophyseal diabetes insipidus is a rare disorder in children caused by an inadequate release of the antidiuretic hormone, arginine vasopressin (AVP). CDI is clinically caracterised by polyuria and polydipsia. Methods and materials Clinical, auxological, biological and neuroradiological characteristics of 10 children with central diabetes insipidus (CDI) were retrospectively analysed during a period of 18 years. Results Five girls and five boys with permanent diabetes insipidus were enrolled in the study. The mean age at diagnosis was 6 years five months (range: 4 months -14 years). The major cumulative and often subtle presenting manifestations were: polyuria (n = 10), polydipsia (n = 10), fatigue (n = 2), growth retardation (n = 4), headache (n = 1). All patients had low urine osmolality and elevated plasma osmolality on diagnosis. The aetiology of central DI was organic in 8 patients, craniopharyngioma in 3 patients, Langerhans cell histiocytosis in 2 patients, neurosarcoidosis in one case, Pituitary stalk interruption in one patient and wolfram syndrome in one patient. Three patients had anterior pituitary hormone deficiency and growth hormone deficiency. Polyuria and polydipsia have regressed in all patients put under desmopressin. Patients with craniopharyngioma were operated with a tumour recurrence in one case. Conclusion DIC is a rare disease in Paediatrics. The circumstances of discovery and positive diagnosis are often easy. The underlying aetiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Central Diabetes Insipidus in Children and Young Adults: Etiological Diagnosis and Long-Term Outcome of Idiopathic Cases

Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects. The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia. This is a prospective study conducted at a tertiary referral center. Patients underwent clinical and endocrine evaluations every 6 months and neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine function and neuroimaging were also reassessed after adult height achievement. A total of 85 consecutive patients with CDI were enrolled at a median age of 7.5 years; those with idiopathic CDI were stratified based on pituitary stalk thickness. To establish the etiology of CDI, we determined the time lag between its onset and the specific diagnosis, the long-term impact on pituitary function, and the overall long-term outcomes. Of the subjects, 24 (28.2%) received an etiologic diagnosis at presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were considered to have idiopathic disease and were followed until the median age of 17.3 years. Neuroimaging identified 40 of 43 patients with self-limited inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the severity of which was significantly correlated to pituitary dysfunction. The probability of >10-year-survival without an anterior pituitary defect was related to the severity of pituitary stalk thickness, and 53% showed permanent anterior pituitary defects. Three patients developed Langerhans cell histiocytosis and 1 developed Hodgkin lymphoma after a median of 9 and 13 years, respectively. A diagnostic etiology was achieved in 96% of patients with CDI. Risk stratification based on the degree of pituitary stalk thickness is of prognostic value for long-term outcomes including permanent pituitary dysfunction. New guidance is provided for the management of these patients.

Clinical characteristics of central diabetes insipidus in Taiwanese children

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Clinical features and molecular analysis of arginine-vasopressin neurophysin II gene in long-term follow-up patients with idiopathic central diabetes insipidus

Central diabetes insipidus (DI) characterized by polyuria, polydipsia and inability to concentrate urine, has different etiologies including genetic, autoimmune, post-traumatic, among other causes. Autosomal dominant central DI presents the clinical feature of a progressive decline of arginine-vasopressin (AVP) secretion. In this study, we characterized the clinical features and sequenced the AVP-NPII gene of seven long-term follow-up patients with idiopathic central DI in an attempt to determine whether a genetic cause would be involved. The diagnosis of central DI was established by fluid deprivation test and hyper-tonic saline infusion. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified by polymerase chain reaction and sequenced. Sequencing analysis revealed a homozygous guanine insertion in the intron 2 (IVS2 +28 InsG) of the AVP-NPII gene in four patients, which represents an alternative gene assembly. No mutation in the code region of the AVP-NPII gene was found. The homozygous guanine insertion in intron 2 (IVS2 +28 InsG) is unlikely to contribute to the AVP-NPII gene modulation in DI. In addition, the etiology of idiopathic central DI in children may not be apparent even after long-term follow-up, and requires continuous etiological surveillance.

Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin‐cell antibodies and markers of autoimmunity

Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin‐cell antibodies and markers of autoimmunity

Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin‐cell antibodies and markers of autoimmunity

Autoimmune targeting of hypothalamic-neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood. We aimed to (1) evaluate the presence of circulating vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of autoimmunity, and (3) define the relationship between immune markers and neuroimaging findings. Twenty patients were evaluated at a median age of 16.3 years. Twelve patients had idiopathic CDI, six had Langerhans cell histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed longitudinally in all subjects. Circulating arginine vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA), parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSH-receptor (TSHr) autoantibodies were evaluated. Circulating AVPc-Abs were found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with germinoma; the pituitary stalk was involved in most of them. Five patients with idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients (70%) and 21-OH autoantibodies in three of them. In idiopathic CDI, circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal system. The identification of AVPc-Abs in subjects who could have either idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be considered a completely reliable marker of autoimmune CDI. Thus, close clinical and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH.

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

To study the clinical, endocrine and radiological features and progress of children presenting with acquired diabetes insipidus (CDI). Chart review of children presenting because of CDI to Brisbane paediatric endocrine clinics between 1987 and 1999. 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. 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.

Diabetes insipidus.

Diabetes insipidus.