Transient postpartum diabetes insipidus associated with HELLP syndrome.

PubMed

Ellidokuz, Ender; Uslan, Ihsan; Demir, Serap; Cevrioglu, Serhan; Tufan, Gulnihal

2006-12-01

Diabetes insipidus in pregnancy has different causes. The association of diabetes insipidus with disturbances of liver function has been reported, however, diabetes insipidus has rarely been reported in HELLP syndrome. We present a 23-year-old primigravida with a singleton gestation complicated by HELLP syndrome who developed postpartum diabetes insipidus. Labor was induced promptly to terminate pregnancy because of intrauterine fetal death and liver dysfunction. 1-deamino-8-D-arginine-vasopressin was administered. Diabetes insipidus and liver dysfunction resolved within 2 weeks. Development of diabetes insipidus may result from increased vasopressinase activity mainly caused by deterioration of liver functions caused by HELLP syndrome. In pregnant women with liver disease as a result of any cause, the development of diabetes insipidus should be assessed with particular attention.

Diabetes Insipidus

MedlinePlus

Diabetes insipidus (DI) causes frequent urination. You become extremely thirsty, so you drink. Then you urinate. This ... is almost all water. DI is different from diabetes mellitus (DM), which involves insulin problems and high ...

[Nephrogenic diabetes insipidus].

PubMed

Velásquez-Jones, Luis; Medeiros-Domingo, Mara

The anti-diuretic hormone arginine-vasopressin (AVP) is released from the pituitary and regulates water reabsorption in the principal cells of the kidney collecting duct. Binding of AVP to the arginine-vasopressin receptor type-2 in the basolateral membrane leads to translocation of aquaporin-2 water channels to the apical membrane of the principal cells of the collecting duct, inducing water permeability of the membrane. This results in water reabsorption in the collecting duct of the nephron following an osmotic gradient. Nephrogenic diabetes insipidus is caused by partial or complete renal resistance to the effects of AVP. Congenital nephrogenic diabetes insipidus is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their urine. Acquired nephrogenic diabetes insipidus can be caused by electrolyte imbalances (e.g., hypercalcemia, hypokalemia), renal/extra-renal diseases and drugs (e.g., lithium toxicity). This article reviews the causes, clinical manifestations, diagnosis and treatment of patients with nephrogenic diabetes insipidus. Based on more in-depth mechanistic understanding, new therapeutic strategies are current being explored. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Idiopathic central diabetes Insipidus.

PubMed

Grace, Mary; Balachandran, Venu; Menon, Sooraj

2011-10-01

Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.

Diabetes insipidus in a patient with diabetes mellitus.

PubMed

Paulose, K P; Padmakumar, N

2002-09-01

The association of Diabetes Mellitus (DM) and Diabetes Insipidus (DI) without any congenital defects is very rare and we report here a case of type 2 diabetes mellitus (NIDDM) whose blood sugar was controlled by insulin, developing central diabetes insipidus 2 years later, which could be successively controlled by synthetic vasopressin.

Diabetes insipidus in pregnancy

PubMed Central

Hague, William M

2009-01-01

Diabetes insipidus is an uncommon condition with various aetiologies. Recent research has uncovered new mechanisms underlying the syndrome. Careful attention to management is essential in pregnant women to avoid serious complications. Diabetes insipidus in pregnancy may be due to relative reduction in secretion of AVP from the posterior pituitary (cranial DI), increase in breakdown of AVP by placental cystine aminopeptidase with vasopressinase activity, or resistance of the rental tubules to AVP (nephrogenic DI). PMID:27579058

Gestational diabetes insipidus. Case Report.

PubMed

Ejmocka-Ambroziak, Anna; Grzechocińska, Barbara; Jastrzebska, Helena; Kochman, Magdalena; Cyganek, Anna; Wielgoś, Mirosław; Zgliczyński, Wojciech

2015-01-01

Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

Familial forms of diabetes insipidus: clinical and molecular characteristics.

PubMed

Babey, Muriel; Kopp, Peter; Robertson, Gary L

2011-07-05

Over the past two decades, the genetic and molecular basis of familial forms of diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The most common type of diabetes insipidus is caused by lack of the antidiuretic hormone arginine vasopressin (vasopressin), which is produced in the hypothalamus and secreted by the neurohypophysis. This type of diabetes insipidus is referred to here as neurohypophyseal diabetes insipidus. The syndrome can also result from resistance to the antidiuretic effects of vasopressin on the kidney, either at the level of the vasopressin 2 receptor or the aquaporin 2 water channel (which mediates the re-absorption of water from urine), and is referred to as renal or nephrogenic diabetes insipidus. Differentiation between these two types of diabetes insipidus and primary polydipsia can be difficult owing to the existence of partial as well as complete forms of vasopressin deficiency or resistance. Seven different familial forms of diabetes insipidus are known to exist. The clinical presentation, genetic basis and cellular mechanisms responsible for them vary considerably. This information has led to improved methods of differential diagnosis and could provide the basis of new forms of therapy.

Nephrogenic diabetes insipidus: treat with caution.

PubMed

Boussemart, Thierry; Nsota, Jacqueline; Martin-Coignard, Dominique; Champion, Gérard

2009-09-01

Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.

Post-hemorrhagic hydrocephalus and diabetes insipidus in preterm infants.

PubMed

Borenstein-Levin, Liron; Koren, Ilana; Kugelman, Amir; Bader, David; Toropine, Arina; Riskin, Arieh

2014-11-01

We present two cases of transient central diabetes insipidus in preterm neonates with post-hemorrhagic hydrocephalus. Although the association between intraventricular hemorrhage and diabetes insipidus has been described in preterm infants, the association between diabetes insipidus and hydrocephalus, and the fact that such central diabetes insipidus could be reversible with the reduction of ventricular size, either because of spontaneous resolution or the placement of ventriculo-peritoneal shunt is first described here in neonates.

Systemic lupus erythematosus with Sjögren's syndrome and renal tubular acidosis presenting as nephrogenic diabetes insipidus.

PubMed

Parrey, Ashaq Hussain; Ahmad, Fayaz; Ahmad, Mushtaq; Basher, Adil

2018-01-01

Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a rare association; there is a case report of neurogenic DI in patients of SLE; however, SLE and nephrogenic DI has not been reported in literature. We present a case of SLE presenting as nephrogenic DI. We report a case who presented with DI (nephrogenic) and fulfilled criteria for SLE and Sjögren's syndrome with renal tubular acidosis.

Gestational diabetes insipidus: a review of an underdiagnosed condition.

PubMed

Aleksandrov, Nikolay; Audibert, François; Bedard, Marie-Josée; Mahone, Michèle; Goffinet, François; Kadoch, Isaac-Jacques

2010-03-01

To review the etiology, diagnosis, and management of diabetes insipidus during pregnancy. A search of the literature was performed in PubMed using key word searching and citation snowballing to identify articles published in English between January 1, 1980, and December 31, 2008, on the subject of diabetes insipidus during pregnancy. Once the articles were identified, a thorough review of all results was conducted. Results and conclusions were compiled and summarized. We reviewed 50 studies selected using the following key words: diabetes insipidus, pregnancy, arginine vasopressin, vasopressinase. Gestational diabetes insipidus is underdiagnosed because polyuria is often considered normal during pregnancy. Clinicians caring for pregnant women should consider screening for gestational diabetes insipidus, because it could be associated with serious underlying pathology.

[Gestational diabetes insipidus during a twin pregnancy].

PubMed

De Mesmay, M; Rigouzzo, A; Bui, T; Louvet, N; Constant, I

2013-02-01

Gestational diabetes insipidus is an uncommon clinical disease whose prevalence is approximately two to three pregnancies per 100,000. It may be isolated or associated with preeclampsia. We report a case of gestational diabetes insipidus in a twin pregnancy, originally isolated during two months, and secondarily complicated by HELLP-syndrome. We recall the specific pathophysiology of polyuric-polydipsic syndrome during pregnancy and summarize its various causes. Finally, we discuss the indications, in case of isolated gestational diabetes insipidus, of treatment by dDAVP. Copyright © 2013. Published by Elsevier SAS.

Central diabetes insipidus in pediatric severe traumatic brain injury.

PubMed

Alharfi, Ibrahim M; Stewart, Tanya Charyk; Foster, Jennifer; Morrison, Gavin C; Fraser, Douglas D

2013-02-01

To determine the occurrence rate of central diabetes insipidus in pediatric patients with severe traumatic brain injury and to describe the clinical, injury, biochemical, imaging, and intervention variables associated with mortality. Retrospective chart and imaging review. Children's Hospital, level 1 trauma center. Severely injured (Injury Severity Score ≥ 12) pediatric trauma patients (>1 month and <18 yr) with severe traumatic brain injury (presedation Glasgow Coma Scale ≤ 8 and head Maximum Abbreviated Injury Scale ≥ 4) that developed acute central diabetes insipidus between January 2000 and December 2011. Of 818 severely injured trauma patients, 180 had severe traumatic brain injury with an overall mortality rate of 27.2%. Thirty-two of the severe traumatic brain injury patients developed acute central diabetes insipidus that responded to desamino-8-D-arginine vasopressin and/or vasopressin infusion, providing an occurrence rate of 18%. At the time of central diabetes insipidus diagnosis, median urine output and serum sodium were 6.8 ml/kg/hr (interquartile range = 5-11) and 154 mmol/L (interquartile range = 149-159), respectively. The mortality rate of central diabetes insipidus patients was 87.5%, with 71.4% declared brain dead after central diabetes insipidus diagnosis. Early central diabetes insipidus onset, within the first 2 days of severe traumatic brain injury, was strongly associated with mortality (p < 0.001), as were a lower presedation Glasgow Coma Scale (p = 0.03), a lower motor Glasgow Coma Scale (p = 0.01), an occurrence of fixed pupils (p = 0.04), and a prolonged partial thromboplastin time (p = 0.04). Cerebral edema on the initial computed tomography, obtained in the first 24 hrs after injury, was the only imaging finding associated with death (p = 0.002). Survivors of central diabetes insipidus were more likely to have intracranial pressure monitoring (p = 0.03), have thiopental administered to induce coma (p = 0.04) and have received a

Diabetes insipidus in pregnancy: how to advice the patient?

PubMed

Refardt, Julie; Christ-Crain, Mirjam

2018-02-19

Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease during pregnancy. Nevertheless, its recognition is important to avoid complications due to dehydration and hypernatremia. Its manifestation during pregnancy ranges from exacerbation of pre-existing central or nephrogenic diabetes insipidus to transient pregnancy-induced diabetes insipidus due to the increased metabolism of the antidiuretic hormone vasopressin by the placental vasopressinase. Diagnosis can be challenging, as urinary frequency is common during pregnancy and primary polydipsia also needs to be excluded. Also the standard water deprivation test is not recommended during pregnancy due to the increased risk of complications. Treatment depends upon the final diagnosis, with desmopressin (DDAVP) being the medication of choice in AVP-deficient diabetes insipidus, whereas nephrogenic diabetes insipidus requires treatment of the underlying disease and supportive measures.

[Analysis of the factors contributing to diabetes insipidus after surgeries for craniopharyngiomas].

PubMed

Luo, Shi; Pan, Jun; Qi, Song-Tao; Fang, Lu-Xiong; Fan, Jun; Liu, Bao-Guo

2009-03-01

To analyze the factors contributing to the occurrence of diabetes insipidus after operations for craniopharyngiomas. A total of 121 cases of diabetes insipidus following surgeries for craniopharyngiomas were retrospectively analyzed and the factors associated with postoperative diabetes insipidus were analyzed. The incidence of diabetes insipidus was 27.3% (33/121 cases) before the operation, 89.9% (107/1119) early after the operation and 39.8%(37/93) in later stages after the operation. The occurrence of early postoperative diabetes insipidus showed a significant relation to the classification and calcification of the craniopharyngioma. Patients with supradiaphragmatic and extraventricular tumors had the lowest incidence of postoperative diabetes insipidus. Late postoperative diabetes insipidus was closely correlated to such factors as age, classification of craniopharyngioma, and intraoperative treatment of the pituitary stalk, but not to the scope of tumor resection or tumor calcification. Late diabetes insipidus was more frequent in children and patients with severed pituitary stalk. The incidence of late postoperative diabetes insipidus was significantly higher in patients with supradiaphragmatic and extra-intraventricular tumors than in those with tumors beneath the diaphragma sellae and extraventricular tumors. Postoperative diabetes insipidus following surgeries for craniopharyngiomas is closely related to the tumor classification, calcification and pituitary stalk protection.

Diabetes mellitus, diabetes insipidus, and optic atrophy. An autosomal recessive syndrome?

PubMed Central

Fraser, F C; Gunn, T

1977-01-01

Twenty-one families were selected from the published reports in which the propositus had the triad of juvenile diabetes mellitus, diabetes insipidus, and optic atrophy. The data were consistent with the hypothesis of an autosomal gene which, in the homozygote, causes juvenile diabetes mellitus and one or more of diabetes insipidus, optic atrophy, and nerve deafness. Heterozygotes appear to have an increased probability of developing juvenile diabetes mellitus. PMID:881709

Maternal rhabdomyolysis and twin fetal death associated with gestational diabetes insipidus.

PubMed

Price, Joan T; Schwartz, Nadav

2013-08-01

Gestational diabetes insipidus is a rare, transient complication of pregnancy typically characterized by polyuria and polydipsia that may lead to mild electrolyte abnormalities. More severe sequelae of gestational diabetes insipidus are uncommon. We present a case of a 25-year-old woman at 23 weeks of gestation in a dichorionic-diamniotic twin pregnancy who developed severe symptomatic gestational diabetes insipidus complicated by rhabdomyolysis and death of both fetuses. Maternal rhabdomyolysis caused by gestational diabetes insipidus is extremely rare. Early recognition and treatment of gestational diabetes insipidus is necessary to prevent maternal and fetal morbidity and mortality.

Central diabetes insipidus: a previously unreported side effect of temozolomide.

PubMed

Faje, Alexander T; Nachtigall, Lisa; Wexler, Deborah; Miller, Karen K; Klibanski, Anne; Makimura, Hideo

2013-10-01

Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ.

Central diabetes insipidus in children with acute brain insult.

PubMed

Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

2011-12-01

Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

Acute diabetes insipidus in severe head injury: a prospective study.

PubMed

Hadjizacharia, Pantelis; Beale, Elizabeth O; Inaba, Kenji; Chan, Linda S; Demetriades, Demetrios

2008-10-01

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. 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. 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). 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.

[Association between central diabetes insipidus and type 2 diabetes mellitus].

PubMed

Palumbo, Claudia; Nicolaci, Nora; La Manna, Andrés A; Branek, Natalia; Pissano, María N

2018-01-01

Central diabetes insipidus is a rare disease of the hypothalamus and neurohypophysis. It is very unusually found in the adult with type 2 diabetes mellitus. It is manifested by a polydipsic polyuric syndrome, which must be distinguished from the poorly controlled type 2 diabetes mellitus. Given the similarity of both entities and the unusual nature of their coexistence, their suspicion is difficult. The case of a 72-year-old male with type 2 diabetes mellitus with poor insulin control (fasting hyperglycemia greater than 180 mg/dl) who had a long-standing polyuric syndrome is here presented. Hypernatremia and plasma osmolality elevated together with a low urinary osmolality led to the suspicion of diabetes insipidus, which was subsequently confirmed by the dehydration test and the administration of desmopressin sc. With 61% increase in the calculated urinary osmolarity one hour post desmopressin s.c., diabetes insipidus of central type was diagnosed. Nuclear Magnetic Resonance showed a bright spot with normal neurohypophysis, contributing to the diagnosis of the idiopathic form.

Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide

PubMed Central

Nachtigall, Lisa; Wexler, Deborah; Miller, Karen K.; Klibanski, Anne; Makimura, Hideo

2013-01-01

Context: Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. Case Presentations: A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Conclusions: Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ. PMID:23928668

One too many diabetes: the combination of hyperglycaemic hyperosmolar state and central diabetes insipidus.

PubMed

Burmazovic, Snezana; Henzen, Christoph; Brander, Lukas; Cioccari, Luca

2018-01-01

The combination of hyperosmolar hyperglycaemic state and central diabetes insipidus is unusual and poses unique diagnostic and therapeutic challenges for clinicians. In a patient with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology that is considered, and achieving glycaemic control remains the first course of action. However, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and urine osmolality suggest concurrent symptomatic diabetes insipidus. We report a rare case of concurrent manifestation of hyperosmolar hyperglycaemic state and central diabetes insipidus in a patient with a history of craniopharyngioma. In patients with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology to be considered.However, a history of craniopharyngioma, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and osmolality provide evidence of concurrent diabetes insipidus.Therefore, if a patient with diabetes mellitus presents with severe hypernatraemia, hyperglycaemia, a low or low normal urinary-specific gravity and worsening polyuria despite correction of hyperglycaemia, concurrent diabetes insipidus should be sought.

One too many diabetes: the combination of hyperglycaemic hyperosmolar state and central diabetes insipidus

PubMed Central

Burmazovic, Snezana; Henzen, Christoph; Brander, Lukas; Cioccari, Luca

2018-01-01

Summary The combination of hyperosmolar hyperglycaemic state and central diabetes insipidus is unusual and poses unique diagnostic and therapeutic challenges for clinicians. In a patient with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology that is considered, and achieving glycaemic control remains the first course of action. However, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and urine osmolality suggest concurrent symptomatic diabetes insipidus. We report a rare case of concurrent manifestation of hyperosmolar hyperglycaemic state and central diabetes insipidus in a patient with a history of craniopharyngioma. Learning points: In patients with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology to be considered. However, a history of craniopharyngioma, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and osmolality provide evidence of concurrent diabetes insipidus. Therefore, if a patient with diabetes mellitus presents with severe hypernatraemia, hyperglycaemia, a low or low normal urinary-specific gravity and worsening polyuria despite correction of hyperglycaemia, concurrent diabetes insipidus should be sought. PMID:29675260

Pemetrexed-Induced Nephrogenic Diabetes Insipidus

PubMed Central

Fung, Enrica; Anand, Shuchi; Bhalla, Vivek

2016-01-01

Pemetrexed is an approved anti-metabolite agent, now widely used for treating locally advanced or metastatic non-squamous, non–small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed. PMID:27241854

Adipsic diabetes insipidus revealing a bifocal intracranial germinoma.

PubMed

Kreutz, Julie; Potorac, Iulia; Lutteri, Laurence; Gennigens, Christine; Martin, Didier; Daly, Adrian F; Bonneville, Jean-Francois; Tshibanda, Luaba; Beckers, Albert

2017-07-01

Adipsic diabetes insipidus is a rare complication of intracranial tumors in which impaired antidiuretic hormone secretion is associated with the loss of thirst sensation. Here, we present the case of a patient with bifocal intracranial germinoma, diagnosed due to symptoms mainly caused by adipsic diabetes insipidus. This is, to our knowledge, the first case of adipsic diabetes insipidus revealing an intracranial germinoma reported in the literature. We describe the diagnostic procedures and the three-year follow-up of this patient. Management of intracranial germ-cell tumors is made complex by the wide range of histological features. Although germinomas have a generally better prognosis than most nongerminomatous tumors, they can have severe or even life-threatening presentations. Adipsic diabetes insipidus is one such severe presentation and its rarity can make it difficult to recognize and manage. Awareness of this potential entity is therefore important for clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Gestational diabetes insipidus: a morphological study of the placenta.

PubMed

Castiglione, F; Buccoliero, A M; Garbini, F; Gheri, C F; Moncini, D; Poggi, G; Saladino, V; Rossi Degl'Innocenti, D; Gheri, R G; Taddei, G L

2009-12-01

Gestational diabetes insipidus (GDI) refers to the state of excessive water intake and hypotonic polyuria. Those cases manifesting in pregnancy and referred to as GDI may persist thereafter or may be a transient latent form that resolves after delivery. Microscopic examination of affected subjects has not been previously reported. In the literature, there are various case reports and case series on diabetes insipidus in pregnancy. In this study, we present a case that had transient diabetes insipidus during pregnancy in which the placenta was examined.

[A disseminated form of Langerhans histiocytosis associated with diabetes insipidus and diabetes mellitus].

PubMed

Ben Ghorbel, I; Houman, M H; B'chir, S; Chamakhi, S; Miled, M

2001-05-01

Langerhans' cell histiocytosis is a rare disorder of unknown etiology characterized by a wide clinical spectrum and varied behavior. Diabetes insipidus is a relatively common feature in Langerhans' cell histiocytosis. The presence of both diabetes insipidus and mellitus associated with histiocytosis in an adult is rare. To our knowledge, only three previous cases have been reported. We report the clinical presentation, pathologic findings and clinical progress in an adult female who had disseminated Langerhans' cell histiocytosis (hypothalamic infiltration, multifocal bone involvement) associated with both diabetes insipidus and mellitus. The pathogenesis of diabetes mellitus in such an association will be discussed.

Autoimmune endocrinopathy associated with diabetes insipidus

PubMed Central

Bhan, G. L.; O'Brien, T. D.

1982-01-01

A case is described in which diabetes insipidus was associated with hypopituitarism, insulin-independent diabetes mellitus, pernicious anaemia and circulating antibodies to the thyroid gland, adrenal gland and the pancreatic islet cells. PMID:7100039

Diabetes Insipidus: A Challenging Diagnosis with New Drug Therapies

PubMed Central

Saifan, Chadi; Nasr, Rabih; Mehta, Suchita; Sharma Acharya, Pranab; Perrera, Isera; Faddoul, Giovanni; Nalluri, Nikhil; Kesavan, Mayurakhan; Azzi, Yorg; El-Sayegh, Suzanne

2013-01-01

Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems. PMID:24977135

ADIPSIC DIABETES INSIPIDUS: A REVIEW.

PubMed

Eisenberg, Yuval; Frohman, Lawrence A

2016-01-01

Adipsic diabetes insipidus (ADI) is a rare disorder consisting of central diabetes insipidus (CDI) and a deficient or absent thirst response to hyperosmolality. Patients with ADI experience marked morbidity and mortality. Diagnosis and management of these patients is quite challenging, even in expert hands. In this review, we aim to provide an updated overview of this difficult clinical scenario. We conducted a PubMed search for articles related to ADI. The search terms "adipsia," "adipsic," "thirst," and "diabetes insipidus" were used to identify relevant literature. ADI has been described in only approximately 100 patients. This rarity has limited the quality and quantity of literature to case reports, case series, and expert opinion. Diagnosis focuses on confirmation of CDI followed by documenting subnormal or completely absent thirst in response to a hypertonic stimulus. Among the described patients with ADI, the majority experience morbidity (e.g., severe hypernatremia, sleep apnea, venous thromboembolism [VTE], and obesity) and an increased mortality risk. Management focuses on frequent reassessment of daily prescribed water intake with fixed antidiuretic therapy (desmopressin) and comorbidity screening. The complexity of patients with ADI provides a difficult challenge for clinicians. Prompt recognition of thirst disorders in patients with CDI should lead to appropriately regimented management strategies and can result in safe outpatient care for these unique patients.

The Value of Urine Specific Gravity in Detecting Diabetes Insipidus in a Patient with Uncontrolled Diabetes Mellitus

PubMed Central

Akarsu, Ersin; Buyukhatipoglu, Hakan; Aktaran, Sebnem; Geyik, Ramazan

2006-01-01

When a patient with diabetes mellitus presents with worsening polyuria and polydipsia, what is a sensible, cost-effective approach? We report the unique coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old woman with poorly controlled type 2 diabetes complained of polyuria with a daily output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes insipidus was suspected owing to a low urine specific gravity (1.008). The low specific gravity persisted during a water deprivation test. Ultimately, diabetes insipidus was confirmed when urine specific gravity and urine osmolality normalized following desmopressin administration. This case emphasizes the importance of accurately interpreting the urine specific gravity in patients with polyuria and diabetes mellitus to detect diabetes insipidus. PMID:17026722

Recurrent pregnancy-induced diabetes insipidus in a woman with hemochromatosis.

PubMed

Krysiak, Robert; Kobielusz-Gembala, Iwona; Okopien, Boguslaw

2010-01-01

Diabetes insipidus is a rare disorder in pregnant women, predating pregnancy or appearing for the first time during gestation. In pregnancy it usually affects women with HELLP syndrome or acute fatty liver of pregnancy and results from the reduced hepatic degradation of placental vasopressinase leading to its increased activity. Although infiltrative diseases have been found to cause diabetes insipidus in non-pregnant population, very few studies showed that these disorders may manifest for the first time during gestation. We describe here the case of transient diabetes insipidus in two subsequent pregnancies of a female with hemochromatosis. The first symptoms of this disease appeared for the first time at the beginning of the third trimester of her second pregnancy, and diagnosis was established on the basis of typical clinical presentation, confirmed by a water deprivation test. Diabetes insipidus resulted from the increased activity of vasopressinase, caused by hemochromatosis-induced liver dysfunction, the presence of which was confirmed between the pregnancies by liver biopsy and identification of the HFE gene mutation. Subsequent desferrioxamine treatment resulted in a less severe clinical course of diabetes insipidus in the last patient's pregnancy. In both pregnancies, the patient was successfully treated with oral desmopressin, which is resistant to degradation by placental vasopressinase. Although unrecognized pituitary disorders may pose a serious health problem to the mother and fetus, hemochromatosis-induced diabetes insipidus, as the case of our patient demonstrates, if effectively diagnosed and treated, cannot be regarded as a contraindication for pregnancy.

Gestational Diabetes Insipidus Associated with HELLP Syndrome: A Case Report

PubMed Central

Gambito, Renela; Chan, Michael; Sheta, Mohamed; Ramirez-Arao, Precious; Gurm, Harmeet; Tunkel, Allan; Nivera, Noel

2012-01-01

Gestational diabetes insipidus is a rare, but well recognized, complication of pregnancy. It is related to excess vasopressinase enzyme activity which is metabolized in the liver. A high index of suspicion of gestational diabetes insipidus is required in a correct clinical setting especially in the presence of other risk factors such as preeclampsia, HELLP syndrome, and twin pregnancies. We are presenting a case of gestational diabetes insipidus in a patient with HELLP syndrome. The newborn in this case also had hypernatremia thereby raising possibilities of vasopressinase crossing the placenta. PMID:24555139

Korsakoff's psychosis due to massive beer intake provoked by diabetes insipidus.

PubMed

Farr, R W; Blankenship, D C; Viti, A; Albrink, M J

1988-05-01

Posttraumatic diabetes insipidus, acute pancreatitis, and Wernicke's encephalopathy and Korsakoff's psychosis in a 33-year-old white male alcohol abuser resulted in near-fatal cardiovascular collapse. The Wernicke's encephalopathy and Korsakoff's psychosis resulted from drinking massive quantities of beer to satisfy the thirst induced by diabetes insipidus. Although the diabetes insipidus was controlled with vasopressin, and the need for vasopressin resolved two months after diagnosis, the Wernicke-Korsakoff syndrome had not resolved by six months.

Vasopressin function in familial cranial diabetes insipidus.

PubMed Central

Baylis, P. H.; Robertson, G. L.

1981-01-01

A family suffering from cranial diabetes insipidus, that extends over 4 generations, is described. Inheritance of polyuria was autosomal dominant. Vasopressin function was studied in members of the last 2 generations, 4 of whom had polyuria. Osmoregulation of vasopressin secretion was assessed by infusion of hypertonic saline. Plasma vasopressin remained undetectable in one patient, while 2 others had very blunted vasopressin responses to osmotic stimulation. Three non-osmotic stimuli were applied. Controlled hypotension produced by trimetaphan infusion and insulin-induced hypoglycaemia did not increase plasma vasopressin but apomorphine-induced nausea caused a minimal rise in plasma vasopressin to 0.7 pg/ml. Polyuria and thirst resolved with antidiuretic therapy in all patients studied. Congenital absence of vasopressin as in Brattleboro rats is unlikely to account for diabetes insipidus in this disorder since small increases in vasopressin have been demonstrated in these patients. In view of previous post-mortem findings, familial cranial diabetes insipidus is most likely to be due to degeneration of vasopressin-synthesizing neurones. PMID:7279821

Current perspective on the pathogenesis of central diabetes insipidus.

PubMed

Ghirardello, Stefano; Malattia, Clara; Scagnelli, Paola; Maghnie, Mohamad

2005-07-01

Diabetes insipidus is a heterogeneous condition characterised by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. The clinical and laboratory diagnosis is confirmed by standard tests, but recent advances in molecular biology and imaging techniques have shed new light on the pathophysiology of this disease. In many patients, central diabetes insipidus is caused by a germinoma or craniopharyngioma; Langerhans' cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma from surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Tumour-associated central diabetes insipidus is uncommon in children younger than 5 years old. Biopsy of enlarged pituitary stalk should be reserved for patients with hypothalamic-pituitary mass and progressive thickening of the pituitary stalk since spontaneous recovery may occur. Molecular biology in selected patients may identify those with apparently idiopathic diabetes insipidus carrying the vasopressin-neurophysin II gene mutation.

Molecular biology of hereditary diabetes insipidus.

PubMed

Fujiwara, T Mary; Bichet, Daniel G

2005-10-01

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

Use of acetazolamide in lithium-induced nephrogenic diabetes insipidus: a case report.

PubMed

Macau, Ricardo A; da Silva, Tiago Nunes; Silva, Joana Rego; Ferreira, Ana Gonçalves; Bravo, Pedro

2018-01-01

Lithium-induced nephrogenic diabetes insipidus (Li-NDI) is a rare and difficult-to-treat condition. A study in mice and two recent papers describe the use of acetazolamide in Li-NDI in 7 patients (a case report and a 6 patient series). We describe the case of a 63-year-old woman with bipolar disorder treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to a bowel obstruction and developed severe dehydration after surgery when she was water deprived. After desmopressin administration and unsuccessful thiazide and amiloride treatment, acetazolamide was administrated to control polyuria and hydroelectrolytic disorders without significant side effects. To our knowledge, this is the third publication on acetazolamide use in Li-NDI patients. Treatment of lithium-induced nephrogenic diabetes insipidus might be challenging.Vasopressin, amiloride and thiazide diuretics have been used in lithium-induced nephrogenic diabetes insipidus treatment.Acetazolamide might be an option to treat lithium-induced nephrogenic diabetes insipidus patients who fail to respond to standard treatment.The use of acetazolamide in lithium-induced nephrogenic diabetes insipidus must be monitored, including its effects on glomerular filtration rate.

A vasopressin analogue in treatment of diabetes insipidus

PubMed Central

Kauli, Rivka; Laron, Zvi

1974-01-01

Six children, 3 adolescents, and 3 adults with vasopressin-sensitive diabetes insipidus were treated with a vasopressin analogue, DDAVP (1-deamino-8-D-arginine vasopressin), at a daily dose ranging from 5 to 20 μg administered twice a day intranasally. The period of follow-up of these patients has been from 3 months to 1 year. DDAVP was effective in maintaining normal diuresis and normal urine concentration during both day and night. No local or vasopressor side effects were observed. Compared to other antidiuretic drugs, such as nasal pitressin powder, lysine-vasopressin nasal spray, or pitressin tannate injections, used previously by the patients, DDAVP proved to be superior in the control of the diabetes insipidus and in the subjective feeling of the patients. It is concluded that DDAVP is the drug of choice in the treatment of vasopressinsensitive diabetes insipidus. PMID:4850356

Genetics and diagnosis of central diabetes insipidus.

PubMed

Bichet, Daniel G

2012-04-01

Most of the central diabetes insipidus cases seen in general practice are acquired but the rare cases of hereditary autosomal dominant or recessive neurohypophyseal diabetes insipidus have provided further cellular understanding of the mechanisms responsible for pre-hormone folding, maturation and release. Autosomal dominant central diabetes insipidus is secondary to the toxic accumulation of vasopressin mutants as fibrillar aggregates in the endoplasmic reticulum of hypothalamic magnocellular neurons producing vasopressin. As well, Trpv1(-/-) and Trpv4(-/-) mice have shed new light on the perception of tonicity through the stretch receptors TRPVs expressed both in central and peripheral neurons. The genomic information provided by sequencing the AVP gene is key to the routine care of these patients and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families. In addition, simple, inexpensive blood and urine measurements together with clinical characteristics and brain magnetic resonance imaging (MRI) could distinguish between central, nephrogenic and polydipsic cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Combined central diabetes insipidus and cerebral salt wasting syndrome in children.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong

2009-02-01

Central diabetes insipidus, a common consequence of acute central nervous system injury, causes hypernatremia; cerebral salt wasting syndrome can cause hyponatremia. The two conditions occurring simultaneous are rarely described in pediatric patients. Pediatric cases of combined diabetes insipidus and cerebral salt wasting after acute central nervous system injury between January 2000 and December 2007 were retrospectively reviewed, and clinical characteristics were systemically assessed. Sixteen patients, aged 3 months to 18 years, met study criteria: 11 girls and 5 boys. The most common etiologies were severe central nervous system infection (n = 7, 44%) and hypoxic-ischemic event (n = 4, 25%). In 15 patients, diabetes insipidus was diagnosed during the first 3 days after acute central nervous system injury. Onset of cerebral salt wasting syndrome occurred 2-8 days after the onset of diabetes insipidus. In terms of outcome, 13 patients died (81%) and 3 survived under vegetative status (19%). Central diabetes insipidus and cerebral salt wasting syndrome may occur after acute central nervous system injury. A combination of both may impede accurate diagnosis. Proper differential diagnoses are critical, because the treatment strategy for each entity is different.

Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

PubMed

Uwumugambi, Nsabimana A; Sanchorawala, Vaishali; Shelton, Anthony C; Stern, Lauren; Gordon, Craig E

2017-02-01

Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[Germinoma responsible for central diabetes insipidus].

PubMed

Bakoto, N; Strivay, M

2009-01-01

We report the case of a 20-year-old woman who presented with sudden onset of polydipsia and polyuria. A diagnosis of diabetes insipidus was confirmed and the MRI showed a pituitary stalk enlargement. The patient was treated with Minirin. Two years later, she developed a panhypopituitarism. The MRI showed an intrasellar mass with an enlargement of the pituitary gland. A biopsy confirmed a germinoma. The patient was treated with radiotherapy with a partial response as only a part of the mass disappeared. This case highlights the importance of the clinical and radiological follow-up of central diabetes insipidus, especially when it is of unknown origin. The differential diagnosis will be reviewed.

Diabetes insipidus following resection of pituitary tumors.

PubMed

Schreckinger, Matthew; Szerlip, Nicholas; Mittal, Sandeep

2013-02-01

Diabetes insipidus (DI) is a common complication following pituitary surgery and can be transient or permanent. Neurogenic DI occurs following injury to the magnocellular neurons in the hypothalamus that produce and transport arginine vasopressin (AVP) and form the hypothalamo-hypophyseal tract. DI is defined by a constellation of signs and symptoms resulting in dilute high-volume urine output and increasing serum osmolality. The body's inability to concentrate urine leaves the patient dehydrated and leads to metabolic abnormalities that can be life threatening if not recognized and treated in a timely manner with an exogenous AVP analog. The reported incidence of postsurgical central DI varies from 1 to 67%. This wide range likely reflects inconsistencies in the working definition of DI across the literature. Factors affecting the rate of DI include pituitary tumor size, adherence to surrounding structures, surgical approach, and histopathology of pituitary lesion. The likelihood of postoperative DI can be reduced by careful preservation of the neurovascular structures of the hypothalamus, infundibulum, and neurohypophysis. Vigilance and meticulous surgical technique are essential to minimize injury to these critical regions that can lead to postsurgical DI. Copyright © 2012 Elsevier B.V. All rights reserved.

The syndrome of diabetes insipidus, diabetes mellitus and optic atrophy (DIDMOA) with diabetic cheiroarthropathy

PubMed Central

FitzGerald, G. A.; Greally, J. F.; Drury, M. I.

1978-01-01

Two sisters with diabetes mellitus and optic atrophy are described. One of them also has vasopressin responsive diabetes insipidus. Both have diabetic cheiroarthropathy, an unusual deformity of the hands. ImagesFig. 1

Oxcarbazepine Therapy for Complete Central Diabetes Insipidus.

PubMed

Abdallah, Basmah; Hodgins, Spencer; Landry, Daniel; O'shea, Michael; Braden, Gregory

2018-01-01

Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We describe a patient with complete central diabetes insipidus and seizures who developed worsening hyponatremia when her dose of oxcarbazepine was increased. The patient maintained a normal serum sodium level and has had appropriately concentrated urine for 5 years on just oxcarbazepine, despite undetectable antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of its metabolites) may stimulate collecting tubule V2 receptor-G protein complex independent of ADH, resulting in increased renal tubular water reabsorption. Oxcarbazepine may be useful as an alternative therapy for patients with central diabetes insipidus.

Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus.

PubMed

Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

2015-01-01

Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness.

Manifestation of Central Diabetes Insipidus in a Patient with Thyroid Storm.

PubMed

Nakamichi, Akiko; Ocho, Kazuki; Oka, Kosuke; Yasuda, Miho; Hasegawa, Kou; Iwamuro, Masaya; Obika, Mikako; Rai, Kammei; Otsuka, Fumio

2018-02-28

We herein report a case of central diabetes insipidus complicated with thyroid storm. A middle-aged woman who was receiving treatment for Graves' disease suddenly complained of polydipsia, polyuria and general fatigue. Laboratory tests showed hyperthyroidism, hypernatremia, hypoosmolar urine and a decreased plasma vasopressin level. The occurrence of central diabetes insipidus with hyperthyroidism was revealed on the basis of pituitary magnetic resonance imaging, a water deprivation test and a desmopressin test. The clinical co-existence of diabetes insipidus and hyperthyroidism is very rare; however, the complication should be considered when hypernatremia and/or dehydration progress in patients with Graves's disease as a common autoimmune-related etiology.

Genetics Home Reference: neurohypophyseal diabetes insipidus

MedlinePlus

... G, Colao A. Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin- ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Incidence of Diabetes Insipidus in Postoperative Period among the Patients Undergoing Pituitary Tumour Surgery.

PubMed

Kadir, M L; Islam, M T; Hossain, M M; Sultana, S; Nasrin, R; Hossain, M M

2017-07-01

Post operative complications after pituitary tumour surgery vary according to procedure. There are several surgical procedures being done such as transcranial, transsphenoidal microsurgical and transsphenoidal endoscopic approaches. One of the commonest complications is diabetes insipidus (DI). Our main objective was to find out the incidence of diabetes insipidus in post operative period among patients undergoing surgical intervention for pituitary tumour in our institute. The presence of diabetes insipidus in the postoperative period was established by measuring serum Na+ concentration, hourly urine output and urinary specific gravity to find out the incidence of diabetes insipidus in postoperative period in relation to age, gender, tumour diameter, function of tumour (i.e., either hormone secreting or not) and operative procedure used for surgical resection of pituitary tumor. As it is the most common postoperative complication so, in this study we tried to find out how many of the patients develop diabetes insipidus in postoperative period following surgical resection of pituitary tumour. This cross sectional type of observational study was carried out in the department of Neurosurgery, BSMMU from May 2014 to October 2015 on 33 consecutive patients who underwent surgical intervention for pituitary tumour for the first time. Data was collected by using a data collection sheet. The incidence of diabetes insipidus was found 23.1% of patients in <30 year age group, 38.5% of patients in 31-40 year age group and 38.5% of patients in ≥40 year age group (p=0.764). In case of distribution of patients according to gender 38.5% of male and 61.5% of female developed diabetes insipidus (p=0.073). Regarding tumour size 30.8% and 69.2% of patients developed diabetes insipidus having tumour diameter <30mm and ≥30mm respectively (p=0.590). In case of operative procedure 69.2% of patients developed diabetes insipidus who was operated by transsphenoidal endoscopic approach

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

PubMed

Hannon, M J; Orr, C; Moran, C; Behan, L A; Agha, A; Ball, S G; Thompson, C J

2012-05-01

Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology. © 2012 Blackwell Publishing Ltd.

Diabetes insipidus secondary to sarcoidosis presenting with caseating granuloma

PubMed Central

Alam, Taimour; Thomas, Steven

2011-01-01

Diabetes insipidus is a rare complication of sarcoid infiltration of the hypothalamic-pituitary region. Non-caseating granuloma formation is typical of sarcoidosis. Anterior and posterior pituitary function may be affected. MRI coupled with endocrinology assessment is the usual method of investigation. A 25-year-old Caucasian male with no significant medical history presented with polyuria and polydipsia. Water deprivation test confirmed diabetes insipidus. CT scanning of the chest confirmed lymphadenopathy. Lymph node biopsy revealed caseating granuloma. Extensive investigation for tuberculosis was negative. The patient was started on intranasal desmopressin and steroids with marked improvement in symptoms. This is the first reported case of neurosarcoidosis with diabetes insipidus and caseation on histology that we are aware of. Differentiating between caseation due to sarcoidosis and tuberculosis on histology is possible by the use of special stains. Return of normal endocrine function is unusual and the patient is likely to require desmopressin therapy for life. PMID:22707619

Association of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The Wolfram or DIDMOAD syndrome.

PubMed Central

Najjar, S S; Saikaly, M G; Zaytoun, G M; Abdelnoor, A

1985-01-01

Seven patients with a rare syndrome of diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), neurosensory deafness (D), atony of the urinary tract, and other abnormalities (Wolfram or DIDMOAD syndrome) are reported. Of the seven patients, three siblings were followed up for 10-17 years. All seven patients had diabetes mellitus and optic atrophy; six had diabetes insipidus; and in the four patients investigated there was dilatation of the urinary tract. The severity of diabetes varied, and all required insulin for control of the hyperglycaemia. In one patient the course of the disease simulated maturity onset diabetes of the young; another presented with ketoacidosis; but none had haplotypes usually associated with insulin dependent diabetes mellitus. The diabetes insipidus responded to chlorpropamide, suggesting partial antidiuretic hormone deficiency. Onset of optic atrophy and loss of vision occurred relatively late and progressed slowly, although in one patient there was a rapid deterioration in visual acuity. Deafness was mild, of late onset, and of sensorineural origin. A degenerative process affecting the central and peripheral nervous system can explain all the manifestations of the syndrome except diabetes mellitus. The pathogenesis of the diabetes mellitus remains obscure. PMID:4051539

Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus.

PubMed Central

Azam, H.; Newton, R. W.; Morris, A. D.; Thompson, C. J.

1998-01-01

A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration. PMID:9538487

Pulmonary Langerhans cell histiocytosis and diabetes insipidus in pregnant women: our experience.

PubMed

Fuks, Leonardo; Kramer, Mordechai R; Shitrit, David; Raviv, Yael

2014-04-01

Pulmonary Langerhans cell histiocytosis (PLCH) occurs predominantly in young adult smokers. Diabetes insipidus occurs in up to 15 % patients with PLCH. Information on PLCH in pregnancy is sparse, especially associated with diabetes insipidus. We report three patients with these conditions and describe the disease history and pregnancy outcomes.

DDAVP in Treatment of Vasopressin-Sensitive Diabetes Insipidus

PubMed Central

Ward, M. K.; Fraser, T. Russell

1974-01-01

In 11 patients with vasopressin-sensitive diabetes insipidus the effectiveness of the vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) for controlling diabetes insipidus has been compared with that of lysine vasopressin. DDAVP in equivalent intravenous dosage has been found to be at least as potent and to have a more prolonged action, lasting 13-22 hours instead of 1-2 hours. Twice-daily intranasal DDAVP effected satisfactory control in all these patients, without side effects, and all the patients preferred this to their previous treatment. Single daily intramuscular injections of DDAVP were found to offer excellent control for any subject unable to manage intranasal administration. PMID:4851464

Vasopressin Analogue DDAVP in Diabetes Insipidus: Clinical and Laboratory Studies

PubMed Central

Edwards, C. R. W.; Kitau, M. J.; Chard, T.; Besser, G. M.

1973-01-01

In seven patients with cranial diabetes insipidus an analogue of vasopressin, DDAVP, produced an antidiuresis lasting up to 20 hours after a single intranasal dose. Lysine vasopressin (LVP) in the same dose produced a less potent antidiuresis which lasted for only three to four hours. The plasma half life of DDAVP was 7·8 and 75·5 min for the fast and slow phases, compared with 2·5 and 14·5 min for LVP. Radioiodine-labelled DDAVP was not destroyed by incubation with late pregnancy plasma, which contains an enzyme that inactivates vasopressin. The slow metabolic clearance of DDAVP, its absorption through the nasal mucosa, and its lack of side effects make this the ideal drug for the treatment of vasopressin-sensitive diabetes insipidus. Patients usually require 10 to 20 μg DDAVP given intranasally twice daily for good clinical control of their diabetes insipidus. PMID:4581079

Diabetes insipidus-like state complicating percutaneous transluminal renal stenting for transplant renal artery stenosis.

PubMed

Tian, Lu; He, Yangyan; Zhang, Hongkun; Wu, Ziheng; Li, Donglin; Chen, Shanwen

2014-07-01

To report the incidence, etiology, and treatments of diabetes insipidus-like state that complicate percutaneous transluminal renal stenting (PTRS) for transplant renal artery stenosis (TRAS). Data from 7 patients on whom PTRS for TRAS was performed between October 2008 and March 2012 were reviewed retrospectively. The parameters investigated included blood flow velocity, blood pressure, and creatinine levels before and after the intervention. The procedural success rate was 100%. Three cases developed a diabetes insipidus-like state in the immediate postprocedural period. Urine output returned to normal within 2 weeks after treatment. The median blood flow velocity was significantly reduced from 4.51 m/sec (4.31-4.61 m/sec) at the time of TRAS diagnosis to 1.33 m/sec (1.31-1.51 m/sec) at the most recent follow-up of the group with a diabetes insipidus-like state. The ratio of median blood flow velocity before and after stenting in the group with a diabetes insipidus-like state was significantly higher than that in the group without a diabetes insipidus-like state (3.39 vs. 1.93). Diabetes insipidus-like state that complicates PTRS for TRAS is not an uncommon event, but appears to be underreported in the medical literature. A high ratio of pre- and poststenting median blood flow velocity may be a predictor for a postprocedural diabetes insipidus-like state. The most probable cause may be the marked increase in renal arterial flow. Early recognition of the condition is essential to avoid dehydration and electrolyte imbalance. Copyright © 2014 Elsevier Inc. All rights reserved.

Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.

PubMed

Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K

2010-08-01

Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.

[Granulomatosis with polyangiitis manifested as diabetes insipidus].

PubMed

Pátek, Ondřej; Horáčková, Miroslava; Vítová, Lenka; Horváth, Rudolf; Háček, Jaromír; Schück, Otto

The case report shows a surprising presentation of pulmonary granulomatosis with polyangiitis (GPA) through symptoms of diabetes insipidus (DI) with granulomatous infiltration of the pituitary gland. The pituitary hormonal dysfunction as a result of granulomatosis of the pituitary gland is rare. Several studies have demonstrated that the incidence of the pituitary dysfunction reaches approx. 1 % of the patients with GPA. However it is mostly presented in patients with the disease already diagnosed. The patient described by us had no clinical expressions of GPA in the respiratory tract. He presented with polyuria and polydipsia. It was not until a more detailed examination of these symptoms was performed that a focal lung disease was detected and diagnosed as GPA. diabetes insipidus - granulomatosis with polyangiitis - granulomatous infiltration of the pituitary gland - pituitary hormonal dysfunction.

Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis.

PubMed

Karadag, Ahmet; Erdeve, Omer; Atasay, Begum; Arsan, Saadet; Deda, Gulhis; Ince, Erdal; Ocal, Gonul; Berberoglu, Merih

2006-02-01

We present a 5 day-old male newborn with isolated central diabetes insipidus due to congenital toxoplasmosis. This patient was referred to us for hydrocephalus. As we investigated the aetiology of the hydrocephalus, the patient's serum and cerebrospinal fluid tested positive for toxoplasmosis via ELISA and polymerase chain reaction. Computed tomography showed obstructive hydrocephalus and disseminated cranial calcifications. Central diabetes insipidus developed on the 10th day, apparently as a result of the toxoplasmosis infection, and was treated successfully with oral desmopressin.

The value of urine specific gravity in detecting diabetes insipidus in a patient with uncontrolled diabetes mellitus: urine specific gravity in differential diagnosis.

PubMed

Akarsu, Ersin; Buyukhatipoglu, Hakan; Aktaran, Sebnem; Geyik, Ramazan

2006-11-01

When a patient with diabetes mellitus presents with worsening polyuria and polydipsia, what is a sensible, cost-effective approach? We report the unique coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old woman with poorly controlled type 2 diabetes complained of polyuria with a daily output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes insipidus was suspected owing to a low urine specific gravity (1.008). The low specific gravity persisted during a water deprivation test. Ultimately, diabetes insipidus was confirmed when urine specific gravity and urine osmolality normalized following desmopressin administration. This case emphasizes the importance of accurately interpreting the urine specific gravity in patients with polyuria and diabetes mellitus to detect diabetes insipidus.

Continuous vasopressin replacement in diabetes insipidus.

PubMed Central

Ralston, C; Butt, W

1990-01-01

Five children who developed diabetes insipidus as a manifestation of severe brain injury received continuous intravenous treatment with a solution containing both aqueous vasopressin and appropriate crystalloid replacement. Polyuria, hypernatraemia, and decreased urine osmolalities were safely corrected in all patients within eight to 28 hours. PMID:2400231

Suprasellar ganglioglioma presenting with diabetes insipidus in a young boy: a rare clinical presentation.

PubMed

Gupta, Ruchika; Suri, Vaishali; Arora, Raman; Sharma, Mehar C; Mishra, Shashwat; Singh, Manmohan; Sarkar, Chitra

2010-02-01

Gangliogliomas are rare tumors composed of an admixture of glial and neuronal components. These usually occur in young patients, who present with therapy-resistant seizures. Clinical presentation of ganglioglioma with diabetes insipidus is extremely rare with only one case reported earlier in the available literature. Due to this rarity, ganglioglioma is not considered in the differential diagnosis in a patient with diabetes insipidus. A 7-year boy presented with polyuria, polydipsia, and progressive visual loss for 18 months. Investigations revealed diabetes insipidus. Radiographic studies of the brain showed a solid and cystic mass in the suprasellar region effacing the third ventricle. Intraoperatively, diffuse thickening of bilateral optic nerves and optic chiasma was noted and a diagnosis of optic glioma was considered. A biopsy of the mass was taken, which on histopathological examination showed features of ganglioglioma. The patient was referred for further radiotherapy but was lost to follow-up. Diabetes insipidus as a presenting symptom of ganglioglioma is extremely rare. This benign tumor should be kept in mind in patients with central diabetes insipidus and a suprasellar mass lesion. This report describes the second such case in the literature.

Genetic forms of neurohypophyseal diabetes insipidus.

PubMed

Rutishauser, Jonas; Spiess, Martin; Kopp, Peter

2016-03-01

Neurohypophyseal diabetes insipidus is characterized by polyuria and polydipsia owing to partial or complete deficiency of the antidiuretic hormone, arginine vasopressin (AVP). Although in most patients non-hereditary causes underlie the disorder, genetic forms have long been recognized and studied both in vivo and in vitro. In most affected families, the disease is transmitted in an autosomal dominant manner, whereas autosomal recessive forms are much less frequent. Both phenotypes can be caused by mutations in the vasopressin-neurophysin II (AVP) gene. In transfected cells expressing dominant mutations, the mutated hormone precursor is retained in the endoplasmic reticulum, where it forms fibrillar aggregates. Autopsy studies in humans and a murine knock-in model suggest that the dominant phenotype results from toxicity to vasopressinergic neurons, but the mechanisms leading to cell death remain unclear. Recessive transmission results from AVP with reduced biologic activity or the deletion of the locus. Genetic neurohypophyseal diabetes insipidus occurring in the context of diabetes mellitus, optic atrophy, and deafness is termed DIDMOAD or Wolfram syndrome, a genetically and phenotypically heterogeneous autosomal recessive disorder caused by mutations in the wolframin (WFS 1) gene. Copyright © 2016 Elsevier Ltd. All rights reserved.

A history of diabetes insipidus: paving the road to internal water balance.

PubMed

Eknoyan, Garabed

2010-12-01

Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive term for polyuria, which was unrecognized even after the sweetness of urine was reported as a characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its increased recognition, pathologic observations and experimental studies connected diabetes insipidus to the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As vasopressin was purified and synthesized and its assay became available, it was shown to be released in response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers has led to their increasing use in managing hypo-osmolar states. Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[Clinical characteristics of 7 patients with gestational diabetes insipidus].

PubMed

Wu, Li-Qun; Xiong, Chun-Qiu; Wu, Min; Dong, Ruo-Lin; Chen, Yun-Qin; Gao, Jie; Chen, Ou-Jing; Huang, Yin-Ping

2008-04-01

To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus. A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively. Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth. Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium

Diabetes insipidus in children.

PubMed

Jain, Vandana; Ravindranath, Aathira

2016-01-01

Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to negotiate its actions on the renal collecting tubules through aquaporins. The diagnostic algorithm starts with exclusion of other causes of polyuria and establishing low urine osmolality in the presence of high serum osmolality. In this paper, we have reviewed the diagnosis, etiology and management of DI in children, with special emphasis on recent advances in the field.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus.

PubMed

Leem, Ah Young; Kim, Han Sang; Yoo, Byung Woo; Kang, Beo Deul; Kim, Min Hwan; Rha, Sun Young; Kim, Hyo Song

2014-03-01

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m(2), a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.

PubMed

Behl, Tapan; Kotwani, Anita; Kaur, Ishneet; Goel, Heena

2015-05-15

Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body. Copyright © 2015 Elsevier B.V. All rights reserved.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus

PubMed Central

Leem, Ah Young; Kim, Han Sang; Yoo, Byung Woo; Kang, Beo Deul; Kim, Min Hwan; Rha, Sun Young

2014-01-01

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication. PMID:24648810

Mice deficient for ERAD machinery component Sel1L develop central diabetes insipidus.

PubMed

Bichet, Daniel G; Lussier, Yoann

2017-10-02

Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

Temporary diabetes insipidus in 2 men after on-pump coronary artery bypass grafting.

PubMed

Uyar, Ihsan Sami; Sahin, Veysel; Akpinar, Besir; Yurtman, Volkan; Abacilar, Feyzi; Okur, Faik Fevzi; Ates, Mehmet

2013-01-01

Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.

Oral Therapy of Diabetes Insipidus with Chlorpropamide

PubMed Central

Cushard, William G.; Beauchamp, Charles J.; Martin, Neil D.

1971-01-01

Chlorpropamide was found to be an effective antidiuretic agent in vasopressin-sensitive diabetes insipidus. Full clinical use of this action is limited by the frequent occurrence of hypoglycemia on higher doses. This complication can be avoided, however, by restricting the dose and by employing combination therapy with hydrochlorothiazide. PMID:5563815

[Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

PubMed

Krysiak, Robert; Okopień, Bogusław

2015-01-01

Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

V2R structure and diabetes insipidus.

PubMed

Birnbaumer, Mariel

2002-01-01

For most audiences, the term "diabetes" conjures thoughts of high levels of blood glucose and of the symptoms that characterize diabetes mellitus. In the last few years, a spirited campaign spear-headed by the families of affected individuals has made progress in educating nonprofessional and medical communities about diabetes insipidus (DI), the other disease characterized by polyuria (i.e., diabetes). Much work lies ahead to find better treatments for this affliction, but the progress in molecular biology over the last years made possible the identification of the genetic defects underlying the inherited forms of the disease. Numerous cases of adult-onset DI are triggered by toxic damage to the kidneys that impairs the concentrating capacity of the nephrons by a nonspecific mechanism. In these pages I shall deal mostly with the inherited forms of the disease. Diabetes insipidus is characterized by the inability of the kidneys of affected individuals to produce concentrated urine (Morello and Bichet 2001). The elimination of large volumes of diluted urine (polyuria) and excessive thirst (polydipsia) are the chief symptoms of the disease. Although this condition and the hints that it was a hereditary disease were described at the end of the 19th century, it took almost 100 years to gain molecular knowledge about its etiology. A brief review of the important role played by vasopressin in the maintenance of body fluids will help the reader understand the severity of this disease.

Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

PubMed

Scheinpflug, K; Schalk, E; Reschke, K; Franke, A; Mohren, M

2006-01-01

The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

Genoa Syndrome and Central Diabetes Insipidus: A Case Report

PubMed Central

Şıklar, Zeynep; Erdeve, Şenay Savaş; Berberoğlu, Merih; Deda, Gülhiz; Tıraş, Serap Teber; Fitöz, Suat; Öçal, Gönül

2010-01-01

Genoa syndrome was first described by Camera et al in 1993 in two patients with semilobar holoprosencephaly (HPE), craniosynostosis and abnormal small hands with cone−shaped epiphyses and hypoplastic terminal phalanges of fingers (OMIM: 601370). In 2001, Lapunzina et al reported a case of craniosynostosis and HPE associated with several other malformations and suggested that these findings could be attributed to a severe form of Genoa syndrome or to a newly recognized syndrome. Endocrinopathies in association with HPE are frequently reported in the literature. Diabetes insipidus, hypothyroidism, hypocortisolism, and growth hormone deficiency are frequently associated with HPE. We here report a case of semilobar HPE, craniosynostosis and cleft lip/palate, possibly a case of Genoa syndrome, associated with central diabetes insipidus. Conflict of interest:None declared. PMID:21274346

A non-invasive test for receptor binding applied to nephrogenic diabetes insipidus.

PubMed Central

Britton, K. E.; Tedder, R. S.; Khokhar, A. M.; Brown, N. J.; Davison, A.; Slater, J. D.

1977-01-01

Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids. PMID:196275

Newly developed central diabetes insipidus following kidney transplantation: a case report.

PubMed

Kim, K M; Kim, S M; Lee, J; Lee, S Y; Kwon, S K; Kim, H-Y

2013-09-01

Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

PubMed

Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae; Kim, Sang-Ha

2015-10-01

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report

PubMed Central

Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae

2015-01-01

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus. PMID:26508947

Diabetes insipidus as a rare cause of acute cognitive impairment in multiple sclerosis.

PubMed

Tiedje, V; Schlamann, M; Führer, D; Moeller, L C

2013-10-01

Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

Adipsic diabetes insipidus in adult patients.

PubMed

Cuesta, Martín; Hannon, Mark J; Thompson, Christopher J

2017-06-01

Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI. A literature search was performed to review the background, etiology, management and associated complications of this rare condition. ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI. The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

Monostotic Langerhans' cell histiocytosis in a child with central diabetes insipidus.

PubMed

Soares, Eduardo Costa Studart; Quidute, Ana Rosa Pinto; Costa, Fábio Wildson Gurgel; Gurgel, Maria Helane Costa; Alves, Ana Paula Negreiros Nunes; Fonteles, Cristiane Sá Roriz

2012-01-01

Langerhans'cell histiocytosis (LCH) comprises a rare group of reticuloendothelial system disorders that can produce focal or systemic manifestations. Diabetes insipidus is considered to be an important indicator of serious underlying diseases in children, including LCH. We report the case of a young patient with monostotic LCH confined to the mandibular ramus, who was diagnosed with the disease after presenting symptoms of central diabetes insipidus and was satisfactorily treated with multi-agent chemotherapy. Additionally, we discuss the clinical, radiographic, histological and immunohistochemical findings, as well as the multidisciplinary approach of this important disease, which should receive attention by dental practitioners, especially when it occurs in children.

[Treatment with sublingual desmopressin in two infants with hydranencephaly and central diabetes insipidus].

PubMed

Marín, Gustavo R; Baspineiro, Berta; Vilca, Iris

2018-02-01

Central diabetes insipidus is a rare disease in children caused by a deficiency of vasopressin. Its main clinical manifestations are polyuria and polydipsia. Brain malformations are one of the main causes. Desmopressin is the synthetic drug of choice for the treatment. One of the routes of administration is sublingual and its use in infants is very limited. We describe two infants with central diabetes insipidus and hydranencephaly who were successfully treated with sublingual desmopressin. Sociedad Argentina de Pediatría.

Control of sodium excretion in patients with cranial diabetes insipidus maintained on desamino-[8-D-arginine]vasopressin.

PubMed

Sutters, M; Brace, C; Hatfield, E; Whitehurst, A; Lightman, S L; Peart, W S

1993-11-01

1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus. 4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 +/- 1.5 to 73 +/- 1.2 versus from 71.7 +/- 1 to 73.2 +/- 1.1 milligrams). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus. 5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid. 6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical observation of 5 cases of diabetes insipidus complicated with skeletal fluorosis].

PubMed

Wang, Shuan-Chi; Tao, Xiao-Bing; Wang, Fang-Fang; Zhang, Nan

2017-07-25

To investigate the mechanism of diabetes insipidus complicated with skeletal fluorosis and the surgical treatment of spinal canal stenosis caused by skeletal fluorosis. From January 2000 to November 2011, 5 patients with diabetes insipidus complicated with skeletal fluorosis were treated with drug and cervical or thoracic posterior decompression including 2 males and 3 females with age of 35, 45, 47, 49, 55 years old respectively. The symptoms was mainly limb motor sensory disturbance accompanied by polyuria and polyuria. Imaging showed that cervical and thoracic multi-segmental continuous spinal stenosis. It was diagnosed with diabetes insipidus according to the symptoms and laboratory tests. According to the symptoms, the vertebral with problems were located and treated by posterior laminectomy decompression or the expansive open-door laminectomy. The recovery of neurological symptoms were recorded and the operation result were evaluate by JOA score improvement rate. The wound healed well in 5 cases, and 1 case of cervical axial pain was improved after symptomatic treatment. Five patients were followed up for 2 to 6 years with an average of 4 years. Numbness of limb and weakness symptoms of follow-up patients were significantly improved, muscle strength and acupuncture hypothyroidism were significantly improved compared with preoperative, the JOA score was significantly improved. At the final follow-up, the improvement rate got excellent results in 2 cases, good in 2 and fair in 1. Long-term high intake of fluoride can cause skeletal fluorosis in patients with diabetes insipidus. The posterior decompression is effective for the majority of spinal canal stenosis caused by skeletal fluorosis.

Diabetes Insipidus in Mice with a Mutation in Aquaporin-2

PubMed Central

Lloyd, David J; Hall, Frank Wesley; Tarantino, Lisa M; Gekakis, Nicholas

2005-01-01

Congenital nephrogenic diabetes insipidus (NDI) is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2) gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2) gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI. PMID:16121255

Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. 3 cases of 'DIDMOAD' syndrome.

PubMed Central

Richardson, J E; Hamilton, W

1977-01-01

Three children with diabetes insipidus, diabetes mellitus, optic atrophy, and high-tone deafness were shown to lack vasopressin, indicative of degeneration of the cells of the hypothalamic supraoptic nuclei. The syndrome being due to a single gene defect, inherited as an autosomal recessive, is therefore likely to be the result of an inborn error of metabolism with variable periods of latency in those affected. PMID:931428

Functional characterization of AVPR2 mutants found in Turkish patients with nephrogenic diabetes insipidus

PubMed Central

Schulz, Angela; Saglar, Emel; Deniz, Ferhat; Schöneberg, Torsten; Mergen, Hatice

2018-01-01

Diabetes insipidus is a rare disorder characterized by an impairment in water balance because of the inability to concentrate urine. While central diabetes insipidus is caused by mutations in the AVP, the reason for genetically determined nephrogenic diabetes insipidus can be mutations in AQP2 or AVPR2. After release of AVP from posterior pituitary into blood stream, it binds to AVPR2, which is one of the receptors for AVP and is mainly expressed in principal cells of collecting ducts of kidney. Receptor activation increases cAMP levels in principal cells, resulting in the incorporation of AQP2 into the membrane, finally increasing water reabsorption. This pathway can be altered by mutations in AVPR2 causing nephrogenic diabetes insipidus. In this study, we functionally characterize four mutations (R68W, ΔR67-G69/G107W, V162A and T273M) in AVPR2, which were found in Turkish patients. Upon AVP stimulation, R68W, ΔR67-G69/G107W and T273M showed a significantly reduced maximum in cAMP response compared to wild-type receptor. All mutant receptor proteins were expressed at the protein level; however, R68W, ΔR67-G69/G107W and T273M were partially retained in the cellular interior. Immunofluorescence studies showed that these mutant receptors were trapped in ER and Golgi apparatus. The function of V162A was indistinguishable from the indicating other defects causing disease. The results are important for understanding the influence of mutations on receptor function and cellular trafficking. Therefore, characterization of these mutations provides useful information for further studies addressing treatment of intracellularly trapped receptors with cell-permeable antagonists to restore receptor function in patients with nephrogenic diabetes insipidus. PMID:29117938

Functional characterization of AVPR2 mutants found in Turkish patients with nephrogenic diabetes insipidus.

PubMed

Erdem, Beril; Schulz, Angela; Saglar, Emel; Deniz, Ferhat; Schöneberg, Torsten; Mergen, Hatice

2018-01-01

Diabetes insipidus is a rare disorder characterized by an impairment in water balance because of the inability to concentrate urine. While central diabetes insipidus is caused by mutations in the AVP , the reason for genetically determined nephrogenic diabetes insipidus can be mutations in AQP2 or AVPR2 After release of AVP from posterior pituitary into blood stream, it binds to AVPR2, which is one of the receptors for AVP and is mainly expressed in principal cells of collecting ducts of kidney. Receptor activation increases cAMP levels in principal cells, resulting in the incorporation of AQP2 into the membrane, finally increasing water reabsorption. This pathway can be altered by mutations in AVPR2 causing nephrogenic diabetes insipidus. In this study, we functionally characterize four mutations (R68W, ΔR67-G69/G107W, V162A and T273M) in AVPR2, which were found in Turkish patients. Upon AVP stimulation, R68W, ΔR67-G69/G107W and T273M showed a significantly reduced maximum in cAMP response compared to wild-type receptor. All mutant receptor proteins were expressed at the protein level; however, R68W, ΔR67-G69/G107W and T273M were partially retained in the cellular interior. Immunofluorescence studies showed that these mutant receptors were trapped in ER and Golgi apparatus. The function of V162A was indistinguishable from the indicating other defects causing disease. The results are important for understanding the influence of mutations on receptor function and cellular trafficking. Therefore, characterization of these mutations provides useful information for further studies addressing treatment of intracellularly trapped receptors with cell-permeable antagonists to restore receptor function in patients with nephrogenic diabetes insipidus. © 2018 The authors.

Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin.

PubMed

Bernal, Antonio; Mahía, Javier; Puerto, Amadeo

2016-07-01

The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

An unusual case of central diabetes insipidus & hyperglycemic hyperosmolar state following cardiorespiratory arrest

PubMed Central

2013-01-01

Background We are describing an unusual case of severe hyperglycemia and hypernatremia, resistant to treatment. Case presentation A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. Her initial serum glucose and sodium were normal, but after receiving dexamethasone and mannitol, the serum glucose progressively increased to 54.7 mmol/L and sodium to 175 mmol/L, despite receiving very high dose of intravenous (IV) insulin infusion. She was evaluated for diabetes insipidus because of continued polyuria even after correction of hyperglycemia. Her serum osmolality was 337 mmol/kg, and urine osmolality was 141 mmol/kg which rose to 382 mmol/kg, after receiving 4 mcg of IV Desmopressin. Conclusion Our patient developed central diabetes insipidus post cardiac arrest and severe dehydration because of diabetes insipidus. Stress of critical illness, dehydration, dexamethasone and IV dextrose infusion were likely responsible for this degree of severe and resistant to treatment hyperglycemia. PMID:23947429

[Etiological diagnosis of central diabetes insipidus: about 41 cases].

PubMed

Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

2016-01-01

The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

Partial central diabetes insipidus in patient with common variable immunodeficiency.

PubMed

Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto

2012-07-03

Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient's symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients.

Partial central diabetes insipidus in patient with common variable immunodeficiency

PubMed Central

Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto

2012-01-01

Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient’s symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients. PMID:22761233

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

PubMed

Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

2017-08-01

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus

PubMed Central

Ho, Horace T. B.; Chung, Sookja K.; Law, Janice W. S.; Ko, Ben C. B.; Tam, Sidney C. F.; Brooks, Heddwen L.; Knepper, Mark A.; Chung, Stephen S. M.

2000-01-01

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus. PMID:10913167

Dominant-negative diabetes insipidus and other endocrinopathies

PubMed Central

Phillips, John A.

2003-01-01

Familial neurohypophyseal diabetes insipidus (FNDI) in humans is an autosomal dominant disorder caused by a variety of mutations in the arginine vasopressin (AVP) precursor. A new report demonstrates how heterozygosity for an AVP mutation causes FNDI (see the related article beginning on page 1697). Using an AVP knock-in mutation in mice, the study shows that FNDI is caused by retention of AVP precursors and progressive loss of AVP-producing neurons. PMID:14660740

[Growth in children with diabetes insipidus].

PubMed

Morla Báez, E; Dorantes Alvarez, L M; Chavarría Bonequi, C

1980-01-01

Commercial preparations of vasopressin for the treatment of diabetes insipidus are not available in Mexico. Besides, the hormone is useless in the nephrogenic variety. In the department of Endocrinology at the Hospital Infantil de Mexico, a preparation containing hydrochlorothiazide, aminopyrine and potassium chloride, which reduces urinary volumes in about two thirds, is employed in all varieties of the disease. Growth in stature was investigated in 44 patients under treatment, attending the Endocrine Outpatient Clinic since 1967 for a period of 2 to 12 years. Clinical material included 29 males and 15 females. There were 23 idiopathic, 7 histiocytosis, 5 nephrogenic, 4 craniopharyngiomas, 2 psychogenic polydipsia, 2 traumatic and 1, as a sequel of tuberculous meningoencephalitis. Six idiopathic, 2 nephrogenic, 2 traumatic, 1 histiocytosis, and 1 psychogenic proceeded between percentiles 3 and 97, parallel to the nearest line of reference along the whole period of study. Two nephrogenic, 2 histiocytosis, 1 psychogenic, 1 post-meningoencephalitis and 14 idiopathic, grew below the third percentile, but parallel to it. One nephrogenic, 4 histiocytosis, 4 craniopharyngioma and 3 idiopathic progressively departed from the initial centile. Two of the latter had growth hormone deficiency, and 1 had been very irregularly treated. It is concluded that the therapy employed limits stature impairment but does not produce catch-up growth. Accordingly, it is proposed that the treatment of diabetes insipidus should be started as early as possible, and that if progress in stature is appreciably deteriorated, the presence of additional pathology should be suspected.

Adipsic diabetes insipidus in pediatric patients.

PubMed

Janus, Dominika Malgorzata; Wojcik, Malgorzata; Zygmunt-Górska, Agata; Wyrobek, Lukasz; Urbanik, Andrzej; Starzyk, Jerzy Bogdan

2014-12-01

To present symptoms, complications and proposition of management protocol in children diagnosed with adipsic diabetes insipidus (aDI). Clinical and biochemical analysis of six pediatric patients diagnosed with aDI, four boys aged 5, 13, 16, and 17 y and two girls aged 2.5 and 10 y. The etiology of aDI was germinoma (n = 2), extensive surgery due to optic glioma (n = 1) and astrocytoma (n = 1), congenital brain malformations (n = 1) and complications secondary to bacterial meningitis (n = 1). Two patients had severely impaired vision and two had hemiparesis. In all the patients, loss of thirst reflex was observed. The serum electrolytes in all patients showed sodium concentration from 159 to 176.6 mmol/L with plasma osmolality from above 297 mOsmol/kg. Polyuria was absent in three most severely dehydrated patients on admission. In two patients in whom DDAVP (1-desamino-8-D-arginine vasopressin; Desmopressin) therapy was withdrawn based on lack of polyuria deep venous thrombosis developed. Lack of polydipsia and polyuria, the key symptoms of diabetes insipidus (DI), may delay the diagnosis of aDI and may lead to severe complications of chronic hyperosmolar status. The fluid intake in patients diagnosed with aDI need to be supervised daily based on calculated constant volume of oral fluids, daily measurements of fluid balance, body weight and sodium levels, especially in patients whose vision is compromised or who are physically unable to take care of themselves.

Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations.

PubMed

Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy

2016-01-01

Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.

Diabetes insipidus, diabetes mellitus, optic atrophy and deafness. A clinical and genetic study.

PubMed Central

Nagi, N. A.

1979-01-01

Two Iraqi sisters and a female cousin developed diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D), (the 'DIDMOAD' syndrome) before the age of 12 years. One girl exhibited all the features of this disease complex only 3 months after an unusually late onset of recognizable symptoms at 11 years 9 months. Another girl died suddenly and unexpectedly. This family study illustrates the recessive inheritance pattern of the syndrome. Images Fig. 2 Fig. 3 PMID:482181

Undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a young soldier.

PubMed

Kim, Hyung Jin; Shin, Y S; Choi, H; Kim, M K; Jeong, Y B; Park, J K

2016-10-01

We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a 21-year-old male soldier. Soldiers live in close quarters, and have a regimented lifestyle that may not allow for frequent voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in acute urinary retention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[Congenital nephrogenic diabetes insipidus: about a case report].

PubMed

Esselmani, Hicham; Yassine, Asmaa; Bouabdellah, Mounya; Benchekroun, Laila; Handor, Najat; Elalami, Sanae; Chabraoui, Layachi

2013-01-01

Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

[Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

PubMed

Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

2016-10-28

To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (P<0.05). There was high incidence of diabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (P<0.05). Under such conditions, the incidence of diabetes insipidus in the vasopressin tannate group was decreased compared with the control group (P<0.05). Postoperative hypernatremia occurred in 37 patients (44.6%), and hyponatremia occurred in 60 patients (72.3%), the average time of the occurrence of hpernatremia and hyponatremia was 1.4 and 3.7 days after surgery. Postoperative high serum sodium and low serum sodium appeared alternately in 19 patients (22.9%). There was significant difference in the serum sodium distribution in the first day after surgery in both groups (P<0.05), and the percent of hpernatremia in the vasopressin tannate group was significantly less than that in the control group (P<0.05).
 Conclusion: Preventive use of vasopressin tannate can effectively reduce diabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.

Use of Chlorothiazide in the Management of Central Diabetes Insipidus in Early Infancy

PubMed Central

Palliyil Gopi, Resmy

2017-01-01

Management of central diabetes insipidus in infancy is challenging. The various forms of desmopressin, oral, subcutaneous, and intranasal, have variability in the duration of action. Infants consume most of their calories as liquids which with desmopressin puts them at risk for hyponatremia and seizures. There are few cases reporting chlorothiazide as a temporizing measure for central diabetes insipidus in infancy. A male infant presented on day of life 30 with holoprosencephaly, cleft lip and palate, and poor weight gain to endocrine clinic. Biochemical tests and urine output were consistent with central diabetes insipidus. The patient required approximately 2.5 times the normal fluid intake to keep up with the urine output. Patient was started on low renal solute load formula and oral chlorothiazide. There were normalization of serum sodium, decrease in fluid intake close to 1.3 times the normal, and improved urine output. There were no episodes of hyponatremia/hypernatremia inpatient. The patient had 2 episodes of hypernatremia in the first year of life resolving with few hours of hydration. Oral chlorothiazide is a potential bridging agent for treatment of central DI along with low renal solute load formula in early infancy. It can help achieve adequate control of DI without wide serum sodium fluctuations. PMID:28553553

Central diabetes insipidus and hypothalamic hypothyroidism associated with aceruloplasminemia.

PubMed

Watanabe, Minemori; Asai, Chikako; Ishikawa, Kota; Kiyota, Atsushi; Terada, Tatsuhiro; Kono, Satoshi; Miyajima, Hiroaki; Okumura, Ataru

2010-01-01

Aceruloplasminemia is a rare autosomal recessive disease first reported by Miyajima et al. (Neurology 37: 761-767, 1987); it is clinically characterized by diabetes mellitus, retinal degeneration and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs and dementia. Aceruloplasminemia is caused by mutations in the ceruloplasmin gene, which results in the absence of serum ceruloplasmin and iron overload in the brain, liver, pancreas and other organ tissues. However, little is known about endocrine diseases associated with aceruloplasminemia. We report herein a case of aceruloplasminemia accompanied by central diabetes insipidus and hypothalamic hypothyroidism.

Diabetes insipidus and pregnancy.

PubMed

Chanson, Philippe; Salenave, Sylvie

2016-06-01

Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].

PubMed

Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji; Horimasu, Yasushi; Nakashima, Taku; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Murakami, Yuji; Hamada, Hironobu; Nagata, Yasushi; Hattori, Noboru

2017-06-01

Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

Diabetes insipidus with impaired osmotic regulation in septo-optic dysplasia and agenesis of the corpus callosum.

PubMed Central

Masera, N; Grant, D B; Stanhope, R; Preece, M A

1994-01-01

The clinical and endocrinological findings in 24 children with septo-optic dysplasia and/or agenesis of the corpus callosum are described with particular reference to posterior pituitary function. Nine had diabetes insipidus. The prevalence of diabetes insipidus was similar in children with complete and incomplete forms of septo-optic dysplasia. Maintenance of normal osmotic balance was very difficult in six of these children, even after the introduction of treatment with vasopressin, either as desmopressin, or lysine vasopressin spray in one of the early cases. PMID:8110009

Nephrogenic diabetes insipidus with idiopathic Fanconi's syndrome in a child who presented as vitamin D resistant rickets.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2011-10-01

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycaemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium, and magnesium. Whereas diabetes insipidus is a disease of collecting tubules and child mainly presents with dehydration and hypernatremia. Though all the cases published till date were secondary to drugs, myeloma, hematological disorders, etc., we are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to of severe hypokalemia induced tubular dysfunction.

INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA.

PubMed

Haddad, Nadine G; Nabhan, Zeina M; Eugster, Erica A

2016-12-01

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.

Early central diabetes insipidus: An ominous sign in post-cardiac arrest patients.

PubMed

Chae, Minjung Kathy; Lee, Jeong Hoon; Lee, Tae Rim; Yoon, Hee; Hwang, Sung Yeon; Cha, Won Chul; Shin, Tae Gun; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

2016-04-01

Central diabetes insipidus (CDI) after cardiac arrest is not well described. Thus, we aim to study the occurrences, outcomes, and risk factors of CDI of survivors after out-of-hospital cardiac arrest (OHCA). We retrospectively analyzed post-OHCA patients treated at a single center. Central diabetes insipidus was retrospectively defined by diagnostic criteria. One-month cerebral performance category (CPC) scores were collected for outcomes. Of the 169 patients evaluated, 36 patients (21.3%) were diagnosed with CDI. All CDI patients had a poor neurologic outcome of either CPC 4 (13.9%) or CPC 5 (86.1%), and CDI was strongly associated with mortality. Age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93-0.99), respiratory arrest (OR, 6.62; 95% CI, 1.23-35.44), asphyxia (OR, 9.26; 95% CI, 2.17-34.61), and gray to white matter ratio on brain computed tomogram (OR, 0.88; 95% CI, 0.81-0.95) were associated with the development of CDI. The onset of CDI was earlier (P < .001) and the maximum 24-hour urine output was larger (P = .03) in patients with worst outcomes. All patients diagnosed with CDI had poor neurologic outcomes, and occurrence of CDI was associated with mortality. Central diabetes insipidus patients with death or brain death had earlier occurrence of CDI and more maximum urine output. Copyright © 2015 Elsevier Inc. All rights reserved.

Concurrent central diabetes insipidus and panhypopituitarism in a German shepherd dog.

PubMed

Ramsey, I K; Dennis, R; Herrtage, M E

1999-06-01

This report describes a German shepherd dog that was presented with proportionate dwarfism and coat changes typical of hypopituitarism but that was also profoundly polydipsic and polyuric. Investigations established a diagnosis of concurrent central diabetes insipidus. Treatment with desmopressin was successful in managing the polyuria and polydipsia.

[Alobar holoprosencephaly associated with diabetes insipidus and hypothyroidism in a 10-month old infant].

PubMed

Seck, Ndiogou; Basse, Idrissa; Keita, Younoussa; Boiro, Djiril; Thiam, Lamine; Ndongo, Aliou Adoulaye; Diagne, Ibrahima

2017-01-01

Holoprosencephaly (HPE) is a serious brain malformation due to a failure of medial forebrain cleavage. This is an abnormality which is more often associated with craniofacial malformations, psychomotor development delay, diabetes insipidus and variable endocrine disorders. It is due to different causes including chromosomal abnormalities (trisomy 13, 18)and polymalformative syndromes (CHARGE Syndrome). Diagnosis is based on brain imaging. A few rare cases have been described in the literature. We here report the case of alobar HPE in a 10-month old infant. Diagnosis was based on cerebral CT scan performed due to delayed psychomotor development and in the absence of visible malformations. Endocrine assessment allowed to detect central diabetes insipidus and central hypothyroidism, probably of hypothalamic origin.

The clinical pattern of diabetes Insipidus in a large university hospital in the Middle East.

PubMed

Babiker, Amir M I; Al Jurayyan, Nasir A M; Al Jurayyan, Rushaid N A; Al Gadi, Iman; Drop, Stenvert L S

2015-04-01

Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Xanthoma Disseminatum in a Young Patient with Diabetes Insipidus.

PubMed

Hui, Yun; Zhang, Cheng-Zhen; Chen, Jun; Kong, Qing-Tao; Chen, Huan; Du, Xue; Sang, Hong

2017-05-01

Xanthoma disseminatum (XD) is a nonfamilial type of normolipidemic mucocutaneous xanthomatosis that belongs to the group of non-Langerhans cell histiocytoses. More than 100 cases of XD have been reported. In this study we report a case of XD in a 4-year-old boy with diabetes insipidus (DI). This boy is one of the youngest patients ever to present with XD combined with DI. © 2017 Wiley Periodicals, Inc.

Masking of central diabetes insipidus and hypogonadotrophic hypogonadism by germ cell tumour in suprasellar--pineal region.

PubMed

Isa, S H Md; Wong, M; Khalid, B A K

2006-12-01

A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.

Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes insipidus in the third trimester of pregnancy.

PubMed

Sakurai, Kanako; Yamashita, Rika; Niituma, Satsuki; Iwama, Shintaro; Sugimura, Yoshihisa; Arihara, Zenei; Takahashi, Kazuhiro

2017-06-29

We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma osmolality (300 mOsm/kgH 2 O) and low urinary osmolality (92 mOsm/kgH 2 O) were observed at the admission to our hospital. Plasma arginine vasopressin (AVP) level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality. Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine osmolality increased in response to desmopressin. The diagnosis of central diabetes insipidus was made from these results. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti-rabphilin-3A antibodies that have been recently reported as a biomarker of lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus continued after delivery, suggesting that polyuria was not mainly due to excessive vasopressinase activity or reduced renal sensitivity to AVP by prostaglandin E 2 that can cause temporal polyuria during pregnancy. We therefore clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo-neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy. This case suggested the usefulness of anti-rabphilin-3A antibodies for the etiological diagnosis of central diabetes insipidus during pregnancy.

Diabetes insipidus during pregnancy.

PubMed

Ananthakrishnan, Sonia

2016-03-01

Diabetes insipidus (DI) in pregnancy is a heterogeneous syndrome, most classically presenting with polyuria and polydipsia that can complicate approximately 1 in 30,000 pregnancies. The presentation can involve exacerbation of central or nephrogenic DI during pregnancy, which may have been either overt or subclinical prior to pregnancy. Women without preexisting DI can also be affected by the actions of placental vasopressinase which increases in activity between the 4th and 38th weeks of gestation, leading to accelerated metabolism of AVP and causing a transient form of DI of pregnancy. This type of DI may be associated with certain complications during pregnancy and delivery, such as preeclampsia. Management of DI of pregnancy depends on the pathophysiology of the disease; forms of DI that lack AVP can be treated with desmopressin (DDAVP), while forms of DI that involve resistance to AVP require evaluation of the underlying causes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

PubMed

Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

2015-12-01

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

A case of idiopathic diabetes insipidus presented with bilateral hydroureteronephrosis and neurogenic bladder: A pediatric case report and literature review

PubMed Central

Yuksel, Ozgur Haki; Kivrak, Mithat; Sahin, Aytac; Akan, Serkan; Urkmez, Ahmet; Verit, Ayhan

2015-01-01

Diabetes insipidus (DI) is a condition with heterogeneous clinical symptoms characterized by polyuria (urine output >4 mL/kg/hr) and polydipsia (water intake >2 L/m 2/d). In children, acquired nephrogenic DI (NDI) is more common than central DI (CDI). Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. A water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI from CDI and diagnose their incomplete forms. Neonates and young infants are better managed with hydration therapy alone. Older children with CDI are treated with desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP). Its oral form is safe, highly effective and has dosing flexibility. We report a case of an 8-year-old male patient with CDI with severe bilateral non-obstructive hydronephrosis and megaureter. Dramatic clinical and radiological responses to dDAVP treatment were achieved and therapy reduced urine volume and led to marked radiological improvement in hydronephrosis. PMID:26600892

A case of idiopathic diabetes insipidus presented with bilateral hydroureteronephrosis and neurogenic bladder: A pediatric case report and literature review.

PubMed

Yuksel, Ozgur Haki; Kivrak, Mithat; Sahin, Aytac; Akan, Serkan; Urkmez, Ahmet; Verit, Ayhan

2015-01-01

Diabetes insipidus (DI) is a condition with heterogeneous clinical symptoms characterized by polyuria (urine output >4 mL/kg/hr) and polydipsia (water intake >2 L/m (2)/d). In children, acquired nephrogenic DI (NDI) is more common than central DI (CDI). Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. A water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI from CDI and diagnose their incomplete forms. Neonates and young infants are better managed with hydration therapy alone. Older children with CDI are treated with desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP). Its oral form is safe, highly effective and has dosing flexibility. We report a case of an 8-year-old male patient with CDI with severe bilateral non-obstructive hydronephrosis and megaureter. Dramatic clinical and radiological responses to dDAVP treatment were achieved and therapy reduced urine volume and led to marked radiological improvement in hydronephrosis.

A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus.

PubMed

Ilhan, M; Tiryakioglu, N O; Karaman, O; Coskunpinar, E; Yildiz, R S; Turgut, S; Tiryakioglu, D; Toprak, H; Tasan, E

2016-03-01

Familial neurohypophyseal diabetes insipidus (FNDI) is a rare, autosomal dominant, inherited disorder which is characterized by severe polydipsia and polyuria generally presenting in early childhood. In the present study, we aimed to analyze the AVP gene in a Turkish family with FNDI. Four patients with neurohypophyseal diabetes insipidus and ten healthy members of the family were studied. Diabetes insipidus was diagnosed by the water deprivation test in affected family members. Mutation analysis was performed by sequencing the whole coding region of AVP-NPII gene using DNA isolated from peripheral blood samples. Urine osmolality was low (<300 mOsm/kg) during water deprivation test, and an increase more than 50 % in urine osmolality and recovery of the symptoms were observed by the administration of desmopressin in all patients. Plasma copeptin levels were lower than expected according to plasma osmolality. Pituitary MRI revealed partial empty sella with a bright spot in index patient and a normal neurohypophysis in the other affected subjects. Genetic screening revealed a novel, heterozygous mutation designated as c.-3A>C in all patients. c.-3A>C mutation in 5'UTR of AVP gene in this family might lead to the truncation of signal peptide, aggregation of AVP in the cytoplasm instead of targeting in the endoplasmic reticulum, thereby could disrupt AVP secretion without causing neuronal cytotoxicity, which might explain the presence of bright spot. The predicted effect of this mutation should be investigated by further in vitro molecular studies.

On the Mechanism of Lithium-Induced Diabetes Insipidus in Man and the Rat

PubMed Central

Forrest, John N.; Cohen, Alan D.; Torretti, Jorge; Himmelhoch, Jonathan M.; Epstein, Franklin H.

1974-01-01

The mechanism of lithium-induced diabetes insipidus was investigated in 96 patients and in a rat model. Polydipsia was reported by 40% and polyuria (more than 3 liter/day) by 12% of patients receiving lithium. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in 10 polyuric patients and was reduced in 7 of 10 nonpolyuric patients studied before and during lithium therapy. Severe polyuria (more than 6 liter/day) was unresponsive to trials of vasopressin and chlorpropamide, but improved on chlorothiazide. Rats receiving lithium (3-4 meq/kg/day) developed massive polyuria that was resistant to vasopressin, in comparison to rats with comparable polyuria induced by drinking glucose. Analysis of renal tissue in rats with lithium polyuria showed progressive increase in the concentration of lithium from cortex to papilla with a 2.9-fold corticopapillary gradient for lithium. The normal corticopapillary gradient for sodium was not reduced by lithium treatment. The polyuria was not interrupted by brief intravenous doses of vasopressin (5-10 mU/kg) or dibutyryl cyclic AMP (10-15 mg/kg) capable of reversing water diuresis in normal and hypothalamic diabetes insipidus rats (Brattleboro strain). The present studies suggest that nephrogenic diabetes insipidus is a common finding after lithium treatment and results in part from interference with the mediation of vasopressin at a step distal to the formation of 3′,5′ cyclic AMP. PMID:4360856

Transient diabetes insipidus in a preterm neonate and the challenge of desmopressin dosing.

PubMed

Van der Kaay, Danielle C M; Van Heel, Willemijn J M; Dudink, Jeroen; van den Akker, Erica L T

2014-07-01

As neonatal central diabetes insipidus is rare in preterm neonates with intraventricular hemorrhage (IVH), very little is known about dosing and the route of administration of desmopressin treatment. We present a preterm neonate born at 29 weeks' gestation. Within 24 h, she developed bilateral IVH with subsequent post-hemorrhagic hydrocephalus. On the 3rd postnatal day, she developed diabetes insipidus for which she was intranasally administered 0.2 mg desmopressin. This resulted in oliguria with several hours of anuria and a 25-point drop in sodium levels within 15 h. The determination of the desmopressin dose in a preterm neonate is a challenge and there is no consistent literature about the dosing or the route of administration. We suggest starting with a low dose of intranasal desmopressin (0.05-0.1 μg) and titrate in accordance with clinical and laboratory parameters.

Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study.

PubMed

García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Chocron, Sara; Madrid, Alvaro; Lafita Tejedor, Francisco Javier; Gil Campos, Mercedes; Sánchez Del Pozo, Jaime; Ruiz Cano, Rafael; Espino, Mar; Gomez Vida, Jose Maria; Santos, Fernando; García Nieto, Victor Manuel; Loza, Reyner; Rodríguez, Luis Miguel; Hidalgo Barquero, Emilia; Printza, Nikoleta; Camacho, Juan Antonio; Castaño, Luis; Ariceta, Gema

2015-10-01

Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height -1.9 ± 2.1 and Z-weight -2.4 ± 1.7), severe hypernatremia (mean ± SD; Na 150 ± 10 mEq/L), increased plasma osmolality (mean ± SD; 311 ± 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration. Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms. • In most cases (90 %), inherited nephrogenic diabetes insipidus (NDI) is an X-linked disease, caused by mutations in the AVPR2 gene. • In rare occasions (10 %), it is caused by mutations in the AQP2 gene. What is new: • In this study, we report 10 novel mutations associated with NDI. • We have detected a high presence (50 %) of heterozygous carriers with clinical NDI symptoms.

[Diagnosis and treatment of adipsic diabetes insipidus accompanied with intracranial calcification].

PubMed

Hu, Ming-ming; Liu, Min; Liu, Wei

2013-04-01

To summarize our experience in the management of adipsic central diabetes insipidus(ADI) accompanied with intracranial calcification. The clinical data of one ADI patient accompanied with intracranial calcification who was treated in our hospital since December 2011 were retrospectively summarized. The 24-hour urine volume was 800 ml. She didn't feel thirsty even with increased plasma sodium concentration(153 mmol/L) and blood osmotic pressure(333 mmol/L) . Combined water deprivation and vasopressin test revealed the diagnosis of central diabetes insipidus. The high intensity signal(on T1-weighted magnetic resonance imaging) in the posterior lobe of pituitary gland was found. Computed tomography showed calcifications in the bilateral basal ganglia.Serum cytomegalovirus IgG was positive. She was treated with desmopressin and asked for regular water intake regardless of the adipsia. The plasma sodium concentration was still below 150 mmol/L during the 4-month follow-up. Routine adipsia evaluation and combined water deprivation and vasopressin test are critical for the diagnosis and treatment of ADI. Past insidious intracranial cytomegalovirus infection may explain the cause of ADI and calcification.

Diabetes insipidus: The other diabetes

PubMed Central

Kalra, Sanjay; Zargar, Abdul Hamid; Jain, Sunil M.; Sethi, Bipin; Chowdhury, Subhankar; Singh, Awadhesh Kumar; Thomas, Nihal; Unnikrishnan, A. G.; Thakkar, Piya Ballani; Malve, Harshad

2016-01-01

Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefits over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin. PMID:26904464

Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a case report

PubMed Central

2014-01-01

Background Congenital toxoplasmosis has a wide range of presentation at birth varying from severe neurological features such as hydrocephalus and chorioretinitis to a well appearing baby, who may develop complications late in infancy. While neuroendocrine abnormalities associated with congenital toxoplasmosis are uncommon, isolated central diabetes insipidus is extremely rare. Case presentation Here, we report on a female infant who presented with fever, convulsions, and polyuria. Examination revealed weight and length below the 3rd centile along with signs of severe dehydration. Fundal examination showed bilateral chorioretinitis. This infant developed hypernatremia together with increased serum osmolality and decreased both urine osmolality and specific gravity consistent with central diabetes insipidus. Serology for toxoplasma specific immunoglobulin M was high for both the mother and the baby and polymerase chain reaction for toxoplasma deoxyribonucleic acid was positive in the infant confirming congenital toxoplasmosis. Brain computerized tomography scans demonstrated ventriculomegaly associated with cerebral and cortical calcifications. Fluid and electrolyte abnormalities responded to nasal vasopressin therapy. Conclusion This report highlights central diabetes inspidus as a rare presentation of congenital toxoplasmosis. PMID:24674575

Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a case report.

PubMed

Mohamed, Sarar; Osman, Abdaldafae; Al Jurayyan, Nasir A; Al Nemri, Abdulrahman; Salih, Mustafa A M

2014-03-28

Congenital toxoplasmosis has a wide range of presentation at birth varying from severe neurological features such as hydrocephalus and chorioretinitis to a well appearing baby, who may develop complications late in infancy. While neuroendocrine abnormalities associated with congenital toxoplasmosis are uncommon, isolated central diabetes insipidus is extremely rare. Here, we report on a female infant who presented with fever, convulsions, and polyuria. Examination revealed weight and length below the 3rd centile along with signs of severe dehydration. Fundal examination showed bilateral chorioretinitis. This infant developed hypernatremia together with increased serum osmolality and decreased both urine osmolality and specific gravity consistent with central diabetes insipidus. Serology for toxoplasma specific immunoglobulin M was high for both the mother and the baby and polymerase chain reaction for toxoplasma deoxyribonucleic acid was positive in the infant confirming congenital toxoplasmosis. Brain computerized tomography scans demonstrated ventriculomegaly associated with cerebral and cortical calcifications. Fluid and electrolyte abnormalities responded to nasal vasopressin therapy. This report highlights central diabetes inspidus as a rare presentation of congenital toxoplasmosis.

[Central diabetes insipidus: diagnosis and management].

PubMed

Ballan, B Köhler; Hernandez, A; Rodriguez, E Gonzalez; Meyer, P

2012-11-14

Central diabetes insipidus (CDI) is caused by deficient secretion of antidiuretic hormone (ADH) due to different conditions that can affect the hypothalamic neurons. It results in an inability to retain normal quantities of free water, which leads to polyuria, including at night, and polydipsia. In adults, it is mostly due to the "idiopathic" form or present after pituitary surgery or a traumatic brain injury. In rare cases, an underlying systemic disease is found. The diagnosis of CDI is based on the water deprivation test. Pituitary MRI and specific clinical and biological work-up are recommended to precise etiology. Treatment of choice is desmopressin, a synthetic analogue of the endogenous ADH hormone. A multidisciplinary team generally provides management and monitoring of CDI.

A case report of nephrogenic diabetes insipidus with idiopathic Fanconi syndrome in a child who presented with vitamin D resistant rickets.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2014-05-01

Fanconi syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells, occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and children mainly present with dehydration and hypernatremia. We are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us with vitamin D resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus (NDI) associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to to severe hypokalemia induced tubular dysfunction.

Pituitary apoplexy precipitating diabetes insipidus after living donor liver transplantation.

PubMed

Matsusaki, Takashi; Morimatsu, Hiroshi; Matsumi, Junya; Matsuda, Hiroaki; Sato, Tetsufumi; Sato, Kenji; Mizobuchi, Satoshi; Yagi, Takahito; Morita, Kiyoshi

2011-02-01

Pituitary apoplexy occurring after surgery is a rare but life-threatening acute clinical condition that follows extensive hemorrhagenous necrosis within a pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in the majority of cases or in association with various inducing factors. Reported is a case of pituitary apoplexy complicated by diabetes insipidus following living donor liver transplantation (LDLT). To the best of our knowledge, this has not been previously reported. A 56-year-old woman with nonalcoholic steatohepatitis underwent LDLT from her daughter. The patient also required dopamine support and transfusions because of massive intraoperative bleeding. Postoperatively, her coagulopathy continued, and she underwent a second laparotomy because of unknown bleeding on postoperative day 7, when she needed transfusions and dopamine support to maintain her vital signs. She complained of severe headache, excessive thirst, frequent urination, and diplopia from postoperative day 10. She also had polyuria greater than 300 ml/h and was diagnosed with pituitary apoplexy precipitating diabetes insipidus on postoperative day 13. She was treated conservatively without surgery because of the hormonally inactive status and slight mass effect of her tumor. It is important for anesthesiologists and critical care personnel in LDLT settings to take into consideration this complication as a differential diagnosis.

Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus.

PubMed

Duzenli, Duygu; Saglar, Emel; Deniz, Ferhat; Azal, Omer; Erdem, Beril; Mergen, Hatice

2012-12-01

The aim of this study was to identify mutations in three different genes, the arginine-vasopressin-neurophysin II (AVP-NPII) gene, the arginine-vasopressin receptor 2 (AVPR2) gene, and the vasopressin-sensitive water channel aquaporin-2 (AQP2) gene in Turkish patients affected by central diabetes insipidus or nephrogenic diabetes insipidus. This study included 15 patients from unrelated families. Prospective clinical data were collected for all patients including the patients underwent a water deprivation-desmopressin test. The coding regions of the AVPR2, AQP2, and AVP-NPII genes were amplified by polymerase chain reaction and submitted to direct sequence analysis. Of the 15 patients with diabetes insipidus referred to Gulhane Military Medical Academy, Department of Endocrinology and Metabolism, eight patients have AVPR2 mutations, five patients have AQP2 mutations and two patients have AVP-NPII mutations. Of the patients, which have AVPR2 mutations, one is compound heterozygous for AVPR2 gene. Seven of these mutations are novel. Comparison of the clinical outcomes of these mutations may facilitate in understanding the functions of AVP-NPII, AQP2, and AVPR2 genes in future studies.

Transient diabetes insipidus in a post-partum woman with pre-eclampsia associated with residual placental vasopressinase activity.

PubMed

Rodrigo, Natassia; Hocking, Samantha

2018-01-01

This case illustrates the exceedingly rare phenomenon of transient diabetes insipidus, in association with pre-eclampsia, occurring in the post-partum period following an in vitro fertilisation pregnancy, in an otherwise well 48-year-old lady. Diabetes insipidus can manifest during pregnancy, induced by increased vasopressinase activity secreted by placental trophoblasts and usually manifests in the third trimester. This presentation elucidates not only the intricate balance between the physiology of pregnancy and hormonal homeostasis, but also the importance of post-partum care as the physiological changes of pregnancy still hold pathological potential in the weeks immediately following delivery. Diabetes insipidus (DI) is a rare complication of pregnancy occurring in 1 in 30 000 pregnancies.It is associated with excessive vasopressinase activity, secreted by placental trophoblasts, which increases the rate of degradation of anti-diuretic hormone.It is responsive to synthetic desmopressin 1-deanimo-8-d-arginine vasopressin as this form is not degraded by placental vasopressinase.Vasopressinase is proportional to placental weight, which is increased in pregnancies conceived with assisted reproductive techniques including in vitro fertilisation.Vasopressinase-induced DI is associated with pre-eclampsia.

The diagnosis of children with central diabetes insipidus.

PubMed

Ghirardello, Stefano; Garrè, Maria-Luisa; Rossi, Andrea; Maghnie, Mohamad

2007-03-01

Central diabetes insipidus is the end result of a number of different diseases that affect the hypothalamic-neurohypophyseal system. In many patients, especially children and young adults, it is caused by the destruction or degeneration of neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. The known causes of these lesions include germinoma or craniopharyngioma; Langerhans cell histiocytosis; local inflammatory, autoimmune or vascular diseases; trauma resulting from surgery or an accident; sarcoidosis; metastases; and midline cerebral and cranial malformations. In rare cases, genetic defects in AVP synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits are the underlying cause. Accurate diagnostic differentiation is essential for both safe and effective disease management. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress, as needed, to more sophisticated methods. Indeed, magnetic resonance imaging (MRI) represents the examination method of choice for evaluating hypothalamic-pituitary-related endocrine diseases due to its ability to provide strongly-contrasted high-resolution multi-planar and spatial images. Specifically, MRI allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered to be a clear marker of neurohypophyseal functional integrity, together with careful analysis of pituitary stalk shape and size, have provided the most striking recent findings contributing to the diagnosis and understanding of some forms of 'idiopathic' central diabetes insipidus.

Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

PubMed

Ingemi, Amanda I; Bota, Vasile M; Peguero, Anyeri; Charpentier, Margaret

2012-01-01

Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option. © 2012 Pharmacotherapy Publications, Inc.

Permanent Central Diabetes Insipidus as a Complication of S. pneumoniae Meningitis in the Pediatric Population.

PubMed

Statz, Hannah; Hsu, Benson S

2016-05-01

Diabetes insipidus is a rare but recognized complication of meningitis. The occurrence of diabetes insidipus has been previously attributed to Streptococcus pneumoniae (S. pneumoniae) in a handful of patients and only once within the pediatric subpopulation. We present the clinical course of a previously healthy 2-year, 8-month-old male child ultimately diagnosed with central diabetes insipidus (CDI) secondary to S. pneumoniae meningitis. Permanent CDI following S. pneumoniae meningitis is unique to our case and has not been previously described. Following the case presentation, we describe the etiology, pathophysiology, diagnosis, and treatment of CDI. The mechanism proposed for this clinical outcome is cerebral herniation for a sufficient duration and subsequent ischemia leading to the development of permanent CDI. Providers should be aware of CDI resulting from S. pneumoniae meningitis as prompt diagnosis and management may decrease the risk of permanent hypothalamo-pituitary axis damage. Copyright© South Dakota State Medical Association.

Acute Sheehan's syndrome presenting as central diabetes insipidus.

PubMed

Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

2012-11-06

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

Gestational diabetes insipidus, HELLP syndrome and eclampsia in a twin pregnancy: a case report.

PubMed

Woelk, J L; Dombroski, R A; Brezina, P R

2010-02-01

We report a case of eclampsia in a twin pregnancy complicated by HELLP syndrome and diabetes insipidus. This confluence of disease processes suggests that a modification of common magnesium sulfate treatment protocols may be appropriate in a certain subset of patients.

[Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

PubMed

Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

2011-01-01

We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

[Transient central diabetes insipidus associated with pregnancy. Case report and bibliography review].

PubMed

Del Carpio-Orantes, Luis

2017-01-01

The case of a patient affected by transient diabetes insipidus associated with pregnancy, in the context of eclampsia, which was presented during seizures and identified by polyuria important, as well as changes in the urinary density occurs, and improving after nasal administration of desmopressin, which confirmed the diagnosis and treatment served completely by sending the picture without any sequel.

Congenital Nephrogenic Diabetes Insipidus Presented With Bilateral Hydronephrosis and Urinary Infection: A Case Report.

PubMed

Zheng, Kewen; Xie, Yi; Li, Hanzhong

2016-05-01

Nephrogenic diabetes insipidus (NDI) is a condition resulting from the kidney's impaired response to circulating antidiuretic hormone (ADH), leading to polydipsia and polyuria. Urinary tract dilatation caused by NDI is a rare situation. Here, we report a case of congenital NDI presented with bilateral hydronephrosis.A 15-year-old boy complaining a history of intermittent fever was admitted to Peking Union Medical College Hospital. He voided 10 to 15 L of urine daily. Radiographic examination revealed severe dilatation of bilateral renal pelvis, ureter, and bladder. Urinalysis shows hyposthenuria.He was diagnosed NDI since born. Transient insertion of a urethral catheter helped to relieve fever. Medical therapy of hydrochlorothiazide and amiloride was prescribed and effective.Dilatation of urinary tract caused by diabetes insipidus is rare, but may be present in severe condition. Therefore, it is crucial for clinicians to perform early treatment to avoid impairment of renal function.

Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery.

PubMed

Kalelioglu, Ibrahim; Kubat Uzum, Ayse; Yildirim, Alkan; Ozkan, Tulay; Gungor, Funda; Has, Recep

2007-01-01

Gestational diabetes insipidus (GDI) is a rare disorder characterised by polyuria, polydypsia, and excessive thirst usually manifesting in the third trimester of pregnancy. The etiology is thought to depend on excessive vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-D: -arginine vasopressin (dDAVP), which is a synthetic form. This is a transient syndrome and may be associated with acute fatty liver of pregnancy and preeclampsia. The use of dDAVP in symptomatic cases has been proven as a safe method for both the mother and the fetus during the pregnancy. We report a case of recurrent gestational diabetes insipidus in successive pregnancies, which responded to dDAVP and subsided after delivery.

Familial neurohypophyseal diabetes insipidus associated with a novel mutation in the vasopressin-neurophysin II gene.

PubMed

Fujii, H; Iida, S; Moriwaki, K

2000-03-01

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder of renal water conservation due to deficiency of arginine vasopressin as the result of mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene that encodes the hormone or its carrier protein. Thirty-one different mutations have been reported. In this study, we evaluated the AVP-NPII gene in a family with FNDI and identified a new mutation (1911Gright curved arrow A) in the coding sequence for NPII in affected family members. This mutation substitutes Tyr for 74 Cys in the NPII moiety. NPII is an intracellular carrier protein for AVP during the axonal transport from the hypothalamus to the posterior pituitary and contains 14 conserved cysteine residues forming 7 disulfide bonds. Because the mutation cosegregates with the phenotype, it is possible that this mutation causes neurohypophyseal diabetes insipidus in this family.

Compound heterozygous mutation of aquaporin 2 gene in woman patient with congenital nephrogenic diabetes insipidus.

PubMed

Tsutsumi, Zenta; Inokuchi, Taku; Tamada, Daisuke; Moriwaki, Yuji; Ka, Tsuneyoshi; Takahashi, Sumio; Yamamoto, Tetsuya

2009-01-01

We performed mutational analyses of a woman patient with congenital nephrogenic diabetes insipidus referred to us during pregnancy. The diagnosis was made during the neonatal period, after which she was treated with spironolactone and hydrochlorothiazide. Our examination showed the patient to be apparently in good health without definite evidence of dehydration. Serum and urine osmolality were 220 mOsm/L and 50 mOsm/L, respectively, and the serum concentration of AVP was 2.7 pg/mL. Results of a water-deprivation test performed after delivery were compatible with nephrogenic diabetes insipidus. Mutational analyses showed that the patient was a compound heterozygote with point mutations at nucleotide position 298 (G to A; G100R) in exon 1 and nucleotide position 374 (C to T; T125M) in exon 2 of the aquaporin 2 gene, which have been previously described.

Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

PubMed

Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

2015-04-01

Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

Simultaneous occurrence of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and diabetes insipidus following pituitary apoplexy

PubMed Central

Sasaki, Haruka; Ohnishi, Osamu; Okudera, Toshio; Okumura, Makoto

1991-01-01

A rare case of concomitant association of transient thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus following spontaneous pituitary apoplexy is presented. ImagesFigure 1 PMID:2057436

Clinical characteristics of central diabetes insipidus in Taiwanese children.

PubMed

Liu, Shih-Yao; Tung, Yi-Ching; Lee, Cheng-Ting; Liu, Hon-Man; Peng, Shinn-Forng; Wu, Mu-Zon; Kuo, Meng-Fai; Tsai, Wen-Yu

2013-10-01

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. Copyright © 2013. Published by Elsevier B.V.

Central Diabetes Insipidus Linked to Rathke's Cleft Cyst, Polyuria in a 17-year-old Girl.

PubMed

Kim, Ha Yeon; Lee, Seung Jin; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2017-09-01

A 17-year-old girl presented with polyuria (7 L/day) and polydipsia for one year. Initial urine osmolality was 113mOsm/kg H 2 O. Following 6 h of fluid restriction, serum plasma osmolality reached 300mOsm/kg H 2 O, whereas urine osmolality was 108mOsm/kg H 2 O. Urine osmolality was increased by 427% from 108 to 557mOsm/kg after vasopressin challenge. The patient was diagnosed with central diabetes insipidus, possibly derived from the atypical occupation of a Rathke's cleft cyst at the pituitary stalk following magnetic resonance imaging with enhancement. She was discharged with desmopressin nasal spray (10 µg); urine output was maintained at 2-3 L/day, and urine osmolality was >300 mOsm/kg. Additional pituitary image studies and evaluation of hypopituitarism should be included in the differential diagnosis of patients with central diabetes insipidus.

Polyuria and polydipsia in a young child: diagnostic considerations and identification of novel mutation causing familial neurohypophyseal diabetes insipidus.

PubMed

Stephen, Matthew D; Fenwick, Raymond G; Brosnan, Patrick G

2012-12-01

A 3-year 5-month-old boy was seen for second opinion regarding polydipsia and polyuria. Previously, a diagnosis of primary polydipsia was made after normal urine concentration after overnight water deprivation testing. The boy's father, paternal grandfather, and paternal aunt had diabetes insipidus treated with desmopressin acetate. Based on this young boy's symptoms, ability to concentrate urine after informal overnight water deprivation, and family history of diabetes insipidus, we performed AVP gene mutation testing. Analysis of the AVP gene revealed a novel mutation G54E that changes a normal glycine to glutamic acid, caused by a guanine to adenine change at nucleotide g.1537 (exon 2) of the AVP gene. Commonly, patients with familial neurohypophyseal diabetes insipidus (FNHDI) present within the first 6 years of life with progressively worsening polyuria and compensatory polydipsia. Since these patients have progressive loss of arginine vasopressin (AVP), they may initially respond normally to water deprivation testing and have normal pituitary findings on brain MRI. Genetic testing may be helpful in these patients, as well as preemptively diagnosing those with a mutation, thereby avoiding unnecessary surveillance of those unaffected.

Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.

PubMed

Joyce, Emily; Ho, Jacqueline; El-Gharbawy, Areeg; Salgado, Cláudia M; Ranganathan, Sarangarajan; Reyes-Múgica, Miguel

2017-01-01

Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. A 20-month-old boy presented with failure to thrive, polyuria, polydipsia, and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency, and nephrogenic diabetes insipidus. His initial ophthalmologic examination did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance, and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.

Hypoparathyroidism and central diabetes insipidus: in search of the link.

PubMed

Eyal, Ori; Oren, Asaf; Jüppner, Harald; Somech, Raz; De Bellis, Annamaria; Mannstadt, Michael; Szalat, Auryan; Bleiberg, Margalit; Weisman, Yosef; Weintrob, Naomi

2014-12-01

Two siblings (a 15-year-old boy and an 11-year-old girl) who presented with hypocalcemic seizure at the age of 2 years and 2 months (boy) and 2 years and 4 months (girl) were diagnosed with hypoparathyroidism. At the age of 3 years, the girl developed central diabetes insipidus with good response to desmopressin acetate treatment. The family history was unremarkable, and there was no consanguinity between the parents. The father is of Iraqi/Egyptian Jewish origin and the mother is of Iranian/Romanian Jewish origin. Sequence analysis of the candidate genes for isolated hypoparathyroidism encoding calcium-sensing receptor, parathyroid hormone, and glial cells missing homolog B did not reveal any mutations. Whole-exome sequencing identified a homozygous mutation in the autoimmune regulatory gene (AIRE), c.374A>G;p.Y85C, characteristic for Jewish Iranians with autoimmune polyendocrine syndrome type 1 (APS1), which was confirmed by the Sanger sequencing. Antibodies against the adrenal, pancreatic islet cell, ovary, thyroid, pituitary, celiac, and parietal cell were negative in both siblings, while anti-diuretic hormone antibodies were positive only in the girl. No other symptoms or signs of APS1 developed during all the years of follow-up. APS1 should be part of the differential diagnosis in children presenting with isolated hypoparathyroidism or hypoparathyroidism with central diabetes insipidus (CDI). These cases show that the AIRE mutation characteristic of Iranian Jews can also be found in non-Iranian Jews.

Effect of Preserving the Pituitary Stalk During Resection of Craniopharyngioma in Children on the Diabetes Insipidus and Relapse Rates and Long-Term Outcomes.

PubMed

Cheng, Jing; Fan, Yanqin; Cen, Bo

2017-09-01

The objective of this study was to investigate the effect of preserving an infiltrated pituitary stalk during the resection of craniopharyngioma of pituitary stalk origin on postoperative outcomes and thus provide a theoretical basis for microsurgical treatment and prognosis. We screened the clinical data of all 103 pediatric patients with craniopharyngioma undergoing surgical treatment at our department between January 2006 and January 2013 and conducted a retrospective analysis of 82 patients with craniopharyngioma originating in the pituitary stalk. The patients were followed up from 12 months to 8 years. We analyzed the effect of preserving the pituitary stalk on the early and persistent diabetes insipidus rates, postoperative relapse rate, and mortality. In the total resection group (n = 67), the early and persistent diabetes insipidus rates were significantly lower in the 46 patients (68.7%) with a pituitary stalk than in those whose pituitary stalk was removed (P < 0.05); no significant difference was observed in the relapse rate between the 2 subgroups (P > 0.05). In the subtotal resection group (n = 15), a significant difference was observed in the early and persistent diabetes insipidus rates (P < 0.05), but no significant difference was observed in the relapse rate between the patients with a pituitary stalk and those whose pituitary stalk was removed (P > 0.05). For children with craniopharyngioma of pituitary stalk origin, preserving the pituitary stalk has a significant effect on the early and persistent diabetes insipidus rates. When intraoperative exploration showed excessive adhesion between the tumor and pituitary stalk, we opted to preserve the pituitary stalk, which significantly reduced the early and persistent postoperative diabetes insipidus rates, without significantly increasing the relapse or mortality rate.

Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

PubMed

Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

2017-11-01

We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

PubMed

Ahn, Hee Jung; Chung, Jong-Hoon; Kim, Dong-Min; Yoon, Na-Ra; Kim, Choon-Mee

2018-03-05

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

Central diabetes insipidus: clinical profile that suggests organicity in Peruvian children: Lima - Peru 2001-2013.

PubMed

De Los Santos, Miguel Angel; Águila, Carlos Manuel Del; Rojas, Maria Isabel; Falen, Juan Manuel; Nuñez, Oswaldo; Chávez, Eliana Manuela; Espinoza, Oscar Antonio; Pinto, Paola Marianella; Calagua, Martha Rosario

2016-12-01

Central diabetes insipidus (CDI) is a heterogeneous disease caused by arginine vasopressin deficiency; its management implies a profound understanding of the pathophysiology and the clinical spectrum. The aim of the study was to describe the clinical characteristics that indicate organicity in children and adolescents with central diabetes insipidus treated at the Department of Endocrinology from The Child Health's Institute during 2001 to 2013. Cross-sectional, retrospective study. 79 cases of patients diagnosed with CDI (51 males and 28 females) from 1 month to 16 years of age were reviewed. For the descriptive analysis, measures of central tendency and dispersion were used; groups of organic and idiopathic CDI were compared using χ2-test and t-test. A p-value<0.05 was considered significant. The average age of patients was 8.1±4.2 years. Organic causes were intracranial tumors, 44 (55.7%), Langerhans cell histiocytosis (LCH), 11 (13.9%) and cerebral malformations in 7 (8.9%) patients, while the idiopathic group was 14 (17.7%) patients. Regarding clinical characteristics suggestive of organicity, headache (p=0.02) and visual disturbances (p=0.01) were found statistically significant. The anterior pituitary hormonal abnormalities were documented in 34 (52.3%) organic CDI patients. Furthermore, we did not find a significant difference in the average daily dose of desmopressin between patients with permanent vs. transitory CDI (0.81±0.65 vs. 0.59±0.62; p=0.363). The main clinical features suggestive of organicity in pediatric patients with central diabetes insipidus were headache and visual disturbances; furthermore, anterior pituitary hormonal abnormalities suggest an underlying organic etiology.

A novel mutation in the AVPR2 gene (222delA) associated with X-linked nephrogenic diabetes insipidus in a boy with growth failure.

PubMed

Abaci, Ayhan; Wood, Kent; Demir, Korcan; Büyükgebiz, Atilla; Böber, Ece; Kopp, Peter

2010-01-01

To study the case of a 2 10/12-year-old boy who had growth failure and delayed bone maturation. We reviewed the history, which revealed that he had had polyuria, polydipsia, lack of weight gain, and frequent vomiting since the age of 5 months. On physical examination, his height was 86 cm (-1.93 standard deviation [SD]), his weight 10.5 kg (-2.67 SD), and he had motor and mental retardation. His maternal great-grandfather also had polyuria and polydipsia (but not diabetes mellitus), suggesting X-linked nephrogenic diabetes insipidus as the underlying cause. The patient underwent a water deprivation-desmopressin test. The coding region of the AVPR2 gene was amplified by polymerase chain reaction and submitted to direct sequence analysis. The water deprivation test confirmed the diagnosis of diabetes insipidus, and administration of desmopressin did not diminish his water secretion. Direct sequencing of the AVPR2 gene revealed a novel deletion of adenine at position 222 (222delA) in exon 2. This mutation is predicted to lead to a frameshift beginning at amino acid 75 and a premature stop codon at position 115 (FS75>115X). His height and weight, as well as his motor skills, improved after initiation of therapy with hydrochlorothiazide and amiloride. Growth delay can be associated with diabetes insipidus. The X-linked nephrogenic diabetes insipidus in this boy is caused by a novel mutation in the AVPR2 gene that is predicted to truncate the receptor protein.

Physiopathology and diagnosis of nephrogenic diabetes insipidus.

PubMed

Devuyst, Olivier

2012-04-01

Nephrogenic diabetes insipidus (NDI) is caused by an improper response of the kidney to the antidiuretic hormone arginine vasopressin (AVP), leading to a decreased ability to concentrate urine which results in polyuria and polydipsia. The clinical diagnosis of NDI relies on demonstration of subnormal ability to concentrate urine despite the presence of AVP. NDI is most commonly acquired, secondary to kidney disorders, electrolyte imbalance and various drugs. Congenital forms of NDI are rare, and most commonly inherited in a X-linked manner with mutations of the AVP receptor type 2 (AVPR2). Mutations of the water channel aquaporin-2 (AQP2) can be detected in autosomal recessive or dominant forms of NDI. Management of NDI should focus on free access to drinking water and reduction of polyuria. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis

PubMed Central

Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

2017-01-01

We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case. PMID:28943556

Idiopathic Fanconi's syndrome with nephrogenic diabetes insipidus in a child who presented as vitamin D resistant rickets--a case report and review of literature.

PubMed

Patra, Soumya; Nadri, Gulnaz; Chowdhary, Harish; Pemde, Harish K; Singh, Varinder; Chandra, Jagdish

2011-01-01

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and a child mainly presents with dehydration and hypernatremia. We report the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus (NDI) in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi's syndrome. We hypothesized that the NDI may be due to severe hypokalemia induced tubular dysfunction. The child was treated for hypophosphatemic rickets with severe metabolic acidosis and the treatment for NDI was also given. Now he has healed rickets and normal blood pH, sodium and osmolarity.

A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.

PubMed

Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R; Fagerberg, Christina; Dieperink, Hans; Rittig, Søren; Jensen, Boye L

2016-04-01

Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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

PubMed

Vergier, J; Fromonot, J; Alvares De Azevedo Macedo, A; Godefroy, A; Marquant, E; Guieu, R; Tsimaratos, M; Reynaud, R

2018-01-01

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 (<4h). 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. A 7-month-old infant presented polyuria-polydipsia syndrome with poor weight gain. Laboratory tests pointed out hypernatremia (170mmol/L) and blood hyperosmolarity (330mOsm/L) with inappropriate urinary hypoosmolarity (168mOsm/L). Plasmatic copeptin measurement was found at a very high level, 303pmol/L (1-14pmol/L). DdAVP administration did not improve the polyuria, confirming the final diagnosis of NDI. Hyperhydration with a hypoosmolar diet normalized the hydration status and circulating levels of copeptin within 1 week. Copeptin, a stable peptide reflecting AVP secretion, could be a safer and faster biomarker for etiological diagnosis of polyuria-polydipsia syndrome in children. Before regularization of hydration status, a single baseline measurement may be enough to discriminate NDI from other etiologies without the water deprivation test. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

PubMed

Schreckinger, Matthew; Walker, Blake; Knepper, Jordan; Hornyak, Mark; Hong, David; Kim, Jung-Min; Folbe, Adam; Guthikonda, Murali; Mittal, Sandeep; Szerlip, Nicholas J

2013-12-01

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus

Pitfall in the Diagnosis of Diabetes Insipidus and Pregnancy

PubMed Central

Fleischer, Jessica B.; Khandji, Alexander G.; Wardlaw, Sharon L.

2017-01-01

Diabetes insipidus (DI) during pregnancy and the perinatal period is an uncommon medical problem characterized by polyuria and excessive thirst. Diagnosis of DI may be overlooked in the setting of pregnancy, a time when increased water intake and urine output are commonly reported. We report two cases: one of transient DI in a young woman during her third trimester of twin pregnancy in association with acute fatty liver and hypertension and one of postpartum DI secondary to Sheehan syndrome from rupture of a splenic artery aneurysm. These cases illustrate the spectrum with which DI related to pregnancy and delivery can present and highlight the difficulty in making the diagnosis since the symptoms are often initially overlooked. PMID:28819576

Exacerbation of pre-existing diabetes insipidus during pregnancy, mechanisms and management.

PubMed

Tack, Lloyd J W; T'Sjoen, Guy; Lapauw, Bruno

2017-06-01

During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed.

Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

PubMed

Sanghi, Vedha; Kapoor, Aanchal

2016-01-01

Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

[Clinical characteristics of central diabetes insipidus: a retrospective analysis of 230 cases].

PubMed

Zhang, J P; Guo, Q H; Mu, Y M; Lyu, Z H; Gu, W J; Yang, G Q; Du, J; Ba, J M; Lu, J M

2018-03-01

Objective: To evaluate the clinical characteristics and etiologies of central diabetes insipidus (CDI). Methods: The clinical data of 230 patients with CDI in the Department of Endocrinology of Chinese PLA General Hospital from 2008 June to 2014 December were collected and analyzed retrospectively. Results: The three most common causes of CDI were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. Among all the CDI, the idiopathic CDI accounted for 37.48%. There were significant differences in age onset and gender distribution among the different causes of CDI. The patients with intracranial germ cell tumors [age of onset(19.2±10.2) years] were younger than the other types of CDI. Germ cell tumors patients were more common in male, and lymphocytic hypophysitis patients were more common in female. The most frequent abnormality of anterior pituitary in patients with CDI was growth hormone deficiency, followed by hypogonadism, adrenal insufficiency and hypothyroidism. The dysfunction of thyroid axis and adrenal axis in patients with germ cell tumor was more common than those in patients with idiopathic and lymphocytic hypophysitis. Conclusions: The most common causes of central diabetes insipidus were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. There were differences in age of onset, gender distribution and abnormal production of anterior pituitary hormones among all causes of CDI patients.

[Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

PubMed

Morin, Denis

2014-12-01

Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

[Acute myeloid leukemia with monosomy 7 and inv(3)(q21q26.2) complicated with central diabetes insipidus].

PubMed

Nanno, Satoru; Hagihara, Kiyoyuki; Sakabe, Manami; Okamura, Hiroshi; Inaba, Akiko; Nagata, Yuki; Nishimoto, Mitsutaka; Koh, Hideo; Nakao, Yoshitaka; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

2013-04-01

A 20-year-old female presented with thirst, polyposia, and polyuria and was referred to our hospital because of leukocytosis and anemia. Bone marrow aspiration revealed 66.8% myeloperoxidase-positive blasts and trilineage myelodysplasia. The karyotype was 45, XX, inv(3)(q21q26.2), -7[19]. Therefore, a diagnosis of AML with inv(3)(q21q26.2) complicated by -7 was made. Moreover, hyposthenuria and a low anti-diuretic hormone (ADH) level were observed. Although cerebrospinal fluid analysis was normal, magnetic resonance imaging (MRI) revealed the absence of hyperintensity in the neurohypophysis in T1-weighted images. Therefore, she was also diagnosed with diabetes insipidus. After she was administered a desmopressin nasal spray, the volume of urine produced decreased. Following treatment with second induction therapy containing high-dose cytarabine for AML, she achieved complete remission in the bone marrow. Moreover, when the abnormality on MRI and the volume of urine were normalized, she discontinued desmopressin. Although diabetes insipidus is a rare complication of AML, the majority of AML patients who have diabetes insipidus have the abnormal karyotypes with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7. Further study is required to clarify the pathogenesis and develop a strategy for the treatment of this category of AML.

[Importance of long-term follow-up of diabetes insipidus; from lymphocytic hypophysitis to germinoma].

PubMed

Amat Madramany, A; Gastaldo Simeón, E; Revert Ventura, A; Escobar Hoyos, L A; Riesgo Suárez, P

2015-01-01

A case is presented of a 10-year old boy who had a hypothalamic-pituitary axis disorder. He initially presented with diabetes insipidus that progressed to panhypopituitarism. A hidden hypothalamic lesion should be suspected in all these cases, and should be followed up. New lesions were found in the pituitary stem three years later. Although tumor markers were negative, there was an increase in size, and a biopsy was performed. The histopathology reported a Lymphocytic Hypophysitis. There were increases in the tumor markers during the follow-up, thus a second biopsy was performed, with the diagnosis of Germinoma. Lymphocytic Hypophysitis is an uncommon diagnosis in children. Few cases have been reported, and in some cases, they were later diagnosed with Germinoma. We believe this case highlights the importance of the follow-up of children with Central Diabetes Insipidus with a normal MRI, as well as not taking the diagnosis of Lymphocytic Hypophysitis/lymphocytic Infundibular neurohypophysitis as definitive, as it is a rare diagnosis at this age, and could mask a Germinoma, as recorded in some cases. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter.

PubMed

Giri, Dinesh; Hart, Rachel; Jones, Caroline; Ellis, Ian; Ramakrishnan, Renuka

2016-01-01

Hereditary nephrogenic diabetes iInsipidus (HNDI) is an uncommon disorder due to a resistance to anti-diuretic hormone leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes. We report a mother and daughter in the same family with HNDI due to a heterozygous deletion in exon 1 of the AVPR2 gene, not previously described in the literature. A 5-year-old girl was referred for investigation of polyuria and polydipsia. The patient had a water deprivation test elsewhere at the age of 3 that was inconclusive. A degree of water restriction was imposed leading to headaches. The thyroid, cortisol, renal, and calcium profiles were normal. Her mother showed similar symptoms that had not been previously investigated. AQP2 (Aquaporin) and initial AVPR2 gene sequencing had not identified a mutation, but subsequent quantitative polymerase chain reaction analysis revealed a heterozygous large exon 1 deletion of the AVPR2 gene. The same deletion was also found in the child's mother. The patient's symptoms have significantly improved on appropriate treatment. Further analysis revealed skewed X inactivation in mother and daughter.

A Rare Case of Congenital Diabetes Insipidus.

PubMed

Rege, Tanvi; Polsani, Srujana; Jim, Belinda

2015-01-01

Congenital nephrogenic diabetes insipidus (NDI) is a conformation disease resulting from protein misfolding. Ninety percent of mutations result from the inactivating mutations of the arginine vasopressin receptor 2 (AVPR2) gene transmitted in an X-linked fashion, blocking the response to vasopressin, resulting in the inability to concentrate urine. Clinical features include polyuria, polydispsia, dehydration, and hypernatremia. They are generally more severely in affected males but present variably in females due to skewed inactivation of the X chromosome. We describe a case of a 40-year-old woman with a history of Type 2 diabetes mellitus, hyperlipidemia, and obesity, who presents with debilitating polyuria since the age of 5 with no clear diagnosis. Interestingly, her son was diagnosed with NDI. Genetic testing revealed that she was heterozygous for the Val88Met mutation in the AVPR2 gene while her son was hemizygous for the same. The patient has since been successfully treated with diuretics and a low solute diet. We highlight that although X-linked NDI patients are mostly males, it should be considered in symptomatic females to prevent delays in the diagnosis. Conformational diseases such as NDI are presently the subject of research using pharmacological chaperones to restore proper receptor membrane localization and function.

A Rare Case of Congenital Diabetes Insipidus

PubMed Central

Rege, Tanvi; Polsani, Srujana; Jim, Belinda

2015-01-01

Congenital nephrogenic diabetes insipidus (NDI) is a conformation disease resulting from protein misfolding. Ninety percent of mutations result from the inactivating mutations of the arginine vasopressin receptor 2 (AVPR2) gene transmitted in an X-linked fashion, blocking the response to vasopressin, resulting in the inability to concentrate urine. Clinical features include polyuria, polydispsia, dehydration, and hypernatremia. They are generally more severely in affected males but present variably in females due to skewed inactivation of the X chromosome. We describe a case of a 40-year-old woman with a history of Type 2 diabetes mellitus, hyperlipidemia, and obesity, who presents with debilitating polyuria since the age of 5 with no clear diagnosis. Interestingly, her son was diagnosed with NDI. Genetic testing revealed that she was heterozygous for the Val88Met mutation in the AVPR2 gene while her son was hemizygous for the same. The patient has since been successfully treated with diuretics and a low solute diet. We highlight that although X-linked NDI patients are mostly males, it should be considered in symptomatic females to prevent delays in the diagnosis. Conformational diseases such as NDI are presently the subject of research using pharmacological chaperones to restore proper receptor membrane localization and function. PMID:26217664

Diabetes insipidus: Differential diagnosis and management.

PubMed

Robertson, Gary L

2016-03-01

Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of dilute urine. It can be caused by any of 4 fundamentally different defects that must be distinguished for safe and effective management. They are: (1) pituitary DI, due to inadequate production and secretion of antidiuretic hormone, arginine-vasopressin (AVP); (2) gestational DI due to degradation of AVP by an enzyme made in placenta; (3) primary polydipsia, due to suppression of AVP secretion by excessive fluid intake; and (4) nephrogenic DI due to renal insensitivity to the antidiuretic effect of AVP. This review describes several methods of differential diagnosis, indicates the advantages and disadvantages of each and presents a new approach that is simpler and less costly but just as reliable as the best of the older methods. The various treatments for the different types of DI and recent findings on the genetic basis of the familial forms of DI are also discussed with emphasis on their contributions to improved diagnosis and management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spontaneous intermittent MRI changes of a pituitary stalk lesion causing diabetes insipidus and amenorrhea.

PubMed

Curtò, Lorenzo; Trimarchi, Francesco; Cannavo, Salvatore

2017-04-01

Lymphocytic infundibulo-neurohypophysitis is a rare disorder. We report the case of a 29 year-old woman with diabetes insipidus and amenorrhea, in whom the magnetic resonance imaging demonstration of a pituitary stalk lesion was intermittent. We suggest that, in patients with endocrine dysfunction and positivity of circulating antipituitary antibodies at high title, magnetic resonance imaging should be repeated after few months, if negative.

Nephrogenic diabetes insipidus.

PubMed

Bockenhauer, D; Bichet, Daniel G

2017-04-01

In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In congenital NDI, polyuria and polydipsia are present from birth and should be immediately recognized to avoid severe episodes of dehydration. Unfortunately, NDI is still often recognized late after a 'diagnostic odyssey' involving false leads and dangerous treatments.Once diagnosed, appropriate treatment can be started. Moreover, laboratory studies have identified promising new compounds, which may help achieve urinary concentration independent of vasopressin. MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome.We distinguish two types of hereditary NDI: a 'pure' type with loss of water only and a complex type with loss of water and ions. Mutations in the AVPR2 or AQP2 genes, encoding the vasopressin V2 receptor and the water channel Aquaporin2, respectively, lead to a 'pure' NDI with loss of water but normal conservation of ions. Mutations in genes that encode membrane proteins involved in sodium chloride reabsorption in the thick ascending limb of Henle's loop lead to Bartter syndrome, a complex polyuric-polydipsic disorder often presenting with polyhydramnios. A new variant of this was recently identified: seven families were described with transient antenatal Bartter's syndrome, polyhydramnios and MAGED2 mutations.Multiple compounds have been identified experimentally that may stimulate urinary concentration independently of the vasopressin V2 receptor. These compounds may provide new treatments for patients with X-linked NDI. A plea for early consideration of the diagnosis of NDI, confirmation by phenotypic and/or genetic testing and appropriate adjustment of treatment in affected patients.

Diabetes insipidus after discontinuation of vasopressin infusion for septic shock.

PubMed

Rana, H; Ferguson, N; Dicpinigaitis, P V

2018-04-01

Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported. A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption. Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated. © 2017 John Wiley & Sons Ltd.

Rathke cleft cyst in seven-year-old girl presenting with central diabetes insipidus and review of literature.

PubMed

Evliyaoglu, Olcay; Evliyaoglu, Cetin; Ayva, Sebnem

2010-05-01

Rathke cleft cysts (RCC) are benign cysts derived from remnants of Rathke cleft, and are rarely symptomatic in children. Symptoms due to RCC are associated with mass effect and pituitary hormone deficiencies. Slow growth rate of the cyst makes its incidence increase with aging. Here we report on a seven-year-old girl who presented with central diabetes insipidus (CDI). Her sella MRI revealed a lesion in the sellar region which grew rapidly in follow-up. She underwent microneurosurgical operation and the lesion was totally excised. Pathologic examination revealed RCC with degenerative changes. In her follow-up, growth hormone deficiency developed in addition to arginine vasopressin deficiency. Rapid growth of the cyst is not the usual course of RCC's. Mechanisms regarding the cyst growth are unclear as they are in this case. This is the youngest child to date presenting with central diabetes insipidus due to RCC. Rapid growth of RCC can cause CDI in young children.

Diabetes insipidus--diagnosis and management.

PubMed

Di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna Elsa Maria; Olivieri, Irene; Bertelli, Enrica; Gallizia, Annalisa; Rossi, Andrea; Maghnie, Mohamad

2012-01-01

Central diabetes insipidus (CDI) is the end result of a number of conditions that affect the hypothalamic-neurohypophyseal system. The known causes include germinoma/craniopharyngioma, Langerhans cell histiocytosis (LCH), local inflammatory, autoimmune or vascular diseases, trauma resulting from surgery or an accident, sarcoidosis, metastases and midline cerebral and cranial malformations. In rare cases, the underlying cause can be genetic defects in vasopressin synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits. The diagnosis of the underlying condition is challenging and raises several concerns for patients and parents as it requires long-term follow-up. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress to more sophisticated tools. Specifically, MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered a clear marker of neurohypophyseal functional integrity, together with the careful analysis of pituitary stalk shape and size, have provided the most striking findings contributing to the diagnosis and understanding of some forms of 'idiopathic' CDI. MRI STIR (short-inversion-time inversion recovery sequencing) is a promising technology for the early identification of LCH-dependent CDI. Copyright © 2012 S. Karger AG, Basel.

Acquired nephrogenic diabetes insipidus in a dog with leptospirosis

PubMed Central

2014-01-01

A 5 year old male neutered Cairn Terrier was evaluated for signs of polyuria and polydipsia. Initial hematology and chemistry panels were unremarkable and urinalysis showed a persistent hyposthenuria. Eleven days later, the dog became lethargic, inappetent and had developed acute renal failure. The dog was ultimately euthanized due to a poor response to treatment. Microscopic agglutination titres were consistent with a diagnosis of leptospirosis. The initial hyposthenuria in this case was consistent with acquired nephrogenic diabetes insipidus. This is an uncommon presentation of leptospirosis that has not previously been described to progress to acute renal failure. Leptospirosis should be considered as a differential diagnosis in any dog presenting with polyuria and polydipsia and these patients should be treated as a zoonotic risk. PMID:24739820

Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

PubMed

Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

2016-04-01

Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

Partial Nephrogenic Diabetes Insipidus in a Burned Patient Receiving Sevoflurane Sedation With an Anesthetic Conserving Device-A Case Report.

PubMed

Muyldermans, Marie; Jennes, Serge; Morrison, Stuart; Soete, Olivier; François, Pierre-Michel; Keersebilck, Elkana; Rose, Thomas; Pantet, Olivier

2016-12-01

To describe a case of partial nephrogenic diabetes insipidus in a burned patient after prolonged delivery of low inspired concentrations of sevoflurane via an Anesthetic Conserving Device. Clinical observation. Case report. Relevant clinical information. A 34-year-old man was admitted with burns covering 52% of his total body surface area. Mechanical ventilation was provided during sedation with continuous infusions of sufentanil and midazolam. Sedation became increasingly difficult, and in order to limit administration of IV agents, sevoflurane was added to the inspiratory gas flow. This was provided using an Anesthetic Conserving Device and continued for 8 days. The patient rapidly developed polyuria and hypernatremia with an inappropriate decrease in urinary osmolality. Administration of desmopressin resulted in only a modest effect on renal concentrating ability. After cessation of sevoflurane, all variables returned to normal within 5 days. The results of further investigations (cerebral computed tomographic scan, cerebral magnetic resonance imaging, and serum arginine vasopressin concentration) were compatible with a diagnosis of partial nephrogenic diabetes insipidus. The temporal sequence of clinical findings in relation to sevoflurane administration suggests that the sevoflurane was the probable underlying cause. Clinicians should be aware of the possibility of sevoflurane-induced diabetes insipidus not only during general anesthesia but also in the intensive care setting of sedation in critically ill patients. This is especially important in patients, such as those with severe burns, in whom preserved renal concentrating ability is important to ensure compensation for extrarenal fluid losses.

Hereditary Nephrogenic Diabetes Insipidus: Pathophysiology and Possible Treatment. An Update

PubMed Central

Milano, Serena; Carmosino, Monica; Gerbino, Andrea; Svelto, Maria

2017-01-01

Under physiological conditions, excessive loss of water through the urine is prevented by the release of the antidiuretic hormone arginine-vasopressin (AVP) from the posterior pituitary. In the kidney, AVP elicits a number of cellular responses, which converge on increasing the osmotic reabsorption of water in the collecting duct. One of the key events triggered by the binding of AVP to its type-2 receptor (AVPR2) is the exocytosis of the water channel aquaporin 2 (AQP2) at the apical membrane the principal cells of the collecting duct. Mutations of either AVPR2 or AQP2 result in a genetic disease known as nephrogenic diabetes insipidus, which is characterized by the lack of responsiveness of the collecting duct to the antidiuretic action of AVP. The affected subject, being incapable of concentrating the urine, presents marked polyuria and compensatory polydipsia and is constantly at risk of severe dehydration. The molecular bases of the disease are fully uncovered, as well as the genetic or clinical tests for a prompt diagnosis of the disease in newborns. A real cure for nephrogenic diabetes insipidus (NDI) is still missing, and the main symptoms of the disease are handled with s continuous supply of water, a restrictive diet, and nonspecific drugs. Unfortunately, the current therapeutic options are limited and only partially beneficial. Further investigation in vitro or using the available animal models of the disease, combined with clinical trials, will eventually lead to the identification of one or more targeted strategies that will improve or replace the current conventional therapy and grant NDI patients a better quality of life. Here we provide an updated overview of the genetic defects causing NDI, the most recent strategies under investigation for rescuing the activity of mutated AVPR2 or AQP2, or for bypassing defective AVPR2 signaling and restoring AQP2 plasma membrane expression. PMID:29125546

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency☆

PubMed Central

Frank, Graeme R.; Fox, Joyce; Candela, Ninfa; Jovanovic, Zorica; Bochukova, Elena; Levine, Jeremiah; Papenhausen, Peter R.; O'Rahilly, Stephen; Farooqi, I. Sadaf

2013-01-01

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation. PMID:23800642

Diabetes Insipidus after Traumatic Brain Injury

PubMed Central

Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki

2015-01-01

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685

Diabetes Insipidus: An Unusual Presentation of Adenocarcinoma of the Lung in a Patient with no Identifiable Lung Mass.

PubMed

Gulati, Shuchi; Kiefer, Christoper; Karim, Nagla Abdel

2015-10-01

Lung cancers are known to metastasize to unusual sites. Despite this knowledge often times the diagnosis of a primary lung cancer gets delayed especially when the patient presents without respiratory symptoms. The patient discussed in our review is a 47-year-old female, smoker who had presented to several hospitals with months of headache, nausea and intermittent episodes of vomiting. She was noted to have hypernatremia due to diabetes insipidus and a pituitary lesion on her magnetic resonance images. The pituitary mass on biopsy was found to represent a metastatic focus from a primary lung adenocarcinoma. Clinicians should be aware of malignancies that are well known to metastasize to the posterior pituitary. Conversely, since not every patient presents with symptoms of metastasis, there is a need to recognize the clinical syndromes (e. g., diabetes insipidus-like symptoms or more subtle symptoms like cranial nerve palsies) associated with potential metastasis to the pituitary.

Desmopressin administration in children with central diabetes insipidus: a retrospective review.

PubMed

Ooi, Hooi Leng; Maguire, Ann M; Ambler, Geoffrey R

2013-01-01

Central diabetes insipidus (DI) is a rare disorder in children caused by a deficiency of antidiuretic hormone arginine (vasopressin). Desmopressin is the first line agent in management of central DI. However, one of the side effects of desmopressin is water intoxication and hyponatraemia. This study reviews the patterns of desmopressin use and side effects in our institution. Retrospective chart review of all patients with central DI followed up in one tertiary centre between 1 January 2008 and 31 December 2010. Forty-one patients (22 males and 19 females) were included. Twelve patients (29.3%) had congenital and 29 patients (70.7%) had acquired DI, mostly as a result of intracranial tumours. Thirty-six (87.8%) patients were on oral desmopressin and the remaining on nasal formulation. The median oral dose was 9.5 (4.2-17.0) μg/kg/day with median frequency of 2.5 (2-3). The median nasal dose was 0.7 (0.4-1.4) μg/kg/day with median frequency of 2.0 (2-3.5). Fourteen patients (34.1%) were switched from nasal to oral desmopressin with the median dose conversion factor of 20.1 (10.7-31.8). Forty percent of patients on nasal desmopressin experienced hypo/hypernatraemia compared to 18.1% on oral, however, there were no significance difference between standardized hypo/hypernatraemia episodes per treatment year. Oral desmopressin is used in the majority of our patients including infants and toddlers. There is wide inter-individual variation in dose requirement and dosing intervals. Management of central diabetes insipidus remains a challenge in adipsic patients and in young children during intercurrent illness regardless of the desmopressin formulation.

Diabetes insipidus.

PubMed

Leroy, Clara; Karrouz, Wassila; Douillard, Claire; Do Cao, Christine; Cortet, Christine; Wémeau, Jean-Louis; Vantyghem, Marie-Christine

2013-12-01

Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of dehydration, bladder distention, pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome, granulomatosis and cancer is required. The diagnosis is based on biological assessment, pituitary magnetic resonance imaging (MRI) and results of a desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years, and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to hypopituitarism, including DI in 2% of

Prevalence and risk factors for central diabetes insipidus in cardiac arrest survivor treated with targeted temperature management.

PubMed

Lee, Dong Hun; Lee, Byung Kook; Song, Kyoung Hwan; Jung, Yong Hun; Park, Jung Soo; Lee, Sung Min; Cho, Yong Soo; Kim, Jin Woong; Jeung, Kyung Woon

2016-08-01

Central diabetes insipidus (CDI) is a marker of severe brain injury. Here we aimed to investigate the prevalence and risk factors of CDI in cardiac arrest survivors treated with targeted temperature management (TTM). This retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM between 2008 and 2014. Central diabetes insipidus was confirmed if all of the following criteria were met: urine volume >50 cc kg(-1) d(-1), serum osmolarity >300 mmol/L, urine osmolarity <300 mmol/L, and serum sodium >145 mEq/L. The primary outcome was the incidence of CDI. Of the 385 included patients, 45 (11.7%) had confirmed central CDI. Univariate analysis showed that younger age, nonwitness of collapse, nonshockable rhythm, a high incidence of asphyxia arrest, longer downtime, and lower initial core temperature were associated with CDI development. Patients with CDI had a higher incidence of poor neurologic outcomes at discharge and higher in-hospital mortality rate (20/45 vs 76/340, P= .001) as well as 180-day mortality (44/45 vs 174/340, P< .001). Multivariate analysis revealed that age (odds ratio [OR], 0.963; 95% confidence interval [CI], 0.942-0.984), shockable rhythm (OR, 0.077; 95% CI, 0.009-0.662), downtime (OR, 1.025; 95% CI, 1.006-1.044), and asphyxia etiology (OR, 6.815; 95% CI, 2.457-18.899) were independently associated with CDI development. Central diabetes insipidus developed in 12% of cardiac arrest survivors treated with TTM, and those with CDI showed poor neurologic outcomes and high mortality rates. Younger age, nonshockable rhythm, long downtime, and asphyxia arrest were significant risk factors for development of CDI. Copyright © 2016 Elsevier Inc. All rights reserved.

Two novel mutations in seven Czech and Slovak kindreds with familial neurohypophyseal diabetes insipidus-benefit of genetic testing.

PubMed

Hrčková, Gabriela; Jankó, Viktor; Kytnarová, Jitka; Čižmárová, Michaela; Tesařová, Markéta; Košťálová, Ľudmila; Virgová, Daniela; Dallos, Tomáš; Hána, Václav; Lebl, Jan; Zeman, Jiří; Kovács, László

2016-09-01

Familial neurohypophyseal diabetes insipidus (FNDI) is a rare hereditary disorder with unknown prevalence characterized by arginine-vasopressin hormone (AVP) deficiency resulting in polyuria and polydipsia from early childhood. We report the clinical manifestation and genetic test results in seven unrelated kindreds of Czech or Slovak origin with FNDI phenotype. The age of the sign outset ranged from 2 to 17 years with remarkable interfamilial and intrafamilial variability. Inconclusive result of the fluid deprivation test in three children aged 7 and 17 years old might cause misdiagnosis; however, the AVP gene analysis confirmed the FNDI. The seven families segregated together five different mutations, two of them were novel (c.164C > A, c.298G > C). In addition, DNA analysis proved mutation carrier status in one asymptomatic 1-year-old infant. The present study together with previously published data identified 38 individuals with FNDI in the studied population of 16 million which predicts a disease prevalence of 1:450,000 for the Central European region. The paper underscores that diagnostic water deprivation test may be inconclusive in polyuric children with partial diabetes insipidus and points to the clinical importance and feasibility of molecular genetic testing for AVP gene mutations in the proband and her/his first degree relatives. • At least 70 different mutations were reported to date in about 100 families with neurohypophyseal diabetes insipidus (FNDI), and new mutations appear sporadically. What is New: • Two novel mutations of the AVP gene are reported • The importance of molecular testing in children with polyuria and inconclusive water deprivation test is emphasized.

A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree

PubMed Central

Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi

2016-01-01

Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 (AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband’s mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene. PMID:27565746

A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

PubMed

Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

2016-10-01

Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 ( AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM)

PubMed Central

Shin, Hyun-Jong; Kim, Jae-Ha; Han, Sang-Woong; Kim, Ho-Jung

2012-01-01

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature. PMID:23508726

Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM).

PubMed

Shin, Hyun-Jong; Kim, Jae-Ha; Yi, Joo-Hark; Han, Sang-Woong; Kim, Ho-Jung

2012-12-01

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.

Hypervitaminosis D causing nephrogenic diabetes insipidus in a 5-month-old infant.

PubMed

Ahmad, Ihab A; Al-Agha, Abdulmoein E

2013-02-01

Vitamin D intoxication in infancy leads to acute hypercalcemia and subsequent hypercalcuria with nephrocalcinosis. Strategies used for patients with vitamin D intoxication are unsatisfactory and associated with prolonged periods of hypercalcemia. We present a 5-month-old infant who had failure to thrive, refusal to feed, delayed motor development, truncal hypotonia, and dehydration. She had high plasma sodium and osmolality with low urine osmolality, and did not respond to intravenous desmopressin administration. She was diagnosed as nephrogenic diabetes insipidus due to hypercalcemia caused by hypervitaminosis D, and was treated with hydrochlorothiazide 2 mg/kg twice daily, and hydration.

Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

PubMed

Frank, Graeme R; Fox, Joyce; Candela, Ninfa; Jovanovic, Zorica; Bochukova, Elena; Levine, Jeremiah; Papenhausen, Peter R; O'Rahilly, Stephen; Farooqi, I Sadaf

2013-01-01

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

PubMed

Bockenhauer, D; Bichet, D G

2013-04-15

The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

Lymphocytic hypophysitis in a dog with diabetes insipidus.

PubMed

Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J

2012-11-01

An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mechanisms underlying progressive polyuria in familial neurohypophysial diabetes insipidus.

PubMed

Arima, H; Oiso, Y

2010-07-01

Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). The analyses of knock-in mice expressing a mutant NPII that causes FNDI in humans demonstrated that polyuria progressed substantially in the absence of loss of AVP neurones. Morphological analyses revealed that inclusion bodies were present in the AVP neurones in the supraoptic nucleus and that the size and numbers of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) of AVP neurones. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregate formation in the ER is likely to be related to the pathogenesis of the progressive polyuria.

Central diabetes insipidus following cardiopulmonary arrest in a dog.

PubMed

Bellis, Tara; Daly, Meredith; Davidson, Benjamin

2015-01-01

To describe a clinical case of transient central diabetes insipidus (CDI) occurring post cardiopulmonary arrest (CPA) in a dog. An 8-week-old dog presented for intensive care after successful resuscitation following CPA. The patient exhibited neurologic deficits at initial presentation and over the following days developed marked polyuria, isosthenuria, and low urine osmolality. Treatment with synthetic vasopressin resulted in a reduction in urine output, increase in urine specific gravity (>50%), and increase in urine osmolality, suggesting a diagnosis of partial CDI. Clinical signs resolved over the following weeks and treatment was discontinued. CPA has been described as a cause of ischemic injury to the pituitary gland resulting in CDI in people. To the authors' knowledge, this is the first report of a dog developing transient partial CDI following CPA and successful resuscitation. © Veterinary Emergency and Critical Care Society 2015.

Type III Bartter-like syndrome in an infant boy with Gitelman syndrome and autosomal dominant familial neurohypophyseal diabetes insipidus.

PubMed

Brugnara, Milena; Gaudino, Rossella; Tedeschi, Silvana; Syrèn, Marie-Louise; Perrotta, Silverio; Maines, Evelina; Zaffanello, Marco

2014-09-01

We report the case of an infant boy with polyuria and a familial history of central diabetes insipidus. Laboratory blood tests disclosed hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Plasma magnesium concentration was slightly low. Urine analysis showed hypercalciuria, hyposthenuria, and high excretion of potassium. Such findings oriented toward type III Bartter syndrome (BSIII). Direct sequencing of the CLCNKB gene revealed no disease-causing mutations. The water deprivation test was positive. Magnetic resonance imaging showed a lack of posterior pituitary hyperintensity. Finally, direct sequencing of the AVP-NPII gene showed a point mutation (c.1884G>A) in a heterozygous state, confirming an autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). This condition did not explain the patient's phenotype; thus, we investigated for Gitelman syndrome (GS). A direct sequencing of the SLC12A3 gene showed c.269A>C and c.1205C>A new mutations. In conclusion, the patient had a genetic combination of GS and adFNDI with a BSIII-like phenotype.

Objective assessment of thirst recovery in patients with adipsic diabetes insipidus.

PubMed

Sinha, A; Ball, S; Jenkins, A; Hale, J; Cheetham, T

2011-12-01

Adipsic diabetes insipidus (ADI) is characterised by impaired thirst and defective AVP secretion. We have assessed the thirst response to graded osmotic stimulation using a visual analog scale (VAS) in patients with a history of ADI following surgery for a craniopharyngioma. The patients were thought to be regaining their thirst response but we wanted to confirm that this was the case objectively before relaxing their strict fluid balance regimen. Three patients with adipisa in the presence of hypernatremia following surgery for a craniopharyngioma are described. Their median age at surgery was 13 years (range 11-15 years). All patients had previously demonstrated no desire to drink despite a serum osmolality in excess of 300 mOsmol/kg. Fluid balance was maintained postoperatively with a regimen involving a fixed daily fluid intake and DDAVP dose together with daily weights and regular assessment of capillary sodium concentrations. Patients were thought to be regaining thirst sensation and so were assessed by hypertonic saline infusion (HSI) with thirst measured using a VAS. Patients underwent a HSI test 4, 6 and 9 months post surgery. All had abnormally low AVP production at raised plasma osmolalities but the visual analogue scale confirmed partial or complete thirst recovery. The intensive regimen used to maintain stable serum sodium concentrations was relaxed without the patients subsequently developing a significant hyperosmolar state. We have shown objective recovery of thirst perception in patients with adipsia within 9 months of surgery, despite persistence of cranial diabetes insipidus. These observations indicate that both osmoreceptors regulating thirst and their efferent pathways demonstrate more plasticity than those regulating AVP production. The HSI and thirst VAS are an objective way of assessing patients known to have ADI who are thought to be recovering thirst perception.

Dilatative uropathy as a manifestation of neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin-II gene.

PubMed

Lindenthal, V; Mainberger, A; Morris-Rosendahl, D J; Löning, L; Mayer, W; Müller, H L

2013-12-01

Polydypsia and polyuria are frequent symptoms in patients with sellar masses caused by neurohypophyseal diabetes insipidus. Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the arginine vasopressin (AVP) -neurophysin II (NPII) gene, should be considered as a rare differential diagnosis. A delayed diagnosis bears the risk of life-threatening electrolyte imbalances and permanent urinary tract damage, leading to impaired quality of life.We present a Caucasian kindred of at least 4 generations with FNDI.Clinical histories, endocrine para-meters, and results of molecular analyses of the AVP gene are presented with a review of the literature on diabetes insipidus (DI) related urinary tract dilatation.Polyuria and polydipsia were only reported based on explicit and thorough interrogation after more than 4 years of clinical follow-up. A novel heterozygous mutation in the AVP gene was found in all examined symptomatic subjects (c.1-33_c.4del37nt). A literature review revealed that non-obstructive hydronephrosis (NOH) is a rare but known complication of DI.Since increased fluid intake is often a typical familial pattern in adFNDI, it is frequently missed as being pathologic in affected patients, therefore a detailed clinical history of drinking volumes is of critical importance. AVP gene testing is an important component in the confirmation of the diagnosis. Otherwise unexplainable NOH should lead to further investigations and evaluation of rare diseases like FNDI. © Georg Thieme Verlag KG Stuttgart · New York.

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

PubMed

Schernthaner-Reiter, Marie Helene; Adams, David; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fabio R; Nilsson, Ola; Nella, Aikaterini A; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William; Stratakis, Constantine A

2016-05-01

X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis. • X-linked nephrogenic diabetes insipidus is caused by AVPR2 mutations, and disease severity can vary depending on the functional effect of the mutation. What is New: • We demonstrate here that a splice site mutation in AVPR2 leads to partial X-linked NDI in two brothers. • Treatment with high-dose DDAVP led to improvement of polyuria and polydipsia, weight gain, and growth.

Frequent occurrence of the triphasic response (diabetes insipidus/hyponatremia/diabetes insipidus) after surgery for craniopharyngioma in childhood.

PubMed

Finken, Martijn J J; Zwaveling-Soonawala, Nitash; Walenkamp, Marie J E; Vulsma, Thomas; van Trotsenburg, A S Paul; Rotteveel, Joost

2011-01-01

It is not exactly known how many children develop the triphasic response (diabetes insipidus (DI)/hyponatremia/DI) immediately after surgery for childhood craniopharyngioma; neither is it known which factors predict this. We studied the occurrence of the triphasic response after primary surgery for craniopharyngioma in children, and aimed to identify possible predictors. Patients <18 years old who had undergone a primary craniopharyngioma resection between January 1990 and February 2010 in either of the 2 academic centers in Amsterdam were studied retrospectively. Twenty-one patients (5 males) fulfilled the inclusion criteria. Median age at surgery was 9.1 (range: 4.0-15.1) years. Six patients developed a triphasic response (29%). Of all factors, only the duration of surgery was found to be a predictor of a triphasic response: 8.5 (6.0-11.0) versus 4.6 (3.5-11.5) h in patients who did not develop a triphasic response (p = 0.03). After primary surgery for a craniopharyngioma, a considerable number of patients develop a triphasic response in the regulation of the sodium and water balance. This is predicted by (factors associated with) a longer duration of surgery. Other predictors could not be identified, which may be due to the small sample size. Copyright © 2011 S. Karger AG, Basel.

Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2.

PubMed

Knops, Noël B B; Bos, Krista K; Kerstjens, Mieke; van Dael, Karin; Vos, Yvonne J

2008-07-15

We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism. 2008 Wiley-Liss, Inc.

A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus.

PubMed Central

Ito, M; Mori, Y; Oiso, Y; Saito, H

1991-01-01

To elucidate the molecular mechanism of familial central diabetes insipidus (FDI), we sequenced the arginine vasopressin-neurophysin II (AVP-NPII) gene in 2 patients belonging to a pedigree that is consistent with an autosomal dominant mode of inheritance. 10 patients with idiopathic central diabetes insipidus (IDI) and 5 normals were also studied. The AVP-NPII gene, locating on chromosome 20, consists of three exons that encode putative signal peptide, AVP, NPII, and glycoprotein. Using polymerase chain reaction, fragments including the promoter region and all coding regions were amplified from genomic DNA and subjected to direct sequencing. Sequences of 10 patients with IDI were identical with those of normals, while in 2 patients with FDI, a single base substitution was detected in one of two alleles of the AVP-NPII gene, indicating they were heterozygotes for this mutation. It was a G----A transition at nucleotide position 1859 in the second exon, resulting in a substitution of Gly for Ser at amino acid position 57 in the NPII moiety. It was speculated that the mutated AVP-NPII precursor or the mutated NPII molecule, through their conformational changes, might be responsible for AVP deficiency. Images PMID:1840604

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus

PubMed Central

Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management. PMID:29527380

Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus.

PubMed

Vergine, Gianluca; Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò

2018-01-01

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.

Acute myeloid leukemia and diabetes insipidus with monosomy 7.

PubMed

Harb, Antoine; Tan, Wei; Wilding, Gregory E; Battiwalla, Minoo; Sait, Sheila N J; Wang, Eunice S; Wetzler, Meir

2009-04-15

The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus.

PubMed

Grunert, Steffen; Labudde, Dirk

2015-01-01

The importance of short membrane sequence motifs has been shown in many works and emphasizes the related sequence motif analysis. Together with specific transmembrane helix-helix interactions, the analysis of interacting sequence parts is helpful for understanding the process during membrane protein folding and in retaining the three-dimensional fold. Here we present a simple high-throughput analysis method for deriving mutational information of interacting sequence parts. Applied on aquaporin water channel proteins, our approach supports the analysis of mutational variants within different interacting subsequences and finally the investigation of natural variants which cause diseases like, for example, nephrogenic diabetes insipidus. In this work we demonstrate a simple method for massive membrane protein data analysis. As shown, the presented in silico analyses provide information about interacting sequence parts which are constrained by protein evolution. We present a simple graphical visualization medium for the representation of evolutionary influenced interaction pattern pairs (EIPPs) adapted to mutagen investigations of aquaporin-2, a protein whose mutants are involved in the rare endocrine disorder known as nephrogenic diabetes insipidus, and membrane proteins in general. Furthermore, we present a new method to derive new evolutionary variations within EIPPs which can be used for further mutagen laboratory investigations.

Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus

PubMed Central

Labudde, Dirk

2015-01-01

The importance of short membrane sequence motifs has been shown in many works and emphasizes the related sequence motif analysis. Together with specific transmembrane helix-helix interactions, the analysis of interacting sequence parts is helpful for understanding the process during membrane protein folding and in retaining the three-dimensional fold. Here we present a simple high-throughput analysis method for deriving mutational information of interacting sequence parts. Applied on aquaporin water channel proteins, our approach supports the analysis of mutational variants within different interacting subsequences and finally the investigation of natural variants which cause diseases like, for example, nephrogenic diabetes insipidus. In this work we demonstrate a simple method for massive membrane protein data analysis. As shown, the presented in silico analyses provide information about interacting sequence parts which are constrained by protein evolution. We present a simple graphical visualization medium for the representation of evolutionary influenced interaction pattern pairs (EIPPs) adapted to mutagen investigations of aquaporin-2, a protein whose mutants are involved in the rare endocrine disorder known as nephrogenic diabetes insipidus, and membrane proteins in general. Furthermore, we present a new method to derive new evolutionary variations within EIPPs which can be used for further mutagen laboratory investigations. PMID:26180540

Central diabetes insipidus: alert for dehydration in very low birth weight infants during the neonatal period. A case report.

PubMed

Ferlin, Maria Lúcia Silveira; Sales, Débora Simone; Celini, Fábia Pereira Martins; Martinelli Junior, Carlos Eduardo

2015-02-01

Central diabetes insipidus (CDI) is a rare cause of hypernatremia during the neonatal period. The diagnosis is particularly difficult in very low birth weight (VLBW) newborns. We report on a preterm newborn who presented CDI soon after birth. On the third day of life, signs of dehydration were present despite normal fluid supply. The diuresis rate was 4.4 ml/kg/h. Although the fluid supply was then increased, the dehydration continued, with hypernatremia, normal glycemia, diuresis of 7.4 ml/kg/h and urine density of 1005 mOsmol/l. Thus, a diagnostic hypothesis of diabetes insipidus was raised. A test with a nasal vasopressin analogue (dDAVP) was performed and CDI was confirmed. Reduction of the fluid supply became possible through appropriate treatment. The diagnosis of CDI is rarely made during the neonatal period, especially in VLBW newborns, because of the difficulty in detecting elevated diuresis. Persistent hypernatremia, usually accompanied by hyperthermia despite abundant fluid supply, weight loss and low urine osmolality are important signs of alert.

Oral desmopressin in central diabetes insipidus.

PubMed Central

Westgren, U; Wittström, C; Harris, A S

1986-01-01

Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12.5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adverse reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision. PMID:3963868

Dengue fever with diffuse cerebral hemorrhages, subdural hematoma and cranial diabetes insipidus.

PubMed

Jayasinghe, Nayomi Shermila; Thalagala, Eranga; Wattegama, Milanka; Thirumavalavan, Kanapathipillai

2016-05-10

Neurological manifestations in dengue fever occur in <1 % of the patients and known to be due to multisystem dysfunction secondary to vascular leakage. Occurrence of wide spread cerebral haemorrhages with subdural hematoma during the leakage phase without profound thrombocytopenia and occurrence of cranial diabetes insipidus are extremely rare and had not been reported in published literature earlier, thus we report the first case. A 24 year old previously healthy lady was admitted on third day of fever with thrombocytopenia. Critical phase started on fifth day with evidence of pleural effusion and moderate ascites. Thirty one hours into critical phase she developed headache, altered level of consciousness, limb rigidity and respiratory depression without definite seizures. Non-contrast CT brain done at tertiary care level revealed diffuse intracranial haemorrhages and sub arachnoid haemorrhages in right frontal, parietal, occipital lobes and brainstem, cerebral oedema with an acute subdural hematoma in right temporo- parietal region. Her platelet count was 40,000 at this time with signs of vascular leakage. She was intubated and ventilated with supportive care. Later on she developed features of cranial diabetes insipidus and it responded to intranasal desmopressin therapy. In spite of above measures signs of brainstem herniation developed and she succumbed to the illness on day 8. Dengue was confirmed serologically. Exact pathophysiological mechanism of diffuse cerebral haemorrhages without profound thrombocytopenia is not well understood. Increased awareness and high degree of clinical suspicion is needed among clinicians for timely diagnosis of this extremely rare complication of dengue fever. We postulate that immunological mechanisms may play a role in pathogenesis. However further comprehensive research and studies are needed to understand the pathophysiological mechanisms leading to this complication.

Management of diabetes insipidus and adipsia in the child.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Napoli, Flavia; Allegri, Anna Elsa Maria; Rossi, Andrea; Maghnie, Mohamad

2015-06-01

Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent national surveillance in Denmark showed a prevalence rate of twenty-three CDI patients per 100,000 inhabitants in five years. The differential diagnosis between several presenting conditions with polyuria and polydipsia is puzzling, and the etiological diagnosis of CDI remains a challenge before the identification of an underlying cause. For clinical practice, a timely diagnosis for initiating specific treatment in order to avoid central nervous system damage, additional pituitary defects and the risk of dissemination of germ cell tumor is advisable. Proper etiological diagnosis can be achieved via a series of steps that start with careful clinical observation of several signs and endocrine symptoms and then progress to more sophisticated imaging tools. This review summarizes the best practice and approach for the diagnosis and treatment of patients with CDI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency

PubMed Central

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-01

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. PMID:25612752

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency.

PubMed

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-22

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. 2015 BMJ Publishing Group Ltd.

Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes.

PubMed

Cano, Aline; Molines, Laurent; Valéro, René; Simonin, Gilbert; Paquis-Flucklinger, Véronique; Vialettes, Bernard

2007-09-01

Some previous studies suggested that patients suffering from Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) might be relatively preserved from diabetic retinopathy and nephropathy. However, these data were not conclusive because either observations were only anecdotic or did not match with control type 1 diabetic populations. A group of 26 French diabetic patients with DIDMOAD was compared with a population of 52 patients with common type 1 diabetes matched for age at diabetes diagnosis (8.62 +/- 1.84 vs. 8.27 +/- 1.30 years; P = NS) and diabetes duration (12.88 +/- 1.58 vs. 12.87 +/- 1.13 years; P = NS) to study the quality of glycemic control and the incidence of microvascular complications. Glycemic control was significantly better in the DIDMOAD group than in the type 1 diabetic group (A1C: 7.72 +/- 0.21 vs. 8.99 +/- 0.25%, respectively; P = 0.002), with significant lower daily insulin requirements (0.71 +/- 0.07 vs. 0.88 +/- 0.04 UI x kg(-1) x day(-1), respectively; P = 0.0325). The prevalence of microvascular complications in the DIDMOAD group was half that observed in the type 1 diabetic group, but the difference was not significant. Diabetes in DIDMOAD patients is more easily controlled despite the presence of other handicaps. This better glycemic control could explain the trend to decreased microvascular diabetes complications observed in previous studies.

Nephrogenic diabetes insipidus with intracranial calcification in a child with thalassemia minor.

PubMed

Dimple, Jain; Alka, Jadhav; Mona, Gajre; Atul, Deshmukh

2013-09-01

There are numerous causes for intracranial calcification in children. We describe an unusual cause of intracranial calcification in a child, namely, nephrogenic diabetes insipidus (NDI). A 12-year-old boy presented with seizures and developmental delay. MRI of the brain revealed intracranial calcification. Evaluation showed findings suggestive of NDI. The lack of evidence of any other metabolic defect suggests that these calcifications were secondary to NDI. He also had anemia for which he was investigated and diagnosed as thalassemia minor. Detailed literature review failed to reveal any reported association between NDI and thalassemia minor. We report this case to emphasize the importance of early diagnosis and treatment of NDI to prevent organic brain damage.

Response to low dose indomethacin in two children with nephrogenic diabetes insipidus.

PubMed

Dayal, Devi; Verma Attri, Savita; Kumar Bhalla, Anil; Kumar, Rakesh

2015-01-01

Two children with nephrogenic diabetes insipidus (NDI) were treated with oral indomethacin (0.75-1.2 mg/kg/day) three times a day for a mean duration of 3 yrs. Remission occurred in both patients in terms of achieving a normal fluid balance and body growth and the drug was withdrawn in one patient after 2 yrs. The treatment was well tolerated and no side effects were noted. The mean duration of follow-up was 6.5 yrs. These long-term observations of a favourable response to low dose indomethacin in 2 children with NDI need to be tested on larger number of patients. © Polish Society for Pediatric Endocrinology and Diabetology.

Neurogenic Causes of Detrusor Underactivity

PubMed Central

Kadow, Brian T.; Tyagi, Pradeep; Chermansky, Christopher J.

2015-01-01

Detrusor underactivity (DU) is a poorly understood dysfunction of the lower urinary tract which arises from multiple etiologies. Symptoms of DU are non-specific, and a pressure-flow urodynamic study is necessary to differentiate DU from other conditions such as overactive bladder (OAB) or bladder outlet obstruction (BOO). The prevalence of DU ranges from 10–48%, and DU is most prevalent in elderly males. The pathophysiology underlying DU can be from both neurogenic and non-neurogenic causes. In this article, we review the neurogenic causes of detrusor underactivity, including diabetic bladder dysfunction, spinal cord injury, multiple sclerosis, Parkinson’s disease, cerebrovascular accident, traumatic brain injury, and Fowler’s syndrome. As knowledge about the underlying causes of DU advances, there have been several potential therapeutic approaches proposed to help those who suffer from this condition. PMID:26715948

Nephrogenic Diabetes Insipidus (NDI): Clinical, Laboratory and Genetic Characterization of Five Brazilian Patients

PubMed Central

Vaisbich, Maria Helena; Carneiro, Juliana; Bóson, Wolfanga; Resende, Bruna; De Marco, Luiz; Honjo, Rachel S; Kim, Chong Ae; Koch, Vera H

2009-01-01

INTRODUCTION: Nephrogenic diabetes insipidus is characterized by a lack of response in the distal nephron to the antidiuretic hormone arginine vasopressin. Manifestations include polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration and fever and growth failure. Most cases are caused by mutations in the AVPR2 gene. The mutant receptors are trapped intracellularly. METHOD: We studied five boys using clinical, laboratory and molecular data. The mean age at diagnosis was 14.6 months (range 6 to 24) and 12.2 years (7.8 to 19) after the follow-up period. The mean period of follow-up was 132.2 ± 50.9 months. RESULTS: The geometric means of the z-scores of weight and stature were −4.5 and −3.6, respectively, at diagnosis. At the last medical appointment, the z-scores of weight and stature were −0.3 and −0.9, respectively. Three patients were diagnosed with ureterohydronephrosis and exhibited increased post-void urine volume. Mutations in the AVPR2 gene were found in all patients, and the carrier status was confirmed in four of five cases. Two unrelated children presented identical mutations (S167L) in arginine vasopressin R2. Two of the patients had a mutation that has already been described in other Brazilian families (R337X), and one patient showed a de novo mutation (Y128D) in arginine vasopressin R2, since his mother’s molecular analysis was normal. The recurrence risk for this family was significantly reduced. CONCLUSION: This study reports the clinical and laboratory characterization of Nephrogenic diabetes insipidus and reiterates the importance of the genetic basis that underlies the disease diagnosis and genetic counseling. PMID:19488606

Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

PubMed

Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

2016-05-01

We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury. © 2016 Wiley Periodicals, Inc.

Central diabetes insipidus, central hypothyroidism, renal tubular acidosis and dandy-walker syndrome: new associations.

PubMed

Alafif, M M; Aljaid, S S; Al-Agha, A E

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis.

Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular Acidosis and Dandy-Walker Syndrome: New Associations

PubMed Central

Alafif, MM; Aljaid, SS; Al-Agha, AE

2015-01-01

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis. PMID:25861538

A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation.

PubMed

Chen, Xiaoyan; Huang, Xiaochun; Qiu, Yuan; Chen, Hanzhang; Fu, Yingyu; Li, Xinchun

2013-03-01

Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

Iatrogenic water intoxication during pelvic ultrasonography in a patient with diabetes insipidus.

PubMed

Derinöz, Okşan; Emeksiz, Hamdi Cihan; Kalkan, Gökhan; Camurdan, Orhun

2012-01-01

Pelvic ultrasonography (US) is a simple and non-invasive radiologic test to evaluate the pelvic organs. It requires a full bladder for better visualization. Our case is a 14-year-old female with diabetes insipidus (DI) who admitted to the pediatric emergency service with the complaints of seizure and agitation after drinking 4 liters of water in one hour for a pelvic US examination due to work-up for delayed puberty. Her biochemical and clinical evaluation revealed water intoxication (WI). To our knowledge, this is the first WI case developed in a patient with DI. Here, we discuss the underlying factors leading to this complication and recommended an approach to obtain a better sonographic image without necessitating oral water intake to fill the urinary bladder.

Diabetes insipidus: celebrating a century of vasopressin therapy.

PubMed

Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse

2014-12-01

Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus.

PubMed

Bockenhauer, Detlef; Bichet, Daniel G

2015-10-01

Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.

Transient central diabetes insipidus induced by ketamine infusion.

PubMed

Hatab, Sarah Z; Singh, Arun; Felner, Eric I; Kamat, Pradip

2014-12-01

Report a case of central diabetes insipidus (DI) associated with ketamine infusion. A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy was admitted to the pediatric intensive care with pneumonia. She subsequently developed respiratory failure and required intubation. Continuous ketamine infusion was used for the sedation and facilitation of mechanical ventilation. Shortly after infusion of ketamine, the patient developed DI and responded appropriately to vasopressin. The Naranjo adverse drug reaction probability scale indicated a probable relationship between the development of central DI and ketamine. The most likely mechanism involves ketamine's antagonist action on N-methyl-d-aspartate receptors, resulting in inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis. This is the second case report of ketamine-induced central DI and the only report in children. Clinicians who sedate children with continuous ketamine infusions should monitor patients for developing signs and symptoms of DI by measuring serum sodium and urine output prior to, during, and after ketamine infusion in order to make a timely diagnosis of this potentially serious complication. © The Author(s) 2014.

Nephrotic syndrome complicated by idiopathic central diabetes insipidus.

PubMed

Konomoto, Takao; Tanaka, Etsuko; Imamura, Hideaki; Orita, Mayuko; Sawada, Hirotake; Nunoi, Hiroyuki

2014-05-01

There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP). We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed. This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.

Heterogenous patterns of recovery of thirst in adult patients with adipsic diabetes insipidus.

PubMed

Cuesta, M; Gupta, S; Salehmohamed, R; Dineen, R; Hannon, M J; Tormey, W; Thompson, C J

2016-05-01

The natural history of adipsic diabetes insipidus (ADI) is not well described, and reports of recovery of thirst are rare. Case histories presentation. ADI was identified by demonstrating absent thirst and arginine vasopressin (AVP) responses to hypertonic saline infusion. Twelve patients with ADI were identified (craniopharyngioma 5, anterior communicating artery aneurysm (ACOM) repair 4, congenital 1, neurosarcoidosis 1, prolactinoma 1). Three patients died. Six patients had permanent ADI. Three patients had recovery of thirst, with a heterogenous pattern of recovery. In the first case, ADI had developed after clipping of an ACOM aneurysm. Ten years after surgery; he sensed the return of thirst; repeated hypertonic saline infusion showed recovery of thirst and AVP secretion. In the second case, a 41-year-old female with an intrasellar craniopharyngioma developed post-operative ADI with persistent hypernatremia. Two years post-operatively, she complained of thirst, and hypertonic saline infusion showed normalization of thirst but absent AVP responses, confirming recovery of thirst, but with persistent diabetes insipidus (DI). In the third case, a 29-year-old Caucasian had craniotomy and radiotherapy for craniopharyngioma and developed ADI post-operatively. Eight years post-op, she presented with thirst, seizures and pNa of 112 mmol/l. Hypertonic saline infusion showed persistent DI but thirst responses typical of compulsive water drinking; she has had recurrent hyponatraemia since then. We report that 3/12 patients with ADI recovered thirst after longstanding adipsia with heterogenous pattern of recovery. Both the mortality of 25% and the recovery rate of 25% should be considered when planning long-term surveillance. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Congenital nephrogenic diabetes insipidus: the current state of affairs.

PubMed

Wesche, Daniel; Deen, Peter M T; Knoers, Nine V A M

2012-12-01

The anti-diuretic hormone arginine vasopressin (AVP) is released from the pituitary upon hypovolemia or hypernatremia, and regulates water reabsorption in the renal collecting duct principal cells. Binding of AVP to the arginine vasopressin receptor type 2 (AVPR2) in the basolateral membrane leads to translocation of aquaporin 2 (AQP2) water channels to the apical membrane of the collecting duct principal cells, inducing water permeability of the membrane. This results in water reabsorption from the pro-urine into the medullary interstitium following an osmotic gradient. Congenital nephrogenic diabetes insipidus (NDI) is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their pro-urine, which leads to a high risk of dehydration. This review focuses on the current knowledge regarding the cell biological aspects of congenital X-linked, autosomal-recessive and autosomal-dominant NDI while specifically addressing the latest developments in the field. Based on deepened mechanistic understanding, new therapeutic strategies are currently being explored, which we also discuss here.

X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

PubMed

Hong, Che Ry; Kang, Hee Gyung; Choi, Hyun Jin; Cho, Min Hyun; Lee, Jung Won; Kang, Ju Hyung; Park, Hye Won; Koo, Ja Wook; Ha, Tae-Sun; Kim, Su-Yung; Il Cheong, Hae

2014-01-01

A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

A novel therapeutic effect of statins on nephrogenic diabetes insipidus

PubMed Central

Bonfrate, Leonilde; Procino, Giuseppe; Wang, David Q-H; Svelto, Maria; Portincasa, Piero

2015-01-01

Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional ‘pleiotropic’ effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed. PMID:25594563

Cooperative mechanisms involved in chronic antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

PubMed

Moosavi, S M S; Karimi, Z

2014-03-01

Previous studies of central diabetes insipidus suggested that thiazides acutely exerted a paradoxical antidiuresis by either indirectly activating volume-homeostatic reflexes to decrease distal fluid-delivery, or directly stimulating distal water-reabsorption. This study investigated whether the direct and indirect actions of bendroflumethiazide (BFTZ) simultaneously cooperated and also whether the renal nerves were involved in inducing long-term antidiuresis in nephrogenic diabetes insipidus (NDI). BFTZ or vehicle was gavaged into bilateral renal denervated and innervated rats with lithium-induced NDI for 10 days, constituting four groups. At one day before (D0) and one, five and ten days after starting administration of BFTZ or vehicle, rats were placed in metabolic cages to collect urine for 6 hours. BFTZ-treatment in both renal innervated and denervated rats caused equivalent reductions in urine-flow, creatinine clearance, lithium clearance and free-water clearance, but rises in urine-osmolality, fractional proximal reabsorption and fractional distal reabsorption at all days compared to D0, as well as to those of their relevant vehicle-received group. Therefore, the chronic antidiuretic response to BFTZ in conscious NDI rats was exerted through a concomitant cooperation of its direct distal effect of stimulating water-reabsorption and its indirect effect of reducing distal fluid-delivery by activating volume-homeostatic mechanisms, which appeared independent of the renal nerves.

3T renal (23)Na-MRI: effects of desmopressin in patients with central diabetes insipidus.

PubMed

Haneder, Stefan; Michaely, Henrik J; Konstandin, Simon; Schad, Lothar R; Morelli, John N; Krämer, Bernhard K; Schoenberg, Stefan O; Lammert, Alexander

2014-02-01

The purpose of this prospective study was to assess physiologic changes in the renal corticomedullary (23)Na-concentration ([(23)Na]) gradient with (23)Na-MRI at 3.0T in patients with central diabetes insipidus (CDI) before and after intranasal administration of 20 μg desmopressin (DDAVP). Four patients with CDI (all male, mean age 60.2 years) were included in this IRB-approved study. For (23)Na-imaging, a 3D density adapted, radial GRE-sequence (TE = 0.55 ms; TR = 120 ms; projections = 8,000; spatial resolution = 5 × 5 × 5 mm(3)) was used in combination with a dedicated (23)Na-coil and reference phantoms. The corticomedullary [(23)Na] gradient (in mmol/L/mm) was calculated pixel-by-pixel along a linear region-of-interest (ROI) spanning from the renal cortex in the direction of the medulla. Mean ± SDs of [(23)Na] were calculated for each patient as well as for the entire group. Mean [(23)Na] increased along the corticomedullary gradient from the cortex (pre-DDAVP 38.0 ± 6.3 mmol/L vs. post-DDAVP 30.7 ± 3.5 mmol/L) to the medulla (pre-DDAVP 71.6 ± 14.8 mmol/L vs. post-DDAVP 59.7 ± 10.8 mmol/L). The overall mean decrease of [(23)Na] after DDAVP administration was 17.1 ± 1.1 %. (23)Na-MRI with state-of-the-art techniques at 3T depicts the physiologic renal response to the administration of desmopressin in patients with central diabetes insipidus.

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus

PubMed Central

Olesen, Emma T. B.; Rützler, Michael R.; Moeller, Hanne B.; Praetorius, Helle A.; Fenton, Robert A.

2011-01-01

In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause X-linked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus. PMID:21768374

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus.

PubMed

Olesen, Emma T B; Rützler, Michael R; Moeller, Hanne B; Praetorius, Helle A; Fenton, Robert A

2011-08-02

In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause X-linked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus.

Resolution of Diabetes Insipidus After Pyeloplasty: A Case Report and Review of the Literature.

PubMed

Carpenter, Christina P; Rawson, Ashley; Hains, David S; Giel, Dana W

2018-05-01

Nephrogenic diabetes insipidus (NDI), a rare cause of polyuria and polydipsia in children, is usually managed with medications and careful monitoring of water intake. We present a child who was incidentally found to have right hydronephrosis secondary to ureteropelvic junction obstruction, and was subsequently also diagnosed with NDI. After being medically managed, he underwent open right pyeloplasty. His polydipsia abated within 1 month of surgery, and he has done well off of medications since that time. NDI resolution after correction of obstructive uropathy in adults has been reported, but this represents a novel case in pediatrics. Copyright © 2018 Elsevier Inc. All rights reserved.

Bilateral Ossified Chronic Subdural Hematoma Presenting as Diabetes Insipidus-Case Report and Literature Review.

PubMed

Siddiqui, Saquib A; Singh, Pankaj Kumar; Sawarkar, Dattaraj; Singh, Manmohanjit; Sharma, Bhawani S

2017-02-01

Calcified chronic subdural hematomas are an occurrence rarely seen in neurosurgical clinical practice. And when they occur bilaterally, the radiologic image they present is fascinating, as is the clinical presentation, but their management may be challenging. They have been reported to present with a multitude of neurologic deficits but never with diabetes insipidus, which is described here. Due to the rarity of this pathology, the management protocol is not well defined, though there have been quite a few papers on this condition. This review article gathers information published over the years on this rare entity to suggest a treatment protocol. Copyright © 2016 Elsevier Inc. All rights reserved.

Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

PubMed

Surapolchai, Pacharapan; Ha, Shau-Yin; Chan, Godfrey Chi-Fung; Lukito, Johannes B; Wan, Thomas S K; So, Chi-Chiu; Chiang, Alan Kwok-Shing

2013-03-01

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

Management of diabetes insipidus in children

PubMed Central

Mishra, Garima; Chandrashekhar, Sudha Rao

2011-01-01

Diabetes Insipidus (DI) is a heterogeneous clinical syndrome of disturbance in water balance, characterized by polyuria (urine output > 4 ml/kg/hr), polydypsia (water intake > 2 L/m2/d) and failure to thrive. In children, Nephrogenic DI (NDI) is more common than Central DI (CDI), and is often acquired. The signs and symptoms vary with etiology, age at presentation and mode of onset. Neonates and infants with NDI are severely affected and difficult to treat. Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. Water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI and CDI and diagnose their partial forms. Measurement of urinary aquaporin 2 and serum copeptin levels are being studied and show promising diagnostic potential. Magnetic Resonance Imaging (MRI) pituitary helps in the etiological diagnosis of CDI, absence of posterior pituitary bright signal being the pathognomic sign. If pituitary stalk thickening of < 2 mm is present, these children need to be monitored for evolving lesion. Neonates and young infants are better managed with fluids alone. Older children with CDI are treated with desmopressin. The oral form is safe, highly effective, with more flexibility of dosing and has largely replaced the intranasal form. In NDI besides treatment of the underlying cause, use of high calorie low solute diet and drugs to ameliorate water excretion (thiazide, amelioride, indomethacin) are useful. Children with NDI however well treated, remain short and have mental retardation on follow up. PMID:22029022

Enteroviral Meningoencephalitis Complicated by Central Diabetes Insipidus in a Neonate: A Case Report and Review of the Literature.

PubMed

Jones, Garrett; Muriello, Michael; Patel, Aloka; Logan, Latania

2015-06-01

Enterovirus is a known cause of central nervous system infection in the neonatal population and typically has a benign course; however, neurologic complications have been reported. We describe what we believe to be the first documented case of enteroviral meningoencephalitis complicated by central diabetes insipidus in a neonate. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The mutant vasopressin gene from diabetes insipidus (Brattleboro) rats is transcribed but the message is not efficiently translated.

PubMed Central

Schmale, H; Ivell, R; Breindl, M; Darmer, D; Richter, D

1984-01-01

The vasopressin gene from normal and diabetes insipidus (Brattleboro) rats has been isolated and sequenced. Except for a single deletion of a G residue in region coding for the neurophysin carrier protein the approximately 2300 nucleotides of both genes are identical. Blot analysis of hypothalamic RNA as well as transfection and microinjection experiments indicate that the mutant gene is correctly transcribed and spliced, however the resulting mRNA is not efficiently translated. Images Fig. 2. Fig. 3. PMID:6526016

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

PubMed

Nozaki, Aya; Ando, Takao; Akazawa, Satoru; Satoh, Tsuyoshi; Sagara, Ikuko; Horie, Ichiro; Imaizumi, Misa; Usa, Toshiro; Yanagisawa, Robert T; Kawakami, Atsushi

2016-01-01

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.

PubMed Central

Ito, M; Oiso, Y; Murase, T; Kondo, K; Saito, H; Chinzei, T; Racchi, M; Lively, M O

1993-01-01

A transition of G to A at nucleotide position 279 in exon 1 of the vasopressin gene has been identified in patients with familial central diabetes insipidus. The mutation predicts an amino acid substitution of Thr (ACG) for Ala (GCG) at the COOH terminus of the signal peptide in preprovasopression (preproVP). Translation in vitro of wild-type and mutant mRNAs produced 19-kD preproVPs. When translated in the presence of canine pancreatic rough microsomes, wild-type preproVP was converted to a 21-kD protein, whereas the mutant mRNA produced proteins of 21 kD and 23 kD. NH2-terminal amino acid sequence analysis revealed that the 21-kD proteins from the wild-type and the mutants were proVPs generated by the proteolytic cleavage of the 19-residue signal peptide and the addition of carbohydrate. Accordingly, mutant preproVP was cleaved at the correct site after Thr-19, but the efficiency of cleavage by signal peptidase was < 25% that observed for the wild-type preproVP, resulting in the formation of a predominant glycosylated but uncleaved 23-kD product. These data suggest that inefficient processing of preproVP produced by the mutant allele is possibly involved in the pathogenesis of diabetes insipidus in the affected individuals. Images PMID:8514868

Coexistence of autoimmune polyglandular syndrome type 2 and diabetes insipidus in pregnancy.

PubMed

Krysiak, Robert; Samborek, Malgorzata

2011-11-01

Autoimmune polyglandular syndromes are rarely diagnosed conditions characterized by the association of at least 2 organ-specific autoimmune disorders. Very few cases of these syndromes have been described during pregnancy. The authors report a case of a patient diagnosed with autoimmune thyroiditis and a history of HELLP (hemolysis, elevated liver enzymes and low platelet) syndrome in a prior pregnancy. After increasing the levothyroxine dose, she developed Addisonian crisis. Normalization of adrenal cortex function resulted in the appearance of diabetes insipidus. This report shows that pregnancy may influence the course of preexisting endocrine disorders and lead to their unmasking. Although the risk of the development of autoimmune polyglandular syndromes during pregnancy is small, they may pose a serious health problem. The possible presence of these clinical entities should be considered in every woman with 1 or more endocrine disturbances.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PubMed

Check, J H; Weidner, J

2015-01-01

To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

PubMed

Lamas, Cristina; del Pozo, Carlos; Villabona, Carles

2014-04-01

Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

From idiopathic diabetes insipidus to neurodegenerative Langerhans cell histiocytosis--an unusual presentation and progression of disease.

PubMed

Hayward, Rachel M; Nicolin, Gary; Kennedy, Charles; Joy, Harriet; Davies, Justin H

2011-01-01

Diabetes insipidus (DI) is rare in childhood and has a wide-ranging aetiology including the involvement of uncontrolled proliferation of dendritic cells in the hypothalamic-pituitary axis, characteristic of Langerhans cell histiocytosis (LCH). DI may manifest as a sequela of multisystem LCH disease involving skin, bone, liver, spleen and lymph nodes. In very rare cases patients diagnosed with LCH exhibit neurodegenerative changes, such as severe ataxia, tremor, dysarthria and intellectual impairment. We report a 2 1/2-year-old boy who presented initially with apparent idiopathic DI, developed anterior pituitary hormone deficiency and progressive neurological deterioration secondary to neurodegenerative LCH.

Evaluation of patients with intracranial tumors and central diabetes insipidus.

PubMed

Varan, Ali; Atas, Erman; Aydın, Burça; Yalçın, Bilgehan; Akyüz, Canan; Kutluk, Tezer; Büyükpamukçu, Münevver

2013-10-01

The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

Opioid-induced hyponatremia in a patient with central diabetes insipidus: independence from ADH.

PubMed

Bhat, Nandini; Balliu, Erjola; Osipoff, Jennifer; Lane, Andrew; Wilson, Thomas

2017-05-24

Hyponatremia can be a complication of opioid therapy, which has been postulated to occur secondary to inappropriate antidiuretic hormone secretion (syndrome of inappropriate antidiuretic hormone secretion [SIADH]). We report severe hyponatremia following wisdom teeth extraction with opioid analgesia in a 19-year-old female with diabetes insipidus (DI) and acquired panhypopituitarism that challenges this theory. As this patient has DI, we believe opioid treatment caused severe hyponatremia by the following mechanisms: (1) Opioids have a direct antidiuretic effect independent of changes in ADH, as demonstrated in Brattleboro rats with central DI. (2) Hydrocodone may have stimulated this patient's thirst center contributing to hyponatremia, as demonstrated in animal studies. Opioid use can cause hyponatremia in patients independent of ADH. It is important for clinicians to be aware of this so that patients can be appropriately counseled.

Adipsic diabetes insipidus and venous thromboembolism (VTE): recommendations for addressing its hypercoagulability.

PubMed

Miljic, Dragana; Miljic, Predrag; Doknic, Mirjana; Pekic, Sandra; Stojanovic, Marko; Petakov, Milan; Popovic, Vera

2014-01-01

Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.

A case of transient central diabetes insipidus after aorto-coronary bypass operation.

PubMed

Yu, Chung-Hoon; Cho, Jang-Hee; Jung, Hee-Yeon; Lim, Jeong-Hoon; Jin, Mi-Kyung; Kwon, Owen; Hong, Kyung-Deuk; Choi, Ji-Young; Yoon, Se-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Kim, Gun-Jik; Park, Sun-Hee

2012-09-01

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.

Identification, Characterization and Rescue of a Novel Vasopressin-2 Receptor Mutation Causing Nephrogenic Diabetes Insipidus

PubMed Central

Ranadive, Sayali A.; Ersoy, Baran; Favre, Helene; Cheung, Clement C.; Rosenthal, Stephen M.; Miller, Walter L.; Vaisse, Christian

2018-01-01

SUMMARY Objective X-linked nephrogenic diabetes insipidus (XNDI), caused by mutations in the V2 vasopressin receptor (V2R), is clinically distinguished from central diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and unresponsiveness to 1-desamino-8-D-arginine vasopressin (DDAVP). We report two infants with XNDI, and present the characterization and functional rescue of a novel V2R mutation. Patients Two male infants presented with poor growth and hypernatremia. Both patients had measurable pre-treatment serum AVP and polyuria that did not respond to DDAVP, suggesting NDI. However, both also had absent posterior pituitary bright spot on MRI, which is a finding more typical of CDI. Methods The AVPR2 gene encoding V2R was sequenced. The identified novel missense mutation was re-created by site-directed mutagenesis and expressed in HEK293 cells. V2R activity was assessed by the ability of transfected cells to produce cAMP in response to stimulation with DDAVP. Membrane localization of V2R was assessed by fluorescence microscopy. Results Patient 1 had a deletion of AVPR2; patient 2 had the novel mutation L57R. In transiently transfected HEK293 cells, DDAVP induced detectable but severely impaired L57R V2R activity compared to cells expressing wild-type V2R. Fluorescence microscopy showed that myc-tagged wild-type V2R localized to the cell membrane while L57R V2R remained intracellular. A non-peptide V2R chaperone, SR121463, partially rescued L57R V2R function by allowing it to reach the cell membrane. Conclusions L57R V2R has impaired in vitro activity that can be partially improved by treatment with a V2R chaperone. The posterior pituitary hyperintensity may be absent in infants with XNDI. PMID:19170711

CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

PubMed

Masri-Iraqi, Hiba; Hirsch, Dania; Herzberg, Dana; Lifshitz, Avner; Tsvetov, Gloria; Benbassat, Carlos; Shimon, Ilan

2017-05-01

Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. Forty women and 30 men were included. Mean age was 46.8 ± 15 years at the time of this study and 29.3 ± 20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth hormone-secreting adenoma; 12 patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% adrenocorticotropic hormone-cortisol deficiency. Patients with postoperative/trauma CDI (n = 44) tended to have multiple anterior pituitary axes deficits compared to the nonsurgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women, and was severe (<125 mEq/L) in 10 patients. Hypernatremia (>150 mEq/L) was noticed in 5 patients. Overall, the calculated complication rate was 22 in 1,250 treatment-years. Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate. ACTH = adrenocorticotropic hormone CDI = central diabetes insipidus GH = growth hormone MRI = magnetic

Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β.

PubMed

Gabbi, Chiara; Kong, Xiaomu; Suzuki, Hitoshi; Kim, Hyun-Jin; Gao, Min; Jia, Xiao; Ohnishi, Hideo; Ueta, Yoichi; Warner, Margaret; Guan, Youfei; Gustafsson, Jan-Åke

2012-02-21

The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.

Secondary nocturnal enuresis related to central diabetes insipidus as an early manifestation of intracranial germinomatous germ cell tumors in a series of male youngsters.

PubMed

Papaefthimiou, Apostolos; Kyrgios, Ioannis; Kotanidou, Eleni P; Maggana, Ioanna; Mouzaki, Konstantina; Galli-Tsinopoulou, Assimina

2015-02-01

Nocturnal enuresis is a common symptom in children. It is usually attributed to benign causes and diagnostic evaluation is not carried out. We report three male young patients initially presenting with short stature and nocturnal enuresis, related to diabetes insipidus, caused by intracranial germinomatous germ cell tumors. In all three cases, water deprivation tests confirmed diabetes insipidus. Extensive endocrinological investigation also showed further hormone deficiencies. Magnetic resonance imaging of the brain revealed the presence of a central nervous system lesion and histology confirmed the final diagnosis. Surgery, radiation with or without chemotherapy was conducted and the patients were treated with hormone replacement therapies. The patients after a long follow-up were free of disease. We present these cases to alert clinicians to bear in mind that the presence of an intracranial germinomatous germ cell tumor should at least be considered in a child presenting with bed wetting, especially if additional symptoms and signs, including late onset puberty and growth delay or morning hypernatremia, may coexist. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.

PubMed Central

van Lieburg, A. F.; Verdijk, M. A.; Knoers, V. V.; van Essen, A. J.; Proesmans, W.; Mallmann, R.; Monnens, L. A.; van Oost, B. A.; van Os, C. H.; Deen, P. M.

1994-01-01

Mutations in the X-chromosomal V2 receptor gene are known to cause nephrogenic diabetes insipidus (NDI). Besides the X-linked form, an autosomal mode of inheritance has been described. Recently, mutations in the autosomal gene coding for water-channel aquaporin 2 (AQP2) of the renal collecting duct were reported in an NDI patient. In the present study, missense mutations and a single nucleotide deletion in the aquaporin 2 gene of three NDI patients from consanguineous matings are described. Expression studies in Xenopus oocytes showed that the missense AQP2 proteins are nonfunctional. These results prove that mutations in the AQP2 gene cause autosomal recessive NDI. PMID:7524315

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature

PubMed Central

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

2017-01-01

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999

Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

PubMed

Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

Lithium intoxication and nephrogenic diabetes insipidus: a case report and review of literature

PubMed Central

Erden, Abdulsamet; Karagöz, Hatice; Başak, Mustafa; Karahan, Samet; Çetinkaya, Ali; Avci, Deniz; Bugǧday, İrfan

2013-01-01

Lithium is one of the drugs used widely in the treatment of mood disorders. However, it has a very narrow therapeutic index and side effects can be seen in many organ systems, one of which affects the kidneys. We can see varying degrees of renal damage associated with acute or chronic lithium use. Lithium intoxication is diagnosed by a rise in the serum lithium concentration, but it must be remembered that serum levels and clinical findings do not always overlap. Treatment of lithium intoxication varies according to the clinical findings. There are various ways of treating lithium intoxication, but there is no specific antidote. The purpose of treatment is to remove the toxin from the body. Here we report a patient who was treated for lithium intoxication and developed diabetes insipidus during follow-up, and discuss the relevant literature. PMID:23861592

Growth hormone deficiency and diabetes insipidus as a complication of endoscopic third ventriculostomy.

PubMed

Tafuri, Kimberly S; Wilson, Thomas A

2012-12-01

Endoscopic third ventriculostomy (ETV) has become the procedure of choice for the treatment of obstructive hydrocephalus in children and adults. Endocrinological complications of ETV in children are rare. Diabetes insipidus (DI) is the most common and accounts for only 0.5% of complications from ETV. The majority of documented cases are transient. To date, there are no documented cases of multiple pituitary hormone deficiencies. We present here a 6-year-old girl with growth hormone deficiency and permanent DI which developed as a complication of ETV. This patient is unique in both demonstrating multiple pituitary hormone deficiencies and the classical triphasic response of DI after ETV. We postulate that these complications were caused by compression of the pituitary stalk and hypothalamic injury during the procedure. We compare our case presentation to experimental studies conducted in rats.

Refractory diabetes insipidus following drainage of chronic subdural haematoma.

PubMed

Won, Yu Deok; Kim, Choong Hyun; Cheong, Jin Hwan; Kim, Jae Min

2013-01-01

Post-traumatic diabetes insipidus (DI) is a relatively common complication after head injury. The authors report a fatal case of refractory DI, which developed in a patient with chronic subdural haematoma. A 38-year-old woman presented to the emergency room with a headache for over a week. She was alert and neurological examination demonstrated no significant deficits or external wounds in her head. Brain computed tomography (CT) scans revealed a small amount of chronic subdural haematoma bilaterally. She was treated conservatively and her hospital course was uneventful until she developed a convulsive seizure and mental change on the 3rd day after admission. Immediate follow-up CT scans showed no significant change in the amount of haemorrhage except effacement of gyral marking. Bilateral trephination and drainage of the haematoma were performed immediately. Post-operatively, she developed a refractory DI and was managed in the intensive care unit. However, she died on the 6th day after the operation ultimately. The authors emphasize the importance of timely drainage of chronic subdural haematoma to prevent a fatal endocrinologic complication after head injury. This study also discusses the possible mechanism of DI after head injury, management and review of the pertinent literatures.

A Case of Transient Central Diabetes Insipidus after Aorto-Coronary Bypass Operation

PubMed Central

Yu, Chung-Hoon; Cho, Jang-Hee; Jung, Hee-Yeon; Lim, Jeong-Hoon; Jin, Mi-Kyung; Kwon, Owen; Hong, Kyung-Deuk; Choi, Ji-Young; Yoon, Se-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Kim, Gun-Jik

2012-01-01

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB. PMID:22969261

Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

PubMed Central

Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H.; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

2017-01-01

NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2. PMID:28233855

Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus.

PubMed

Nielsen, Jakob; Kwon, Tae-Hwan; Christensen, Birgitte Mønster; Frøkiaer, Jørgen; Nielsen, Søren

2008-05-01

Lithium is used commonly to treat bipolar mood disorders. In addition to its primary therapeutic effects in the central nervous system lithium has a number of side effects in the kidney. The side effects include nephrogenic diabetes insipidus with polyuria, mild sodium wasting, and changes in acid/base balance. These functional changes are associated with marked structural changes in collecting duct cell composition and morphology, likely contributing to the functional changes. Over the past few years, investigations of lithium-induced renal changes have provided novel insight into the molecular mechanisms that are responsible for the disturbances in water, sodium, and acid/base metabolism. This includes dysregulation of renal aquaporins, epithelial sodium channel, and acid/base transporters. This review focuses on these issues with the aim to present this in context with clinically relevant features.

A de novo novel missense mutation in AVPR2 with severe nephrogenic diabetes insipidus

PubMed Central

Kobayashi, Daisuke; Nagaraj, Shashi K.; Lin, Jen-Jar; Bichet, Daniel G.

2010-01-01

We describe a paediatric case of nephrogenic diabetes insipidus (NDI) with a novel mutation in the arginine vasopressin receptor 2 gene (AVPR2) in the absence of a family history of congenital polyuria. The patient, a 5-month-old Caucasian boy, had failure to thrive and hypernatraemia. On admission to hospital, he had a plasma sodium of 171 mEq/L with a concomittant urine osmolality of 131 mOsm/kg. Molecular genetic analysis demonstrated that the patient had an AVPR2 mutation (c.861C > G) resulting in a substitution of tryptophan for serine at amino acid position 167 (p.Ser167Trp). His mother was heterozygous for the same Ser167Trp mutation which was found to be de novo from the DNA analysis of the maternal grandparents. PMID:25949462

Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports

PubMed Central

2009-01-01

Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade. This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities. In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram. PMID:20062605

A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

PubMed

Saglar, Emel; Deniz, Ferhat; Erdem, Beril; Karaduman, Tugce; Yönem, Arif; Cagiltay, Eylem; Mergen, Hatice

2014-05-01

X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β

PubMed Central

Gabbi, Chiara; Kong, Xiaomu; Suzuki, Hitoshi; Kim, Hyun-Jin; Gao, Min; Jia, Xiao; Ohnishi, Hideo; Ueta, Yoichi; Warner, Margaret; Guan, Youfei; Gustafsson, Jan-Åke

2012-01-01

The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ−/− but not LXRα−/− mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ−/− mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ−/− mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ−/− mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ−/− mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance. PMID:22323586

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma.

PubMed

Raghunathan, Veena; Dhaliwal, Maninder Singh; Gupta, Aditya; Jevalikar, Ganesh

2015-03-01

Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus

PubMed Central

de Groot, Theun; Sinke, Anne P.; Kortenoeven, Marleen L.A.; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F.

2016-01-01

To reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects. PMID:26574046

Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

PubMed

de Groot, Theun; Sinke, Anne P; Kortenoeven, Marleen L A; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F; Deen, Peter M T

2016-07-01

To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects. Copyright © 2016 by the American Society of Nephrology.

Nephrogenic diabetes insipidus secondary to syphilis infection.

PubMed

Zhou, Jiaqiang; Hu, Chaohui; Zheng, Fenping; Cheng, Hao; Xuan, Junli; Li, Hong

2013-07-01

Nephrogenic diabetes insipidus (NDI) is caused by partial or complete renal resistance to the effects of antidiuretic hormone. Acquired NDI can be caused by electrolyte imbalances (eg, hypercalcemia), renal/extrarenal diseases (eg, chronic pyelonephritis), and drugs (eg, lithium toxicity). Syphilis has never been reported to cause NDI. The aim of this study was to report the case of a 56-year-old man with NDI secondary to syphilis. The 56-year-old patient presented with polyuria and polydipsia lasting more than 40 days. His urine specific gravity was 1.002. He had no history of chronic kidney disease or contact with toxicants. He had normal blood glucose levels. A water-deprivation test and vasopressin administration indicated NDI. His rapid plasma reagin titer was 1:128. The serum Treponema pallidum-particle agglutination test was positive. He reported engaging in unprotected, extramarital sex 6 months before polydipsia onset and thereafter developing a skin lesion on the external genitalia and arthralgia, both of which resolved spontaneously. Examination of renal biopsy specimens showed abundant plasmacytic and lymphocytic infiltration of the interstitium and low and flat tubular epithelial cells, indicating renal tubular injury. Silver staining revealed T. pallidum-like organisms. Immunohistochemical analysis with T. pallidum-specific antibody confirmed the presence of treponemes. The patient received 2.4 million U of benzathine penicillin im once a week for 3 weeks. His urine output gradually reduced; he recovered 1 month later. His urine specific gravity was 1.026, and his syphilis rapid plasma reagin titer was 1:8. Syphilis can cause NDI. The manifestations of syphilis and causes of acquired NDI are diverse.

Nephrogenic diabetes insipidus: an X chromosome-linked dominant inheritance pattern with a vasopressin type 2 receptor gene that is structurally normal.

PubMed Central

Friedman, E; Bale, A E; Carson, E; Boson, W L; Nordenskjöld, M; Ritzén, M; Ferreira, P C; Jammal, A; De Marco, L

1994-01-01

Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly transmitted in an X chromosome-linked recessive manner and characterized by the lack of renal response to the action of antidiuretic hormone [Arg8]vasopressin. The vasopressin type 2 receptor (V2R) has been suggested to be the gene that causes the disease, and its role in disease pathogenesis is supported by mutations within this gene in affected individuals. Using the PCR, denaturing gradient gel electrophoresis, and direct DNA sequencing, we examined the V2R gene in four unrelated kindreds. In addition, linkage analysis with chromosome Xq28 markers was done in one large Brazilian kindred with an apparent unusual X chromosome-linked dominant inheritance pattern. In one family, a mutation in codon 280, causing a Tyr-->Cys substitution in the sixth transmembrane domain of the receptor, was found. In the other three additional families with nephrogenic diabetes insipidus, the V2R-coding region was normal in sequence. In one large Brazilian kindred displaying an unusual X chromosome-linked dominant mode of inheritance, the disease-related gene was localized to the same region of the X chromosome as the V2R, but no mutations were found, thus raising the possibility that this disease is caused by a gene other than V2R. Images PMID:8078903

Acute diabetes insipidus mediated by vasopressinase after placental abruption.

PubMed

Wallia, Amisha; Bizhanova, Aigerim; Huang, Wenyu; Goldsmith, Susan L; Gossett, Dana R; Kopp, Peter

2013-03-01

Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

PubMed

Hammami, Muhammad M; Duaiji, Najla; Mutairi, Ghazi; Aklabi, Sabah; Qattan, Nasser; Abouzied, Mohei El-Din M; Sous, Mohamed W

2015-09-09

Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione

Central diabetes insipidus in an African Grey parrot.

PubMed

Starkey, Simon R; Wood, Catherine; de Matos, Ricardo; Ledbetter, Eric C; Morrisey, James K

2010-08-15

A 5.5-year-old sexually intact female African Grey parrot (Psittacus erithacus) was evaluated for a 1-year history of pronounced polyuria and polydipsia. The bird also had a 1-month history of signs of mild depression and mydriasis. Physical examination revealed a thin body condition and incomplete bilateral mydriasis. Other examination findings as well as CBC and screening radiography results were unremarkable. Plasma biochemical analysis revealed mild hypernatremia. The bird had a 3.3% loss in body weight over 170 minutes during a water deprivation test, and urine osmolality remained low. After IM administration of 0.9 microg of desmopressin, the rate of weight loss decreased substantially and urine osmolality increased 300% over the following 200 minutes. Initial attempts to treat the bird with orally administered desmopressin failed to correct the polydipsia and polyuria. Ultimately, IM administration of 24 microg of desmopressin/kg (10.9 microg/lb) every 12 hours yielded a noticeable reduction in water consumption and urine production over a 6- to 8-hour period. Eight months later, the bird was returned for a recheck examination, at which time it was in good health and continued to respond to the medication. Despite continued response to the medication, right-sided internal ophthalmoparesis was detected 16 months after the initial diagnosis. To the authors' knowledge, central diabetes insipidus in birds has not been reported. The condition should be considered in birds with clinical signs of disease similar to those in mammals. Long-term IM administration of desmopressin may be a viable treatment option.

Clinical review: Treatment of neurohypophyseal diabetes insipidus.

PubMed

Oiso, Yutaka; Robertson, Gary L; Nørgaard, Jens Peter; Juul, Kristian Vinter

2013-10-01

In recent years, there have been several improvements in the treatment of neurohypophyseal diabetes insipidus (DI). They include new formulations of the vasopressin analog, desmopressin; a better understanding of the effect of fluid intake on dosing; and more information about treatments of infants, children, and pregnant women who present special challenges. This review aims to summarize past and current information relative to the safety and efficacy of treatments for the types of DI caused by a primary deficiency of vasopressin. The review is based on publications identified primarily by a PubMed search of the international literature without limitations of date. In acute settings where fluid intake is determined by factors other than thirst, desmopressin should be given iv in doses that have a short duration of action and can be adjusted quickly in accordance with changes in hydration as indicated by plasma sodium. In ambulatory patients, the oral formulations (tablet or melt) are preferred for their convenience. If fluid intake is regulated normally by the thirst mechanism, the tablets or melt can be taken safely 1 to 3 times a day in doses sufficient to completely eliminate the polyuria. However, if fluid intake consistently exceeds replacement needs as evidenced by the development of hyponatremia, the dose should be reduced to allow higher than normal rates of urine output or intermittent breakthrough diuresis. This regimen is often indicated in infants or children because their rate of fluid intake tends to be greater than in adults. In all cases, the appropriate dose should be determined by titration, owing to considerable interindividual differences in bioavailability and antidiuretic effect. Desmopressin can provide effective and safe therapy for all patients with neurohypophyseal or gestational DI if given in doses and by a route that takes into account the determinants of fluid intake.

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Transient polyuria related to central diabetes insipidus caused by lymphocytic infundibulo-neurohypophysitis in a patient treated for Graves' disease.

PubMed

Yamazaki, Masanori; Sato, Ai; Nishio, Shin-ichi; Uehara, Takeshi; Komatsu, Mitsuhisa

2010-01-01

A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst, polydipsia and increased urinary frequency. He was diagnosed with Graves' disease (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed the enlarged posterior pituitary with thickened stalk. Histological examination obtained from biopsy of the pituitary revealed lymphocytic infundibulo-neurohypophysitis. He received treatment with thiamazole (MMI) for GD and desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be discontinued as GD was gradually improved. This course indicates that not only the recovered renal response to arginine-vasopressin but also the immunomodulative effects of MMI might attribute to the improvement of polyuria.

Cholesteatoma in the Sellar Region Presenting as Hypopituitarism and Diabetes Insipidus

PubMed Central

Kong, Xiangyi; Wu, Huanwen; Ma, Wenbin; Li, Yongning; Xing, Bing; Kong, Yanguo; Wang, Renzhi

2016-01-01

Abstract Clinically significant sellar cysts unrelated to pituitary adenomas are uncommon. Intracranial cholesteatomas are also rare and are most common in the middle ear and mastoid region. We report an even rarer case of cholesteatoma in the sellar region—a challenging diagnosis guided by clinical presentations, radiological signs, and biopsy, aiming at emphasize the importance of considering cholesteatoma when making differential diagnoses of sellar lesions. We present a case of cholesteatoma in the sellar region in a 56-year-old man with hypopituitarism, diabetes insipidus, and cystic imaging findings. It was difficult to make an accurate diagnosis before surgery. We present detailed analysis of the patient's disease course and review pertinent literature. The patient underwent a surgical exploration and tumor resection through a transsphenoidal approach. Pathologic results revealed a cholesteatoma. The patient's symptoms improved a lot after surgery, and the postoperative period was uneventful. Taken together, the lesion's imaging appearance, pathological characteristics, and clinical features were all unique features that lead to a diagnosis of cholesteatoma. As we did not see such reports by Pubmed and EMBASE, we believe this is the first reported case of sellar cholesteatoma presenting in this manner. This article emphasized that cholesteatomas, although rare, should be considered part of the differential diagnosis of sellar lesions. PMID:26962793

Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus

PubMed Central

Kamsteeg, Erik-Jan; Bichet, Daniel G.; Konings, Irene B.M.; Nivet, Hubert; Lonergan, Michelle; Arthus, Marie-Françoise; van Os, Carel H.; Deen, Peter M.T.

2003-01-01

Vasopressin regulates body water conservation by redistributing aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical surface of renal collecting ducts, resulting in water reabsorption from urine. Mutations in AQP2 cause autosomal nephrogenic diabetes insipidus (NDI), a disease characterized by the inability to concentrate urine. Here, we report a frame-shift mutation in AQP2 causing dominant NDI. This AQP2 mutant is a functional water channel when expressed in Xenopus oocytes. However, expressed in polarized renal cells, it is misrouted to the basolateral instead of apical plasma membrane. Additionally, this mutant forms heterotetramers with wild-type AQP2 and redirects this complex to the basolateral surface. The frame shift induces a change in the COOH terminus of AQP2, creating both a leucine- and a tyrosine-based motif, which cause the reversed sorting of AQP2. Our data reveal a novel cellular phenotype in dominant NDI and show that dominance of basolateral sorting motifs in a mutant subunit can be the molecular basis for disease. PMID:14662748

Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family.

PubMed

Yamashita, Sumie; Hata, Astuko; Usui, Takeshi; Oda, Hirotsugu; Hijikata, Atsushi; Shirai, Tsuyoshi; Kaneko, Naoto; Hata, Daisuke

2016-05-01

X-linked recessive congenital nephrogenic diabetes insipidus (NDI) is caused by mutations of the arginine vasopressin type 2 receptor gene (AVPR2). More than 200 mutations of the AVPR2 gene with complete NDI have been reported although only 15 mutations with partial NDI has been reported to date. We herein report a Japanese kindred with partial NDI. The proband is an 8-year-old boy who was referred to our hospital for nocturnal enuresis. Water deprivation test and hypertonic saline test suggested partial renal antidiuretic hormone arginine vasopressin (AVP) resistance. Analysis of genomic DNA revealed a novel missense mutation (p.L161P) in the patient. The patient's mother was heterozygous for the mutation. Three-dimensional (3-D) modeling study showed that L161P possibly destabilizes the transmembrane domain of the V2 receptor, resulting in its misfolding or mislocalization. Distinguishing partial NDI from nocturnal enuresis is important. A clinical clue for diagnosis of partial NDI is an incompatibly high level of AVP despite normal serum osmolality.

Amyloid-like aggregation of provasopressin in diabetes insipidus and secretory granule sorting.

PubMed

Beuret, Nicole; Hasler, Franziska; Prescianotto-Baschong, Cristina; Birk, Julia; Rutishauser, Jonas; Spiess, Martin

2017-01-26

Aggregation of peptide hormone precursors in the trans-Golgi network is an essential process in the biogenesis of secretory granules in endocrine cells. It has recently been proposed that this aggregation corresponds to the formation of functional amyloids. Our previous finding that dominant mutations in provasopressin, which cause cell degeneration and diabetes insipidus, prevent native folding and produce fibrillar aggregates in the endoplasmic reticulum (ER) might thus reflect mislocalized amyloid formation by sequences that evolved to mediate granule sorting. Here we identified two sequences responsible for fibrillar aggregation of mutant precursors in the ER: the N-terminal vasopressin nonapeptide and the C-terminal glycopeptide. To test their role in granule sorting, the glycopeptide was deleted and/or vasopressin mutated to inactivate ER aggregation while still permitting precursor folding and ER exit. These mutations strongly reduced sorting into granules and regulated secretion in endocrine AtT20 cells. The same sequences - vasopressin and the glycopeptide - mediate physiological aggregation of the wild-type hormone precursor into secretory granules and the pathological fibrillar aggregation of disease mutants in the ER. These findings support the amyloid hypothesis for secretory granule biogenesis.

Transient diabetes insipidus in pregnancy

PubMed Central

Gunawardana, Kavinga; Grossman, Ashley

2015-01-01

Summary Gestational diabetes insipidus (DI) is a rare complication of pregnancy, usually developing in the third trimester and remitting spontaneously 4–6 weeks post-partum. It is mainly caused by excessive vasopressinase activity, an enzyme expressed by placental trophoblasts which metabolises arginine vasopressin (AVP). Its diagnosis is challenging, and the treatment requires desmopressin. A 38-year-old Chinese woman was referred in the 37th week of her first single-gestation due to polyuria, nocturia and polydipsia. She was known to have gestational diabetes mellitus diagnosed in the second trimester, well-controlled with diet. Her medical history was unremarkable. Physical examination demonstrated decreased skin turgor; her blood pressure was 102/63 mmHg, heart rate 78 beats/min and weight 53 kg (BMI 22.6 kg/m2). Laboratory data revealed low urine osmolality 89 mOsmol/kg (350–1000), serum osmolality 293 mOsmol/kg (278–295), serum sodium 144 mmol/l (135–145), potassium 4.1 mmol/l (3.5–5.0), urea 2.2 mmol/l (2.5–6.7), glucose 3.5 mmol/l and HbA1c 5.3%. Bilirubin, alanine transaminase, alkaline phosphatase and full blood count were normal. The patient was started on desmopressin with improvement in her symptoms, and normalisation of serum and urine osmolality (280 and 310 mOsmol/kg respectively). A fetus was delivered at the 39th week without major problems. After delivery, desmopressin was stopped and she had no further evidence of polyuria, polydipsia or nocturia. Her sodium, serum/urine osmolality at 12-weeks post-partum were normal. A pituitary magnetic resonance imaging (MRI) revealed the neurohypophyseal T1-bright spot situated ectopically, with a normal adenohypophysis and infundibulum. She remains clinically well, currently breastfeeding, and off all medication. This case illustrates some challenges in the diagnosis and management of transient gestational DI. Learning points Gestational DI is a rare complication of

Transient diabetes insipidus in pregnancy.

PubMed

Marques, Pedro; Gunawardana, Kavinga; Grossman, Ashley

2015-01-01

Gestational diabetes insipidus (DI) is a rare complication of pregnancy, usually developing in the third trimester and remitting spontaneously 4-6 weeks post-partum. It is mainly caused by excessive vasopressinase activity, an enzyme expressed by placental trophoblasts which metabolises arginine vasopressin (AVP). Its diagnosis is challenging, and the treatment requires desmopressin. A 38-year-old Chinese woman was referred in the 37th week of her first single-gestation due to polyuria, nocturia and polydipsia. She was known to have gestational diabetes mellitus diagnosed in the second trimester, well-controlled with diet. Her medical history was unremarkable. Physical examination demonstrated decreased skin turgor; her blood pressure was 102/63 mmHg, heart rate 78 beats/min and weight 53 kg (BMI 22.6 kg/m(2)). Laboratory data revealed low urine osmolality 89 mOsmol/kg (350-1000), serum osmolality 293 mOsmol/kg (278-295), serum sodium 144 mmol/l (135-145), potassium 4.1 mmol/l (3.5-5.0), urea 2.2 mmol/l (2.5-6.7), glucose 3.5 mmol/l and HbA1c 5.3%. Bilirubin, alanine transaminase, alkaline phosphatase and full blood count were normal. The patient was started on desmopressin with improvement in her symptoms, and normalisation of serum and urine osmolality (280 and 310 mOsmol/kg respectively). A fetus was delivered at the 39th week without major problems. After delivery, desmopressin was stopped and she had no further evidence of polyuria, polydipsia or nocturia. Her sodium, serum/urine osmolality at 12-weeks post-partum were normal. A pituitary magnetic resonance imaging (MRI) revealed the neurohypophyseal T1-bright spot situated ectopically, with a normal adenohypophysis and infundibulum. She remains clinically well, currently breastfeeding, and off all medication. This case illustrates some challenges in the diagnosis and management of transient gestational DI. Gestational DI is a rare complication of pregnancy occurring in two to four out of

Sildenafil for the Treatment of Congenital Nephrogenic Diabetes Insipidus.

PubMed

Assadi, Farahnak; Sharbaf, Fatemeh Ghane

2015-01-01

Congenital nephrogenic diabetes insipidus (NDI) is characterized by massive polyuria and polydipsia due to defects in the vasopressin-sensitive signaling system expression of the acuaporin-2 (AQP2) water channel of the kidney collecting duct principal cells. Current conventional treatment regimen including hydration, diuretics and nonsteroidal anti-inflammatory drugs can only partially reduce polyuria. Recent experimental studies have suggested that treatment with sildenafil, a selective phosphodiesterase inhibitor, may enhance cyclic guanosine monophosphate (cGMP)-mediated apical trafficking of AQP2 and may be effective in increasing water reabsorption in patients with congenital NDI. A 4-year old boy with X-linked NDI resistant to conventional therapy was treated with sildenafil for 10 days after a 2-day washout period between the 2 treatment regimens. Aliquots of the 24-hour urine collections before and after treatment were analyzed for urine volume, osmolality, cGMP and AQP2 determinations. Blood samples were also obtained for sodium and osmolality measurements. The primary endpoint was 24-hour urine volume after 10 days of sildenafil and conventional treatments. Compared to conventional therapy, treatment with sildenafil resulted in substantial reduction in 24-hour urine volume (1,764 vs. 950 ml) and serum sodium (148 vs. 139) mEq/l, and increased urine osmolality (104 vs. 215 mOsm/l), and AQP2 excretion (5 vs. 26 fmol/mg creatinine). The patient tolerated sildenafil well and experienced no adverse effects. Sildenafil citrate should be considered an alternative agent in the treatment of X-linked NDI resistant to conventional therapy. © 2015 S. Karger AG, Basel

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

PubMed

Deniz, Ferhat; Kepez, Alper; Ay, Seyit Ahmet; Ergogan, Okan; Baskoy, Kamil; Guncıkan, Mustafa Nuri; Dogan, Zekeriya; Yonem, Arif

2015-11-01

There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

Physiological insights into novel therapies for nephrogenic diabetes insipidus

PubMed Central

2016-01-01

Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for nephrogenic diabetes insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter. If it is possible to phosphorylate and/or increase the apical membrane accumulation of these proteins, independent of vasopressin or cAMP, one may be able to treat NDI. Sildenifil (through cGMP), erlotinib, and simvastatin each stimulate AQP2 insertion into the apical plasma membrane. Some recent human data suggest that sildenafil and simvastatin may improve urine concentrating ability. ONO-AE1-329 (ONO) stimulates the EP4 prostanoid receptor (EP4), which stimulates kinases that in turn phosphorylate AQP2 and UT-A1. Clopidogrel is a P2Y12-R antagonist that potentiates the effect of vasopressin and increases AQP2 abundance. Metformin stimulates AMPK to phosphorylate and activate AQP2 and UT-A1, and it increases urine concentrating ability in two rodent models of NDI. Since metformin, sildenafil, and simvastatin are commercially available and have excellent safety records, the potential for rapidly advancing them into clinical trials is high. PMID:27534996

Diagnosis of diabetes insipidus observed in Swiss Duroc boars.

PubMed

Grahofer, Alexander; Wiedemar, Natalie; Gurtner, Corinne; Drögemüller, Cord; Nathues, Heiko

2016-01-29

Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

A case of central diabetes insipidus after ketamine infusion during an external to internal carotid artery bypass.

PubMed

Gaffar, Sharib; Eskander, Jonathan P; Beakley, Burton D; McClure, Brian P; Amenta, Peter; Pierre, Nakeisha

2017-02-01

We report the first teenage case of ketamine-induced transient central diabetes insipidus. The patient was an 18-year-old woman with moyamoya disease undergoing an external carotid to internal carotid bypass and given a low-dose ketamine infusion. After approximately 2 hours in the supine position, with 0.5 Minimum Alveolar Concentration (MAC) of sevoflurane, a propofol infusion at 50 μg/kg/min, a remifentanil infusion at 0.5 μg/kg/min, and a ketamine infusion at a dose of 10 μg/kg/min, this patient had an excessive urine output. Initially, the Foley catheter contained 50 mL of urine. She was given 1500 mL of crystalloid during the case but produced 2700 mL of urine output. Increasing urine output was noted 1 hour into the procedure around the time that the patient experienced a 2-minute Cushing-like response characterized by bradycardia and hypertension. Several I-Stat samples revealed a worsening hypernatremia. The decision was made to check the urine osmolality and treat the patient with 4 μg of desmopressin (DDAVP). Urine output began to slow down to a normal rate of 2 mg/kg/h, as the patient was transferred from the operating room to the computed tomographic (CT) scanning room for a CT and CT angiogram; both were unremarkable. The neurosurgery team waited until the next day to complete the procedure. The procedure was completed successfully and uneventfully the next day without a ketamine infusion as part of the general anesthetic plan. The Naranjo Adverse Drug Reaction score of 4 suggested a possible relationship between the patient's ketamine infusion and subsequent central diabetes insipidus. The 2 previous cases on this topic have suggested that ketamine, as an N-methyl-d-aspartate receptor antagonist, inhibits vasopressin release in the neurohypophysis. Urine output, urine osmolarity, and serum osmolarity should be monitored in patients given ketamine anesthetic; desmopressin should be present to prevent dangerous long-term sequela. Copyright © 2016

Partial nephrogenic diabetes insipidus caused by a novel AQP2 variation impairing trafficking of the aquaporin-2 water channel.

PubMed

Dollerup, Pia; Thomsen, Troels Møller; Nejsum, Lene N; Færch, Mia; Österbrand, Martin; Gregersen, Niels; Rittig, Søren; Christensen, Jane H; Corydon, Thomas J

2015-12-29

Autosomal dominant inheritance of congenital nephrogenic diabetes insipidus (CNDI) is rare and usually caused by variations in the AQP2 gene. We have investigated the genetic and molecular background underlying symptoms of diabetes insipidus (DI) in a Swedish family with autosomal dominant inheritance of the condition. The proband and her father were subjected to water deprivation testing and direct DNA sequencing of the coding regions of the AQP2 and AVP genes. Madin-Darby canine kidney (MDCK) cells stably expressing AQP2 variant proteins were generated by lentiviral gene delivery. Localization of AQP2 variant proteins in the cells under stimulated and unstimulated conditions was analyzed by means of immunostaining and confocal laser scanning microscopy. Intracellular trafficking of AQP2 variant proteins was studied using transient expression of mutant dynamin2-K44A-GFP protein and AQP2 variant protein phosphorylation levels were assessed by Western blotting analysis. Clinical and genetic data suggest that the proband and her father suffer from partial nephrogenic DI due to a variation (g.4807C > T) in the AQP2 gene. The variation results in substitution of arginine-254 to tryptophan (p.R254W) in AQP2. Analysis of MDCK cells stably expressing AQP2 variant proteins revealed disabled phosphorylation, impaired trafficking and intracellular accumulation of AQP2-R254W protein. Notably, blocking of the endocytic pathway demonstrated impairment of AQP2-R254W to reach the cell surface. Partial CNDI in the Swedish family is caused by an AQP2 variation that seems to disable the encoded AQP2-R254W protein to reach the subapical vesicle population as well as impairing its phosphorylation at S256. The AQP2-R254W protein is thus unable to reach the plasma membrane to facilitate AVP mediated urine concentration.

Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus.

PubMed

Barak, L S; Oakley, R H; Laporte, S A; Caron, M G

2001-01-02

Agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCR) are mediated by the binding of arrestins to phosphorylated receptors. The affinity of arrestins for the phosphorylated GPCR regulates the ability of the internalized receptor to be dephosphorylated and recycled back to the plasma membrane. In this study, we show that the naturally occurring loss of function vasopressin receptor mutation R137H, which is associated with familial nephrogenic diabetes insipidus, induces constitutive arrestin-mediated desensitization. In contrast to the wild-type vasopressin receptor, the nonsignaling R137H receptor is phosphorylated and sequestered in arrestin-associated intracellular vesicles even in the absence of agonist. Eliminating molecular determinants on the receptor that promote high affinity arrestin-receptor interaction reestablishes plasma membrane localization and the ability of the mutated receptors to signal. These findings suggest that unregulated desensitization can contribute to the etiology of a GPCR-based disease, implying that pharmacological targeting of GPCR desensitization may be therapeutically beneficial.

Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus

PubMed Central

Barak, Larry S.; Oakley, Robert H.; Laporte, Stéphane A.; Caron, Marc G.

2001-01-01

Agonist-dependent desensitization and internalization of G protein-coupled receptors (GPCR) are mediated by the binding of arrestins to phosphorylated receptors. The affinity of arrestins for the phosphorylated GPCR regulates the ability of the internalized receptor to be dephosphorylated and recycled back to the plasma membrane. In this study, we show that the naturally occurring loss of function vasopressin receptor mutation R137H, which is associated with familial nephrogenic diabetes insipidus, induces constitutive arrestin-mediated desensitization. In contrast to the wild-type vasopressin receptor, the nonsignaling R137H receptor is phosphorylated and sequestered in arrestin-associated intracellular vesicles even in the absence of agonist. Eliminating molecular determinants on the receptor that promote high affinity arrestin–receptor interaction reestablishes plasma membrane localization and the ability of the mutated receptors to signal. These findings suggest that unregulated desensitization can contribute to the etiology of a GPCR-based disease, implying that pharmacological targeting of GPCR desensitization may be therapeutically beneficial. PMID:11134505

Central diabetes insipidus is not a common and prognostically worse type of hypernatremia in neurointensive care.

PubMed

Spatenkova, Vera; Bradac, Ondrej; Kazda, Antonin; Suchomel, Petr

2011-01-01

Hypernatremia is a common sodium dysbalance in neurointensive care which is associated with worse outcome. It can be caused by central diabetes insipidus (cDI) or by other mechanisms, more often from osmotherapy and furosemide. The aim of this study was to determine the incidence of cDI and to analyse outcome as compared with other causes of hypernatremias found in neurointesive care. We analysed 75 hypernatremic (serum sodium, SNa+ >150 mmol/l) patients (pts) with brain diseases admitted over a period of five years to Neurologic-Neurosurgical Intensive Care Unit (NNICU). Firstly we diagnosed cDI according to measured serum and urine osmolality, eletrolyte free water clearance (EWC) and response to desmopressin acetate. The remaining hypernatremias were categorised as "non cDI". We observed Glasgow Coma Scale (GCS) on onset of hypernatremia, incidence of cerebral complications, Glasgow Outcome Scale (GOS) upon discharge from NNICU and mortality in NNICU. We found cDI in 8 pts (mean SNa+ 154.8 ± 5.4 mmol/l). Most pts (67) were classified as "non cDI" hypernatremias (mean SNa+ 154.3 ± 3.6 mmol/l). There were no differences in serum sodium (p=0.682), serum osmolality (p=0.476) between the two groups, however patients with cDI indicated low urine osmolality (p=0.001) and positive EWC (p=0.049). We did not find any differences in GCS score on onset of hypernatremia (p=0.395), incidence of cerebral complications (p=0.705), GOS score upon discharge from NNICU (p=0.61) and mortality in NNICU (p=0.638). More patients in the "non cDI" group received antiedematic therapy (p=0.028) and diuretic furosemide (p=0.026). Multivariate logistic regression analysis showed that independent predictors of NNICU mortality was the highest level of serum sodium (Odds ratio, OR 1.13, per 1 mmol/l increase in maximal hypernatremia during NNICU stay, 95% confidence interval, CI 1.01-1.26, p=0.027), and GCS on admission of less than 9 (OR 2.61, 95% CI 1.41-5.44, p=0.003). Central

Management of central diabetes insipidus with oral desmopressin lyophilisate in infants.

PubMed

Korkmaz, Hüseyin Anıl; Demir, Korcan; Kılıç, Fatma Kaya; Terek, Demet; Arslanoğlu, Sertaç; Dizdarer, Ceyhun; Ozkan, Behzat

2014-09-01

To assess the efficiency of oral desmopressin lyophilisate (ODL) in neonatal central diabetes insipidus (CDI). The characteristics of four newborns with CDI treated with ODL were evaluated. Four newborns with polyuria and hypernatremia were included [male, 2 (50%); mean postnatal age, 19±17 days]. At the time of hypernatremia, the mean serum and urine osmolality values were 310±16 and 179±48 mOsm/kg, respectively. Antidiuretic hormone levels were undetectable (<0.5 pmol/L) in all cases. Magnetic resonance imaging revealed anatomical malformations in all cases. ODL (60 μg/tablet) dissolved in water (3-5 mL) was initiated with a dose of 5 μg/kg/day in two equal doses, together with limitation of water intake to avoid hyponatremia. Serum sodium levels returned to normal in a mean duration of 58±9.9 h with a mean decline rate of 0.37±0.1 mEq/L/h after desmopressin administration. Rehospitalization was required for one of the infants because of hypernatremia due to non-compliance. No episode of hyponatremia was encountered. Weight gain and growth of the infants were normal during the mean follow-up duration of 8.5±1 months. ODL appears to be practical and safe in the treatment of CDI during the first year of life.

Congenital central diabetes insipidus and optic atrophy in a Wolfram newborn: is there a role for WFS1 gene in neurodevelopment?

PubMed

Ghirardello, Stefano; Dusi, Elisa; Castiglione, Bianca; Fumagalli, Monica; Mosca, Fabio

2014-09-26

Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus (DM), optic atrophy (OA), central diabetes insipidus (CDI) and deafness (D). The phenotype of the disease has been associated with several mutations in the WFS1 gene, a nuclear gene localized on chromosome 4. Since the discovery of the association between WFS1 gene and Wolfram syndrome, more than 150 mutations have been identified in WS patients. We previously described the first case of perinatal onset of Wolfram syndrome newborn carrying a segmental uniparental heterodysomy affecting the short arm of chromosome 4 responsible for a significant reduction in wolframin expression. Here we review and discuss the pathophysiological mechanisms that we believe responsible for the perinatal onset of Wolfram syndrome as these data strongly suggest a role for WFS1 gene in foetal and neonatal neurodevelopment. We described a male patient of 30 weeks' gestation with intrauterine growth restriction and poly-hydramnios. During the first days of life, the patient showed a 19% weight loss associated with polyuria and hypernatremia. The presence of persistent hypernatremia (serum sodium 150 mEq/L), high plasma osmolarity (322 mOsm/L) and low urine osmolarity (190 mOsm/l) with a Uosm/Posm ratio < 1 were consistent with CDI. The diagnosis of CDI was confirmed by the desmopressin test and the brain magnetic resonance imaging (MRI) at 34 weeks of age, that showed the lack of posterior pituitary hyperintense signal. In addition, a bilateral asymmetrical optic nerve hypoplasia associated with right orbital bone hypoplasia was observed, suggesting the diagnosis of WF. During the five years follow-up the patient did not developed glucose intolerance or diabetes mellitus. By the end of the second year of life, primary non-autoimmune central hypothyroidism and mild neurodevelopment retardation were diagnosed. The analysis of our case, in the light of the most recent literature

Signaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus

PubMed Central

Harikumar, Kaleeckal G.; Miller, Laurence J.; Chow, Billy K. C.

2016-01-01

The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT’s potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear. Here, we demonstrate the interaction between SCTR and AVPR2 to modulate cellular signaling in vitro. Interestingly, we show in this report that upon heteromer formation with SCTR, R137H, a NDI-causing AVPR2 mutant that is defective in trafficking to cell surface, can functionally be rescued. Our data may provide an explanation for this clinically mild case of NDI, and insights into the pathological development of NDI in the future. PMID:27649563

Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.

PubMed

Zhao, Chen; Tella, Sri Harsha; Del Rivero, Jaydira; Kommalapati, Anuhya; Ebenuwa, Ifechukwude; Gulley, James; Strauss, Julius; Brownell, Isaac

2018-02-01

Immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient's symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. To our knowledge, this is the first report of central DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality. Copyright © 2017 Endocrine Society

Physiological insights into novel therapies for nephrogenic diabetes insipidus.

PubMed

Sands, Jeff M; Klein, Janet D

2016-12-01

Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for nephrogenic diabetes insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter. If it is possible to phosphorylate and/or increase the apical membrane accumulation of these proteins, independent of vasopressin or cAMP, one may be able to treat NDI. Sildenifil (through cGMP), erlotinib, and simvastatin each stimulate AQP2 insertion into the apical plasma membrane. Some recent human data suggest that sildenafil and simvastatin may improve urine concentrating ability. ONO-AE1-329 (ONO) stimulates the EP4 prostanoid receptor (EP4), which stimulates kinases that in turn phosphorylate AQP2 and UT-A1. Clopidogrel is a P2Y12-R antagonist that potentiates the effect of vasopressin and increases AQP2 abundance. Metformin stimulates AMPK to phosphorylate and activate AQP2 and UT-A1, and it increases urine concentrating ability in two rodent models of NDI. Since metformin, sildenafil, and simvastatin are commercially available and have excellent safety records, the potential for rapidly advancing them into clinical trials is high. Copyright © 2016 the American Physiological Society.

Factors Associated with Postoperative Diabetes Insipidus after Pituitary Surgery.

PubMed

Faltado, Antonio L; Macalalad-Josue, Anna Angelica; Li, Ralph Jason S; Quisumbing, John Paul M; Yu, Marc Gregory Y; Jimeno, Cecilia A

2017-12-01

Determining risk factors for diabetes insipidus (DI) after pituitary surgery is important in improving patient care. Our objective is to determine the factors associated with DI after pituitary surgery. We reviewed records of patients who underwent pituitary surgery from 2011 to 2015 at Philippine General Hospital. Patients with preoperative DI were excluded. Multiple logistic regression analysis was performed and a predictive model was generated. The discrimination abilities of the predictive model and individual variables were assessed using the receiving operator characteristic curve. A total of 230 patients were included. The rate of postoperative DI was 27.8%. Percent change in serum Na (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.15 to 1.69); preoperative serum Na (OR, 1.19; 95% CI, 1.02 to 1.40); and performance of craniotomy (OR, 5.48; 95% CI, 1.60 to 18.80) remained significantly associated with an increased incidence of postoperative DI, while percent change in urine specific gravity (USG) (OR, 0.53; 95% CI, 0.33 to 0.87) and meningioma on histopathology (OR, 0.05; 95% CI, 0.04 to 0.70) were significantly associated with a decreased incidence. The predictive model generated has good diagnostic accuracy in predicting postoperative DI with an area under curve of 0.83. Greater percent change in serum Na, preoperative serum Na, and performance of craniotomy significantly increased the likelihood of postoperative DI while percent change in USG and meningioma on histopathology were significantly associated with a decreased incidence. The predictive model can be used to generate a scoring system in estimating the risk of postoperative DI. Copyright © 2017 Korean Endocrine Society

Thiazide Diuretics in the Management of Young Children with Central Diabetes Insipidus.

PubMed

Al Nofal, Alaa; Lteif, Aida

2015-09-01

To report our experience in treating infants and toddlers with central diabetes insipidus (DI) with thiazide diuretics. A retrospective chart review of all infants and toddlers who were treated with thiazide diuretics for central DI at the Mayo Clinic between 1996 and 2014. Our cohort consisted of 13 patients. The median age at the start of therapy was 6 months (IQR, 1-14 months). Eight patients were given chlorothiazide at a starting dose of 5-10 mg/kg/day, and 5 patients were treated with hydrochlorothiazide at a starting dose of 1-2 mg/kg/day. The median age at the cessation of thiazide therapy was 18 months (IQR, 11.5-39 months). The main reason for stopping was the lack of continued response, in addition to hypernatremia. There was no hospitalization secondary to hyponatremia and only 1 hospitalization secondary to hypernatremia while receiving thiazide therapy. Calcium was checked periodically in 7 of the 13 patients, and 2 of these 7 patients had persistent hypercalcemia. Thiazide diuretics appear to be safe and effective in treating infants with central DI. They can be continued after the introduction of solid food, and until a lack of response is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

A missense mutation in the arginine-vasopressin neurophysin-II gene causes autosomal dominant neurohypophyseal diabetes insipidus in a Chinese family.

PubMed

Ye, Dan; Dong, FengQin; Lu, WeiQin; Zhang, Zhe; Lu, XunLiang; Li, ChengJiang; Liu, YanNing

2013-06-01

Familial neurohypophyseal diabetes insipidus, an autosomal dominant disorder, is mostly caused by mutations in the genes that encode AVP or its intracellular binding protein, neurophysin-II. The mutations lead to aberrant preprohormone processing and progressive destruction of AVP-secreting cells, which gradually manifests a progressive polyuria and polydipsia during early childhood, and a disorder of water homeostasis. We characterized the clinical and biochemical features, and sequenced the AVP neurophysin-II(AVP-NPII) gene of the affected individuals with autosomal dominant neurohypophyseal diabetes insipidus(ADNDI)to determine whether this disease was genetically determined. We obtained the histories of eight affected and four unaffected family individuals. The diagnosis of ADNDI was established using a water deprivation test and exogenous AVP administration. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified using polymerase chain reaction and sequenced. The eight affected individuals showed different spectra of age of onsets (7-15 years) and urine volumes (132-253 ml/kg/24 h). All affected individuals responded to vasopressin administration, with a resolution of symptoms and an increase in urine osmolality by more than 50%. The characteristic hyperintense signal in the posterior pituitary on T1-weighted magnetic resonance imaging was absent in six family members and present in one. Sequencing analysis revealed a missense heterozygous mutation 1516G > T (Gly17Val) in exon 2 of the AVP-NPII gene among the ADNDI individuals. We identified a missense mutation in the AVP-NPII gene and the same mutation showed different spectra of age of onsets and urine volumes in a new Chinese family with ADNDI. The mutation may provide a molecular basis for understanding the characteristics of NPII and add to our knowledge of the pathogenesis of ADNDI, which would allow the presymptomatic diagnosis of asymptomatic subjects. © 2012 John Wiley

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

PubMed

Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

2016-07-01

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

Acute myeloid leukemia presenting with panhypopituitarism or diabetes insipidus: a case series with molecular genetic analysis and review of the literature.

PubMed

Cull, Elizabeth H; Watts, Justin M; Tallman, Martin S; Kopp, Peter; Frattini, Mark; Rapaport, Franck; Rampal, Raajit; Levine, Ross; Altman, Jessica K

2014-09-01

Central diabetes insipidus (DI) is a rare finding in patients with acute myeloid leukemia (AML), usually occurring in patients with chromosome 3 or 7 abnormalities. We describe four patients with AML and concurrent DI and a fifth patient with AML and panhypopituitarism. Four of five patients had monosomy 7. Three patients had chromosome 3q21q26/EVI-1 gene rearrangements. The molecular genotype of patients with AML and DI is not known. Therefore, we performed gene sequencing of 30 genes commonly mutated in AML in three patients with available leukemia cell DNA. One patient had no identifiable mutations, and two had RUNX1 F158S mutations.

Metformin improves urine concentration in rodents with nephrogenic diabetes insipidus

PubMed Central

Efe, Orhan; Klein, Janet D.; LaRocque, Lauren M.; Ren, Huiwen; Sands, Jeff M.

2016-01-01

Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily. Urine osmolality in tolvaptan-treated rats (1,303 ± 126 mOsM) was restored to control levels by metformin (2,335 ± 273 mOsM) within 3 days and was sustained for up to 10 days. Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation. Outer medullary Na+-K+-2Cl– cotransporter 2 (NKCC2) abundance increased (117%) with AMPK stimulation in control rats but not in V2R-blocked rats. Metformin increased V2R KO mouse urine osmolality within 3 hours, and the increase persisted for up to 12 hours. Metformin increased AQP2 in the V2R KO mice similar to the tolvaptan-treated rats. These results indicate that AMPK activators, such as metformin, might provide a promising treatment for congenital NDI. PMID:27478876

Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus

PubMed Central

Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L.

2016-01-01

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca2+) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca2+ levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca2+ mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca2+ levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling. PMID:26574044

Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

PubMed

Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

2016-07-01

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling. Copyright © 2016 by the American Society of Nephrology.

Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.

PubMed

Winzeler, Bettina; Zweifel, Christian; Nigro, Nicole; Arici, Birsen; Bally, Martina; Schuetz, Philipp; Blum, Claudine Angela; Kelly, Christopher; Berkmann, Sven; Huber, Andreas; Gentili, Fred; Zadeh, Gelareh; Landolt, Hans; Mariani, Luigi; Müller, Beat; Christ-Crain, Mirjam

2015-06-01

Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.

[Clinical case of the month. Renovascular arterial hypertension complicated by diabetes insipidus: report of a case and review of the literature].

PubMed

Feloni, S; Radermacher, L; Remy, C; Jousten, J; Corman, V

2013-01-01

Mrs. A, a 62 year old patient with a history of hypertension, polyuria and polydipsia is hospitalized after a malaise. A severe hypokalemia, which is the cause of the polyuria and polydipsia, is discovered. The presence of hypertension and hypokalemia arises suspicion of a primary hyperaldosteronism and the plasma levels of renin and aldosterone are measured. Elevated aldosterone levels are combined with high plasma renin concentrations which permits to rule out primary hyperaldosteronism. Further explorations reveal a subocclusive ostial stenosis of the right renal artery. A treatment by sartan is instaured, which allows arterial pressure control and kalemia normalization. Chronic hypokalemia can be the cause of tubular nephropathy manifested by nephrogenic diabetes insipidus.

Augmentation cystoplasty in neurogenic bladder

PubMed Central

Kocjancic, Ervin; Demirdağ, Çetin

2016-01-01

The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

Absence of PKC-Alpha Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus

PubMed Central

Sim, Jae H.; Himmel, Nathaniel J.; Redd, Sara K.; Pulous, Fadi E.; Rogers, Richard T.; Black, Lauren N.; Hong, Seongun M.; von Bergen, Tobias N.; Blount, Mitsi A.

2014-01-01

Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy. PMID:25006961

Biased agonist pharmacochaperones of the AVP V2 receptor may treat congenital nephrogenic diabetes insipidus.

PubMed

Jean-Alphonse, Frédéric; Perkovska, Sanja; Frantz, Marie-Céline; Durroux, Thierry; Méjean, Catherine; Morin, Denis; Loison, Stéphanie; Bonnet, Dominique; Hibert, Marcel; Mouillac, Bernard; Mendre, Christiane

2009-10-01

X-linked congenital nephrogenic diabetes insipidus (cNDI) results from inactivating mutations of the human arginine vasopressin (AVP) V2 receptor (hV(2)R). Most of these mutations lead to intracellular retention of the hV(2)R, preventing its interaction with AVP and thereby limiting water reabsorption and concentration of urine. Because the majority of cNDI-hV(2)Rs exhibit protein misfolding, molecular chaperones hold promise as therapeutic agents; therefore, we sought to identify pharmacochaperones for hV(2)R that also acted as agonists. Here, we describe high-affinity nonpeptide compounds that promoted maturation and membrane rescue of L44P, A294P, and R337X cNDI mutants and restored a functional AVP-dependent cAMP signal. Contrary to pharmacochaperone antagonists, these compounds directly activated a cAMP signal upon binding to several cNDI mutants. In addition, these molecules displayed original functionally selective properties (biased agonism) toward the hV(2)R, being unable to recruit arrestin, trigger receptor internalization, or stimulate mitogen-activated protein kinases. These characteristics make these hV(2)R agonist pharmacochaperones promising therapeutic candidates for cNDI.

Biased Agonist Pharmacochaperones of the AVP V2 Receptor May Treat Congenital Nephrogenic Diabetes Insipidus

PubMed Central

Jean-Alphonse, Frédéric; Perkovska, Sanja; Frantz, Marie-Céline; Durroux, Thierry; Méjean, Catherine; Morin, Denis; Loison, Stéphanie; Bonnet, Dominique; Hibert, Marcel

2009-01-01

X-linked congenital nephrogenic diabetes insipidus (cNDI) results from inactivating mutations of the human arginine vasopressin (AVP) V2 receptor (hV2R). Most of these mutations lead to intracellular retention of the hV2R, preventing its interaction with AVP and thereby limiting water reabsorption and concentration of urine. Because the majority of cNDI-hV2Rs exhibit protein misfolding, molecular chaperones hold promise as therapeutic agents; therefore, we sought to identify pharmacochaperones for hV2R that also acted as agonists. Here, we describe high-affinity nonpeptide compounds that promoted maturation and membrane rescue of L44P, A294P, and R337X cNDI mutants and restored a functional AVP-dependent cAMP signal. Contrary to pharmacochaperone antagonists, these compounds directly activated a cAMP signal upon binding to several cNDI mutants. In addition, these molecules displayed original functionally selective properties (biased agonism) toward the hV2R, being unable to recruit arrestin, trigger receptor internalization, or stimulate mitogen-activated protein kinases. These characteristics make these hV2R agonist pharmacochaperones promising therapeutic candidates for cNDI. PMID:19729439

X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.

PubMed Central

Bichet, D G; Arthus, M F; Lonergan, M; Hendy, G N; Paradis, A J; Fujiwara, T M; Morgan, K; Gregory, M C; Rosenthal, W; Didwania, A

1993-01-01

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene. Images PMID:8104196

Pre- and post-treatment urinary tract findings in children with nephrogenic diabetes insipidus.

PubMed

Caletti, María Gracia; Balestracci, Alejandro; Di Pinto, Diana

2014-03-01

Nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate urine, which causes intense polyuria that may lead to urinary tract dilation. We report the morphological findings of the urinary tract in ten boys with NDI specifically addressing the presence and changes of urinary tract dilation during treatment. Patients were diagnosed at a median age of 1.6 years (range, 0.16-6.33 years) and treated with a low osmotic diet, hydrochlorothiazide-amiloride and indomethacin, which decreased the diuresis from a median of 10.5 ml/kg/h to 4.4 ml/kg/h (p < 0.001). Three patients showed normal renal ultrasound before treatment until last control, while the remaining seven showed urinary tract dilation. In this second group, dilation was reduced with treatment in four patients and disappeared in the remaining three. Children without dilation or in whom the dilation disappeared were diagnosed and treated earlier than those with persistent dilation (median 1.66 versus 4.45 years, respectively). After a median of 10.4 (range, 2.3-20.3) years of follow-up, no patients showed urological complications. Medical treatment of the disease improved the dilation in all cases, preventing its potential complications. Regardless of the good outcome of our patients, periodic urologic follow-up is recommended in NDI patients.

Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges in management during infancy.

PubMed

Rugpolmuang, Rottanat; Deeb, Asma; Hassan, Yousef; Deekajorndech, Tawatchai; Shotelersuk, Vorasuk; Sahakitrungruang, Taninee

2014-01-01

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.

Nephrogenic Diabetes Insipidus: Essential Insights into the Molecular Background and Potential Therapies for Treatment

PubMed Central

Rittig, Søren

2013-01-01

The water channel aquaporin-2 (AQP2), expressed in the kidney collecting ducts, plays a pivotal role in maintaining body water balance. The channel is regulated by the peptide hormone arginine vasopressin (AVP), which exerts its effects through the type 2 vasopressin receptor (AVPR2). Disrupted function or regulation of AQP2 or the AVPR2 results in nephrogenic diabetes insipidus (NDI), a common clinical condition of renal origin characterized by polydipsia and polyuria. Over several years, major research efforts have advanced our understanding of NDI at the genetic, cellular, molecular, and biological levels. NDI is commonly characterized as hereditary (congenital) NDI, arising from genetic mutations in the AVPR2 or AQP2; or acquired NDI, due to for exmple medical treatment or electrolyte disturbances. In this article, we provide a comprehensive overview of the genetic, cell biological, and pathophysiological causes of NDI, with emphasis on the congenital forms and the acquired forms arising from lithium and other drug therapies, acute and chronic renal failure, and disturbed levels of calcium and potassium. Additionally, we provide an overview of the exciting new treatment strategies that have been recently proposed for alleviating the symptoms of some forms of the disease and for bypassing G protein-coupled receptor signaling. PMID:23360744

Effect of administration of corticotropin-releasing hormone and glucocorticoid on arginine vasopressin response to osmotic stimulus in normal subjects and patients with hypocorticotropinism without overt diabetes insipidus.

PubMed

Yamada, K; Tamura, Y; Yoshida, S

1989-08-01

We examined the effect of CRH administration on the response of plasma arginine vasopressin (AVP) induced by an osmotic stimulus in six normal subjects and five patients with hypocorticotropinism without overt diabetes insipidus (four patients with Sheehan's syndrome and one with idiopathic pituitary dwarfism with ACTH deficiency). Hypertonic saline infusion (855 mmol/L saline solutions at a rate of 205 mumol/kg.min for 10 min) increased plasma AVP 5.7-fold (P less than 0.01) in normal subjects and 2.4-fold (P less than 0.05) in the patients. CRH administration significantly augmented the plasma AVP response to the osmotic stimulus in the normal subjects, but not in the patients with hypocorticotropinism. CRH administration alone did not influence plasma AVP. These findings suggest that a central CRH-related mechanism(s) was at least partly involved in the augmentation of AVP release. Based on the relatively low plasma AVP response to the osmotic stimulus in patients and their lower plasma AVP levels and higher plasma osmolality under basal conditions, we suggest that patients with hypocorticotropinism have partial diabetes insipidus, in which impairment of central CRH action might be, at least in part, involved. The response of plasma AVP to the osmotic stimulus was attenuated significantly when the patients were given cortisol. Since basal PRA, plasma aldosterone, plasma osmolality, hematocrit, body weight, mean blood pressure, and heart rate were similar with and without cortisol administration, this effect of cortisol may have been due to central suppression of the AVP response to the osmotic stimulus.

Central diabetes insipidus: clinical profile and factors indicating organic etiology in children.

PubMed

Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

2008-06-01

To evaluate the profile of children with central diabetes insipidus (DI) and identify factors indicating organic etiology. Retrospective chart review. Tertiary referral hospital. Fifty-nine children with central DI (40 boys, 19 girls). Features of organic and idiopathic central DI were compared using students t test and chi square test. Odds ratio was calculated for factors indicating organic etiology. Diagnosis included post-operative central DI (13, 22%), central nervous system (CNS) malformations (5, 8.6% holoprosencephaly 4 and hydrocephalus 1), histiocytosis (11, 18.6%), CNS pathology (11, 18.6%; craniopharyngioma 3, empty sella 2, germinoma 2, neuro-tuberculosis 2, arachnoid cyst 1 and glioma 1) and idiopathic central DI (19, 32.2%). Children with organic central DI were diagnosed later (7.8+/- 3.1 years against 5.3+/-2.4 years, P=0.03) and had lower height standard deviation score (-2.7+/-1.0 versus -1.0+/- 1.0, P<0.001) compared to idiopathic group. A greater proportion of children with organic central DI had short stature (81.8% against 10.5%, P <0.001, odds ratio 38.25), neurological features (45.5% against 0%, p 0.009) and anterior pituitary hormone deficiency (81.8% against 5.3%, P<0.001, odds ratio 81) compared to idiopathic group. A combination of short stature and onset after five years of age led to discrimination of organic central DI from idiopathic group in all cases. Organic central DI should be suspected in children presenting after the age of five years with growth retardation and features of anterior pituitary deficiency.

Diabetes Insipidus Contributes to Traumatic Brain Injury Pathology Via CD36 Neuroinflammation

PubMed Central

Staples, Meaghan; Borlongan, Mia C.; Hernandez, Diana; Acosta, Sandra

2013-01-01

Each year, over one million people in the United States are affected by traumatic brain injury (TBI). Symptoms of both acute and chronic neuroinflammation follow TBI, coinciding with a robust immune response and activation of the brain’s endogenous repair mechanisms. TBI can lead to endocrine failure as a result of damage to the thalamic region of the brain, evidenced by excessive thirst and polyuria often accompanying TBI. These symptoms indicate the presence of diabetes insipidus (DI), a disruption of water homeostasis due to antidiuretic hormone deficiency. This deficiency accompanies a mechanical or neuroinflammatory damage to the thalamic region during TBI, evidenced by increased expression of inflammatory microglial marker MHCII in this brain region. Excessive thirst and urinations, which are typical DI symptoms, in our chronic TBI rats also suggest a close connection between TBI and DI. We seek to bridge this gap between TBI and DI through investigation of the Cluster of Differentiation 36 (CD36) receptor. This receptor is associated with Low-Density Lipoprotein (LDL) deregulation, proinflammatory events, and innate immunity regulation. We posit that CD36 exacerbates TBI through immune activation and subsequent neuroinflammation. Indeed, scientific evidence already supports pathological interaction of CD36 in other neurological disorders including stroke and Alzheimer’s disease. We propose that DI contributes to TBI pathology via CD36 neuroinflammation. Use of CD36 as a biomarker may provide insights into treatment and disease pathology of TBI and DI. This unexplored avenue of research holds potential for a better understanding and treatment of TBI and DI. PMID:24021616

X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking.

PubMed

Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Oberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J; Deen, Peter M T; Törnroth-Horsefield, Susanna

2014-04-29

Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein-protein interactions involved in cellular sorting of AQP2. Two Cd(2+)-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking.

A murine model of autosomal dominant neurohypophyseal diabetes insipidus reveals progressive loss of vasopressin-producing neurons

PubMed Central

Russell, Theron A.; Ito, Masafumi; Ito, Mika; Yu, Richard N.; Martinson, Fred A.; Weiss, Jeffrey; Jameson, J. Larry

2003-01-01

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the arginine vasopressin (AVP) precursor. The pathogenesis of FNDI is proposed to involve mutant protein–induced loss of AVP-producing neurons. We established murine knock-in models of two different naturally occurring human mutations that cause FNDI. A mutation in the AVP signal sequence [A(–1)T] is associated with a relatively mild phenotype or delayed presentation in humans. This mutation caused no apparent phenotype in mice. In contrast, heterozygous mice expressing a mutation that truncates the AVP precursor (C67X) exhibited polyuria and polydipsia by 2 months of age and these features of DI progressively worsened with age. Studies of the paraventricular and supraoptic nuclei revealed induction of the chaperone protein BiP and progressive loss of AVP-producing neurons relative to oxytocin-producing neurons. In addition, Avp gene products were not detected in the neuronal projections, suggesting retention of WT and mutant AVP precursors within the cell bodies. In summary, this murine model of FNDI recapitulates many features of the human disorder and demonstrates that expression of the mutant AVP precursor leads to progressive neuronal cell loss. PMID:14660745

Induced pluripotent stem cells derived from a patient with autosomal dominant familial neurohypophyseal diabetes insipidus caused by a variant in the AVP gene.

PubMed

Toustrup, Lise Bols; Zhou, Yan; Kvistgaard, Helene; Gregersen, Niels; Rittig, Søren; Aagaard, Lars; Corydon, Thomas Juhl; Luo, Yonglun; Christensen, Jane H

2017-03-01

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by variants in the arginine vasopressin (AVP) gene. Here we report the generation of induced pluripotent stem cells (iPSCs) from a 42-year-old man carrying an adFNDI causing variant in exon 1 of the AVP gene using lentivirus-mediated nuclear reprogramming. The iPSCs carried the expected variant in the AVP gene. Furthermore, the iPSCs expressed pluripotency markers; displayed in vitro differentiation potential to the three germ layers and had a normal karyotype consistent with the original fibroblasts. This iPSC line is useful in future studies focusing on the pathogenesis of adFNDI. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene.

PubMed

Park, Youn Jong; Baik, Haing Woon; Cheong, Hae Il; Kang, Ju Hyung

2014-07-01

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 ( AQP2 ) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of 108 Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The 108 Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided.

Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene

PubMed Central

PARK, YOUN JONG; BAIK, HAING WOON; CHEONG, HAE IL; KANG, JU HYUNG

2014-01-01

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of 108Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The 108Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided. PMID:24944815

Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum.

PubMed Central

Ito, M; Jameson, J L; Ito, M

1997-01-01

Mutations in the arginine vasopressin (AVP) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (FNDI). The dominant inheritance pattern has been postulated to reflect neuronal toxicity of the mutant proteins, but the mechanism for such cytotoxicity is unknown. In this study, wild-type or several different mutant AVP genes were stably expressed in neuro2A neuroblastoma cells. When cells were treated with valproic acid to induce neuronal differentiation, each of the mutants caused reduced viability. Metabolic labeling revealed diminished intracellular trafficking of mutant AVP precursors and confirmed inefficient secretion of immunoreactive AVP. Immunofluorescence studies demonstrated marked accumulation of mutant AVP precursors within the endoplasmic reticulum. These studies suggest that the cellular toxicity in FNDI may be caused by the intracellular accumulation of mutant precursor proteins. PMID:9109434

Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

PubMed

Zhang, Yue; Peti-Peterdi, János; Brandes, Anna U; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

2017-06-01

Previously, we localized ADP-activated P2Y 12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N = 5/group) were fed either regular rodent chow (CNT), or with added LiCl (40 mmol/kg chow) or PRSG in drinking water (10 mg/kg bw/day) or a combination of LiCl and PRSG for 14 days and then euthanized. Water intake and urine output were determined and blood and kidney tissues were collected and analyzed. PRSG administration completely suppressed Li-induced polydipsia and polyuria and significantly prevented Li-induced decreases in AQP2 protein abundance in renal cortex and medulla. However, PRSG either alone or in combination with Li did not have a significant effect on the protein abundances of NKCC2 or NCC in the cortex and/or medulla. Immunofluorescence microscopy revealed that PRSG administration prevented Li-induced alterations in cellular disposition of AQP2 protein in medullary collecting ducts. Serum Li, Na, and osmolality were not affected by the administration of PRSG. Similar to CLPD, PRSG administration had no effect on Li-induced increase in urinary Na excretion. However, unlike CLPD, PRSG did not augment Li-induced increase in urinary arginine vasopressin (AVP) excretion. Taken together, these data suggest that the pharmacological inhibition of P2Y 12 -R by the thienopyridine group of drugs may potentially offer therapeutic benefits in Li-induced NDI.

Clinical Predictors of Diabetes Insipidus After Transcranial Surgery for Pituitary Adenoma.

PubMed

Wang, Songquan; Li, Deling; Ni, Ming; Jia, Wang; Zhang, Qing; He, Jue; Jia, Guijun

2017-05-01

Diabetes insipidus (DI) is a well-known complication of transsphenoidal pituitary adenoma surgery. However, the risk factors for DI after transcranial surgery have not been clarified. In this study, the clinical parameters for predicting DI after transcranial surgery were investigated. The perioperative records of 90 patients who underwent transcranial (TC) surgery at the authors' institution between November 2011 and March 2013 were chosen from 1657 patients with pituitary adenoma and retrospectively analyzed. The degree of deformation of the third ventricle and hypothalamus were assessed by preoperative magnetic resonance imaging. Immediate postoperative DI was found in 30 patients (33.3%). Persistent DI was noted in 11 patients (12.6%). Compared with patients in the nonpostoperative DI group, those with postoperative DI had a higher degree of deformation of the third ventricle and hypothalamus (P < 0.001). In a binary logistic regression analysis, the degree of deformation of the third ventricle and hypothalamus (odds ratio [OR], 3.079; 95% confidence interval [CI], 1.600-5.925; P = 0.001) had a significant positive correlation with immediate postoperative DI, as well as postoperative hemorrhage (OR, 6.235, 95% CI, 1.457-26.689; P = 0.014). Postoperative hemorrhage (OR, 4.363; 95% CI, 1.021-18.647; P = 0.047) showed a positive correlation with permanent DI, as well as the degree of deformation of the third ventricle and hypothalamus (OR, 2.336; 95% CI, 1.005-5.427; P = 0.049). The degree of deformation of the third ventricle and hypothalamus assessed by preoperative magnetic resonance imaging may help to predict postoperative DI. Postoperative hemorrhage might increase the incidence of postoperative DI, whether it is immediate postoperative DI or permanent DI. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcome of diabetes insipidus in patients with Rathke's cleft cysts.

PubMed

Oishi, Masahiro; Hayashi, Yasuhiko; Sasagawa, Yasuo; Kita, Daisuke; Tachibana, Osamu; Nakada, Mitsutoshi

2018-04-01

It is well-known that Rathke's cleft cysts (RCCs) infrequently cause headache, endocrinological dysfunction, and visual disturbance, and in rare cases, cause diabetes insipidus (DI). Although surgical evacuation of the cyst content can result in high rates of symptomatic improvement, not only the treatment efficacy but also the pathophysiology of DI with RCC are undetermined. The aim of this study is to elucidate the underlying mechanisms and outcomes of DI associated with RCCs. We retrospectively studied 109 patients with RCCs treated at Kanazawa University Hospital between 2000 and 2016. Their age, sex, symptoms, endocrinological status, DI, visual disturbance, neuroradiological findings, pathological appearances, and pre-/post-operative hormone levels and status of anti-diuretic hormone replacements were assessed. Among 109 cases of RCCs, five cases (4.6%, 2 males and 3 females) manifested with DI as initial presentation were included. These five cases could be divided into two types: the acute type and the chronic type, based on the onset and duration of symptoms. Three acute onset cases presented with not only strong thirst but also sudden headaches without pituitary dysfunction, whereas the two chronic onset cases presented with chronic headaches and hypopituitarism. Pathological examination in the acute type revealed inflammatory cell infiltration into only the posterior lobe of the pituitary and disruption of the cyst wall adjacent to the posterior lobe, which might suggest RCC rupture. In contrast, the chronic type showed inflammatory cell infiltration into both the anterior and posterior lobes of the pituitary and thickened fibrosis beneath the cyst wall. Postoperatively, two cases of the acute type could be controlled with a smaller amount of 1-deamino-8-D-arginine vasopressin (DDAVP) than that required preoperatively, whereas no change was observed in the cases of the chronic type. The cases of DI onset caused by RCCs could be divided into the acute

Surgical biopsies in patients with central diabetes insipidus and thickened pituitary stalks.

PubMed

Jian, Fangfang; Bian, Liuguan; Sun, Shouyue; Yang, Jun; Chen, Xiao; Chen, Yufan; Ma, Qinyun; Miao, Fei; Wang, Weiqing; Ning, Guang; Sun, Qingfang

2014-09-01

Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

Aliskiren increases aquaporin-2 expression and attenuates lithium-induced nephrogenic diabetes insipidus.

PubMed

Lin, Yu; Zhang, Tiezheng; Feng, Pinning; Qiu, Miaojuan; Liu, Qiaojuan; Li, Suchun; Zheng, Peili; Kong, Yonglun; Levi, Moshe; Li, Chunling; Wang, Weidong

2017-10-01

The direct renin inhibitor aliskiren has been shown to be retained and persist in medullary collecting ducts even after treatment is discontinued, suggesting a new mechanism of action for this drug. The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression in the collecting ducts and improves urinary concentrating defect induced by lithium in mice. The mice were fed with either normal chow or LiCl diet (40 mmol·kg dry food -1 ·day -1 for 4 days and 20 mmol·kg dry food -1 ·day -1 for the last 3 days) for 7 days. Some mice were intraperitoneally injected with aliskiren (50 mg·kg body wt -1 ·day -1 in saline). Aliskiren significantly increased protein abundance of aquaporin-2 (AQP2) in the kidney inner medulla in mice. In inner medulla collecting duct cell suspension, aliskiren markedly increased AQP2 and phosphorylated AQP2 at serine 256 (pS256-AQP2) protein abundance, which was significantly inhibited both by adenylyl cyclase inhibitor MDL-12330A and by PKA inhibitor H89, indicating an involvement of the cAMP-PKA signaling pathway in aliskiren-induced increased AQP2 expression. Aliskiren treatment improved urinary concentrating defect in lithium-treated mice and partially prevented the decrease of AQP2 and pS256-AQP2 protein abundance in the inner medulla of the kidney. In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus likely via cAMP-PKA pathways. Copyright © 2017 the American Physiological Society.

The McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study (McGLIDICS).

PubMed

Rej, Soham; Segal, Marilyn; Low, Nancy C P; Mucsi, Istvan; Holcroft, Christina; Shulman, Kenneth; Looper, Karl

2014-06-01

Despite being a common and potentially serious condition, nephrogenic diabetes insipidus (NDI) remains poorly understood in older lithium users. Our main objective was to compare the prevalence of NDI symptoms and decreased urine osmolality ([UOsm] < 300 milli-Osmoles [mOsm/kg]) among geriatric and adult lithium users. We also assessed NDI symptoms, serum sodium (Na+), and urine specific gravity (USG) as possible surrogate measures of decreased UOsm, and ascertained whether potential etiologic factors independently correlated with decreased UOsm. This was a cross-sectional study of 100 consecutive outpatients treated with lithium from 6 tertiary care clinics, of which 45 were geriatric (aged 65 years and older) and 55 adult (aged 18 to 64 years). Patients completed a symptom questionnaire and underwent laboratory tests, including UOsm, serum Na+, and USG. Geriatric and adult lithium users had similar rates of decreased UOsm (12.5%, compared with 17.9%, P = 0.74), but geriatric patients reported less symptoms (P < 0.05). Although UOsm did not correlate with symptoms or current serum Na+, USG of less than 1.010 was suggestive of UOsm of less than 300 mOsm/kg. Age, lithium duration, and serum lithium level were independently associated with UOsm. The prevalence of decreased UOsm is similar in geriatric and adult lithium users, but older patients are less likely to report urinary and thirst symptoms. Although subjective symptoms do not correlate with UOsm, USG may be a cost-efficient clinical surrogate measure for UOsm. We suggest clinicians increase their vigilance for decreased UOsm, especially in lithium users with advanced age, longer duration of lithium exposure, and higher lithium levels. This may potentially prevent lithium intoxication, falls, hypernatremic events, and renal dysfunction.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

PubMed

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Neurogenic Fever.

PubMed

Meier, Kevin; Lee, Kiwon

2017-02-01

Fever is a relatively common occurrence among patients in the intensive care setting. Although the most obvious and concerning etiology is sepsis, drug reactions, venous thromboembolism, and postsurgical fevers are all on the differential diagnosis. There is abundant evidence that fever is detrimental in acute neurologic injury. Worse outcomes are reported in acute stroke, subarachnoid hemorrhage, and traumatic brain injury. In addition to the various etiologies of fever in the intensive care setting, neurologic illness is a risk factor for neurogenic fevers. This primarily occurs in subarachnoid hemorrhage and traumatic brain injury, with hypothalamic injury being the proposed mechanism. Paroxysmal sympathetic hyperactivity is another source of hyperthermia commonly seen in the population with traumatic brain injury. This review focuses on the detrimental effects of fever on the neurologically injured as well as the risk factors and diagnosis of neurogenic fever.

Droxidopa for Symptomatic Neurogenic Hypotension.

PubMed

Ferguson-Myrthil, Nadia

Droxidopa is a first-in-class, orally available, synthetic amino acid precursor of norepinephrine that received accelerated Food and Drug Administration approval in February 2014 after Orphan Drug status for a debilitating condition known as symptomatic neurogenic orthostatic hypotension. Neurogenic disorders often lead to postural hypotension as a result of poor norepinephrine release from its storage sites. Clinical data suggest increases in standing systolic blood pressure and improvements in many other markers for subjective relief in patients with symptomatic neurogenic hypotension who received droxidopa therapy over 1-2 weeks. Studies evaluating the sustained effects of droxidopa are ongoing. With minimal drug interactions (even with carbidopa use) or adverse effects, droxidopa therapy can be used safely in patients with a variety of neurologic conditions; however, more data are needed to determine its appropriate pharmacotherapeutic role. In all, droxidopa is a safe and effective medication for the treatment of orthostatic dizziness/lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic neurogenic orthostatic hypotension secondary to primary autonomic failure (Parkinson's disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.

X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking

PubMed Central

Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Öberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J.; Deen, Peter M. T.; Törnroth-Horsefield, Susanna

2014-01-01

Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein–protein interactions involved in cellular sorting of AQP2. Two Cd2+-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking. PMID:24733887

Two Novel Mutations in the Aquaporin 2 Gene in a Girl with Congenital Nephrogenic Diabetes Insipidus

PubMed Central

Cho, Su Jin; Zheng, Shou Huan; Cho, Hee Yeon; Ha, Il Soo; Choi, Yong

2005-01-01

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: 70Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and 187Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, 70Ala (GCC) to Asp (GAC) and 187Arg (CGC) to His (CAC). PMID:16361827

Xanthomatous Hypophysitis Presenting with Diabetes Insipidus Completely Cured Through Transsphenoidal Surgery: Case Report and Literature Review.

PubMed

Lin, Wei; Gao, Lu; Guo, Xiaopeng; Wang, Wenze; Xing, Bing

2017-08-01

Xanthomatous hypophysitis (XH) is extremely rare. Only 27 cases have been reported in the literature. No XH patient presenting with diabetes insipidus (DI) has been completely cured through surgery. Here, we describe the first XH case of a DI patient whose pituitary function was normalized postoperatively, without hormone replacement therapy. A 41-year-old woman suffered from polydipsia, DI, headache, and breast discharge. Laboratory investigation revealed hyperprolactinemia. Pituitary magnetic resonance imaging showed a 2.0-cm × 1.4-cm × 1.6-cm lesion that demonstrated heterogeneous intensity on T1-weighted imaging and peripheral ring enhancement following contrast; the lesion was totally removed through transsphenoidal surgery. Histopathologic and immunohistochemical examinations confirmed the diagnosis of XH. At the 4- and 15-month follow-up visits, all pituitary-related hormones were normal, and the patient was not taking medication. A repeat pituitary magnetic resonance imaging showed no evidence of recurrence. To the best of our knowledge, this case is the first documented occurrence of XH with DI completely cured through surgery. If XH is suspected, total surgical resection of the lesion is recommended and normal pituitary tissue should be carefully protected intraoperatively. Copyright © 2017 Elsevier Inc. All rights reserved.

What determines neurogenic competence in glia?

PubMed

Costa, Marcos Romualdo; Götz, Magdalena; Berninger, Benedikt

2010-05-01

One of the most intriguing discoveries during the last decade of developmental neurobiology is the fact that both in the developing and adult nervous system neural stem cells often turn out to have a glial identity: Radial glia generates neurons in the developing telencephalon of fish, birds and mammals and astro/radial glial stem cells in specialized neurogenic zones give rise to new neurons throughout life. What are the extrinsic signals acting on and the intrinsic signals acting within these glial populations endowing these with a neurogenic potential, whilst most other glia seemingly lack it? Studies on postnatal astroglia shed interesting light on this question as they are the intermediate between neurogenic radial glia and mature parenchymal astrocytes. At least in vitro their decision to acquire a glial fate is not yet irrevocable as forced expression of a single neurogenic transcription factor enables them to transgress their lineage and to give rise to fully functional neurons acquiring specific subtype characteristics. But even bona fide non-neurogenic glia in the adult nervous system can regain some of their radial glial heritage following injury as exemplified by reactive astroglia in the cerebral cortex and Müller glia in the retina. In this review first we will follow the direction of the physiological times' arrow, along which radial glia become transformed on one side into mature astrocytes gradually losing their neurogenic potential, while some of them seem to escape this dire destiny to settle in the few neurogenic oases of the adult brain where they generate neurons and glia throughout life. But we will also see how pathophysiological conditions partially can reverse the arrow of time reactivating the parenchymal astroglia to re-acquire some of the hallmarks of neural stem cells or progenitors. We will close this review with some thoughts on the surprising compatibility of the co-existence of a neural stem cell and glial identity within the very

Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

PubMed

Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

2015-12-17

Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus

PubMed Central

Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D.; Saeed, Fahad; Michael Payne, D.; Chen, Shu-Hui; Fenton, Robert A.; Pisitkun, Trairak

2015-01-01

Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID:26674602

Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report.

PubMed

Ma, Hongbing; Yang, Jing; Xiang, Bing; Jia, Yongqian

2015-06-01

Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 ( EVI1 )-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression (- 7/EVI1 + ) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with - 7/EVI1 + and without a 3q aberration. The possible mechanisms associated with EVI1 , monosomy 7 and DI were investigated.

Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

PubMed

Bichet, Daniel G; Bockenhauer, Detlef

2016-03-01

Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bartter's syndrome with type 2 diabetes mellitus.

PubMed

See, Ting-Ting; Lee, Siu-Pak

2009-02-01

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.

Neurophysin biosynthesis in normal rats and in rats with hereditary diabetes insipidus.

PubMed Central

Brownstein, M J; Gainer, H

1977-01-01

When [35S]cysteine was injected adjacent to the supraoptic nucleus (SON) in rats, it was rapidly incorporated into proteins in the SON. The [35S]cysteine-labeled proteins extracted from the SON were separated by isoelectric focusing on polyacrylamide gels. Twenty minutes after the injection of [35S]cysteine, two major labeled peaks (pI = 5.4 and 6.1) were found in the SON of normal rats; Brattleboro rats had only one major labeled peak (pI = 5.4). One hour after the injection, four major radioactive peaks were found in the SON of normal animals (pI = 5.1, 5.4, 5.6, and 6.1). Animals with diabetes insipidus had only two major labeled proteins (pI = 5.1 AND 5.4). Twenty-four hours after normal rats were injected with [35S]cysteine, all of the labeled peaks described above, except for the one with pI = 5.1, had decreased markedly in size and a small amount of labeled protein with pI about 4.8 was present in the SON. After 24 hr the posterior pituitary of normal animals contained two [35S]cysteine-labeled proteins with pI = 4.6 AND 4.8. The pituitaries of Brattleboro rats had only the pI = 4.6 labeled protein. These pulse-chase data, with data we have presented elsewhere, indicate that the vasopressin- and oxytocin-neurophysins are synthesized as parts of separate precursors (pI = 6.1 and 5.4, respectively). These precursors are converted into at least two intermediates (pI = 5.6 and 5.1) which, in turn, yield the vasopressin-neurophysin (pI = 4.8) and the oxytocin-neurophysin (pI = 4.6). PMID:269451

4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

PubMed

Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

2016-10-01

Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. Copyright © 2016 the American Physiological Society.

For Debate: Personalized Health Care: As Exemplified by Home Sodium Measurements in a Child with Central Diabetes Insipidus and Impaired Thirst Perception.

PubMed

van der Linde, A A A; van Herwaarden, A E; Oosting, J D; Claahsen-van der Grinten, H L; de Grouw, E P L M

2018-04-01

We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance. In order to provide better self-reliance, home point of care testing (POCT) sodium measurement was introduced. Realizing POCT sodium measurement resulted in a significant decrease of ER visits and clinical admissions due to dysregulation of fluid balance. This case is an example of personalized health care and has led to better self-reliance and quality of life. Copyright© of YS Medical Media ltd.

Neurogenic stuttering: a review of the literature.

PubMed

Cruz, C; Amorim, H; Beca, G; Nunes, R

2018-01-16

Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound. To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering. A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies. Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods.

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

PubMed Central

Tajima, Asako; Miyata, Ichiro; Katayama, Akira; Toyoda, Shigeru; Eto, Yoshikatsu

2005-01-01

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. PMID:24790307

Nature and Recurrence of AVPR2 Mutations in X-linked Nephrogenic Diabetes Insipidus

PubMed Central

Bichet, Daniel G.; Birnbaumer, Mariel; Lonergan, Michèle; Arthus, Marie-Françoise; Rosenthal, Walter; Goodyer, Paul; Nivet, Hubert; Benoit, Stéphane; Giampietro, Philip; Simonetti, Simonetta; Fish, Alfred; Whitley, Chester B.; Jaeger, Philippe; Gertner, Joseph; New, Maria; DiBona, Francis J.; Kaplan, Bernard S.; Robertson, Gary L.; Hendy, Geoffrey N.; Fujiwara, T. Mary; Morgan, Kenneth

1994-01-01

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine-vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. We analyzed 31 independent NDI families to determine the nature and recurrence of AVPR2 mutations. Twenty-one new putative disease-causing mutations were identified: 113delCT, 253del35, 255del9, 274insG, V88M, R106C, 402delCT, C112R, Y124X, S126F, W164S, S167L, 684delTA, 804insG, W284X, A285P, W293X, R337X, and three large deletions or gene rearrangements. Five other mutations—R113W, Y128S, R137H, R181C, and R202C—that previously had been reported in other families were detected. There was evidence for recurrent mutation for four mutations (R113W, R137H, S167L, and R337X). Eight de novo mutation events were detected (274insG, R106C, Y128S, 167L [twice], R202C, 684delTA, and R337X). The origins were maternal (one), grandmaternal (one), and grandpaternal (six). In the 31 NDI families and 6 families previously reported by us, there is evidence both for mutation hot spots for nucleotide substitutions and for small deletions and insertions. More than half (58%) of the nucleotide substitutions in 26 families could be a consequence of 5-methylcytosine deamination at a CpG dinucleotide. Most of the small deletions and insertions could be attributed to slipped mispairing during DNA replication. PMID:8037205

A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus.

PubMed Central

Bahnsen, U; Oosting, P; Swaab, D F; Nahke, P; Richter, D; Schmale, H

1992-01-01

Familial neurohypophyseal diabetes insipidus in humans is a rare disease transmitted as an autosomal dominant trait. Affected individuals have very low or undetectable levels of circulating vasopressin and suffer from polydipsia and polyuria. An obvious candidate gene for the disease is the vasopressin-neurophysin (AVP-NP) precursor gene on human chromosome 20. The 2 kb gene with three exons encodes a composite precursor protein consisting of the neuropeptide vasopressin and two associated proteins, neurophysin and a glycopeptide. Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members. Comparison of the nucleotide sequences shows a G----T transversion within the neurophysin-encoding exon B. This missense mutation converts a highly conserved glycine (Gly17 of neurophysin) to a valine residue. RFLP analysis of six related family members indicates cosegregation of the mutant allele with the DI phenotype. The mutation is not present in 96 chromosomes of an unrelated control group. These data suggest that a single amino acid exchange within a highly conserved domain of the human vasopressin-associated neurophysin is the primary cause of one form of ADNDI. Images PMID:1740104

Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes Insipidus

PubMed Central

Joshi, Shivani; Brandstrom, Per; Gregersen, Niels; Rittig, Søren; Christensen, Jane Hvarregaard

2017-01-01

Early diagnosis and treatment of congenital nephrogenic diabetes insipidus (CNDI) are essential due to the risk of intellectual disability caused by repeated episodes of dehydration and rapid rehydration. Timely genetic testing for disease-causing variants in the arginine vasopressin receptor 2 (AVPR2) gene is possible in at-risk newborns with a known family history of X-linked CNDI. In this study, a Swedish male with no family history was diagnosed with CNDI at 6 months of age during an episode of gastroenteritis. We analyzed the coding regions of AVPR2 by PCR and direct DNA sequencing and identified an 80-bp duplication in exon 2 (GenBank NM_000054.4; c.800_879dup) in the proband. This variant leads to a frameshift and introduces a stop codon four codons downstream (p.Ala294Profs*4). The variant gene product either succumbs to nonsense-mediated decay or is translated to a truncated nonfunctional vasopressin V2 receptor. This variant was absent in four unaffected family members, including his parents, as well as in 100 alleles from healthy controls, and is thus considered a novel de novo disease-causing variant. Identification of the disease-causing variant facilitated precise diagnosis of CNDI in the proband. Furthermore, it allows future genetic counseling in the family. This case study highlights the importance of genetic testing in sporadic infant cases with CNDI that can occur due to de novo variants in AVPR2 or several generations of female transmission of the disease-causing variant. PMID:29177155

The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report.

PubMed

Kondo, Tatsuya; Nakamura, Miwa; Kitano, Sayaka; Kawashima, Junji; Matsumura, Takeshi; Ohba, Takashi; Yamaguchi, Munekage; Katabuchi, Hidetaka; Araki, Eiichi

2018-01-30

Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known. A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient's syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner. Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case.

Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2

PubMed Central

Shi, Peijun P.; Cao, Xiao R.; Qu, Jing; Volk, Ken A.; Kirby, Patricia; Williamson, Roger A.; Stokes, John B.; Yang, Baoli

2009-01-01

In mammals, the hormonal regulation of water homeostasis is mediated by the aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD principal cells, accompanied by increased water permeability. Mutations of AQP2 gene in humans cause both recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. In this study, we generated a line of mice with the distal COOH-terminal tail of the Aqp2 deleted (Aqp2Δ230), including the protein kinase A phosphorylation site (S256), but still retaining the putative apical localization signal (221–229) at the COOH-terminal. Mice heterozygous for the truncation appear normal. Homozygotes are viable to adulthood, with reduced urine concentrating capacity, increased urine output, decreased urine osmolality, and increased daily water consumption. Desmopressin increased urine osmolality in wild-type mice but had no effect on Aqp2Δ230/Δ230 mice. Kidneys from affected mice showed CD and pelvis dilatation and papillary atrophy. By immunohistochemical and immunoblot analyses using antibody against the NH2-terminal region of the protein Aqp2 Δ230/Δ230 mice had a markedly reduced protein abundance. Expression of the truncated protein in MDCK cells was consistent with a small amount of functional expression but no stimulation. Thus we have generated a mouse model of NDI that may be useful in studying the physiology and potential therapy of this disease. PMID:17229678

Membrane Protein Stability Analyses by Means of Protein Energy Profiles in Case of Nephrogenic Diabetes Insipidus

PubMed Central

Heinke, Florian; Labudde, Dirk

2012-01-01

Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems. PMID:22474537

Treatment regimens by pediatric nephrologists in children with congenital nephrogenic diabetes insipidus: A MWPNC study
.

PubMed

D'Alessandri-Silva, Cynthia; Carpenter, Melinda; Mahan, John D

2018-05-01

Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder affecting urinary concentration. Clinicians have varied medication regimens as well as nutritional plan approaches for these children. An electronic survey was distributed to member pediatric nephrologists of the Midwest Pediatric Nephrology Consortium via email (n = 179). Questions included types of drugs prescribed, factors contributing to drug choice, common drug combinations given, and dietary/failure to thrive interventions used. We analyzed results from 72 respondents (42% overall response rate). 72% treated only 1 - 3 patients with NDI per year, 12% treated 4 or more, and 17% had no NDI patients. Of providers treating NDI patients, almost all prescribed thiazides (93%), 62% prescribed amiloride, and 55% reported prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) as part of their drug regimen. gastrointestinal (GI) and renal side effects (43%) were given as reasons for not prescribing indomethacin. For 70%, drug choice was determined by severity of failure to thrive (FTT). Physicians were asked to define the most common drug combinations they prescribed. 48% reported prescribing indomethacin with hydrochlorothiazide. 84% of respondents have a renal dietitian on staff, and half included appointments with a dietitian as part of FTT therapy. The most common intervention for FFT was gastrostomy tube placement (78%). Our results suggest consensus on the use of thiazides, while the use of indomethacin is limited by GI and renal side effect profile. Our results revealed that multiple drug combinations are frequently used without one specific preferred regimen.
.

Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus.

PubMed

Tian, Dan; Cen, Jing; Nie, Min; Gu, Feng

2016-10-01

Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

Renal compensatory adaptation for water handling in a patient with adipsic diabetes insipidus after clipping of a ruptured aneurysm of the anterior communicating artery
.

PubMed

Imai, Eri; Kaneko, Shuzo; Tsukamoto, Yusuke

2017-08-01

A 38-year-old Japanese man who had undergone clipping surgery for a ruptured aneurysm of the anterior communicating artery 2 days prior, suddenly developed refractory hypernatremia (serum sodium (Na) 156 - 162 mmol/L). Symptoms included low plasma vasopressin, fluctuating urine osmolality (120 - 710 mOsm/kg) and lack of thirst, all suggesting adipsic diabetes insipidus (ADI). Hypernatremia was corrected by scheduled water intake with desmopressin administration. During 1-year follow-up after the surgery, his serum Na level normalized despite the suspension of desmopressin, but neither thirst nor osmolality-dependent vasopressin release recovered. Meanwhile, his urine osmolality shifted to a constant high level. The present case suggests that renal compensatory adaptation, apparently independent of the circulating vasopressin level, plays a major role in water handling in longitudinal ADI.
.

Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats.

PubMed Central

Christensen, S; Kusano, E; Yusufi, A N; Murayama, N; Dousa, T P

1985-01-01

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta

Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

PubMed

Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

2015-08-01

Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Clinical Overview of Nephrogenic Diabetes Insipidus Based on a Nationwide Survey in Japan

PubMed Central

Fujimoto, Masanobu; Okada, Shin-ichi; Kawashima, Yuki; Nishimura, Rei; Miyahara, Naoki; Kawaba, Yasuo; Hanaki, Keiichi; Nanba, Eiji; Kondo, Yoshiaki; Igarashi, Takashi; Kanzaki, Susumu

2014-01-01

Background Nephrogenic diabetes insipidus (NDI) is a rare disease whose complications include polyuria, renal dysfunction, growth disorder and mental retardation. The details of NDI’s clinical course have been unclear. To address this uncertainty, we performed a large investigation of the clinical course of NDI in Japan. Methods Between December 2009 and March 2011, we provided a primary questionnaire to 26,282 members of the Japan Endocrine Society, the Japanese Urological Association, the Japanese Society for Pediatric Endocrinology, the Japanese Society for Pediatric Nephrology, the Japanese Society of Nephrology, the Japanese Society of Neurology and the Japanese Society of Pediatric Urology. In addition, we provided a secondary questionnaire to 121 members who reported experience with cases of NDI. We asked about patient’s age at onset, diagnosis, complications, effect of treatment and patient’s genotype. Results We enrolled 173 patients with NDI in our study. Of these NDI patients, 143 were congenital and 30 were acquired. Of the 173, 73 patients (42%) experienced urologic complications. Among the 143 with congenital NDI, 20 patients (14%) had mental retardation. Patients with NDI mainly received thiazide diuretics, and some patients responded to treatment with desmopressin acetate (DDAVP). Gene analyses were performed in 87 patients (61%) with congenital NDI, revealing that 65 patients had an arginine vasopressin receptor type 2 (AVPR2) gene mutation and that 8 patients (9.2%) had an aquaporin 2 (AQP2) gene mutation. Patients with the AVPR2 mutation (D85N) generally showed a mild phenotype, and we found that DDAVP was generally an effective treatment for NDI among these patients. Conclusion We suggest that adequate diagnosis and treatment are the most important factors for improving prognoses. We further suggest that gene analysis should be performed for optimal treatment selection and the early detection of NDI among siblings. PMID:25324589

Targeting Renal Purinergic Signalling for the Treatment of Lithium-induced Nephrogenic Diabetes Insipidus

PubMed Central

Kishore, B. K.; Carlson, N. G.; Ecelbarger, C. M.; Kohan, D. E.; Müller, C. E.; Nelson, R. D.; Peti-Peterdi, J.; Zhang, Y.

2015-01-01

Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats, and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulfate (Plavix®) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unraveled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. PMID:25877068

Targeting renal purinergic signalling for the treatment of lithium-induced nephrogenic diabetes insipidus.

PubMed

Kishore, B K; Carlson, N G; Ecelbarger, C M; Kohan, D E; Müller, C E; Nelson, R D; Peti-Peterdi, J; Zhang, Y

2015-06-01

Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development of nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulphate (Plavix(®)) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unravelled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Nephrogenic diabetes insipidus in initial stage of acute lymphoblastic leukemia and relapse after haploidentical hematopoietic stem-cell transplantation: A case report.

PubMed

Li, Dezhi; Liu, Qian; Feng, Zhifang; Zhang, Qi; Feng, Saran

2018-06-01

Nephrogenic diabetes insipidus (NDI) rarely presents in the initial stage of acute lymphoblastic leukemia (ALL) and relapse due to renal infiltration is also rare. A 19-year-old man presented with weakness, polydipsia, and polyuria for 1 month. NDI was diagnosed with insignificant response to a water deprivation test after stimulation with vasopressin injection. Bone marrow examination combined with immunophenotypic analysis, cerebrospinal cytology, and abdominal ultrasonography confirmed the diagnoses of precursor B cell ALL with renal infiltration. The patient accepted standardized combination chemotherapy and ultimately had sustained remission, and his polydipsia and polyuria disappeared after 3 days of treatment. The ALL relapsed 1 year later and he received haploidentical stem cell transplantation (haplo-SCT) from his father. One year later, he again developed NDI, with bilateral renal enlargement because of extramedullary relapse, leading to subsequent death. This case demonstrates unusual early renal involvement in ALL presenting with initial NDI. Interestingly, the NDI returned with the relapse of renal infiltration 1 year after haplo-SCT. This case suggests that NDI was probably secondary to renal leukemic infiltration.

Progressive polyuria without vasopressin neuron loss in a mouse model for familial neurohypophysial diabetes insipidus.

PubMed

Hayashi, Masayuki; Arima, Hiroshi; Ozaki, Noriyuki; Morishita, Yoshiaki; Hiroi, Maiko; Ozaki, Nobuaki; Nagasaki, Hiroshi; Kinoshita, Noriaki; Ueda, Masatsugu; Shiota, Akira; Oiso, Yutaka

2009-05-01

Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). Previous studies suggest that loss of AVP neurons might be the cause of polyuria in FNDI. Here we analyzed knockin mice expressing mutant NPII that causes FNDI in humans. The heterozygous mice manifested progressive polyuria as do patients with FNDI. Immunohistochemical analyses revealed that inclusion bodies that were not immunostained with antibodies for mutant NPII, normal NPII, or AVP were present in the AVP cells in the supraoptic nucleus (SON), and that the size of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) as well as in the nucleus of AVP neurons in 1-mo-old heterozygous mice. At 12 mo, dilated ER filled with aggregates occupied the cytoplasm of AVP cells, while few aggregates were found in the nucleus. Analyses with in situ hybridization revealed that expression of AVP mRNA was significantly decreased in the SON in the heterozygous mice compared with that in wild-type mice. Counting cells expressing AVP mRNA in the SON indicated that polyuria had progressed substantially in the absence of neuronal loss. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregates accumulated in the ER might be involved in the dysfunction of AVP neurons that lead to the progressive polyuria.

Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

PubMed

Deniz, Ferhat; Acar, Ceren; Saglar, Emel; Erdem, Beril; Karaduman, Tugce; Yonem, Arif; Cagiltay, Eylem; Ay, Seyit Ahmet; Mergen, Hatice

2015-01-01

Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein. © 2015 by the Association of Clinical Scientists, Inc.

Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus.

PubMed

Kataoka, Yuko; Nishida, Sachi; Hirakawa, Akihiro; Oiso, Yutaka; Arima, Hiroshi

2015-01-01

Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.

Novel autosomal recessive gene mutations in aquaporin-2 in two Chinese congenital nephrogenic diabetes insipidus pedigrees

PubMed Central

Cen, Jing; Nie, Min; Duan, Lian; Gu, Feng

2015-01-01

Recent evidence has linked novel mutations in the arginine vasopressin receptor 2 gene (AVPR2) and aquaporin-2 gene (AQP2) present in Southeast Asian populations to congenital nephrogenic diabetes insipidus (NDI). To investigate mutations in 2 distinct Chinese pedigrees with NDI patients, clinical data, laboratory findings, and genomic DNA sequences from peripheral blood leukocytes were analyzed in two 5.5- and 8-year-old boys (proband 1 and 2, respectively) and their first-degree relatives. Water intake, urinary volume, body weight and medication use were recorded. Mutations in coding regions and intron-exon borders of both AQP2 and AVPR2 gene were sequenced. Three mutations in AQP2 were detected, including previously reported heterozygous frameshift mutation (c.127_128delCA, p.Gln43Aspfs ×63) inherited from the mother, a novel frameshift mutation (c.501_502insC, p.Val168Argfs ×30, inherited from the father) in proband 1 and a novel missense mutation (c. 643G>A, p. G215S), inherited from both parents in proband 2. In family 2 both parents and one sister were heterozygous carriers of the novel missense mutation. Neither pedigree exhibited mutation in the AVPR2 gene. The patient with truncated AQP2 may present with much more severe NDI manifestations. Identification of these novel AQP2 gene mutations expands the AQP2 genotypic spectrum and may contribute to etiological diagnosis and genetic counseling. PMID:26064258

Neurogenic vasodilatation and plasma leakage in the skin.

PubMed

Holzer, P

1998-01-01

1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.

Novel large deletion in AVPR2 gene causing copy number variation in a patient with X-linked nephrogenic diabetes insipidus.

PubMed

Cho, Sun Young; Law, Chun Yiu; Ng, Kwok Leung; Lam, Ching Wan

2016-04-01

The diagnosis of cranial and nephrogenic diabetes insipidus (DI) can be clinically challenging. The application of molecular genetic analysis can help in resolving diagnostic difficulties. A 3 month-old boy presented with recurrent polyuria was admitted to Intensive Care Unit and was treated as DI. The patient also had a strong family history of polyuria affecting his maternal uncles. Molecular genetic analysis using Single Nucleotide Polymorphism (SNP) array detected a large deletion located at Xq28 region and the breakpoint was identified using PCR and Sanger sequencing. An 11,535 bp novel deletion affecting the entire APVR2 gene and the last intron and exon of the ARHGAP4 gene was confirmed. This large deletion is likely due to the 7-bp microhomology sequence at the junctions of both 5' and 3' breakpoints. No disease-causing mutation was identified for AQP2. We report a novel deletion in a Chinese patient with congenital nephrogenic DI. We suggested that patients with suspected congenital DI should undergo genetic analysis of AVPR2 and AQP2 genes. A definitive diagnosis can benefit patient by treatment of hydrochlorothiazide and amiloride and avoiding unnecessary investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrical management of neurogenic lower urinary tract disorders.

PubMed

Joussain, C; Denys, P

2015-09-01

Management of lower urinary tract dysfunction (LUTD) in neurological diseases remains a priority because it leads to many complications such as incontinence, renal failure and decreased quality of life. A pharmacological approach remains the first-line treatment for patients with neurogenic LUTD, but electrical stimulation is a well-validated and recommended second-line treatment. However, clinicians must be aware of the indications, advantages and side effects of the therapy. This report provides an update on the 2 main electrical stimulation therapies for neurogenic LUTD - inducing direct bladder contraction with the Brindley procedure and modulating LUT physiology (sacral neuromodulation, tibial posterior nerve stimulation or pudendal nerve stimulation). We also describe the indications of these therapies for neurogenic LUTD, following international guidelines, as illustrated by their efficacy in patients with neurologic disorders. Electrical stimulation could be proposed for neurogenic LUTD as second-line treatment after failure of oral pharmacologic approaches. Nevertheless, further investigations are needed for a better understanding of the mechanisms of action of these techniques and to confirm their efficacy. Other electrical investigations, such as deep-brain stimulation and repetitive transcranial magnetic stimulation, or improved sacral anterior root stimulation, which could be associated with non-invasive and highly specific deafferentation of posterior roots, may open new fields in the management of neurogenic LUTD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

PubMed

Birklein, Frank; Schmelz, Martin

2008-06-06

This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders.

PubMed

Al-Maawali, Almundher; Dupuis, Lucie; Blaser, Susan; Heon, Elise; Tarnopolsky, Mark; Al-Murshedi, Fathiya; Marshall, Christian R; Paton, Tara; Scherer, Stephen W; Roelofsen, Jeroen; van Kuilenburg, André B P; Mendoza-Londono, Roberto

2015-03-01

PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders.

AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance.

PubMed

Spanakis, Elias; Milord, Edrice; Gragnoli, Claudia

2008-12-01

Almost 90% of nephrogenic diabetes insipidus (NDI) is due to mutations in the arginine-vasopressin receptor 2 gene (AVPR2). We retrospectively examined all the published mutations/variants in AVPR2. We planned to perform a comprehensive review of all the AVPR2 mutations/variants and to test whether any amino acid change causing a missense mutation is significantly more or less common than others. We performed a Medline search and collected detailed information regarding all AVPR2 mutations and variants. We performed a frequency comparison between mutated and wild-type amino acids and codons. We predicted the mutation effect or reported it based on published in vitro studies. We also reported the ethnicity of each mutation/variant carrier. In summary, we identified 211 AVPR2 mutations which cause NDI in 326 families and 21 variants which do not cause NDI in 71 NDI families. We described 15 different types of mutations including missense, frameshift, inframe deletion, deletion, insertion, nonsense, duplication, splicing and combined mutations. The missense mutations represent the 55.83% of all the NDI published families. Arginine and tyrosine are significantly (P = 4.07E-08 and P = 3.27E-04, respectively) the AVPR2 most commonly mutated amino acids. Alanine and glutamate are significantly (P = 0.009 and P = 0.019, respectively) the least mutated AVPR2 amino acids. The spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense. The AVPR2 mutations are spread world-wide. Our study may serve as an updated review, comprehensive of all AVPR2 variants and specific gene locations. J. Cell. Physiol. 217: 605-617, 2008. (c) 2008 Wiley-Liss, Inc.

Pediatric Central Diabetes Insipidus: Brain Malformations Are Common and Few Patients Have Idiopathic Disease.

PubMed

Werny, David; Elfers, Clinton; Perez, Francisco A; Pihoker, Catherine; Roth, Christian L

2015-08-01

Pediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalences for the different causes of CDI, including idiopathic. The objective of the study was to determine the causes of CDI at a pediatric tertiary care center and to characterize their clinical outcomes. All patients with CDI at Seattle Children's Hospital were identified and retrospectively analyzed. From 2000 to 2013, 147 patients with CDI were encountered (mean age 7 y at diagnosis, mean follow-up 6.2 y). The different causes of CDI were grouped, and age of diagnosis, anterior pituitary hormone deficiencies (APHDs), and presence of the posterior pituitary bright spot (PPBS) were analyzed. Patients with idiopathic CDI had infundibular thickening measured using a systematic method. Brain malformations caused 24% of CDI cases, and 12.2% were idiopathic. Four of 22 patients with initially idiopathic CDI were diagnosed with an underlying condition, none occurring later than 2.5 years from diagnosis. APHDs were as common in the brain malformation group as they were in the tumor/infiltrative group (72% vs 85%; P = .09). The PPBS was present in at least 13% of patients and in 19% of those with brain malformations. Patients with idiopathic CDI and stalk thickening on the initial magnetic resonance imaging were more likely to have an underlying diagnosis (40% vs 0%; P = .03). Brain malformations were a more common cause of pediatric CDI than previously reported. These patients have a high rate of APHDs, and many have persistence of the PPBS. Idiopathic CDI is an uncommon diagnosis, and none of our patients were diagnosed with Langerhans cell histiocytosis or germinoma for more than 3 years from CDI diagnosis. Providers can consider less frequent magnetic resonance imaging after this time point. A systematic method of infundibular measurement on the initial magnetic resonance imaging may predict an underlying germinoma or Langerhans cell histiocytosis.

Uncoupling neurogenic gene networks in the Drosophila embryo.

PubMed

Rogers, William A; Goyal, Yogesh; Yamaya, Kei; Shvartsman, Stanislav Y; Levine, Michael S

2017-04-01

The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective ( ind ). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity. We suggest that Drosophila is undergoing an evolutionary transition in central nervous system (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm. © 2017 Rogers et al.; Published by Cold Spring Harbor Laboratory Press.

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as

Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype

PubMed Central

Gilbert, Merle L.; Yang, Linghai; Su, Thomas

2015-01-01

PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus. PMID:25587115

Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis.

PubMed

O'Reilly, M W; Sexton, D J; Dennedy, M C; Counihan, T J; Finucane, F M; O'Brien, T; O'Regan, A W

2015-08-01

Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months. A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI. Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNF-α therapy (infliximab) after multidisciplinary team consultation. Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

PubMed

Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; Li, Jian H; Wess, Jürgen; Svelto, Maria

2014-07-01

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice

PubMed Central

Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; H. Li, Jian; Wess, Jürgen; Svelto, Maria

2014-01-01

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI. PMID:24522493

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

PubMed

Catli, Gonul; Abaci, Ayhan; Demir, Korcan; Ulusoy, Emel; Altincik, Ayca; Buyukgebiz, Atilla; Bober, Ece

2012-01-01

The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review.

PubMed

Fenske, Wiebke; Allolio, Bruno

2012-10-01

The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term "polyuria polydipsia syndrome" was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.

Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rittig, S.; Siggaard, C.; Pedersen, E.B.

1996-01-01

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation wasmore » unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons. 63 refs., 5 figs., 6 tabs.« less

Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature.

PubMed

Koufaris, Costas; Alexandrou, Angelos; Sismani, Carolina; Skordis, Nicos

2015-01-01

Familial neurohypophyseal diabetes insipidus (FNDI) is a disorder characterized by excess excretion of diluted urine (polyuria) and increased uptake of fluids (polydipsia). The disorder is caused by mutations affecting the AVP-NPII gene, resulting in absent or deficient secretion of the antidiuretic hormone arginine vasopressin (AVP) by the neurohypophysis. In this study we examined a three-generation Cypriot kindred suspected to have FNDI. Direct sequencing analysis of AVP-NPII identified a missense mutation (NM_000490.4:c.61T>C; p.Tyr21His; rs121964893) within the AVP moiety on exon 1 of the gene in all affected family members. So far, only three studies have reported mutations within the AVP moiety of AVP-NPIIas being associated with FNDI, with the vast majority of identified FNDI mutations being located within the signalling peptide or the neurophysis II (NPII) moiety of the gene. The mutation within the AVP moiety identified here had been reported previously in a Turkish kindred with FNDI. Consequently, the findings of this study confirm the causal role of mutations within the AVP moiety in FNDI. Herein we review reported mutations within the AVP moiety of AVP-NPII and their contribution to FNDI.

Delayed recovery of adipsic diabetes insipidus (ADI) caused by elective clipping of anterior communicating artery and left middle cerebral artery aneurysms.

PubMed

Tan, Jeffrey; Ndoro, Samuel; Okafo, Uchenna; Garrahy, Aoife; Agha, Amar; Rawluk, Danny

2016-12-16

Adipsic diabetes insipidus (ADI) is an extremely rare complication following microsurgical clipping of anterior communicating artery aneurysm (ACoA) and left middle cerebral artery (MCA) aneurysm. It poses a significant challenge to manage due to an absent thirst response and the co-existence of cognitive impairment in our patient. Recovery from adipsic DI has hitherto been reported only once. A 52-year-old man with previous history of clipping of left posterior communicating artery aneurysm 20 years prior underwent microsurgical clipping of ACoA and left MCA aneurysms without any intraoperative complications. Shortly after surgery, he developed clear features of ADI with adipsic severe hypernatraemia and hypotonic polyuria, which was associated with cognitive impairment that was confirmed with biochemical investigations and cognitive assessments. He was treated with DDAVP along with a strict intake of oral fluids at scheduled times to maintain eunatremia. Repeat assessment at six months showed recovery of thirst and a normal water deprivation test. Management of ADI with cognitive impairment is complex and requires a multidisciplinary approach. Recovery from ADI is very rare, and this is only the second report of recovery in this particular clinical setting.

Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus.

PubMed Central

Rittig, S.; Robertson, G. L.; Siggaard, C.; Kovács, L.; Gregersen, N.; Nyborg, J.; Pedersen, E. B.

1996-01-01

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons. Images Figure 3 PMID:8554046

Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones.

PubMed Central

Tamarappoo, B K; Verkman, A S

1998-01-01

Five single-point aquaporin-2 (AQP2) mutations that cause non-X-linked nephrogenic diabetes insipidus (NDI) were characterized to establish the cellular defect and to develop therapeutic strategies. In Xenopus oocytes expressing AQP2 cRNAs, single-channel water permeabilities of mutants L22V, T126M, and A147T were similar to that of wild-type AQP2, whereas R187C and C181W were nonfunctional. In [35S]methionine pulse-chase experiments in transiently transfected CHO cells, half-times for AQP2 degradation were approximately 4 h for wild-type AQP2 and L22V, and mildly decreased for T126M (2.7 h), C181W (2.4 h), R187C (2.0 h), and A147T (1.8 h). Immunofluorescence showed three distinct AQP2-staining patterns: plasma membrane and endosomal staining (wild-type, L22V), endoplasmic reticulum (ER) staining (T126M > A147T approximately R187C), or a mixed pattern of reticular and perinuclear vesicular staining. Immunoblot of fractionated vesicles confirmed primary ER localization of T126M, R187C, and A147T. To determine if the AQP2-trafficking defect is correctable, cells were incubated with the "chemical chaperone" glycerol for 48 h. Immunoblot showed that glycerol produced a nearly complete redistribution of AQP2 (T126M, A147T, and R187C) from ER to membrane/endosome fractions. Immunofluorescence confirmed the cellular redistribution. Redistribution of AQP2 mutants was also demonstrated in transfected MDCK cells, and using the chaperones TMAO and DMSO in place of glycerol in CHO cells. Water permeability measurements indicated that functional correction was achieved. These results indicate defective mammalian cell processing of mutant AQP2 water channels in NDI, and provide evidence for pharmacological correction of the processing defect by chemical chaperones. PMID:9593782

Abnormal plasma sodium concentrations in patients treated with desmopressin for cranial diabetes insipidus: results of a long-term retrospective study.

PubMed

Behan, L A; Sherlock, M; Moyles, P; Renshaw, O; Thompson, C J T; Orr, C; Holte, K; Salehmohamed, M R; Glynn, N; Tormey, W; Thompson, C J

2015-03-01

Patients with cranial diabetes insipidus (CDI) are at risk of developing both hypernatraemia and hyponatraemia, due to the condition itself or secondary to treatment with vasopressin-analogues or during administration of i.v. fluids. We aimed to assess the frequency and impact of dysnatraemias in the inpatient (INPT) and outpatient (OPT) setting in desmopressin-treated CDI, comparing those with normal thirst with those with abnormal thirst. The study included 192 patients with cranial diabetes, who were identified from the Beaumont Pituitary Database, a tertiary referral centre. Retrospective case note audit was performed and the clinical and biochemical information of 147 patients with CDI were available for analysis. A total of 4142 plasma sodium measurements for 137 patients with normal thirst, and 385 plasma sodium measurements for ten patients with abnormal thirst were analysed. In those with normal thirst, the most common OPT abnormality was mild hyponatraemia (pNa(+) 131-134  mmol/l) in 27%, while 14.6% had more significant hyponatraemia (pNa(+) ≤130  mmol/l). Of those patients with normal thirst, 5.8% were admitted due to complications directly related to hyponatraemia. Compared with patients with normal thirst, those with abnormal thirst were more likely to develop significant OPT hypernatraemia (20% vs 1.4%, P=0.02) and significant INPT hyponatraemia (50% vs 11.1%, P 0.02). OPT management of CDI is complicated by a significant incidence of hyponatraemia. In contrast, OPT hypernatraemia is almost exclusively a complication seen in adipsic CDI, who also had more frequent INPT hyponatraemia. CDI associated with thirst disorder requires increased physician attention and patient awareness of potential complications. © 2015 European Society of Endocrinology.

[Visual impairment in juvenile diabetes mellitus due to optic atrophy: Wolfram's syndrome].

PubMed

Immink, Annelies; Reeser, H Maarten; Brus, Frank

2010-01-01

Wolfram's syndrome is a rare neurodegenerative disorder, which usually first manifests itself around the age of 6 years. The diagnosis can be made based on the characteristics incorporated in the 'DIDMOAD' acronym: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. We present 2 boys, diagnosed with diabetes mellitus at the age of 5 and 4 years respectively. Both children developed optic atrophy over the years. These 2 cases illustrate that alongside diabetic retinopathy, possible syndromes, such as Wolfram's syndrome, should also be considered in children with diabetes mellitus and visual impairment.

Bendamustine-induced nephrogenic diabetes insipidus
.

PubMed

Derman, Benjamin A; Jain, Milli; McAninch, Elizabeth A; Gashti, Casey

2017-01-01

A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI). He had no known exposure to other causative agents and had demonstrated a robust response to chemotherapy. The patient became eunatremic once oral intake was resumed and his infection was treated. Two months after presentation, he remained symptomatic. A trial with hydrochlorothiazide resulted in a significant increase in urine osmolality and subsequent decrease in urine output. To our knowledge, this is the first case of nephrogenic diabetes insipidus after rituximab and bendamustine exposure. We propose that bendamustine, similar to the alkylating agent ifosfamide, is toxic to the glomerulus and proximal tubule cells and is the most likely cause of the patient's nephrogenic DI.
.

Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism.

PubMed

Hameed, Shihab; Mendoza-Cruz, Abel C; Neville, Kristen A; Woodhead, Helen J; Walker, Jan L; Verge, Charles F

2012-06-09

Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) vs. only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120-156 on the old regimen. She was discharged home. This practical regimen improved sodium control, parental independence, and allowed discharge home.

Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism

PubMed Central

2012-01-01

Background/Aims Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. Methods A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. Results After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) vs. only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120–156 on the old regimen. She was discharged home. Conclusion This practical regimen improved sodium control, parental independence, and allowed discharge home. PMID:22682315

Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus.

PubMed

Smith, Emery; Janovick, Jo Ann; Bannister, Thomas D; Shumate, Justin; Scampavia, Louis; Conn, P Michael; Spicer, Timothy P

2016-09-01

Pharmacoperones correct the folding of otherwise misfolded protein mutants, restoring function (i.e., providing "rescue") by correcting their trafficking. Currently, most pharmacoperones possess intrinsic antagonist activity because they were identified using methods initially aimed at discovering such functions. Here, we describe an ultra-high-throughput homogeneous cell-based assay with a cAMP detection system, a method specifically designed to identify pharmacoperones of the vasopressin type 2 receptor (V2R), a GPCR that, when mutated, is associated with nephrogenic diabetes insipidus. Previously developed methods to identify compounds capable of altering cellular trafficking of V2R were modified and used to screen a 645,000 compound collection by measuring the ability of library compounds to rescue a mutant hV2R [L83Q], using a cell-based luminescent detection system. The campaign initially identified 3734 positive modulators of cAMP. The confirmation and counterscreen identified only 147 of the active compounds with an EC50 of ≤5 µM. Of these, 83 were reconfirmed as active through independently obtained pure samples and were also inactive in a relevant counterscreen. Active and tractable compounds within this set can be categorized into three predominant structural clusters, described here, in the first report detailing the results of a large-scale pharmacoperone high-throughput screening campaign. © 2016 Society for Laboratory Automation and Screening.

Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

PubMed

Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

2017-05-01

Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI. Copyright © 2016

Analysis of 43 cases of Langerhans cell histiocytosis (LCH)-induced central diabetes insipidus registered in the JLSG-96 and JLSG-02 studies in Japan.

PubMed

Shioda, Yoko; Adachi, Souichi; Imashuku, Shinsaku; Kudo, Kazuko; Imamura, Toshihiko; Morimoto, Akira

2011-12-01

To determine the ability of recent systemic chemotherapy protocols to reduce the incidence of central diabetes insipidus (CDI) in Langerhans cell histiocytosis (LCH), 43 CDI cases that belonged to a cohort of 348 pediatric patients with multi-focal LCH who were treated with the JLSG-96/-02 protocols were analyzed. The overall incidence of CDI was 12.4%, but in 24 cases CDI was already present at the time LCH was diagnosed. Thus, CDI developed during or after systemic chemotherapy over a follow-up period of 5.0 (0.2-14.7) years in only 19 patients (5.9%), with 7.4% at 5-year cumulative risk by Kaplan-Meier analysis. In two cases, complete resolution of CDI was noted. Anterior pituitary hormone deficiency was detected in 13 cases, while CDI-associated neurodegenerative disease was observed in six cases. The JLSG-96/-02 protocol appears to effectively reduce the occurrence of CDI. However, novel therapeutic measures are required to reverse pre-existing CDI and to prevent CDI-associated neurological complications.

A missense mutation encoding Cys73Phe in neurophysin II is associated with autosomal dominant neurohypophyseal diabetes insipidus.

PubMed

Santiprabhob, Jeerunda; Browning, James; Repaske, David

2002-01-01

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is an inherited disease caused by progressive deficiency of the hormone arginine vasopressin (AVP) that typically becomes clinically apparent in the first decade of life. The genetic locus of ADNDI is the arginine vasopressin-neurophysin II (AVP-NPII) gene and mutations that cause ADNDI have been found in the nucleotides encoding the signal peptide, vasopressin, and neurophysin II peptides. In this study we have analyzed the AVP-NPII gene in a 20-year-old female who was diagnosed with ADNDI at 2 years of age. A heterozygous missense mutation (1684G>T) was found in exon 2 that predicts replacement of cysteine with phenylalanine at position 73 of neurophysin II. The mutation was confirmed by subcloning exon 2 PCR products to sequence each allele independently. Two out of four clones were found to have the missense mutation and two have the normal sequence, confirming the presence of the mutation and heterozygosity. Neurophysin II is an intracellular carrier protein for AVP during axonal transport from the hypothalamus to the posterior pituitary and contains 14 cysteine residues forming 7 disulfide bonds. This mutation is predicted to disrupt the disulfide bridge between Cys73 and Cys61 within the neurophysin II moiety. This finding of a novel mutation substituting cysteine with phenylalanine in one AVP-NPII gene allele supports the hypothesis that inability to form normal disulfide bonds in neurophysin II leads to ADNDI.

[Perioperative management of a child with central diabetes insipidus who underwent two surgeries before and after desmopressin administration].

PubMed

Kiriyama, Keiji; Tachibana, Kazuya; Nishimura, Nobuyuki; Takeuchi, Muneyuki; Kinouchi, Keiko

2013-03-01

A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes insipidus. She was treated with levothyroxine and hydrocortisone and urged to take fluid to replace urine. She was scheduled to undergo ventricular drainage to relieve hydrocephalus prior to tumor resection. For the first surgery, desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(-1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia was induced with sevoflurane and maintained with propofol and remifentanil. Maintenance fluid was with acetated Ringer's solution and urine loss was replaced with 5% dextrose. Bradycardia and hypotension occurred after intubation, which was treated with volume load. Infusion volume was 750 ml and urine output was 1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was started. Ten days later, partial tumor resection was performed. Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane and remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151 ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia and hypotension experienced during the first surgery was suspected to be caused by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be effective to treat excessive urine output and to maintain good perioperative water balance.

Exome Sequencing Finds a Novel PCSK1 Mutation in a Child With Generalized Malabsorptive Diarrhea and Diabetes Insipidus

PubMed Central

Yourshaw, Michael; Solorzano-Vargas, R. Sergio; Pickett, Lindsay A.; Lindberg, Iris; Wang, Jiafang; Cortina, Galen; Pawlikowska-Haddal, Anna; Baron, Howard; Venick, Robert S.; Nelson, Stanley F.; Martín, Martín G.

2014-01-01

Objectives Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. Methods We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. Results Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. Conclusions Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations. PMID:24280991

Exome sequencing finds a novel PCSK1 mutation in a child with generalized malabsorptive diarrhea and diabetes insipidus.

PubMed

Yourshaw, Michael; Solorzano-Vargas, R Sergio; Pickett, Lindsay A; Lindberg, Iris; Wang, Jiafang; Cortina, Galen; Pawlikowska-Haddal, Anna; Baron, Howard; Venick, Robert S; Nelson, Stanley F; Martín, Martín G

2013-12-01

Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations.

[Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences].

PubMed

Corredor Andrés, Beatriz; Muñoz Calvo, María Teresa; López Pino, Miguel Ángel; Márquez Rivera, María; Travieso Suárez, Lourdes; Pozo Román, Jesús; Argente, Jesús

2018-06-09

Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period. Copyright © 2018. Publicado por Elsevier España, S.L.U.

AVP-NPII gene mutations and clinical characteristics of the patients with autosomal dominant familial central diabetes insipidus.

PubMed

Turkkahraman, Doga; Saglar, Emel; Karaduman, Tugce; Mergen, Hatice

2015-12-01

Familial central diabetes insipidus (DI), usually an autosomal dominant disorder, is caused by mutations in arginine vasopressin-neurophysin II (AVP-NPII) gene that leads to aberrant preprohormone processing and gradual destruction of AVP-secreting cells. To determine clinical and molecular characteristics of patients with familial central DI from two different Turkish families. The diagnosis of central DI was established by 24-h urine collection, water deprivation test, and desmopressin challenge. To confirm the diagnosis of familial central DI, the entire coding region of AVP-NPII gene was amplified and sequenced. A total of eight affected patients and three unaffected healthy relatives from two families were studied. Genetic analysis revealed a previously reported heterozygous mutation (p.C98X) in family A, and a heterozygous novel mutation (p.G45C) in family B, both detected in exon 2 of AVP-NPII gene. When we compared the clinical characteristics of the two families, it was noticed that as the age of onset of symptoms in family A ranges between 4 and 7 years, it was <1 year in family B. Additionally, pituitary bright spot was present in the affected siblings, but absent in their affected parents. Familial central DI is a progressive disease, and age of onset of symptoms can differ depending on the mutation. Bright spot on pituitary MRI might be present at onset, but become invisible over time. Genetic testing and appropriate counseling should be given in familial cases of central DI to ensure adequate treatment, and to avoid chronic water deprivation that might result in growth retardation in childhood.

Diabetes Insipidus—Difficulties in Diagnosis and Treatment; Use of Synthetic Lysine-8 Vasopressin in Patients Intolerant of Other Therapy

PubMed Central

Eisenberg, Eugene

1965-01-01

Frequent errors in the diagnosis of diabetes insipidus arise from (1) failure to produce an adequate stimulus for release of antidiuretic hormone, and (2) failure to appreciate acute or chronic changes in renal function that may obscure test results. Properly timed determination of body weight, urine volume and serum and urine osmolarity during the course of water deprivation, and comparison of these values with those obtained after administration of exogenous vasopressin, eliminates most diagnostic errors. In four patients who had experienced local and systemic reactions to other exogenous forms of vasopressin, diabetes insipidus was satisfactorily controlled by administration of synthetic lysine-8 vasopressin in nasal spray. A fifth patient was also treated satisfactorily with this preparation. PMID:14290932

A clinician survey of speech and non-speech characteristics of neurogenic stuttering.

PubMed

Theys, Catherine; van Wieringen, Astrid; De Nil, Luc F

2008-03-01

This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for these four etiology groups. Results suggested possible group differences, including site of lesion and influence of speech conditions on stuttering. Other characteristics, such as within-word localization of disfluencies and presence of secondary behaviors were comparable across the etiology groups. The implications of our results for the diagnosis of neurogenic stuttering will be discussed. After reading this article, the reader will be able to: (1) provide a concise overview of the main literature on neurogenic stuttering; (2) discuss the speech and non-speech characteristics of neurogenic stuttering; (3) provide an overview of current clinical practices for intervention with neurogenic stuttering patients and their perceived outcome.

Management of vesicoureteral reflux in neurogenic bladder.

PubMed

Wu, Charlotte Q; Franco, Israel

2017-06-01

Vesicoureteral reflux (VUR) is a significant risk factor for pyelonephritis and renal scarring. VUR can occur through a defective ureterovesical junction (UVJ) or an overwhelmed normal UVJ mechanism such as in bladder dysfunction of congenital, acquired, or behavioral etiology. There are numerous causes for the development of a neurogenic bladder from spinal dysraphisms to spinal cord trauma and even centrally based abnormalities in children with apparently normal motor function (inappropriately termed nonneurogenic neurogenic bladder). The foundation of managing reflux in these neurogenic bladders is to maintain low bladder pressures which will commonly mean that compliance will be normal as well. There have been several publications that have shown that if bladder pressures are lowered simply with clean intermittent catheterization and medications that the reflux can resolve spontaneously. Alternatively, the patients that are in need of bladder augmentation can have spontaneous resolution of their reflux with the resulting increase in capacity. Surgical intervention is called for when bladder capacity is adequate and the reflux persists or if it is part of a larger operation to increase capacity and to manage outlet resistance. In some instances, reimplantation is necessary because the ureters interfere with the bladder neck procedure. Aside from open and robotic surgical intervention the use of endoscopic injectable agents is beginning to become more popular especially when combined with intravesical botulinum toxin A injections. Great strides are being made in the management of patients with neurogenic bladders and we are seeing more choices for the urologist to be able to manage these patients.

Severe localised granulomatosis with polyangiitis (Wegener's granulomatosis) manifesting with extensive cranial nerve palsies and cranial diabetes insipidus: a case report and literature review.

PubMed

Peters, James E; Gupta, Vivek; Saeed, Ibtisam T; Offiah, Curtis; Jawad, Ali S M

2018-05-01

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration. We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab. This case emphasises that serious morbidity can arise from localised cranial Wegener's granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.

A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

PubMed Central

Sanyoura, May; Woudstra, Cédric; Halaby, George; Baz, Patrick; Senée, Valérie; Guillausseau, Pierre-Jean; Zalloua, Pierre; Julier, Cécile

2014-01-01

Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron–exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes. PMID:23652376

Treatment of Neurogenic Cough with Tramadol: A Pilot Study.

PubMed

Dion, Gregory R; Teng, Stephanie E; Achlatis, Efstratios; Fang, Yixin; Amin, Milan R

2017-07-01

This study employs validated cough assessment tools to prospectively determine the impact of tramadol on cough severity and quality of life in subjects with neurogenic cough. The study was a prospective case series with planned data collection at a tertiary care academic medical center laryngology practice. Sixteen consecutive collected subjects with neurogenic cough prospectively completed pre- and posttreatment validated cough assessment tools, the cough severity index (CSI) and Leicester Cough Questionnaire (LCQ). All subjects in the study reported at least some improvement in their cough symptoms. In a Wilcoxon signed rank test that compared paired results, CSI scores improved from 23 to 14 and LCQ scores improved from 74 to 103 ( P = .003 and P = .005, respectively). This small preliminary assessment suggests that tramadol warrants additional evaluation as a treatment for neurogenic cough.

Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension

PubMed Central

Palma, Jose-Alberto; Kaufmann, Horacio

2017-01-01

Background Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing which can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions particularly in the elderly (233 per 100,000 patients over 75 years of age in the US). OH can be due to volume depletion, blood loss, large varicose veins, medications, or due to defective activation of sympathetic nerves and reduced norepinephrine release upon standing (i.e., neurogenic OH). Methods and Findings Literature review. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and is commonly associated with supine hypertension. Several pharmacological and non-pharmacological therapeutic options are available. Conclusions Here we review the epidemiology, diagnosis, and management of neurogenic OH, and provide an algorithm for its treatment emphasizing the importance of removing aggravating factors, implementing non-pharmacologic measures, and selecting appropriate pharmacological treatments. PMID:28713844

Role of vasopressin in regulation of renal kinin excretion in Long-Evans and diabetes insipidus rats.

PubMed Central

Kauker, M L; Crofton, J T; Share, L; Nasjletti, A

1984-01-01

To study the relationship between vasopressin and the renal kallikrein-kinin system we measured the rate of excretion of kinins into the urine of anesthetized rats during conditions of increased and decreased vasopressin level. The excretion of immunoreactive kinins in Brattleboro rats with hereditary diabetes insipidus (DI) (24 +/- 3 pg min-1 kg-1) was lower than in the control Long Evans (LE) rats (182 +/- 22 pg min-1 kg-1; P less than 0.05). The DI rats also exhibited negligible urinary excretion of immunoreactive vasopressin, reduced urine osmolality, and increased urine flow and kininogenase excretion. In LE rats, volume expansion by infusion of 0.45% NaCl-2.5% dextrose to lower vasopressin secretion reduced (P less than 0.05) kinin excretion, vasopressin excretion, and urine osmolality to 41, 26, and 15% of their respective control values, while increasing (P less than 0.05) urine flow and kininogenase excretion. On the other hand, the infusion of 5% NaCl, which promotes vasopressin secretion, increased (P less than 0.05) the urinary excretion of kinins and vasopressin to 165 and 396% of control, while increasing (P less than 0.05) urine flow and kininogenase excretion. Infusion of vasopressin (1.2 mU/h, intravenous) enhanced (P less than 0.05) kinin excretion by two to threefold in DI rats and in LE rats during volume expansion with 0.45% NaCl-2.5% dextrose, while decreasing urine flow and increasing urine osmolality. This study demonstrates that the urinary excretion of immunoreactive kinins varies in relation to the urinary level of vasopressin, irrespective of urine volume and osmolality and of the urinary excretions of sodium and kininogenase. The study suggests a role for vasopressin in promoting the activity of the renal kallikrein-kinin system in the rat. PMID:6561201

Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome.

PubMed

Djermane, Adel; Elmaleh, Monique; Simon, Dominique; Poidvin, Amélie; Carel, Jean-Claude; Léger, Juliane

2016-02-01

Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9-16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Neonatal CDI may be transient or permanent. These vulnerable patients have

Incidence, predictors and early post-operative course of diabetes insipidus in paediatric craniopharygioma: a comparison with adults.

PubMed

Pratheesh, Ravindran; Swallow, Diane Margaret A; Rajaratnam, Simon; Jacob, K S; Chacko, Geeta; Joseph, Mathew; Chacko, Ari G

2013-06-01

This study aims to determine the incidence, predictors, early post-operative course of diabetes insipidus (DI) in paediatric craniopharyngiomas(CP) and compare the findings with adults. Retrospective analysis of clinical, biochemical, radiological and operative data for 102 consecutive CP surgeries (45 paediatric and 57 adult cases) was done. Bivariate and multivariate analyses were done to determine the predictors of DI. The incidence of the triphasic response and electrolyte abnormalities in the first post-operative week was compared between children and adults. Children had larger tumours and higher incidence of cystic tumours and hydrocephalus. Preoperative DI was close to 15 % in both the age groups. Radical/subtotal excision was achieved in 58 % of children and 53 % of adults. The incidence of post-operative DI was 80 % and 63 % in children and adults, respectively. Children had significantly higher incidence of permanent DI (55.6 %). Radical excision in children (p = 0.000); previous tumour surgery (p = 0.014) and new onset hypopituitarism (p = 0.019) in adults were associated with permanent DI. The triphasic response (23 %), wide intra-day serum sodium fluctuations and hyponatraemia were more common in children. Post-operative DI is a frequent and significant cause of morbidity in children undergoing surgery for CP. Children have a higher incidence of permanent DI. Radical excision is a predictor of permanent DI in children, whereas previous tumour excision and new onset hypopituitarism were predictors of permanent DI among adults. The management of post-operative DI is more difficult in children and the treating physician needs to be alert to detect the triphasic response.

[The efficacy of desmopressin in the treatment of central diabetes insipidus after resection of chiasmo-sellar region tumors].

PubMed

Astaf'eva, L I

Central diabetes insipidus (CDI) is a neuroendocrine disease, the pathogenesis of which is associated with abnormal secretion of the antidiuretic hormone. One of the specific causes of CDI is neurosurgical resection of chiasmatic-sellar region tumors. to study the efficacy and safety of desmopressin in CDI patients after resection of chiasmatic-sellar region (CSR) tumors. Examination and treatment of patients were performed at a hospital for 7-14 days after surgery and then were continued after discharge. During treatment, the following tests were performed: a daily fluid intake and excretion volume, serum levels of sodium, potassium, and glucose twice a day, morning urine specific gravity, and Zimnitsky's test. Twenty-three patients with CSR tumors (11 craniopharyngiomas, 10 pituitary adenomas, 1 skull base chordoma, and 1 CSR meningioma) and CDI after neurosurgical treatment received desmopressin. On treatment, a thirst decrease, a reduced rate of diuresis, a reduced amount of excreted urine, and normalization of the sodium level were observed in all patients. In 12 patients (with pituitary adenoma, skull base chordoma, and meningioma) with transient CDI, desmopressin therapy was discontinued upon regression of symptoms 7-30 days after surgery. Eleven patients with permanent CDI continued to receive the drug at a dose of 1 to 4 doses per day. All patients well tolerated the drug without significant adverse effects. Therapy with desmopressin in the form of a nasal spray (vazomirin) in patients with transient and permanent CDI after resection CSR tumors of various histological nature (craniopharyngiomas, pituitary adenomas, meningiomas, and chordomas) was effective and safe in the early postoperative and long-term postoperative periods.

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

PubMed

Kilday, John-Paul; Laughlin, Suzanne; Urbach, Stacey; Bouffet, Eric; Bartels, Ute

2015-01-01

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

PubMed

Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

2017-08-01

Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

Contiguous 22.1-kb deletion embracing AVPR2 and ARHGAP4 genes at novel breakpoints leads to nephrogenic diabetes insipidus in a Chinese pedigree.

PubMed

Bai, Ying; Chen, Yibing; Kong, Xiangdong

2018-02-02

It has been reported that mutations in arginine vasopressin type 2 receptor (AVPR2) cause congenital X-linked nephrogenic diabetes insipidus (NDI). However, only a few cases of AVPR2 deletion have been documented in China. An NDI pedigree was included in this study, including the proband and his mother. All NDI patients had polyuria, polydipsia, and growth retardation. PCR mapping, long range PCR and sanger sequencing were used to identify genetic causes of NDI. A novel 22,110 bp deletion comprising AVPR2 and ARH4GAP4 genes was identified by PCR mapping, long range PCR and sanger sequencing. The deletion happened perhaps due to the 4-bp homologous sequence (TTTT) at the junctions of both 5' and 3' breakpoints. The gross deletion co-segregates with NDI. After analyzing available data of putative clinical signs of AVPR2 and ARH4GAP4 deletion, we reconsider the potential role of AVPR2 deletion in short stature. We identified a novel 22.1-kb deletion leading to X-linked NDI in a Chinese pedigree, which would increase the current knowledge in AVPR2 mutation.

Predictor Variables of Developing Anterior Pituitary Deficiencies in a Group of Paediatric Patients with Central Diabetes Insipidus and Langerhans Cell Histiocytosis.

PubMed

Vaiani, Elisa; Malossetti, Carmen; Vega, Lina Margarita; Zubizarreta, Pedro; Braier, Jorge; Belgorosky, Alicia

2017-01-01

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Central diabetes insipidus (CDI) is the most frequent endocrine manifestation and is a known risk factor for the development of further anterior pituitary hormone deficiencies (APD). However, not all CDI patients develop APD, as observed during prolonged periods of follow-up. To find predictors of developing APD in LCH children with CDI followed in our institution. We retrospectively analysed 44 patients over a median period (quartiles) of 12.3 years (8.79-14.24). Patients were subdivided into group 1 and group 2, according to absence or presence of APD, respectively. The main variables studied were: (1) chronological age (CA) at LCH diagnosis, (2) the primary site of LCH at diagnosis: low risk (LR) and multisystemic risk organs, and (3) the presence of reactivation. Multivariate Cox regression analysis showed that APD was positively associated with CA at LCH diagnosis [relative risk (RR) 1.14, p < 0.01], the LR clinical form (RR 8.6, p < 0.03), and negatively associated with the presence of reactivations (RR 0.3, p < 0.01). Patients with older CA at LCH diagnosis, LR clinical forms, and fewer reactivation episodes might represent a subgroup of paediatric LCH CDI patients with a higher risk of developing APD. © 2016 S. Karger AG, Basel.

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

PubMed

Hunter, Janel D; Calikoglu, Ali S

2016-01-01

Central 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. A 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. The 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. All patients in our cohort had an underlying organic etiology for CDI, with intracranial

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

Primary treatment regimen and diabetes insipidus as predictors of health outcomes in adults with childhood-onset craniopharyngioma.

PubMed

Yuen, Kevin C J; Kołtowska-Häggström, Maria; Cook, David M; Fox, Janet L; Jönsson, Peter J; Geffner, Mitchell E; Abs, Roger

2014-04-01

Craniopharyngiomas are often associated with significant morbidity due to their location and treatment effects. Little is known of the effects of primary treatment regimen and diabetes insipidus (DI), a clinical surrogate of hypothalamic obesity, on health outcomes in adults with childhood-onset craniopharyngioma (COCP). The objective of the study was to examine health outcomes of adults with COCP based on primary treatment regimens and the presence of DI. This study included a retrospective KIMS (Pfizer International Metabolic Database) data analysis of 180 adults with COCP according to the primary treatment regimen [one surgery (1Surg) vs complex treatment regimen (CTrR) of more than 1Surg and/or radiotherapy] and the presence of DI. The majority of COCP patients underwent transcranial surgery (77%) without receiving radiotherapy (84%). Compared with the 1Surg group, more CTrR patients developed visual field defects and ophthalmoplegia (all P < .01). Compared with patients without DI, those with DI had higher rates of anterior pituitary hormone deficits, body mass index, and fat mass (all P < .01). By contrast, fasting glucose, hemoglobin A1c, lipid panel, and quality of life were comparable among 1Surg vs CTrR patients, and patients with vs without DI. Regardless of primary treatment received, the presence of DI in either group was associated with higher rates of anterior pituitary hormone deficits and obesity. CTrR and DI predicted health outcomes differently. CTrR predisposed to the development of visual dysfunction, whereas DI was associated with higher rates of anterior pituitary dysfunction and weight gain. Higher body mass index and fat mass in patients with DI further implicate the role of hypothalamic damage as an important causal factor of obesity in these patients.

Delayed Occurrence of Diabetes Insipidus After Transsphenoidal Surgery with Radiologic Evaluation of the Pituitary Stalk on Magnetic Resonance Imaging.

PubMed

Hayashi, Yasuhiko; Aida, Yasuhiro; Sasagawa, Yasuo; Oishi, Masahiro; Kita, Daisuke; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi

2018-02-01

Diabetes insipidus (DI) is a major complication of transsphenoidal surgery (TSS). DI usually occurs within a couple of days after TSS. Delayed occurrence of postoperative DI is rarely observed and its developing mechanisms remain unknown. Six patients were identified as having postoperative delayed DI, which was defined as DI that first occurred 2 or more weeks after TSS. They consisted of 1 male and 5 females, and their mean age was 38.3 years (range, 10-76 years). Five patients were histologically diagnosed with Rathke cleft cyst (RCC), and one had RCC coexisting with prolactin-secreting adenoma. Sequential T1-weighted magnetic resonance imaging was evaluated for hyperintensity (HI) in the pituitary stalk and the posterior lobe, indicating the location of antidiuretic hormone. No patients had any DI before TSS. Delayed DI occurred 2 weeks to 3 months after TSS and persisted for 2 weeks to 5 months. T1-weighted magnetic resonance imaging showed that the HI in the posterior lobe became faint but did not disappear after DI occurrence, and their intensities increased with recovery from DI. In contrast, the HI in the pituitary stalk was found faintly preoperatively and turned clear postoperatively and decreased with recovery from DI. The morphologic patterns were dependent on DI duration. In the delayed occurrence of DI, it was suggested that preoperative antidiuretic hormone transport was mildly congested yet not completely blocked when DI manifested postoperatively. Gradual spreading of inflammation to the infundibulum after RCC removal was considered as 1 possible mechanism of this delayed DI development. Copyright © 2017 Elsevier Inc. All rights reserved.

Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review.

PubMed

Bohl, Michael A; Forseth, James; Nakaji, Peter

2017-01-01

Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis. A series of 6 neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP. To our knowledge, no previous reports of this phenomenon in neurosurgical patients have been published. We reviewed the clinical histories, intensive care unit treatment, medication administration records, and laboratory values of these patients, and we found recurrent elevated serum sodium and urine output and decreased urine specific gravity after discontinuation of AVP. Resolution of tDI occurred upon resumption of AVP or administration of desmopressin. Elevated serum sodium levels were often severe, resulting in worsened clinical outcomes. When AVP was resumed, tDI typically recurred if AVP was again tapered and discontinued. Routine administration of desmopressin was useful in controlling sodium levels until the tDI resolved. Recognition of this phenomenon has caused us to change our clinical management of neurosurgical patients receiving AVP. We hypothesize that tDI is caused by downregulation of the V2 receptor mass in the renal distal convoluted tubule and collecting duct cells. When AVP is discontinued, patients develop nephrogenic tDI secondary to decreased V2 receptor binding, which explains why desmopressin is effective in correcting tDI. Future research includes a large prospective study to determine risk factors for tDI, its incidence, and its pathophysiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of chronic neurogenic cough with in-office superior laryngeal nerve block.

PubMed

Simpson, C Blake; Tibbetts, Kathleen M; Loochtan, Michael J; Dominguez, Laura M

2018-04-18

Neurogenic cough is believed to result from a sensory neuropathy involving the internal branch of the superior laryngeal nerve (SLN). We present our outcomes for the treatment of neurogenic cough with localized blockade of the internal branch of the SLN. A retrospective chart review of patients who underwent in-office percutaneous SLN block for treatment of neurogenic cough between 2015 and 2017 was conducted. Patient demographics, indications for injection, and response to treatment were recorded and analyzed. Cough severity index (CSI) scores before and after treatment were compared. Twenty-three patients underwent percutaneous blockade of the internal branch of the SLN in the clinic setting, and five patients were excluded for incomplete records. The indication was neurogenic cough as a diagnosis of exclusion. The injectable substance used was a 1:1 mixture of a long-acting particulate corticosteroid and a local anesthetic. Unilateral injections were performed in 13 patients, and five patients underwent bilateral injections. Of the unilateral injections, 10 were left-sided. Patients underwent an average of 2.4 SLN block procedures (range 1-7). Mean follow-up time postinjection was 85.4 days (7-450 days). Cough severity index scores decreased significantly from an average of 26.8 pretreatment to 14.6 posttreatment (P < 0.0001). The SLN block is an effective treatment for neurogenic cough, with average CSI scores significantly improved following injection. Further study is necessary to determine the characteristics of patients' responses to treatment, long-term outcomes, and efficacy of the procedure when compared to placebo and other accepted treatments for neurogenic cough. 4. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated hypertrophic pachymeningitis presenting with multiple cranial nerve palsies and diabetes insipidus.

PubMed

Yasuda, Ken; Sainouchi, Makoto; Goto, Masahiro; Murase, Nagako; Ohtani, Ryo; Nakamura, Michikazu

2016-05-31

A 61-year-old woman developed hearing difficulties and became thirsty after experiencing cold symptoms. A neurological examination revealed a loss of odor sensation, facial palsy, dysphasia, and dysarthria. Vocal cord palsy was observed during pharyngoscopy. Brain magnetic resonance imaging (MRI) showed a thickened pituitary stalk and swelling of the pituitary gland, but no high signal intensity regions were seen in the posterior portion of the pituitary gland. Gadolinium-enhanced MRI demonstrated a thickened dura mater over the anterior cranial fossa. A biopsy specimen of the thickened dura mater showed fibrosis, granulomatous inflammation, and necrotic foci. Blood tests detected myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). The patient's urine osmolarity was low even though she exhibited hypernatremia. We diagnosed her with hypertrophic pachymeningitis associated with MPO-ANCA and diabetes insipidus. The patient received two courses of 5-day high-dose intravenous methylprednisolone (1.0 g/day), and was subsequently administered oral prednisolone, which gradually relieved her symptoms. However, the patient's symptoms recurred despite the high-dose prednisolone treatment. It was difficult to control the patient's symptoms in this case with oral prednisolone monotherapy, but combined treatment with cyclosporine resulted in sustained remission. It is considered that patients with MPO-ANCA-positive hypertrophic pachymeningitis require combination therapy with prednisolone and immunosuppressive agents at an early stage.

A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action

PubMed Central

Chakravarty, Sumana; Maitra, Swati; Reddy, R Gajendra; Das, Tapatee; Jhelum, Priya; Kootar, Scherazad; Rajan, Wenson D.; Samanta, Anumita; Samineni, Ramesh; Pabbaraja, Srihari; Kernie, Steven G.; Mehta, Goverdhan; Kumar, Arvind

2015-01-01

In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds. PMID:26388493

Neurogenic contributions made by dietary regulation to hippocampal neurogenesis.

PubMed

Park, Hee Ra; Lee, Jaewon

2011-07-01

Adult neural stem cells in the dentate gyrus of the hippocampus are negatively and positively regulated by a broad range of environmental stimuli that include aging, stress, social interaction, physical activity, and dietary modulation. Interestingly, dietary regulation has a distinct outcome, such that reduced dietary intake enhances neurogenesis, whereas excess calorie intake by a high-fat diet has a negative effect. As a type of metabolic stress, dietary restriction (DR) is also known to extend life span and increase resistance to age-related neurodegenerative diseases. However, the potential application of DR as a "neurogenic enhancer" in humans remains problematic because of the severity of restriction and the protracted duration of the treatment required. Therefore, the authors consider that an understanding of the neurogenic mechanisms of DR would provide a basis for the identification of the pharmacological and nutraceutical interventions that mimic the beneficial effects of DR without limiting caloric intake. The current review describes the regulatory effect of DR on hippocampal neurogenesis and presents a possible neurogenic mechanism. © 2011 New York Academy of Sciences.

Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury

DTIC Science & Technology

2009-09-01

new onset diabetes mellitus and insipidus , pituitary disorders, adrenal disorders, and sex hormone disorders. • Determine the association between...amyotrophic lateral sclerosis o Endocrinological outcomes: type II diabetes mellitus, diabetes insipidus , thyroid disorders, adrenal disorders, pituitary

UTIs in patients with neurogenic bladder.

PubMed

Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

2014-09-01

Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy.

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.