A patient with congenital nephrogenic diabetes insipidus due to AVPR2 mutation complicated by persisting polydipsia under hemodialysis treatment.

A 17-year-old boy was referred to our institution for a re-evaluation of congenital nephrogenic diabetes insipidus. A water restriction test revealed no urine concentration or volume reduction and a subsequent pitressin test revealed a lack of an anti-diuretic response. Nephrogenic diabetes insipidus was confirmed, and the patient was treated using trichlormethiazide 4 mg, indomethacin 175 mg, and desmopressin 20 µg. His blood pressure and weight were not controlled owing to polydipsia and polyuria secondary to acquired excessive water drinking behavior. Repeated admissions for weight control were necessary and despite consultation with a psychiatrist for his obsessive water drinking behavior, he had end-stage renal failure after 30 years of treatment. Genetic testing revealed AVPR2 mutation (c. T866C: p. L289P) that had previously been reported as a pathogenic mutation. His excessive drinking behavior persisted, leading to hyponatremia even after initiation of hemodialysis. There was also difficulty in achieving body weight control, which was managed by repeated admissions with restriction of water intake, being the mainstay of management.

Primary polydipsia: Update.

In primary polydipsia pathologically high levels of water intake physiologically lower arginine vasopressin (AVP) secretion, and in this way mirror the secondary polydipsia in diabetes insipidus in which pathologically low levels of AVP (or renal responsiveness to AVP) physiologically increase water intake. Primary polydipsia covers several disorders whose clinical features and significance, risk factors, pathophysiology and treatment are reviewed here. While groupings may appear somewhat arbitrary, they are associated with distinct alterations in physiologic parameters of water balance. The polydipsia is typically unrelated to homeostatic regulation of water intake, but instead reflects non-homeostatic influences. Recent technological advances, summarized here, have disentangled functional neurocircuits underlying both homeostatic and non-homeostatic physiologic influences, which provides an opportunity to better define the mechanisms of the disorders. We summarize this recent literature, highlighting hypothalamic circuitry that appears most clearly positioned to contribute to primary polydipsia. The life-threatening water imbalance in psychotic disorders is caused by an anterior hippocampal induced stress-diathesis that can be reproduced in animal models, and involves phylogenetically preserved pathways that appear likely to include one or more of these circuits. Ongoing translational neuroscience studies in these animal models may potentially localize reversible pathological changes which contribute to both the water imbalance and psychotic disorder.

Acquired forms of central diabetes insipidus: Mechanisms of disease.

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80-90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

Central diabetes insipidus in children: Diagnosis and management.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.

Gestational diabetes insipidus: Diagnosis and management.

In the pregnant patient, hypotonic polyuria in the setting of elevated serum osmolality and polydipsia should narrow the differential to causes related to diabetes insipidus (DI). Gestational DI, also called transient DI of pregnancy, is a distinct entity, unique from central DI or nephrogenic DI which may both become exacerbated during pregnancy. These three different processes relate to vasopressin, where increased metabolism, decreased production or altered renal sensitivity to this neuropeptide should be considered. Gestational DI involves progressively rising levels of placental vasopressinase throughout pregnancy, resulting in decreased endogenous vasopressin and resulting hypotonic polyuria worsening through the pregnancy. Gestational DI should be distinguished from central and nephrogenic DI that may be seen during pregnancy through use of clinical history, urine and serum osmolality measurements, response to desmopressin and potentially, the newer, emerging copeptin measurement. This review focuses on a brief overview of osmoregulatory and vasopressin physiology in pregnancy and how this relates to the clinical presentation, pathophysiology, diagnosis and management of gestational DI, with comparisons to the other forms of DI during pregnancy. Differentiating the subtypes of DI during pregnancy is critical in order to provide optimal management of DI in pregnancy and avoid dehydration and hypernatremia in this vulnerable population.

Fifteen-minute consultation: Polydipsia, polyuria or both.

Children can present with polydipsia and/or polyuria for a number of reasons. We will discuss polydipsia and polyuria, how a child may present and how to investigate further in order to establish the cause. We highlight the important areas to cover in the history and examination of a child presenting with polydipsia and/or polyuria.

Nephrocalcinosis among children at king hussein medical center: Causes and outcome.

Nephrocalcinosis (NC) is defined as deposition of calcium crystals in the renal parenchyma and tubules. This is a retrospective review of all the data of 63 children presented to Pediatric Nephrology Clinic at King Hussein Medical Center (KHMC) over a 15-year period with bilateral NC. We determine their causes, clinical presentation and evaluate their growth and renal function during their follow-up. Thirty-five (55.5%) cases were males and 28 (44.5%) were females. The median (range) age at presentation was four (2-192) months. The most common leading cause to NC was hereditary tubulopathy in 48% followed by hyperoxaluria in 35%. The cause of NC remained unknown in 3% and Vitamin D excess accounts for 5% of the cases. The most presenting symptom was a failure to thrive (68%) and the second most common symptom was abdominal pain and recurrent urinary tract infection was found in 40%, polyuria and polydipsia were found in 32% of cases, and 16% of cases were diagnosed incidentally. At a median follow-up of 38 (14-200) months, estimated glomerular filtration rate had decreased from 84.0 (42-110) mL/min per 1.73 m2 body surface area to 68.2 (10-110) mL/min/1.73 m2 body surface (P = 0.001). This study illustrated the need for a national registry of rare renal diseases to help understand the causes of these conditions in our populations and provide support to affected patients and their families.

Effective and Cheap Behavioral Modification Therapy to Manage Complicated Polydipsia and Seizures in a Chronic Mental Health Institute.

PURPOSE: Polydipsia is one of the most serious and complicated problems causing morbidity and mortality in chronic mental health institutes. The pathophysiology of polydipsia in chronic schizophrenia remains unclear; as a result, no effective methods exist to deal with this serious problem. This report describes a patient with schizophrenia with polydipsia and seizures who benefitted from a behavioral modification program at a chronic mental health institute. CASE REPORT: A 56-year-old schizophrenic man did not have a history of physical illnesses or seizures and developed seizures following polydipsia. Despite drug adjustment, his polydipsia was uncontrolled and he suffered from generalized tonic convulsions. After introducing a "water restriction program," his polydipsia and seizures were controlled. CONCLUSION: The "water restriction program" consisted of daily body weight monitoring and frequent checking of electrolyte data, both of which are inexpensive and simple. This program can be carried out by untrained nursing staff, who are the primary caregivers in chronic mental health institutes. Our case highlights an effective and inexpensive behavior modification program to deal with the difficult and complicated problems of polydipsia and seizures in chronic mental health institutes.

Thirst in chronic heart failure: a review.

AIMS AND OBJECTIVES: This review will (1) explore factors related to thirst in chronic heart failure and (2) describe interventions to alleviate thirst in chronic heart failure patients. BACKGROUND: Thirst is a common and troublesome symptom of chronic heart failure. Despite the burden and prevalence of this symptom, there are limited strategies to assist in its management. DESIGN: This is a review of literature on the burden of thirst, contributors to thirst and potential management strategies of thirst in patients with chronic heart failure. METHODS: Medline, Cumulative Index for Nursing and Allied Health, PubMed and Scopus were searched using the key words thirst, chronic heart failure, angiotensin II, fluid restriction and intervention. Of the 165 citations yielded, nine studies (n = 9) were included. The eligibility criteria included participants with confirmed diagnosis of chronic heart failure, randomised controlled studies or any studies with thirst as primary or secondary outcome, in humans and in English. There was no limit to the years searched. RESULTS: Factors related to thirst in chronic heart failure were condition; prolonged neurohormonal activation, treatment; pharmacological interventions and fluid restriction and emotion. No intervention studies were found in chronic heart failure patients. Interventions such as artificial saliva and chewing gum have been investigated for their effectiveness as a thirst reliever in haemodialysis patients. CONCLUSION: Thirst is a frequent and troublesome symptom for individuals with chronic heart failure. It is highly likely that this contributes to poor adherence with fluid restrictions. Chewing gum can help alleviate thirst, but investigation in people with heart failure is needed. RELEVANCE TO CLINICAL PRACTICE: Increasing awareness of thirst and interventions to relieve it in clinical practice is likely to improve the quality of care for people with chronic heart failure.

Context specificity of extinguished schedule-induced drinking within an ABA renewal design in rats / Especificidad contextual de la extinción de la bebida inducida por programa en un diseño de renovación ABA en ratas

The main goal of this study was to explore whether extinction of schedule-induced adjunctive drinking (polydipsia) may become under contextual control. Drinking was induced by a Fixed-Time 30 sec food delivery schedule (FT30). Experiment 1 used a 2 x 2 factorial design with Schedule (FT30 vs. food a the start of the session), and Stimulus (Presenceor absence of a 10 sec tone at the end of each 30 sec period within a session) as factors. Acquisition and extinction were conducted in two different contexts, returning to the acquisition context at testing. Experiment 2 tested contextual control of extinction against a control that remained in the extinction context at testing. Recovery from extinction was observed as an increase in water intake (as well as in magazine entries) during the test, regardless of the presence of the tone. Implications for theunderstanding of schedule-induced drinking as a conditioned response are discusse (AU)

El objetivo principal de este estudio fue evaluar si la extinción de la bebida adjuntiva inducida por programa (polidipsia) podía quedar bajo control contextual. La bebida se indujo mediante un programa de administración de comida de tiempo fijo 30 segundos (TF30). El experimento 1 utilizó un diseño factorial 2 x 2 con Programa (TF30 vs. comida al inicio de la sesión) y Estímulo (presencia o ausencia de un sonido de 10s al final de cada periodo de 30s dentro de la sesión)como factores. La adquisición y la extinción se realizaron en contextos diferentes, regresando al contexto de adquisición durante la prueba. El experimento 2 introdujo una condición de control que recibió la prueba en el contexto de extinción. La recuperación de la extinción se observó como un aumento en la ingesta de agua (así como en las entradas en el comedero) durante la prueba, independientemente de la presencia del sonido. Se discuten las implicaciones de estos resultados para la interpretación de la bebida inducida por programa como una respuesta condicionada (AU)

Rhabdomyolysis associated with polydipsia induced hyponatraemia.

A 41-year-old white male with a history of alcoholism and depression was brought from prison into the emergency department (ED) after having had a witnessed tonic-clonic seizure lasting approximately 5 min. During the 24 h prior to admission, the patient's cell mate reported that he was restless and had consumed 11 litres of water. The patient had also been taking regular escitalopram for his depression. On arrival to the ED, the patient was found to have a sodium level of 112 mmol/l. After correction of his hyponatraemia the patient developed rhabdomyolisis with a creatine kinase level of 65 064 IU/l. To prevent an acute kidney injury a high volume alkaline diuresis protocol was started. Once corrected, his sodium level remained normal and he was discharged home after making a full neurological recovery. Rhabdomyolysis has rarely been associated with the correction of hyponatraemia.