Diagnosis and Management of Central Diabetes Insipidus in Adults.

Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.

Pathological post-obstructive diuresis following obstructive uropathy due to constipation in the post-partum period: a case report.

BACKGROUND: Constipation during pregnancy is not uncommon. Usually, this does not warrant extensive evaluation and settles with minor interventions or lifestyle modifications. Severe fecal impaction in chronically constipated patients can rarely lead to obstructive uropathy. Relief of obstruction can result in a diuretic phase which may be self-limiting or pathological. However, occurrence of pathological post-obstructive diuresis as a result of severe constipation is an extremely rare complication during pregnancy and puerperium which can even be fatal if not promptly diagnosed and adequately monitored and timely intervened. We describe the management of a pathological post-obstructive diuresis which occurred in the immediate postpartum period after treatment of severe constipation and obstructive uropathy. CASE PRESENTATION: A woman who had undergone an emergency caesarean section due to deep transverse arrest 1 week ago, presented with fecal impaction and anuria. On relief of urinary obstruction which had developed secondary to fecal impaction, she developed pathological post-obstructive diuresis. Careful and timely monitoring with exact fluid replacement, correction of electrolyte imbalances and multidisciplinary care ensured complete recovery of the patient. CONCLUSIONS: Despite obstructive uropathy being uncommon in obstetric practice, clinicians need to have a high index of suspicion to monitor and promptly manage the potentially life-threatening condition of post-obstructive diuresis in pregnant and puerperal women undergoing urinary tract decompression. Due to unreliability of laboratory cutoff values in pregnancy and puerperium, a more vigilant and multidisciplinary approach with lower threshold for intervention is more prudent in the management of these patients.

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.

Lessons learnt from an old foe.

Neurotuberculosis usually responds well to standard antitubercular therapy. Some; patients have prolonged course A 11 year old boy diagnosed TBM, an immunocompetent patient, had an unusual course of illness in the form of prolonged fever, persistent hyponatremia and CSF; pleocytosis despite adequate treatment. Clinical course in the management of TBM can be; protracted with complications despite adequate therapy.

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.

Nocturia and Nocturnal Polyuria in Neurological Patients: From Epidemiology to Treatment. A Systematic Review of the Literature.

CONTEXT: Nocturia is among the most common and bothersome lower urinary tract symptoms (LUTS), but there is no clear consensus on how to identify and manage this symptom in the neurological population. OBJECTIVE: To systematically review the literature about nocturia in neurological patients. EVIDENCE ACQUISITION: Studies were identified by electronic search of Cochrane and Medline databases. The studies were included if their participants had acquired neurological pathology among multiple sclerosis (MS), Parkinson's disease (PD), stroke, spinal cord injury (SCI), and reported data on the epidemiology, aetiology, diagnosis, or treatment of nocturia. An independent extraction of the articles was performed by two authors using predetermined datasets, including quality-of-study indicators. EVIDENCE SYNTHESIS: A total of 132 studies were included; 46 evaluated the epidemiology of nocturia, 28 the possible aetiologies, 10 the diagnostic tools, and 60 the treatments. Nocturia prevalence ranged from 15% to 96% depending on the pathology and definition used. It was one of the most frequently reported LUTS in PD and stroke patients. Several validated questionnaires were found to screen for nocturia in this population. Causalities were numerous: LUT, renal, sleep, cardiovascular dysfunctions, etc. Treatments targeted these mechanisms, with an overall risk of bias assessed as high or serious. The highest level of evidence was seen in MS patients: pelvic floor muscle training, cannabinoids, and desmopressin were effective, but not melatonin. In stroke patients, transcutaneous sacral and transcutaneous tibial nerve stimulation (TTNS) improved nocturia; in PD patients, TTNS, solifenacin, and rotigotine did not. CONCLUSIONS: Nocturia is highly prevalent in patients with neurological disorders. Causalities and treatments are not different from the general population, but are poorly studied in neurological patients. PATIENT SUMMARY: In this report, we looked at the published studies about nocturia-the fact of waking to void during the hours of sleep-in patients with neurological diseases. We found that nocturia is very frequent in this population, that the causes are the same as in the general population but may be combined, and that treatments are also the same but have an overall weak level of evidence. We conclude that more research is needed on this topic.

Management of Nocturia and Nocturnal Polyuria.

Nocturnal polyuria (NP), characterized by overproduction of urine at night (greater than 20%-33% of total 24-hour urine volume depending on age), is a major contributing factor in most nocturia cases. Nocturia can be caused by intake, urological, nephrological, hormonal, sleep, and cardiovascular factors. It is therefore important to accurately diagnose both the type of nocturia and the potentially associated medical conditions to determine appropriate treatment. Diagnostic tools, in addition to a thorough history and physical examination, include voiding/bladder diary analyses and questionnaires to diagnose nocturia type (NP, diminished nocturnal/global bladder capacity, global polyuria) and causative factors. Lifestyle modifications are the first intervention implemented for the management of nocturia and NP but, as symptoms progress, such measures may be insufficient, and pharmacotherapy may be initiated. While drugs for benign prostatic hyperplasia and overactive bladder have demonstrated statistically significant reductions in nocturnal voids, patients often fail to achieve a clinically meaningful response. Antidiuretic treatment is warranted for patients with nocturia due to NP because, in many patients, it treats the underlying cause (ie, insufficient secretion of antidiuretic hormone arginine vasopressin) that leads to overproduction of urine at night and has been shown to provide statistically significant reductions in nocturnal voids. Desmopressin, a synthetic analog of arginine vasopressin, is the only antidiuretic treatment indicated specifically for nocturia due to NP. Overall, the pathophysiology of NP is complex and differs from that of other types of nocturia. A multidisciplinary approach is necessary to effectively diagnose and manage this bothersome condition.

Continuous positive airway pressure improves nocturnal polyuria in ischemic stroke patients with obstructive sleep apnea.

OBJECTIVES: To assess the effect of continuous positive airway pressure (CPAP) on nocturia in ischemic stroke patients with obstructive sleep apnea (OSA). METHODS: This was a prospective and non-randomized controlled study in which ischemic stroke patients with OSA being treated in a rehabilitation ward were enrolled. The participants who tolerated CPAP were classified as the CPAP group, while those who refused or could not tolerate CPAP were classified as the control group. The percentage change of nocturia before and after 2 weeks of CPAP therapy between the two groups were compared. RESULTS: A total of 44 participants were enrolled in and 35 participants (mean age= 59.8±11.7 years old; mean apnea hypopnea index=42.9±16.7/h) completed the study (control group: 14, CPAP group: 21). Overall, 69% of the participants had nocturnal polyuria and 69% of them had more than one nocturia episode per night. The baseline and initial nocturia characteristics did not differ significantly between the two groups. As compared to the control group, CPAP therapy significantly decreased the nocturnal polyuria index (mean percentage change: 9% vs -21% (P=0.005)) and nocturnal urine output (mean percentage change: 6% vs -26% (P=0.04)), but not the nocturia episodes or 24-hours total urine output. CONCLUSION: Nocturia due to nocturnal polyuria is very common in post-stroke patients with OSA. Treating OSA by CPAP significantly reduces nocturnal polyuria, but not nocturia frequency, in ischemic stroke patients.

Variations of Nighttime and Daytime Bladder Capacity in Patients with Nocturia: Implication for Diagnosis and Treatment.

PURPOSE: We subtyped patients with nocturia according to daily variations in urine production and bladder capacity. MATERIALS AND METHODS: Patients with 1 or more nocturia episodes per day were prospectively enrolled in this study. Post-void residual urine was collected and a 3-day frequency-volume chart was created. Nocturnal polyuria and bladder capacity were calculated for each patient. Reduced bladder capacity was defined as mean 24-hour bladder capacity less than 200 ml. Patients were categorized into 4 subgroups by the presence or absence of nocturnal polyuria and reduced bladder capacity. RESULTS: Of the 84 patients enrolled in study 50 (59.5%) had nocturnal polyuria and 50 (59.5%) had decreased bladder capacity. Patients with reduced bladder capacity and nocturnal polyuria had significantly greater mean and maximum bladder capacity at night than during the day (p = 0.002) and the highest number of nocturia episodes (3, IQR 2-3). Patients with normal bladder capacity but with nocturnal polyuria had significantly larger mean and maximum bladder capacity at night (p = 0.033 and 0.016, respectively). In patients with reduced bladder capacity and no nocturnal polyuria we observed no significant variation in bladder capacity during the day vs the night. On multivariable analysis the body mass index (OR 1.28 per unit, 95% CI 1.04-1.58, p = 0.019) and severe nocturia (OR 6.26, 95% CI 1.71-22.92, p = 0.006) were risk factors for nocturnal polyuria while only severe nocturia was a predictive factor for reduced bladder capacity (OR 3.77, 95% CI 1.20-11.83, p = 0.023). CONCLUSIONS: Patients with nocturnal polyuria have a different bladder capacity in the day and the night. Severe nocturia (3 or more episodes per night) predicts the presence of nocturnal polyuria and reduced bladder capacity. Our data suggest that in patients with severe nocturia those 2 conditions should be considered and managed.

Conservative treatment for leg oedema and the effect on nocturnal polyuria in patients with spinal cord injury.

OBJECTIVES: To evaluate the possible influence of non-pharmacological interventions, such as compressive bandages and intermittent pneumatic compression (IPC), on leg oedema and nocturnal polyuria (NP), and the possible interrelation between both pathologies in patients with spinal cord injury (SCI), as patients with SCI often have leg oedema and during the night the oedema decreases as a result of natural drainage mechanisms that can cause NP. PATIENTS AND METHODS: Patients with SCI who followed their first rehabilitation after their SCI with bilateral leg oedema and/or with as much or a larger urine volume at night as during the day. The patients were all wheelchair users and followed the rehabilitation programme daily for 3 weeks. In all, 24 patients, aged between 21 and 63 years, were selected for participation in the 3-week rehabilitation programme. During the first week, baseline data were collected. During the second week, IPC was executed from the moment the patient went to lie down. During the third week, the patients wore multilayer compressive bandages. Leg circumference was measured in the morning before sitting up and at the moment they went to lie down in bed. During each study week, a daily frequency-volume chart (24 h) was completed. RESULTS: The leg volume of both legs was significantly different between the morning and evening (right leg F = 103.90, P < 0.001; left leg F = 100.77, P < 0.001) and between the three treatments (right F = 9.70, P < 0.001; left F = 9.66, P < 0.001). There was a significant difference between the compressive bandages and the baseline period (right and left leg, both P < 0.001) and between the compressive bandages and IPC (right leg P = 0.009 and left leg P = 0.015). There was no significant difference between IPC and the baseline. When no treatment or IPC was used, urine production was significantly higher during the bed-rest period. The urine production was significantly lower comparing the use of compressive bandages to baseline and IPC, during bed rest (P = 0.009) and during sleep (P < 0.001). There was a significant decrease in absolute voided volume at night with the compressive bandages as treatment (P < 0.001). There was a significant positive association between the leg volume change during the day and the urine-production ratio, 100 mL increase in leg volume was associated with 8% increase in the log-transformed urine-production ratio. CONCLUSION: There are alternative treatment options for patients with SCI who have oedema or NP. Oedema formation and urine production appear to be related to each other. Therefore, the use of compressive bandages was shown to be a valuable treatment option to improve both leg oedema and NP.

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.

Managing nocturia: The multidisciplinary approach.

Nocturia, defined as waking at night to pass urine, is a common condition which increases with age. Whilst nocturia is known to have an important effect on quality of life, more recent evidence has linked the symptom with significant morbidity and mortality due to the effects of sleep deprivation on glucose metabolism and the immune system. The causes of nocturia are multifactorial and may be related to urine overproduction, storage disorders and primary sleep disorders. The commonest underlying pathology, however, is nocturnal polyuria, which may be associated with a number of medical conditions. This review explores the underlying causes of nocturia and nocturnal polyuria and, by doing so, describes a multidisciplinary approach to managing patients effectively.

ICI-RS 2015-Is a better understanding of sleep the key in managing nocturia?

AIMS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom. However, the applied treatment modalities do not improve symptoms in about half of the patients. The aim of this report is to generate new ideas for future nocturia research, with special emphasis on the role of sleep physiology and sleep disorders. METHODS: The following is a report of the presentations and subsequent discussion of the Nocturia Think Tank session at the annual meeting of the International Consultation on Incontinence Research Society (ICI-RS), which took place in September 2015 in Bristol. General information about the organization of the ICI-RS meeting can be found on the website "www.ici-rs.org." An overview of challenges within the existing evidence, future research ideas, and results of research with regard to nocturia and sleep were presented. RESULTS AND CONCLUSION: In order to optimize the management of nocturia and nocturnal polyuria (NP), future research has to focus on the development of unambiguous terminology regarding nocturia and NP, the role of renal function profiles and simplified frequency volume charts as guidance of individualized therapy and the role of sleep disorders such as periodic limb movements during sleep and habitual voiding as a response to awakening. Neurourol. Urodynam. 37:2048-2052, 2018. © 2016 Wiley Periodicals, Inc.

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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of Polyuria: The Roles of Solute Loading and Water Diuresis.

Polyuria, defined as daily urine output in excess of 3.0 to 3.5L/d, can occur due to solute or water diuresis. Solute-induced polyuria can be seen in hospitalized patients after a high solute load from exogenous protein administration or following relief of urinary obstruction. Similar clinical scenarios are rarely encountered in the outpatient setting. We describe a case of polyuria due to high solute ingestion and excessive water intake leading to a mixed picture of solute and water diuresis. Restriction of the daily solute load and water intake resulted in complete resolution of polyuria. Determination of the daily excreted urinary osmoles may yield important clues to the cause of polyuria and should be included in the routine workup of polyuria.

Would a new definition and classification of nocturia and nocturnal polyuria improve our management of patients? ICI-RS 2014.

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place September 22-24, 2014 in Bristol, UK. The report is organized into sections pertaining to the main topic of discussion focussing on the question as to whether a new definition and classification of nocturia and nocturnal polyuria would improve the outcome of management in our patients. First, discussions identified theoretical and practical shortcomings of current definitions. Secondly, the utility of several nocturnal polyuria definitions was tested in a real life population in relation to the symptom nocturia, in order to display weaknesses of these definitions. Thirdly, we explored in a clinical population the utility of bladder diary based parameters by asking the question: when nocturia improves, which of these parameters improve most? Based on the above explorations the Think Tank summarized elements of the current definitions that need reconsideration and suggests proposals for further research to reach more practical and more clinically meaningful definitions.