pituitrin and Nocturnal-Enuresis

Nocturnal enuresis is the involuntary pass of urine during sleep beyond the age of 5 years. It is a common condition in childhood and has an impact on the child's well-being. Research into the pathophysiology of the condition in the last decades has led to a paradigm shift, and enuresis is no longer considered a psychiatric disorder but rather a maturation defect with a somatic background. An excess urine production during sleep is a common finding in children with enuresis and disturbances in the circadian rhythm of arginine-vasopressin (AVP) is found in the majority of children with nocturnal polyuria. Children with enuresis and nocturnal polyuria lack the physiologic increase in AVP levels during sleep and treatment with the AVP analogue desmopressin can restore this rhythm and lead to dry nights. The reasons for this aberrant circadian AVP rhythm are not established. Furthermore, not all children with enuresis and nocturnal polyuria can be successfully treated with desmopressin suggesting that factors beyond renal water handling can be implicated such as natriuresis, hypercalciuria, and sleep-disordered breathing. The advances in the research of the genetic background of the condition may shed further light on the enuresis pathophysiology.

Topics: Arginine; Arginine Vasopressin; Child; Child, Preschool; Circadian Rhythm; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Vasopressins

Enuresis (intermittent urinary incontinence during sleep in a child aged ≥ 5 years) is commonly seen in paediatric practice. Despite the availability of effective interventions, treatment resistance is encountered in up to 50% of children. In this educational review we attempt to provide insight into the causes of treatment resistance, and offer practical suggestions for addressing this condition using an interprofessional approach. We explore the pathophysiology of and standard treatments for enuresis and discuss why standard treatments may fail. An interprofessional approach to treatment resistance is proposed which utilises the expertise of professionals from different disciplines to address the problems and barriers to treatment. The two interprofessional approaches include a multidisciplinary approach that involves the patient being sent to experts in different disciplines at different times to address their treatment resistance utilising the skills of the respective experts, and an interdisciplinary approach that involves a patient being managed by members of interdisciplinary team who integrate their separate discipline perspectives into a single treatment plan. Although an interdisciplinary approach is ideal, interdisciplinary teams may not be available in all circumstances. Understanding the roles of other disciplines and engaging clinicians from other disciplines when appropriate can still be helpful when treatment resistance is encountered.

Topics: Child; Cognitive Behavioral Therapy; Family; Humans; Interprofessional Relations; Nocturnal Enuresis; Patient Care Planning; Patient Care Team; Patient Education as Topic; Sleep Arousal Disorders; Treatment Failure; Urinary Bladder; Urinary Bladder, Overactive; Vasopressins

Nocturnal enuresis, or bedwetting, is the most common cause of urinary incontinence in children. It is known to have a significant psychosocial impact on the child as well as the family. Nocturnal enuresis typically presents as failure to become dry at night after successful daytime toilet training. It can be primary or secondary (developing after being successfully dry at night for at least 6 months). Children with nocturnal enuresis may have excessive nocturnal urine production, poor sleep arousal and/or reduced bladder capacity. Alarm therapy is the recommended first-line therapy, with treatment choices being influenced by the presence or absence of the abnormalities mentioned above. Children with nocturnal enuresis may also have daytime urinary urgency, frequency or incontinence of urine. This group (non-monosymptomatic nocturnal enuresis) requires a different clinical approach, with a focus on treating daytime bladder symptoms, which commonly involves pharmacotherapy with anticholinergic medications and urotherapy (including addressing bowel problems). This review discusses the current management of nocturnal enuresis using the terminologies recommended by the International Children's Continence Society.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Humans; Imipramine; Mandelic Acids; Neurophysins; Nocturnal Enuresis; Protein Precursors; Risk Factors; Vasopressins

To elucidate the background behind the attenuated circadian rhythm of vasoactive hormones in patients with nocturnal enuresis, we tested the hypothesis that enuretic children exhibit an abnormal neuroendocrine response to a baroreflex stimulus during daytime.. In fifteen children and adolescents (aged 13.4 +/- 0.9 years) with severe nocturnal enuresis and 10 age- and sex-matched healthy controls, we performed a 'daytime supine posture' (DSP) study at 10:00 h.. Blood was sampled for measurements of plasma vasopressin (P(AVP)), angiotensin II (P(ANGII)), atrial natriuretic peptide (P(ANP)) and serum aldosterone (S(ALDO)), and mean arterial blood pressure (MAP) and heart rate (HR) were measured during the study.. In both controls and patients with enuresis, DSP at 10:00 h resulted in a marked fall in MAP and HR, a rise in pulse pressure (PP) and estimated plasma volume (PV) and a significant suppression of P(AVP), P(ANGII) and S(ALDO), whereas P(ANP) increased. There were no significant differences between groups in haemodynamic or neuroendocrine responses to DSP.. The study showed that children with nocturnal enuresis exhibit a normal neuroendocrine response to supine posture during daytime indicating that baroregulatory mechanisms per se are not playing a significant pathogenic role. Interestingly, the normal neuroendocrine response to supine posture seems to undergo marked circadian changes, as supine posture at night-time is associated with increased levels of vasoactive hormones.

Topics: Adolescent; Angiotensin II; Blood Pressure; Body Fluids; Child; Circadian Rhythm; Female; Health; Heart Rate; Humans; Male; Neurosecretory Systems; Nocturnal Enuresis; Posture; Supine Position; Vasopressins

Nocturnal polyuria (NP) due to a suppressed vasopressin circadian rhythm is a well-documented pathogenetic mechanism in enuresis, mainly studied in monosymptomatic enuresis. A substantial percentage of patients do not respond to desmopressin. This suggests that NP may not only be related to vasopressin, but that other kidney components play a role. Solute handling and osmotic excretion have been investigated in the past, especially in refractory patients. Nevertheless, data in treatment-naïve populations with information on timing overnight are sparse. This study aims to investigate the diuresis and solute excretion in treatment-naïve patients with or without NP, with emphasis on circadian rhythms.. Retrospective analysis of 403 treatment-naïve children 5-18 years with severe enuresis (> 8 nights/2 weeks). Circadian rhythms were evaluated by a 24-h urine collection in 8 timed portions (4 day, 4 nighttime) at in-home settings. Urine volume, osmolality, and creatinine were measured. Patients were subdivided into three groups according to nocturnal diuresis (ND) and Expected Bladder Capacity (EBCage) ratio: (a) < 100%, (b) 100-129%, (c) > 130%.. All groups maintained circadian rhythm for diuresis and diuresis rates. Patients with higher ND (100-129% and > 130% EBCage) had higher daytime volumes and less pronounced circadian rhythm. In the ND group > 130% EBCage, the ND rate was higher during the first night collection and osmotic excretion was significantly higher overnight.. Overall 24-h fluid intake (reflected by 24-h diuresis) and nutritional intake (24-h osmotic excretion) might play a role in enuresis. Increased diuresis rate early in the night can be important in some patients, whereas the total night volume can be important in others. A higher resolution version of the Graphical abstract is available as Supplementary Information.

Topics: Child; Circadian Rhythm; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Retrospective Studies; Vasopressins; Water

To evaluate the effects of rapid maxillary expansion (RME) on nocturnal enuresis (NE) related to the nasal airway, nasal breathing, and plasma osmolality (as an indicator for antidiuretic hormone).. Nineteen patients with monosymptomatic primary NE, aged 6-15 years, were treated with RME for 10-15 days. To exclude a placebo effect of the RME appliance, seven patients were first treated with a passive appliance. Computed tomography of nasal cavity, rhinomanometric, and plasma osmolality measurements were made 2-3 days before and 2-3 months after the RME period. RME effects on NE were followed for three more years.. Two to three months after the expansion there were significant improvements in the breathing function and a decrease in the plasma osmolality. NE decreased significantly in all patients after the RME period, and all patients showed full dryness after 3 years.. This study demonstrates that RME causes complete dryness in all patients, with significant effects on pathophysiological mechanisms related to NE.

Topics: Adolescent; Airway Resistance; Blood Glucose; Blood Urea Nitrogen; Child; Female; Follow-Up Studies; Humans; Male; Malocclusion; Mouth Breathing; Nasal Cavity; Nocturnal Enuresis; Nose; Osmolar Concentration; Palatal Expansion Technique; Pulmonary Ventilation; Respiration; Rhinomanometry; Snoring; Sodium; Tomography, X-Ray Computed; Vasopressins

Primary monosymptomatic nocturnal enuresis (PMNE) is the most frequent (85%) type of enuresis in children. It remains a diagnostic and therapeutic challenge to establish its etiology and implement a proper treatment.. The aim of the study was to establish the causes of PMNE in children on the basis of own investigations and assess factors having influence over PMNE etiology, which would enable the choice of effective therapy.. The study concerned 85 children with PMNE aged from 5 to 15 years. The patients were under the care of Nephrology Outpatient Clinic at Institute of Mather and Child in years 2009-2014. The detailed medical history, physical examination as well as laboratory investigations of blood and urine, and radiological investigations of the urinary tract, were carried out. Statistical analysis was performed using R software.. In all patients, we have successfully detected the etiology of children of PMNE. The basic, equally frequent (62.3%), PMNE etiopathogenetic factors turned to be: too small bladder capacity resulting from the detrusor hyperactivity, and night polyuria mainly caused by vasopressin deficiency or abnormal eating and hygienic habits, occurring separately or in conjunction with each other. Too small bladder capacity occurred mainly (37.6%, group C) as the only etiological factor of PMNE, and in 24.7% (group A) in a conjunction with nocturnal polyuria due to decreased excretion of vasopressin. Night polyuria was caused by the deficiency of vasopressin in most cases (37.6%) and occurred mainly (24.7%, group D) in a conjunction with small bladder capacity, and rarely alone (12.9%, group B). In 24.7% (group A) it appeared due to eating and hygienic abnormal habits. We have proved statistically significant differences in mean voiding frequency and volume (p<0.0001) between groups A-B and C-D. Mean morning urine specific gravity (p<0.0001) also differed significantly between group C and B (p<0.0001) as well as C and D (p=0.0004).. PMNE in all patients was attributed to specific causes outside the circle of psychological disorders what reduced patient stigmatization. PMNE etiology is very complex and diverse. It still remains a challenge and requires and individual diagnostic and therapeutic approach. Voiding frequency above 8 daily with voiding volumes usually below 100 ml suggest etiology connected with small bladder capacity, while morning urine specific gravities below 1.021 g/ml can be connected with vasopressin deficiency or excessive fluid intake before the bedtime. The developed diagnostic approach along with borderline values are hints that can aid physicians in establishing PMNE causes.

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Medical History Taking; Nocturnal Enuresis; Physical Examination; Urinary Bladder, Overactive; Vasopressins

We analyzed the outcome of nocturnal enuresis after adenotonsillectomy in children with sleep disordered breathing. We also evaluated differences in demographic, clinical, laboratory and polysomnography parameters between responders and nonresponders after adenotonsillectomy.. We prospectively evaluated children 5 to 18 years old diagnosed with sleep disordered breathing (snoring or obstructive sleep apnea syndrome) on polysomnography and monosymptomatic primary nocturnal enuresis requiring adenotonsillectomy to release upper airway obstruction. Plasma antidiuretic hormone and brain natriuretic peptide were measured preoperatively and 1 month postoperatively.. Sleep studies were done in 46 children and 32 also underwent blood testing preoperatively and postoperatively. Mean ± SD patient age was 8.79 ± 2.41 years and the mean number of wet nights weekly was 6.39 ± 1.26. Polysomnography revealed obstructive sleep apnea syndrome in 71.7% of patients and snoring in 28.3%. After adenotonsillectomy 43.5% of patients became dry. Preoperative polysomnography findings indicated that responders, who were dry, had significantly more arousals and obstructive apnea episodes but fewer awakenings than nonresponders, who were wet. Significant increases in plasma antidiuretic hormone and significant decreases in plasma brain natriuretic peptide were seen in all children with no difference between responders and nonresponders. No difference between the groups was noted in age, gender, race, body mass index, constipation, preoperative number of wet nights weekly or type of sleep disordered breathing.. Nocturnal enuresis resolved after adenotonsillectomy in almost half of the children with sleep disordered breathing. Those who became dry had more frequent arousal episodes caused by apnea events than those who remained wet.

Topics: Adolescent; Child; Child, Preschool; Comorbidity; Female; Humans; Hypertrophy; Male; Natriuretic Peptide, Brain; Nocturnal Enuresis; Palatine Tonsil; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Snoring; Tonsillectomy; Vasopressins

To investigate whether primary nocturnal enuresis (PNE) is related to a disturbance in anti-diuretic hormone (ADH) secretion pattern at night which may be genetically inherited.. This study included 121 children aged 6-18 years with PNE and 45 matched healthy children as controls. Enuretic children were subjected to genetic evaluation and cytogenetic assessment (n = 99). Assay of ADH levels (9-11 am & 9-11 pm) was performed for cases (n = 99) and controls.. There was a positive family history in 82.4% (autosomal dominant in 35.4% and autosomal recessive in 64.6%). ADH morning and evening values were reversed in cases vs controls with significant difference in morning level. Reversal of circadian rhythm was present in 71.7% of cases and normal rhythm in 28.3% of them. Morning and evening ADH levels revealed significant difference between patients with reversed rhythm and those with normal one, and with controls. Mode of inheritance had no influence on hormonal level. Chromosomal abnormality was detected in 3 cases with reversed ADH rhythm, involving chromosome 22 in two of them.. PNE could be attributed in part to reversed ADH circadian rhythm which may be linked to chromosome 22.

Topics: Adolescent; Child; Chromosomes, Human, Pair 22; Circadian Rhythm; Family Health; Female; Genes, Dominant; Genes, Recessive; Genetic Testing; Humans; Karyotyping; Male; Nocturnal Enuresis; Pedigree; Vasopressins

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.

Topics: Antidiuretic Agents; Child; Combined Modality Therapy; Humans; Nocturnal Enuresis; Physical Stimulation; Sleep Arousal Disorders; Vasopressins

Decreased nocturnal antidiuretic hormone (ADH) excretion has been suggested to be a causative factor for PNE in children. We investigate the demographic characteristics and nocturnal ADH levels of children with PNE who attended a tertiary referral center and to determine their response to treatment with desamino-D-arginine vasopressin (DDAVP).. We performed a retrospective study in 90 PNE children aged 6-12 years. We recorded the gender, height, weight, number of children per family, and psychosocial problems and compared these findings with the corresponding data obtained from a national survey. We also measured the nocturnal ADH levels and evaluated the response rate to DDAVP.. The number of PNE patients decreased with an increase in age. Enuresis was significantly associated with male gender (P = 0.044) and more number of children per family (P = 0.043). The rates of comorbidity with defecation problems, obesity, attention-deficit hyperactivity disorder (ADHD), and overweight were 36.7, 17.8, 12.2, and 10%, respectively. Although the prevalence of obesity and ADHD was higher among children with PNE, there was no significant difference between PNE patients and their prevalence in the community. The ADH levels at 2 a.m. and 8 a.m. were 0.87 ± 0.75 and 0.89 ± 0.76 pg/ml, respectively. In the 50 (55.5%) patients who received DDAVP treatment, the complete- and partial response rates were 86 and 14%, respectively.. Our data confirmed that PNE was predominant in boys and larger family, and similar to the findings for disease prevalence, the number of children seeking treatment tended to decrease with increasing age. Low ADH levels were recognized as a possible cause of PNE, thereby explaining the good response to DDAVP treatment in Taiwanese children with PNE.

Topics: Age Factors; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Family Characteristics; Female; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Retrospective Studies; Sex Characteristics; Taiwan; Treatment Outcome; Vasopressins

To identify the relationship between nocturnal AVP deficiency, nocturnal polyuria (NP), and low urinary osmolality in children suffering of primary monosymptomatic nocturnal enuresis (NE).. The study included 50 children (28 males and 22 females) with primary monosymptomatic NE and 30 non enuretic children of the same age group (controls). Night samples of blood and urine were obtained for AVP, blood osmolality, and urine osmolality. In addition, volume frequency charts, arousal threshold, and urodynamics were performed for these children.. Twenty eight (56%) of the enuretic children were considered to have NP. Mean AVP level was 44.80 +/- 8.19 and 32.49 +/- 18.25 pg/ml while mean urine osmolality was 865.07 +/- 158.66 mOsm/kg and 700.06 +/- 84.42 mOsm/kg in controls and enuretic group respectively. These differences were highly significant. No significant difference was found between the controls and enuretics without NP. On the other hand, nocturnal AVP and urine osmolality were significantly lower in enuretics with NP when compared to both controls and enuretics without NP. Blood osmolality did not reach statistically significant difference between subgroups. Arousal threshold was significantly higher in enuretic children irrespective to NP. The timing for NE episodes were predominantly late in the night in NE children without NP while patients suffering of NE with NP typically experienced multiple incidents each night.. We have shown that low nocturnal AVP and urine osmolality may play a role in the pathophysiology of enuretics with NP. This abnormality doesn't occur as an isolated disease as these children suffer from arousal defect as well.

Topics: Adolescent; Case-Control Studies; Child; Circadian Rhythm; Diagnostic Techniques, Urological; Female; Humans; Male; Neurophysins; Nocturnal Enuresis; Osmolar Concentration; Polyuria; Predictive Value of Tests; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sleep Arousal Disorders; Urodynamics; Vasopressins

We correlated the circadian rhythm of plasma arginine vasopressin and urine output profile to desmopressin response, presence or absence of an enuretic episode, and age and gender in children with nocturnal enuresis.. We studied 125 children 6 to 17 years old (mean age 10.4 +/- 3 years) with monosymptomatic nocturnal enuresis. Circadian inpatient studies were performed with standardized fluid intake, 7 blood sampling times and 6 urine collection periods. Subsequently, nocturnal urine volume was measured at home by diaper weighing for 4 weeks in 78 patients (2 weeks without treatment followed by 2 weeks of dose titration from 20 to 40 mug desmopressin at bedtime).. The circadian studies showed that all groups of patients had an attenuated arginine vasopressin rhythm, females generally had lower circadian plasma arginine vasopressin levels than males, desmopressin responders with enuresis during the study night had the largest nocturnal urine excretion rate and most pronounced arginine vasopressin deficiency, and nocturnal urine output was significantly greater during nights with enuresis than nights without. Part of this polyuria was caused by increased sodium excretion. The home recordings confirmed higher nocturnal urine volume on enuresis nights.. In addition to providing further pathophysiological support for the role of a nocturnal arginine vasopressin deficiency behind nocturnal polyuria in a subset of patients with enuresis, the results emphasize the clinical value of estimating nocturnal urine production on wet nights before selecting a therapeutic modality.

Topics: Adolescent; Antidiuretic Agents; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Urine; Vasopressins

Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria.. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria.. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate.. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

Topics: Adolescent; Case-Control Studies; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Diuresis; Drug Resistance; Female; Glomerular Filtration Rate; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Polyuria; Prospective Studies; Reference Values; Severity of Illness Index; Sodium; Statistics, Nonparametric; Urodynamics; Vasopressins

Topics: Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Vasopressins