Stesura Seveso 111Archivio Italiano di Urologia e Andrologia 2016; 88, 2 ORIGINAL PAPER The relationship of enuresis nocturna and adenoid hypertrophy Muhsin Balaban 1, Alper Aktas 2, Cuneyd Sevinc 1, Ugur Yucetas 3 1 Medicana International Istanbul Hospital, Urology Clinic, Istanbul, Turkey; 2 Kartal Training and Research Hospital, Urology Clinic, Istanbul, Turkey; 3 Istanbul Training and Research Hospital, Urology Clinic, Istanbul, Turkey. Objectives: This study was organized to assess the relationship of enuresis noctur- na (EN) and upper airway obstruction (UAO) in children. Material and Methods: This study was multi-centrically and prospectively designed including 79 children who presented to a urology clinic with symptoms of EN between January 2013 and February 2014. Sixty-four age-matched children with no history of urological complaints were randomly recruited from children admitted to a pediatric clinic as a control group. All children and parents were asked to fill out a dys- functional elimination syndrome (DES) questionnaire and children were examined by an ear, nose and throat (ENT) specialist to evaluate the UAO. Descriptive statistics, chi- square and Mann-Whitney-U tests were used to compare variables. Results: The mean ages of the 79 children (48 male, 31 female) in the study group and the 64 children (41 male, 23 female) in the control group were 10.14+/-3.38 and 9.17+/- 2.85, respectively. Family history of the study showed that 19% of the children’s mothers, 10% of the children’s fathers and 37% of the children’s siblings had experienced EN. There was a significant difference between the study and the control groups in terms of urge to urinate, bladder emptying, bowel symptoms and psychological stress. There was also a significant difference between rates of tonsillar hypertrophy and nasopharynx obstruction in the EN group (p = 0.009). Conclusion: In this study we found that half of the children with EN had tonsillar hypertrophy, which was significantly higher than in the control group. Further studies are needed to clarify the exact relationship between UAO and EN. KEY WORDS: Adenoids; Enuresis; Tonsillar hypertrophy. Submitted 5 November 2015; Accepted 5 December 2015 Summary No conflict of interest declared. tions related to the physiopathology of EN. It is caused by a hereditary delay in maturation of the somatic mech- anisms such as reduction of nocturnal urine production, relaxation of the bladder during sleep hours and a nor- mal arousal to a full bladder that prevents the child from bedwetting (2). Evidence suggests a possible association with sleep-disordered breathing. Several studies have reported a close relationship between obstructive sleep apnea (OSA) and EN (3). The most common cause of OSA in children is adenotonsillar hypertrophy, and therefore treatment of adenotonsillar hypertrophy is the treatment of choice for OSA (4). Children with upper airway obstruction have increased negative intrathoracic pressure as a result of increased inspiratory effort during sleep. The continual swing in intrathoracic pressure causes cardiac distension that can lead to release of atri- al natriuretic peptide, triggering enuresis (5). In the present study, we aimed to identify the prevalence of adenotonsillar hypertrophy and upper airway obstruc- tion (UAO) in children with and without EN as well as investigate the risk factors associated with EN in chil- dren. MATERIAL AND METHODS This study was multi-centrically and prospectively designed including 79 non-obese children older than 5 years who presented to a urology clinic with symptoms of EN between January 2013 and February 2014. EN was considered to be present when it occurred in the fre- quent grade (3-6 times per month) or the almost always grade (> 3 times per week) (6). EN was defined in accor- dance with the International Children’s Continence Society’s standardized terminology (7). Parents were asked whether their children currently suffer from enuresis and whether they have ever had a dry period of at least six months in order to distinguish primary from secondary enuresis. Only primary EN patients were enrolled in the study. Sixty-four age-matched children with no history of urological complaints were randomly recruited from children admitted to a pediatric clinic as the control group. All EN patients underwent a detailed urological evalua- DOI: 10.4081/aiua.2016.2.111 INTRODUCTION Enuresis nocturna (EN) is a common childhood condi- tion, present in approximately 5-7 million children in the United States. The prevalence of EN decreases with age, but the severity increases (1). It is reported in about 15-20% of 5 year olds, 5-7% of 10 year old, and 1-2% of 15 year old subjects, reaching a plateau of approxi- mately 0.5-1% in adulthood. EN occurs when a child is unable to suppress nocturnal bladder contraction. There have been several explana- Archivio Italiano di Urologia e Andrologia 2016; 88, 2 M. Balaban, A. Aktas, C. Sevinc, U. Yucetas 112 tion and a thorough clinical and neuro- logical examination to rule out an organic etiology. Exclusion criteria were the presence of cerebral palsy, neuro- muscular diseases or any underlying systemic diseases or acute infectious processes. Additional medical history was taken, including duration of illness- es and current therapies. All children and parents were asked to fill out a 35- item questionnaire related to symptoms of dysfunctional elimination syndrome (DES) such as diurnal/nocturnal enure- sis, voiding habits, urgency, frequency, squatting and bowel movements. The questionnaire consisted of two parts: the first part included 21 multiple- choice questions for the child while the second part consisted of 14 questions asked to the parents. Eight questions included in the first part were also directed to the parents to test whether the children could correctly express their complaints. This confirmed the children’s accuracy in answering the questions and ability to understand the problem. The second part had six addi- tional questions for the parents about the frequency of urinary tract infection, school performance and stressful events. Parents and children were requested to fill out the form completely. Ear, nose and throat (ENT) exami- nation were done by an ENT surgeon to assess obvious hypertrophied adenoids and tonsils clinically. Descriptive statistics, chi-square and Mann-Whitney-U tests were used to compare variables. RESULTS The mean ages of the 79 children (48 male, 31 female) in the study group and the 64 children (41 male, 23 female) in the control group were 10.14+/-3.38 and 9.17+/-2.85, respectively. Forty-one males in the study group and 33 males in the control group were circum- cised. Thirty-three of the 79 children in the study group and 22 of the 64 children in the control group were at pubertal ages. Family history of the study group showed that 19% of the children’s mothers, 10% of the children’s fathers and 37% of children’s siblings had experienced EN. According to first 9 questions about urgency symptoms in the DES questionnaire, the study group’s score was 5.65+/-3.50 and the control group’s score was 1.31+/-2.15 (p < 0.0001). The scores of bowel symptoms (DES questions 10-15) were 2.11+/-1.37 for the study group and 1.61+/- 1.52 for the control group (p < 0.006). The scores of psy- chological stress (DES questions 30-31) were 3.02+/-0.88 in the study group and 2.30+/-0.87 in the control group (p < 0.0001). The total scores of the DES questionnaire were 33.24+ 7-11.97 in the study group and 13.02+/-8.83 in the control group (p < 0.0001) (Table 1). There was also a significant difference between tonsillar hypertrophy and nasopharynx obstruction in the EN group (p = 0.009) (Table 2). Of the 79 EN patients, 46 (58.2%) had mono- symptomatic enuresis (ME) whereas 33 of 79 (41.8%) had nonmonosymptomatic enuresis (NME). DISCUSSION EN is the involuntary loss of urine during the night in the absence of organic disease. It is a very common pedi- atric issue and the number of children who may suffer from this condition is estimated at 3.8% to 25%. In con- trast to the relatively high percentage seen among chil- dren, only 1% to 2% of adults suffer from this disorder. This difference is a result of the increasing number of children who spontaneously achieve nighttime bladder control. Current data suggest an annual healing rate of 15% (8). EN can present as monosymptomatic enuresis (ME) or nonmonosymptomatic enuresis (NME); this classifica- tion should be done before any kind of therapy protocol is initiated due to different treatment approach. The most important criterion of ME is the absence of bladder dys- function, whereas NME is defined by the concomitance of bladder dysfunction such as urge incontinence or dys- functional voiding. True ME is found in less than one- half of all cases of enuretic children (9). In our study, we Enuresis (n = 79) Control (n = 64) p Mean age (years) 10.14 ± 3.38 9.17 ± 2.85 0.106* Gender 48 M/31 F 41 M/23 F 0.685** Prepicium 41 Circumsised/7 Intact 33 Circumsised/8 Intact 0.536** Puberty 33 Pubertal/46 Prepubertal 22 Pubertal/42 Prepubertal 0.366** US 5.65 ± 3.50 1.31 ± 2.15 < 0.0001* BS 2.11 ± 1.37 1.61 ± 1.52 0.006* OS 1.87 ± 1.49 1.34 ± 1.17 0.041* P 4.11 ± 2.42 0.59 ± 1.17 < 0.0001* PS 3.02 ± 0.88 2.30 ± 0.87 < 0.0001* IS 0.17 ± 0.47 0 - HF 2.41 ± 2.22 0 - Total 33.24 ± 11.97 13.02 ± 8.83 < 0.0001* ApB 6.74 ± 3.25 2.20 ± 3.01 < 0.0001* TS 39.98 ± 14.80 15.22 ± 11.75 < 0.0001* Obstruction (+) Obstruction (-) P Enuresis (n = 79) 37 42 (47%) (53%) 0.0009 Control (n = 64) 13 51 (20%) (80%) Table 1. Demographic characteristics of groups and comparison of them according to aquestionnaire for dysfunctional elimination syndrome. Table 2. Compare of groups according to tonsillar hypertrophy and upper airway obstruction. *Mann Whitney Test; **x2 US: Urgency Symptoms (First 9 questions); BS: Bowel Symptoms (10.-15. questions) OS: Obstructive Symptoms (16.-21. questions); P: For Parents to Answer (22.-29. questions) PS: Psychological Stress (30.-31. questions); IS: Infection Symptoms (32.-33. questions) HF: Hereditary Factors (34.-35. questions); Total: First 35 questions score ApB: Appendix B (15 questions); TS: Total Score (Total score of all questions) applied a DES questionnaire to all study and control group members to evaluate EN and its related symp- toms. In this questionnaire, urgency symptoms, bowel symptoms, obstructive symptoms, psychological stress, infection symptoms and hereditary factor were evaluat- ed. We found that 33 (41.8%) cases of enuretic children had ME whereas 46 (58.2%) cases had NME. The genitourinary tract and the gastrointestinal system are interdependent, sharing the same embryological ori- gin, pelvic region and sacral innervations. Although chil- dren with voiding disturbances often present with bowel dysfunction, until recently this coexistence was consid- ered coincidental. However, it is now accepted that dys- function of emptying of both systems, in the absence of anatomical abnormality or neurological disease, are interrelated (10). Children with DES commonly com- plain of urinary incontinence, NME, recurrent urinary tract infections, extreme urgency to void and exception- al urinary frequency. The prevalence of DES in children free of urinary tract infection as been estimated to be 21% (11). The exact etiology of nocturnal enuresis is multifactorial; however, ME has a significant correlation with hereditary factors, arousal problems, overnight polyuria and overac- tive detrusor activity. In our study, EN patients had signif- icant family histories of enuresis, mostly in their siblings. OSA in children is characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction that disrupt normal ventilation during sleep and sleep patterns (12). Goldbart et al. suggested an OSA sufferer repeatedly slips from deep sleep to light sleep, and when this happens, the bladder sphincter relaxes, releasing urine (13). Adults with OSA have been shown to have elevated atri- al natriuretic peptide (ANP), decreased antidiuretic hor- mone (ADH) (14) and no normal decrease in nocturnal urinary output (15). OSA causes oxygen desaturation, which influences the normal secretion of ADH, leading to the change in nocturnal urine volume. Normally the nocturnal secretion of ADH slows nighttime urine pro- duction and prevents nocturia; inappropriate secretion of ADH results in an inability to concentrate the urine, leading to excess urine secretion and bedwetting (16). There is a positive correlation between plasma ANP lev- els and the degree of change in intrathoracic pressure. This correlation may result from elevated preload and atrial volume caused by a more negative intrathoracic pressure, thus stimulating ANP production in OSA patients. Foxman et al. demonstrated a higher occurrence of EN among children with OSA than reported in otherwise healthy pediatric patients (17). According to Weissbach et al., UAO in children is greatly associated with nocturnal enuresis (4). In contrast to previous studies, Aydin et al. did not find any association between adenoid hypertro- phy and nocturnal enuresis (18). The most common cause of OSA in children is adeno- tonsillar hypertrophy and UAO. Waleed et al. showed a relief of EN by removing the UAO which was the cause of OSA and also a reduction in the total and night urine volume and improvement in nocturnal oxygen desatura- tion (19). Firoozi et al. showed the complete resolution of EN in 31-76% of OSA patients within months after ton- sillectomy and/or adenoidectomy (T&A) (20). In this study, half of the EN children had UAO and ton- sillar hypertrophy; this rate is significantly higher than that of the control group. CONCLUSION Children with EN have deep sleep and high arousal lev- els due to hypoxia caused by upper airway obstruction. This study showed that children with EN have more ade- noid hypertrophy and UAO compared with the control group. Children with EN should be referred to ENT sur- geons for possible UAO and tonsillar hypertrophy evalu- ation. Prospective controlled studies are needed to fur- ther clarify these issues and the possible effect of T&A treatment on the EN. REFERENCES 1. Yeung CK, Sreedhar B, Sihoe JD, et al. Differences in characteris- tics of nocturnal enuresis between children and adolescents: a criti- cal appraisal from a large epidemiological study. BJU Int. 2006; 97:1069-73. 2. Hjalmas K. Nocturnal enuresis: basic fact and new horizons. Eur Urol 1993; 33 Suppl 3:53-57. 3. Brooks LJ, Topol HI. Enuresis in children with sleep apnea. J Pediatr. 2003; 142:515-8. 4. Weissbach A, Leiberman A, Tarasiuk A, et al. Adenotonsilectomy improves enuresis in children with obstructive sleep apnea ayn- drome. Int J Pediatr Otorhinolaryngol. 2006; 70:1351-6. 5. Ritting S, Knudsen UB, Norgaard JP,, et al. Diurnal variation of plasma atrial natriuretic peptide in normals and patients with enuresis nocturna. Scand J Clin Lab Invest. 1991; 51:209-17. 6. Hjalmas K, Arnold T, Bower W. Nocturnal enuresis an interna- tional evidence based management strategy. J Urol. 2004; 171:2545-61. 7. Neveus T, Von Gontard A, Hoebeke P,, et al. The standardization of terminology of lower urinary tract function in children and adoles- cents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2006; 176:314-24 8. Robson WL. Clinical practice. Evaluation and management of enuresis. N Engl J Med. 2009; 360:1429-1436. 9. Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol. 2010; 183:441-447. 10. Feng WC and Churchill BM. Dysfunctional elimination syn- drome in children without obvious spinal cord disease. Pediatr Clin North Am. 2001; 48:1489-504. 11. Shaikh N, Hoberman A, Wise B, et al. Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteric reflux. Diagnosed early in life? Pediatrics. 2003; 112:1134-7. 12. Rosen CL. Obstructive Sleep Apnea syndrome (OSAS) in chil- dren: diagnostic challanges. Sleep. 1996; 19:274-277. 13. Goldbart DA, Levitas A, Greenberg-Dotan S, et al. B-type natri- uretic peptide and cardiovascular function in young children with apnea. Chest. 2010; 138:528-535. 113Archivio Italiano di Urologia e Andrologia 2016; 88, 2 Enuresis nocturna and adenoid hypertrophy Archivio Italiano di Urologia e Andrologia 2016; 88, 2 M. Balaban, A. Aktas, C. Sevinc, U. Yucetas 114 14. Krieger J, Follenius M, Sforza E, et al. Effects of treatment with nasal continues positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnea. Clin Sci. 1991; 80:443-449. 15. Ichioka M, Hirata Y, Inase N, et al. Changes of circulating atri- al natriuretic peptide and antidiuretic hormone in obstructive sleep apnea syndrome. Respiration 1992; 59:164-168. 16. Kaditis AG, Finder J, Alexopoulos EI, et al. Sleep-Disordered breathing in 3680 Greek children. Pediatr Pulmonol. 2004; 37:499-509. 17. Foxman B, Valdez RB, Brook RH. Childhood enuresis: preve- lance, perceived impact, and prescribed treatments. Pediatrics. 1986; 77:482-487. 18. Aydin S, Sanli A, Celebi O, et al. Prevelance of adenoid hypertro- phy and nocturnal enuresis in primary school children in Istanbul, Turkey. Int Jof Pediatr Otorhinolaryngol. 2008; 72:665-668. 19. Waleed FE, Samia FA, Samar M. Impact of sleep-disordered breathing and its treatment on children with primary nocturnal enuresis Swiss Med Wkly. 2011; Jul 1;141:w13216. 20. Firoozi F, Batniji R, Aslan AR, et al. Resolution of diurnal incon- tinence and nocturnal enuresis after adenotonsillectomy in children. J Urol. 2006; 175:1885-8. Correspondence Muhsin Balaban, MD (Corresponding Author) muhsinbalaban1980@yahoo.com Cuneyd Sevinc, MD cuneydsevinc@yahoo.com Medicana International Istanbul Hospital, Urology Clinic, Yeni mah., Pegagaz Sok. Soyak Evreka:A5-44, Soganlik, Kartal 34880 Istanbul, Turkey Alper Aktas, MD dralperaktas@hotmail.com Kartal Training and Research Hospital, Urology Clinic, Istanbul, Turkey Ugur Yucetas, MD dryucetas@yahoo.com Istanbul Training and Research Hospital, Urology Clinic, Istanbul, Turkey