Investigation of vitamin D and thyroid hormone levels in children

Received (Başvuru tarihi): 01.02.2022 Accepted (Kabul tarihi): 27.03.2022 Online (Online yayınlanma tarihi): 20.04.2022

Correspondence (İleşim): Dr. Muhammet Hamza Halil Toprak. Başakşehir Çam ve Sakura Şehir Hastanesi, Çocuk Kardiyolojisi Bilim Dalı,

İstanbul, Türkiye.

Phone (Tel): +90 212 909 60 00 e-mail (e-posta): muhammedhamzatopr[email protected]

ORCID ID

M.H.H.T.: 0000-0003-4579-963X; M.Ç.: 0000-0002-0381-8145; G.T.: 0000-0001-6682-3083; M.E.: 0000-0002-0510-965X

Başakşehir Çam ve Sakura Şehir Hastanesi, Çocuk Kardiyolojisi Kliniği, İstanbul, Türkiye

Bahçelievler Memorial Hastanesi, Çocuk Nefrolojisi Kliniği, İstanbul, Türkiye

Sağlık Bilimleri Üniversitesi, Haseki Eğim ve Araşrma Hastanesi, Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul, Türkiye

JOUR UMRANIYE PEDIATR

2022;2(1):15–18 doi: 10.14744/upd.2022.32042

ORIGINAL ARTICLE

Pediatric Endocrinology

Invesgaon of vitamin D and thyroid hormone

levels in children with enuresis nocturna

Muhammet Hamza Halil Toprak,

Mahmut Çivilibal,

Gülşah Toprak,

Murat Elevli

Department of Pediatric Cardiology, Başakşehir Çam and Sakura City Hospital, İstanbul, Turkey

Department of Pediatric Nephrology, Memorial Bahçelievler Hospital, İstanbul, Turkey

Department of Pediatrics, University of Health Sciences Turkey, Haseki Training and Research Hospital, İstanbul, Turkey

ABSTRACT

Objecve: The present study aims to invesgate the levels of 25 (OH)

D vitamins, thyroxine (T4), and thyroid-smulang

hormone (TSH) levels in children diagnosed with monosymptomac Enuresis Nocturna (MEN), and any potenal relaonship

between these levels and the disorder.

Material and Methods: 49 children with Primary Monosymptomac Enuresis Nocturna (PMEN) who applied to our pediatric

departments were included in the study. Paents with secondary enuresis associated with chronic diseases were excluded.

The study took place between February 2012–July 2013. 99 healthy children with age and gender distribuon similar to the

enuresis group were included in the study as well, as the control group. Complete urine analysis and complete blood cell

count were performed on all the children, and their urea, creanine, glucose, serum electrolyte levels, 25 (OH)

vitamin D,

and thyroid hormone levels were measured.

Results: Compared to children who don’t wet themselves, children with MEN were found to have stascally higher 25 (OH)

Vitamin D levels (p<0.001), while the two groups were found to have similar glucose, urea, creanine, sodium, potassium,

hemoglobin, TSH and fT4 values.

Conclusion: In the present study where the paent count was relavely low, no relaonship could be established between enuresis

thyroid hormone levels. Vitamin D levels were signicantly higher in Enuresis group. Yet we sll humbly believe that our study will

provide valuable reference data for future studies which will inspect 25 (OH) Vitamin D levels and urine calcium levels together.

Keywords: Nocturnal enuresis; vitamin D; thyroid hormones.

Cite this arcle as: Toprak MHH, Çivilibal M, Toprak G, Elevli M. Invesgaon of vitamin D and thyroid hormone levels in children with

enuresis nocturna. Jour Umraniye Pediatr 2022;2(1):15–18.

JOUR UMRANIYE PEDIATR 2022;2(1):15–18

INTRODUCTION

Primary monosymptomac enuresis nocturna (PMEN) is de-

ned as frequent urinaon into clothes or bed at least two mes

per week for three successive months in children ≥5 years old

who have not acquired urinary connence (1).

The physiology of enuresis nocturna has not been fully revea-

led. Low bladder capacity, sleep disorders, deciencies in an-

diurec hormone secreon during the night, and consequently

increased urinary producon have been suggested as primary

mechanisms. Such inconnence has been associated with ge-

nec disposion, male gender, low socioeconomic status, crow-

ded families, and diculty in waking up (2–5).

Thyroid hormones are known to inuence numerous mechanis-

ms of the body. It is possible to surmise that changes in thyroid

hormone levels might have a connecon with enuresis, consi-

dering their inuence on the sleep cycle (2).

Meanwhile, changes in vitamin D levels can inuence calcium

levels in urine besides the well-established neuromuscular ef-

fects. As such, this study aimed to invesgate the levels of 25

(OH)

vitamin D, thyroxine (T4), and thyroid-smulang hormo-

ne (TSH) levels in children diagnosed with monosymptomac

enuresis nocturna (MEN) and any potenal relaonship betwe-

en these levels and the disorder.

MATERIAL AND METHODS

Forty-nine children with PMEN who applied to our pediatric

departments were included in the study. Paents with secon-

dary enuresis associated with chronic diseases were excluded.

The study took place between February 2012 and July 2013.

Ninety-nine healthy children with age and gender distribuon

similar to the enuresis group were included in the study as well,

as the control group. Complete urine analysis and complete

blood cell count were performed on all the children, and their

urea, creanine, glucose, serum electrolyte levels, 25 (OH)

vi-

tamin D, and thyroid hormone levels were measured.

Vitamin D level measurements were seasonally similar in the

enuresis and control groups. It is worth menoning here that

none of the paents in any of the groups were medicated with

vitamin D or any form of mulvitamin supplements. Similarly,

paents in the enuresis group were under no medicaon that

would aect levels of thyroid hormones and electrolytes.

Biochemical analyses were performed using an Abbo C-16000

chemical analyzer. Glucose levels were measured using the

photometric hexokinase method, urea levels were determined

using the photometry method, and creanine level was deter-

mined using a photometrical modied Jae method. Sodium

and potassium levels were determined using the ion-selecve

electrode method. The high-pressure liquid chromatography

method was used to determine 25 (OH)

vitamin D levels, whi-

le free T3, free T4, and TSH levels were determined using the

chemiluminescent microparcle immunological assay (CMIA,

Architect system, Abbot Diagnoscs) method. The hemograms

were obtained using a Bayer diagnosc ADVIA 120 device.

Stascal analyses were performed using the SPSS (Stascal Pa-

ckage for Social Sciences, Inc., Chicago, IL, USA) for Windows ver-

sion 16.0 package soware. Frequency analysis was performed

for all the data obtained as part of the study, and median and

standard deviaon values were calculated. To determine the pre-

sence of any signicance between the groups, the Mann–Whit-

ney U test was used when the data did not show a homogenous

distribuon, and Student’s t-test when they did. Our study was

conducted in accordance with the Declaraon of Helsinki. The

ethics commiee approval was obtained from the local hospital.

Enürezis nokturnalı çocuklarda roid hormonları ve D vitamini

düzeylerinin araşrılması

ÖZET

Amaç: Bu çalışmada monosemptomak nokturnal enürezis tanılı çocuklarda 25 (OH)

D vitamini, roksin (T4) ve roid smulan hormon (TSH) düzeylerinin

çalışılması ve hastalıkla ilişkisinin saptanması amaçlanmışr.

Gereç ve Yöntemler: Çalışmamıza çocuk polikliniğinimize başvuran 5–15 yaş arasındaki 49 primer monosemptomak nokturnal enürezisli çocuk alındı.

Kronik hastalıklara bağlı sekonder enürezisli hastalar çalışmadan çıkarıldı. Araşrmamız Şubat 2012, Temmuz 2013 tarihinde bir buçuk yıl süre ile yapıldı.

Çalışmaya kontrol grubu olarak, çalışma grubu ile benzer yaş ve cinsiyeeki 99 sağlıklı çocuk alındı. Laboratuar ölçümlerinde hastaların tam kan sayımları,

böbrek fonksiyon testleri, kan elektrolitleri, kan glukoz değerleri, tam idrar tetkikleri, 25 (OH) vitamin D ve roid hormon düzeylerinin ölçümü yapıldı.

Bulgular: Alnı ıslatmayan çocuklarla karşılaşrıldığında MNE’li çocukların 25(OH) D vitamini düzeylerinin anlamlı düzeyde yüksek olduğu; glukoz, üre,

kreanin, sodyum, potasyum, hemoglobin, TSH ve fT4 düzeylerinin iki grupta benzer olduğu belirlendi.

Tarşma: Göreceli olarak vaka sayısının az olduğu çalışmamızda, enürezis roid hormonları arasında bir ilişki saptayamadık. Çalışmamızda D vitamini

düzeyleri Enürezis grubunda anlamlı olarak yüksek. Fakat bunun hangi mekanizmayla Enürezise sebep olduğu belirlenemedi. Çalışmamızın D vitamini ve

hiperkalsiüri düzeylerinin birlikte değerlendirileceği çalışmalara dayanak sağlayacağını düşünüyoruz.

Anahtar Kelimeler: Noktürnal enürezis; D vitamini; roid hormonları.

Toprak et al., Vitamin D and thyroid hormons in

RESULTS

Of the 148 children included in the study, 76 were males and 72

were female. The demographic properes of the enuresis and

control groups are provided in Table 1.

In children with enuresis nocturna, the parameters of being

male and history of enuresis in the family were found to be hi-

gher compared with the children of the control group, and the

dierence was stascally signicant (p<0.05 and p<0.001, res-

pecvely, Table 1).

Biochemical survey and full blood cell count results for enuresis

and control group children are provided in Table 2.

Compared with children who do not wet themselves, children

with MEN were found to have stascally higher 25 (OH)

vita-

min D levels (p<0.001, Fig. 1), while the two groups were found

to have similar glucose, urea, creanine, sodium, potassium,

hemoglobin, TSH, and fT4 values.

DISCUSSION

Numerous studies were performed on enuresis nocturna. In the

present study, the aim was to compare the serum TSH, free T4,

and 25 (OH)

vitamin D levels of children with enuresis with that

of healthy children and to determine if there were any meanin-

gful dierences between the values.

Thyroid hormones cause an increase in the eciency and con-

centraon of enzymes, structural/transporter proteins, and other

similar agents within almost every type of cell, and increase the

number and acvity of the mitochondria. They also smulate

Na+–K+-ATPase enzyme acvity and increase the pace at which

ions are transported through the cell wall. Thyroids further inc

rease most endocrine gland secreon and net basal metabolism

rates. These hormones have general and specic inuences on

the growth and development of the organism. In fetal life and the

rst years aer birth, they play a signicant role in the growth and

development of the nervous system. They are also required for

opmal growth and development during puberty (to ensure nor

mal sexual development and ferlity). Our study was based on

the idea that hormones with such eects could have a potenal

inuence over urinary system development, which in turn might

aect whether a child wets him/herself during the night or not.

In addion to urinary system development, thyroid hormones

can also have eects on the central nervous system and sleep

physiology especially when bedweng is a problem during sle-

ep (2). This fact formed an addional basis for our study.

In this study, no meaningful dierence was determined betwe-

en the TSH and free T4 levels of the paent and control groups.

No study was encountered in the literature that surveyed TSH

and/or thyroid hormones in children with enuresis nocturna.

One study stands apart regarding the subject, which belongs

to Meir et al. (6) presenng a case of a 9-year-old enuresis noc-

turna paent with hyperthyroidism. The study claimed for this

case was that the central control mechanisms of enuresis were

temporarily disabled, leading to inconnency during sleep. This

situaon requires more inquiry through wide-scope studies.

Enuresis Control p

group group

(n=49) (n=99)

Gender (M/F) 33/16 43/56 0.006

Age (years) 9.3±2.4 9.7±3.4 0.393

Height (cm) 140.2±12.7 135.8±13.0 0.165

Weight (kg) 37.6±10.8 36.6±10.9 0.703

Parental consanguinity (yes/no) 13/27 11/18 0.728

History of enuresis in family (yes/no)

35/5 16/13 <0.001

Table 1. Comparison of the demographic properes of

the children with primary monosymptomac enuresis

nocturna and the control group

Enuresis Control p

group group

(n=49) (n=99)

Glucose (mg/dL) 89.4±9.7 86.0±8.3 0.324

Urea (mg/dL) 24.1±5.3 22.2±5.4 0.065

Creanine (mg/dL) 0.4±0.1 0.5±0.5 0.078

Sodium (mEq/L) 139.0±3.0 139.5±2.5 0.293

Potassium (mEq/L) 4.4±0.4 4.4±0.5 0.622

Hemoglobin (g/dL) 12.3±1.1 12.6±1.1 0.122

25 (OH)

vitamin D 41.8±20.0 28.7±13.6 <0.001

TSH 2.8±2.2 2.4±1.6 0.265

Free T4 0.9±0.1 0.9±0.8 0.373

Table 2. Comparison of blood parameters between groups

Figure 1. Comparison of serum 25(OH) vitamin D levels.

140

120

100

Vitamin D

Group

Enuresis Control

JOUR UMRANIYE PEDIATR 2022;2(1):15–18

The eects of vitamin D are reported not only for regulang cal-

cium homeostasis to maintain bone health but also for pro-a-

poptoc, an-inammatory, and immune-modulang proper-

es. Epidemiological studies performed in recent years have

shown that low vitamin D levels increase cancer incidences and

cardiovascular mortality and accompanied autoimmune disea-

ses such as diabetes and mulple sclerosis. Furthermore, the

fact that vitamin D has signicant eects on encephalic func-

ons and the muscular system has led to the idea might also be

inuenal over enuresis.

The only study that invesgated a potenal relaonship betwe-

en enuresis and vitamin D was performed by Li et al. (7) in China.

The study included a total of 240 enurec children (ages varying

between 5 and 7 years) and, contrary to our study, determined

that 25 (OH)

vitamin D levels were signicantly lower in enu-

rec children compared with the control group. Our study was

performed in children with ages varying between 5 and 14 ye-

ars, and the 25 (OH)

vitamin D levels of enurec children were

higher compared with their healthy counterparts. We believe

that the dierence between the two studies can be aributed

to the dierences in age, race, and geographical condions of

the children involved.

Many studies showed that hypercalcinuria can cause enuresis.

In their study, Vachvanichsanong et al. (8) determined that 23%

of children with hypercalcinuria had inconnence. The reason

for this is described as the irritaon of the bladder with calci-

um crystals, and the bladder contracons and relaxaon of the

bladder outlet are associated with such irritaons. The study

also reports that treatment of hypercalcinuria signicantly re-

duces urinary inconnence.

In another study by Civilibal et al., (9) the calcium excreon

through the urine of 120 children (between 7 and 14 years of

age) with MPEN was measured. The aim of this study was to

determine if any connecon existed between hypercalcinuria

and enuresis. The study revealed that a signicant poron of

the children had hypercalcinuria, and the researchers sugges-

ted that such children should be monitored in terms of urine

calcium levels.

Despite numerous studies focusing on the relaonship betwe-

en hypercalcinuria and enuresis, no study regarding the poten-

al correlaon between high 25 (OH)

vitamin D levels and enu-

resis. It is unfortunate that our previous study did not inspect

the vitamin D levels, while the present study did not measure

urine calcium levels. Yet we sll humbly believe that the results

obtained in our study will provide valuable reference data for

future studies which will inspect 25 (OH)

vitamin D levels and

urine calcium levels together.

Ethics Commiee Approval: The Haseki Training and Research Hospi-

tal Clinical Research Ethics Commiee granted approval for this study

(date: 16.01.2012, number: 33).

Informed Consent: Wrien informed consent was obtained from the

families of the paents who parcipated in this study.

Conict of Interest: No conict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received

no nancial support.

Authorship Contribuons: Concept – MÇ, MHHT; Design – GT, MHHT;

Supervision – MÇ, ME; Fundings – GT, ME; Materials – MHHT, GT; Data

collecon and/or processing – MHHT, GT; Analysis and/or interpreta-

on – MHHT, GT, MÇ, ME; Literature review – MHHT, GT, MÇ, ME; Wri-

ng – MHHT, MÇ; Crical review – MHHT, GT, MÇ, ME.

Ek Kurul Onayı: Haseki Eğim ve Araşrma Hastanesi Klinik Araş-

rmalar Ek Kurulu’ndan bu çalışma için onay alınmışr (tarih:

16.01.2012, sayı: 33).

Hasta Onamı: Yazılı hasta onamı bu çalışmaya kalan hastaların ailele-

rinden alınmışr.

Çıkar Çaşması: Yazarlar çıkar çaşması bildirmemişlerdir.

Mali Destek: Yazarlar bu çalışma için mali destek almadıklarını beyan

etmişlerdir.

Yazarlık Katkıları: Fikir – MÇ, MHHT; Tasarım – GT, MHHT; Denetmele –

MÇ, ME; Kaynaklar – GT, ME; Malzemeler – MHHT, GT; Veri Toplanması

ve/veya İşlemesi – MHHT, GT; Analiz ve/veya Yorum – MHHT, GT, MÇ,

ME; Literatür Taraması – MHHT, GT, MÇ, ME; Yazıyı Yazan – MHHT, MÇ;

Eleşrel İnceleme – MHHT, GT, MÇ, ME.

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