ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 7 Issue : 2 Year : 2024
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Turkish Society for Pediatric Endocrinology and Diabetes
JOURNAL OF CLINICAL RESEARCH IN PEDIATRIC ENDOCRINOLOGY - J Clin Res Pediatr Endocrinol: 7 (2)
Volume: 7  Issue: 2 - 2015
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REVIEW
2.The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia
Klára Rozenková, Maria Güemes, Pratik Shah, Khalid Hussain
doi: 10.4274/jcrpe.1891  Pages 86 - 97
Insulin secretion from pancreatic ß-cells is tightly regulated to keep fasting blood glucose concentrations within the normal range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is a heterozygous condition in which insulin secretion becomes unregulated and its production persists despite low blood glucose levels. It is the most common cause of severe and persistent hypoglycaemia in neonates and children. The most severe and permanent forms are due to congenital hyperinsulinism (CHI). Recent advances in genetics have linked CHI to mutations in 9 genes that play a key role in regulating insulin secretion (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A and HNF1A). Histologically, CHI can be divided into 3 types; diffuse, focal and atypical. Given the biochemical nature of HH (non-ketotic), a delay in the diagnosis and management can result in irreversible brain damage. Therefore, it is essential to diagnose and treat HH promptly. Advances in molecular genetics, imaging methods (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic surgery) have completely changed the management and improved the outcome of these children. This review provides an overview of the genetic and molecular mechanisms leading to development of HH in children. The article summarizes the current diagnostic methods and management strategies for the different types of CHI.

ORIGINAL ARTICLE
3.Normative Data of Thyroid Volume-Ultrasonographic Evaluation of 422 Subjects Aged 0-55 Years
Ömer Aydıner, Elif Karakoç Aydıner, İhsan Akpınar, Serap Turan, Abdullah Bereket
doi: 10.4274/jcrpe.1818  Pages 98 - 101
Objective: To establish local normative data of thyroid volume assessed by ultrasonography in subjects aged 0-55 years living in İstanbul, Turkey.
Methods: Subjects without any known history of thyroid disease, of major surgery and/or chronic disease were enrolled in the study and evaluated by physical examination and thyroid ultrasonography. Thyroid gland and isthmus at usual location, each lateral lobe volume with three dimensions, ectopic thyroid tissue and echogenicity of the gland were assessed.
Results: Initially, 494 subjects were enrolled in the study. Subjects showing heterogeneous thyroid parenchyma (n=21) and/or nodule (n=51) in ultrasonography were excluded. Final analysis covered 422 subjects (216 males, 206 females). Thyroid volume was found to significantly correlate with height, weight, age and body surface area (r=0.661, r=0.712, r=0.772 and r=0.779, respectively; p<0.0001 for all). These correlations were even stronger in subjects younger than 18 years (r=0.758, r=0.800, r=0.815 and r=0.802, respectively; p<0.0001 for all).
Conclusion: The study provides updated reference norms for thyroid volume in Turkish subjects which can be used in the diagnosis and follow-up of patients with thyroid diseases.

4.The Effects of Six-Month L-Thyroxine Treatment on Cognitive Functions and Event-Related Brain Potentials in Children with Subclinical Hypothyroidism
Özlem Sangün, Serpil Demirci, Nihal Dündar, Özgür Pirgon, Tuğba Koca, Melike Doğan, Bumin Dündar
doi: 10.4274/jcrpe.1684  Pages 102 - 108
Objective: The aim of this study was to investigate the cognitive status of children with subclinical hypothyroidism (SH) before and after L-thyroxine (L-T4) treatment using event-related potentials (ERPs) and neuropsychological tests.
Methods: This prospective study was conducted on a series of 20 children with mild SH (free T4 normal and thyroid-stimulating hormone level within 5-10 µIU/L) who underwent clinical and cognitive assessment before L-T4 treatment and 6 months afterwards. The recordings of ERPs were done at the time of diagnosis and after 6 months of euthyroid state. Neuropsychiatric tests for attention, perception, close and remote memory were performed on all patients and on the control group which consisted of 20 healthy children of normal intelligence.
Results: While pretreatment verbal memory (VM) and verbal recall (VR) scores of the SH group were significantly lower than those of the control group (p=0.004 and 0.012, respectively), no significant differences between the post-treatment and control groups were found in these scores after 6 months of L-T4 treatment. Post-treatment VM and VR scores were significantly higher than the pretreatment scores in the SH group (p=0.008 and p=0.0001). There were no significant differences between the pre-and post-treatment values of electrophysiological evaluation in N1, P2, P3 latencies or P3 amplitude (p>0.05), although there was a significant decrease in N2 latency in the post-treatment group (p=0.03).
Conclusion: SH affects cognition in children and L-T4 replacement therapy leads to normalization of cognitive functions. Neuropsychological tests can be used as complementary measures in the evaluation of children with SH. Determining the association between ERPs and SH would contribute to the comprehensive evaluation of these children.

5.Evaluation of Pre-Treatment and Post-Treatment S100B, Oxidant and Antioxidant Capacity in Children with Diabetic Ketoacidosis
Cemil Kaya, Ali Ataş, Nurten Aksoy, Esra Celen Kaya, Mahmut Abuhandan
doi: 10.4274/jcrpe.1716  Pages 109 - 113
Objective: The study aimed to evaluate the pre-treatment and post-treatment oxidant capacity, antioxidant capacity and S100B protein levels in cases of diabetic ketoacidosis (DKA).
Methods: The study included 49 pediatric patients diagnosed with DKA and a control group comprising 49 healthy children. Blood samples were obtained after confirmation of the DKA diagnosis and also after treatment. S100B, total oxidant (TOL) and total antioxidant levels (TAL) were measured and the oxidative stress index (OSI) was calculated.
Results: When the pre-treatment and post-treatment values of patients with DKA were compared with those of the healthy control group, the S100B level, TOL, TAL and OSI were found to be significantly higher in the diabetes group (p<0.001). Pre-treatment TOL and TAL were also significantly higher than post-treatment levels (p<0.001), while no statistically significant difference was found in the S100B levels or the OSI (p>0.05).
Conclusion: We believe that long-term exposure to high blood glucose concentrations leads to an increase in TOL in patients with DKA and that the neurotransmitter changes that develop in response to this exposure lead to an increase in S100B levels, which is an indicator of neuronal damage.

6.Associations of Prenatal and Perinatal Factors with Cortisol Diurnal Pattern and Reactivity to Stress at Preschool Age Among Children Living in Poverty
Maha E. Elhassan, Alison L. Miller, Delia M. Vazquez, Julie C. Lumeng
doi: 10.4274/jcrpe.1685  Pages 114 - 120
Objective: To examine the association of pre- and perinatal factors with diurnal cortisol pattern and reactivity to a stressor at preschool age among children living in poverty.
Methods: Preschool aged children (n=275) provided saliva samples 3 times per day for 3 days to assess circadian rhythmicity (intercept and slope reflected diurnal pattern) and during a behavioral stress elicitation protocol to measure reactivity (5 samples before, during and after the stressor). Pre- and perinatal predictors were pregnancy weight gain, pre-pregnancy body mass index (BMI), infant birth weight z-score and gestational age. We ran 7 linear regression models predicting each of the cortisol outcomes including all pre- and perinatal predictors and covariates simultaneously.
Results: Greater pregnancy weight gain predicted higher morning cortisol [b=0.020 (SE 0.007), p=0.003]. Greater pregnancy weight gain also predicted higher cortisol at recovery from the stressor in girls only [ß=0.002 (SE 0.001), p=0.036]. There was no association of pre-pregnancy BMI with any cortisol outcome. Higher birth weight z-score predicted higher morning cortisol in the total sample [ß=0.134 (SE 0.066, p=0.043]. Greater gestational age predicted lower cortisol during peak stress in the sample who underwent cortisol reactivity testing [ß=-0.015 (SE 0.007), p=0.032] and in boys [ß=-0.032 (SE 0.014), p=0.027].
Conclusion: Pre- and perinatal factors are associated with cortisol patterning in offspring at preschool age. The implications for child health require additional studies.

7.Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in Children with Nonalcoholic Fatty Liver Disease
Mehmet Boyraz, Özgür Pirgon, Bumin Dündar, Ferhat Çekmez, Nihal Hatipoğlu
doi: 10.4274/jcrpe.1749  Pages 121 - 127
Objective: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) treatment in obese children with nonalcoholic fatty liver disease (NAFLD).
Methods: One hundred and eight obese (body mass index (BMI) >95th percentile for age and sex) adolescents with NAFLD were included in the study. Mean age of the subjects was 13.8±3.9 years (9-17 yrs). The diagnosis of NAFLD was based on the presence of liver steatosis with high transaminases. The subjects were randomly divided into two groups. Group 1 (PUFA group, n=52) received a 1000 mg dose of PUFA once daily for 12 months and lifestyle intervention. Group 2 (placebo group, n=56) received a recommended diet plus placebo and lifestyle intervention for 12 months. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) from fasting samples.
Results: BMI, fasting insulin levels and HOMA-IR values in both groups decreased significantly at the end of the study. In group 1, 67.8% of the patients had a decrease from baseline in the prevalence of steatosis (p<0.001). Frequency of elevated alanine aminotransferase (ALT) levels (39.2% to 14.2%; p<0.01) and elevated aspartate aminotransferase (AST) levels (25% to 17.8%; p=0.01) decreased significantly in the PUFA group. Following a 12-month diet plus placebo and lifestyle intervention treatment, 40.3% (21) of the patients in the placebo group also showed a decrease in frequency of steatosis (p=0.04) and slight decreases in frequency of elevated ALT levels (38.4% to 28.8%; p=0.01) and AST levels (30.7% to 28.8%; p>0.05).
Conclusion: Our results indicated that n-3 PUFA treatment is safe and efficacious in obese children with NAFLD and can improve ultrasonographic findings and the elevated transaminase levels.

8.Vitamin D Deficiency and Hashimoto’s Thyroiditis in Children and Adolescents: a Critical Vitamin D Level for This Association?
Olcay Evliyaoğlu, Manolya Acar, Bahar Özcabı, Ethem Erginöz, Feride Bucak, Oya Ercan, Mine Kucur
doi: 10.4274/jcrpe.2011  Pages 128 - 133
Objective: Vitamin D has been suggested to be active as an immunomodulator in autoimmune diseases such as Hashimoto’s thyroiditis (HT). The goal of the present study was to investigate the vitamin D status in HT patients.
Methods: This prevalence case-control study was conducted on 90 patients with HT (of ages 12.32±2.87 years) and 79 age-matched healthy controls (11.85±2.28 years). Serum 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in all 169 subjects.
Results: The prevalence of vitamin D deficiency in HT patients (64 of 90; 71.1%) was significantly higher than that in the control group (41 of 79; 51.9%) (p=0.025). Mean serum 25(OH)D3 level in the HT group was significantly lower compared to the control group (16.67±11.65 vs. 20.99±9.86 ng/mL, p=0.001). HT was observed 2.28 times more frequently in individuals with 25(OH)D3 levels <20 ng/mL (OR: 2.28, CI: 1.21-4.3).
Conclusion: Vitamin D deficiency is associated with HT in children and adolescents. Levels lower than 20 ng/mL seem to be critical. The mechanism for this association is not clear.

9.Vitamin D Deficiency in Children and Adolescents in Bağcılar, İstanbul
Meltem Erol, Özgül Yiğit, Suat Hayri Küçük, Özlem Bostan Gayret
doi: 10.4274/jcrpe.1888  Pages 134 - 139
Objective: This study aimed to evaluate the frequency of seasonal 25-hydroxyvitamin D [25(OH)D] deficiency and insufficiency in children and adolescents living in Bağcılar, district of İstanbul city.
Methods: Serum vitamin D levels of 280 children aged 3-17 years old were measured at the end of winter and at the end of summer. Of the total group, vitamin D levels were re-measured in 198 subjects. Vitamin D deficiency was defined as a serum 25(OH)D level less than 15 ng/mL and insufficiency-as levels between 15 and 20 ng/mL. Patients whose vitamin D levels were less than 15 ng/mL at the end of winter were treated with 2000 units/day of vitamin D for 3 months.
Results: In the “end of winter” samples, 25(OH)D deficiency was present in 80.36% of the subjects and insufficiency in 11.79%. In the “end of summer” samples, vitamin D deficiency was detected in 3.44% and insufficiency in 27.75%. Vitamin D levels in the “end of winter” samples were not significantly different between boys and girls, while “end of summer” levels were significantly lower in girls (p=0.015). Sunlight exposure was significantly higher in boys (p=0.011). The group with sufficient dairy product consumption had significantly higher vitamin D levels in both “end of summer” and “end of winter” samples. Limb pain was frequently reported in children with low vitamin D levels in the “end of winter” samples (p=0.001). Negative correlations were observed between vitamin D levels and season and also between vitamin D levels and age.
Conclusion: It is essential to provide supplemental vitamin D to children and adolescents to overcome the deficiency seen especially at the end of winter.

CASE REPORT
10.The First Turkish Case of Hypoparathyroidism, Deafness and Renal Dysplasia (HDR) Syndrome
Hakan Döneray, Takeshi Usui, Avni Kaya, Ayşe Sena Dönmez
doi: 10.4274/jcrpe.1874  Pages 140 - 143
Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant genetic disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. We herein present the first Turkish patient with HDR syndrome, who has a p.R367X mutation. This report indicates that p.R367X is not a mutation specific for the Far Eastern populations and also that urological findings in infants with hypoparathyroidism should be carefully examined because clinical findings relating to the p.R367X mutation may show a variable age of onset.

11.A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course
Emine Çamtosun, Sarah E. Flanagan, Sian Ellard, Zeynep Şıklar, Khalid Hussain, Pınar Kocaay, Merih Berberoğlu
doi: 10.4274/jcrpe.1963  Pages 144 - 147
Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods. The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically. We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

12.A Case of Subclinical Hypothyroidism with Lingual and Right Pretracheal Ectopic Thyroid
Min Sun Kim, Young Hwa Kong, Dae-Yeol Lee
doi: 10.4274/jcrpe.1791  Pages 148 - 150
Ectopic thyroid tissue is most commonly located in a single location, this being the lingual area. Presentation with two ectopic thyroid foci is quite unusual. A girl patient aged 7 years who presented with complaints of two masses in the right anterior neck and submandibular area is reported. Her growth pattern and development were normal. The masses were detected to be dual ectopic thyroid glands by ultrasonography, computed tomography and 99m-technetium pertechnetate thyroid scan. The patient also had subclinical hypothyroidism. She was treated with oral levothyroxine and the masses slightly decreased in size. The repeated thyroid function tests were within the normal limits. Thyroid function tests and imaging studies need to be conducted in all patients with anterior neck masses.

13.Nifedipine in Congenital Hyperinsulinism-A Case Report
Papiya Khawash, Khalid Hussain, Sarah E. Flanagan, Sudip Chatterjee, Dhananjoy Basak
doi: 10.4274/jcrpe.1978  Pages 151 - 154
Congenital hyperinsulinism (CHI) is the commonest cause of persistent hypoglycemia in neonates. Diazoxide is the first-line drug in its treatment, but the more severe cases are usually diazoxide-resistant. Recessive ABCC8 and KCNJ11 mutations are responsible for most (82%) of the severe diazoxide-unresponsive CHI. Oral nifedipine has been effective in isolated cases of CHI. Successful treatment of diazoxide-unresponsive CHI with a combination of octreotide and nifedipine has been reported in a single isolated case so far. We report here a case of diazoxide-resistant CHI due to homozygous ABCC8 nonsense mutation. In this case, hypoglycaemia uncontrolled by pancreatectomy and octreotide alone showed a good response to a combination of nifedipine and octreotide. Octreotide was tapered off by one year age and thereafter the child is euglycaemic on oral nifedipine alone. Continuous glucose monitoring sensor was used as an aid to monitor glycaemic control and was found to be a safe and reliable option reducing the number of needle-pricks in small children.

14.Dermal and Ophthalmic Findings in Pseudohypoaldosteronism
Sabriye Korkut, Emir Gökalp, Ahmet Özdemir, Selim Kurtoğlu, Şafak Demirtaş, Ülkü Gül, Osman Baştuğ
doi: 10.4274/jcrpe.1740  Pages 155 - 158
Pseudohypoaldosteronism (PHA) is defined as a state of resistance to aldosterone, a hormone crucial for electrolyte equilibrium. The genetically transmitted type of PHA is primary hypoaldosteronism. Secondary hypoaldosteronism develops as a result of hydronephrosis or hydroureter. PHA patients suffer from severe hyponatremia and a severe clinical condition due to severe loss of salt can be encountered in the neonatal period. Dermal findings in the form of miliaria rubra can also develop in these patients. With the loss of salt, abnormal accumulation of sebum in the eye due to a defect in the sodium channels can also occur. In this paper, a case of PHA in a newborn showing typical dermatological and ophthalmological findings is presented.

15.An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation
Gönül Çatlı, Caner Alparslan, P. Şule Can, Sinem Akbay, Sefa Kelekçi, Tahir Atik, Berk Özyılmaz, Bumin N. Dündar
doi: 10.4274/jcrpe.1919  Pages 159 - 162
46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.

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