ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 9 Issue : 3 Year : 2024
Forms

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
JOURNAL OF CLINICAL RESEARCH IN PEDIATRIC ENDOCRINOLOGY - J Clin Res Pediatr Endocrinol: 9 (3)
Volume: 9  Issue: 3 - 2017
1.Cover

Pages I - XI

ORIGINAL ARTICLE
2.Clinicopathological Characteristics of Papillary Thyroid Cancer in Children with Emphasis on Pubertal Status and Association with BRAFV600E Mutation
Şükran Poyrazoğlu, Rüveyde Bundak, Firdevs Baş, Gülçin Yeğen, Yasemin Şanlı, Feyza Darendeliler
doi: 10.4274/jcrpe.3873  Pages 185 - 193
Objective: Papillary thyroid cancer (PTC) may behave differently in prepubertal children as compared to pubertal children and adults. BRAF gene activating mutations may associate with PTC by creating aberrant activation. We aimed to evaluate the clinicopathological characteristics of PTC patients with emphasis on the pubertal status and also to investigate the association of BRAFV600E mutation with disease characteristics.
Methods: The medical records of 75 patients with PTC were reviewed retrospectively. BRAFV600E mutation status was available only in the medical records of 56 patients.
Results: Mean age at diagnosis was 12.4±3.8 years. There was no difference in sex, initial signs, tumor histopathology, and pathological evidence of tumor aggressiveness between prepubertal and pubertal children. Although not statistically significant, lateral neck nodal metastasis and lung metastasis at diagnosis were more prevalent in prepubertal children. After excluding patients with microcarcinoma, prepubertal children were found to require lateral neck dissection and further doses of radioactive iodine more frequently than pubertal patients. Recurrence was also more frequent in prepubertal children (p=0.016). Frequency of BRAFV600E mutation was similar in prepubertal and pubertal patients. BRAFV600E mutation was found in 14/56 (25%) patients and was high in the classic variant PTC (p=0.004). Multicentricity was high in BRAFV600E mutation (p=0.01). There was no relation between BRAFV600E mutation and lymph node and pulmonary metastasis at diagnosis, or between BRAFV600E mutation and pathological evidence of tumor aggressiveness.
Conclusion: PTC is more disseminated in prepubertal children. BRAFV600E mutation does not correlate with a more extensive or aggressive disease. BRAFV600E mutation is not the cause of the differences in the biological behavior of PTC in prepubertal and pubertal children.

3.Congenital Hyperinsulinism in China: A Review of Chinese Literature Over the Past 15 Years
Wei-Yan Wang, Yi Sun, Wen-Ting Zhao, Tai Wu, Liang Wang, Tian-Ming Yuan, Hui-Min Yu
doi: 10.4274/jcrpe.3934  Pages 194 - 201
Objective: Congenital hyperinsulinism (CHI) is a rare but severe cause of hypoglycemia. The present study investigates the clinical presentation, therapeutic outcomes and genetic mutations of CHI in Chinese individuals over the past 15 years.
Methods: The authors retrospectively reviewed one case in their department and 206 cases reported from January 2002 to October 2016 in China. PubMed, Ovid Medline, Springer and Wanfang Database, CBMD database, and CKNI database were the sources used to collect the data.
Results: In total, 207 cases were recruited. Of these, the ages of 100 (48.3%) were within the 4th week after birth. Seventy-seven cases (37.2%) were born large for gestational age (LGA). Seizures occurred in 140 cases (67.6%). Among 140 cases (67.6%) who were administered diazoxide treatment, 90 (64.3%) were responsive. Seven cases (3.4%) received octreotide treatment and 19 cases (9.2%) underwent surgery. 63/129 cases (48.8%) were detected to have gene mutations, including ABCC8 (69.8%), KCNJ11 (12.7%), GLUD1, GCK, HADH, and HNF4A. Among the diazoxide-unresponsive cases, gene mutations were detected in 20/36 (55.6%) cases with ABCC8 and in 2 (5.6%) cases with KCNJ11. Among the diazoxide-responsive cases, gene mutations were detected in 8 patients with ABCC8, 4 with KCNJ11, 5 with GLUD1, and 1 with GCK.
Conclusion: The present study indicates that most CHI cases occurred in neonates and that 1/3 of the cases were born LGA. ABCC8 and KCNJ11 are the most common gene mutations. More than half of the diazoxide-unresponsive CHI detected mutations are in ABCC8 and KCNJ11 genes. The GLUD1 gene mutations cause diazoxide-responsive CHI. Identifying the gene mutations can assist in the diagnosis and treatment of CHI.

4.The Relationship Between Glycemic Variability and Inflammatory Markers in Obese Children with Insulin Resistance and Metabolic Syndrome
Abdurrahman Kaya, Cemil Koçyiğit, Gönül Çatlı, Elif Büşra Özkan, Bumin Nuri Dündar
doi: 10.4274/jcrpe.4031  Pages 202 - 207
Objective: Increased glycemic variability (GV) is associated with increased oxidative stress, vascular complications, and mortality in metabolic syndrome (MS) and diabetes mellitus patients. To investigate the relationship between GV and inflammatory parameters in obese children with insulin resistance (IR) and to elucidate their effects on the development of MS.
Methods: Fifty obese adolescents with IR were included in the study. All patients underwent anthropometric measurements, body fat analysis, and continuous glucose monitoring system (CGMS) for 24 hours. Serum lipids, adiponectin, and interleukin-6 (IL-6) levels were measured. GV coefficient (GVC) was calculated using the standard deviation and the average glucose value obtained by CGMS. IR was diagnosed according to the results of oral glucose tolerance test (OGTT). MS was diagnosed according to the modified World Health Organization and the International Diabetes Federation criteria.
Results: Twenty-seven of the patients had MS and the remaining had only IR. Body fat mass, HbA1c, IL-6 levels, and peak insulin levels in the OGTT were significantly higher in the group with MS, but there was no difference in adiponectin levels. GVC was not different between the groups, but GVC significantly positively correlated with homeostasis model of assessment for IR, as well as with fasting, peak, and total insulin levels when all the patients were analyzed, while no significant relation was detected with adiponectin and IL-6 levels.
Conclusion: This study suggests that GV is not different among obese adolescents with IR and MS. There seems to be a significant association between GV and IR parameters. However, other diagnostic criteria of MS (hypertension and/or dyslipidemia) or elevated IL-6 levels does not cause further increase in GV.

5.Treatment of Pre-pubertal Patients with Growth Hormone Deficiency: Patterns in Growth Hormone Dosage and Insulin-like Growth Factor-I Z-scores
Megan Oberle, Adda Grimberg, Vaneeta Bamba
doi: 10.4274/jcrpe.4125  Pages 208 - 215
Objective: To describe the range of insulin-like growth factor-I (IGF-I) z-score values (IGF-Iz) and growth hormone (GH) dose adjustments in pre-pubertal patients with GH deficiency (GHD) treated with GH in a single tertiary care center.
Methods: This is a retrospective review of GH-treated patients of ages ?9 years with GHD, seen in an endocrinology clinic in 2013-2014. Patient demographics and pre-treatment anthropometrics, GH treatment duration, IGF-Iz, and GH dosage (mg/kg/week) were extracted. Multipredictor linear regression was used to evaluate the associations between IGF-Iz and GH dosage and subject gender, race, insurance type, age, and clinical characteristics. Logistic regression was used to calculate the odds ratio of direction of GH dose adjustment (decrease/no change versus increase) and IGF-Iz category based on patient clinical characteristics, accounting for provider random effect.
Results: Forty-one percent (57/139) of IGF-Iz were outside the “normal” range of between -2 and +2 standard deviation; the majority of IGF-Iz beyond the “normal” range (93%) were supraphysiologic [>+2 standard deviation score (SDS)]. Of the IGF-Iz >+2, 10/53 (18%) were followed by a GH dose increase and 30/53 (57%) had no dose change. Patient clinical characteristics and demographics did not significantly increase the odds of being in the IGF-Iz >+2 SDS category or having a dose increase in multipredictor logistic regression models.
Conclusion: GH dosages and IGF-Iz varied, without significant patient clinical predictors. IGF-Iz was frequently supraphysiologic, and these levels often did not prompt a reduction in GH dose, likely influenced by a variety of factors. Our study emphasizes the need for better understanding of long-term safety and efficacy of maintaining supraphysiologic levels of IGF-Iz.

6.Melanocortin-4 Receptor Gene Mutations in a Group of Turkish Obese Children and Adolescents
Selma Tunç, Korcan Demir, Fatma Ajlan Tükün, Cihan Topal, Filiz Hazan, Burcu Sağlam, Özlem Nalbantoğlu, Melek Yıldız, Behzat Özkan
doi: 10.4274/jcrpe.4225  Pages 216 - 221
Objective: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity. Data regarding MC4R mutations in Turkish subjects are limited. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents.
Methods: MC4R was sequenced in 47 consecutive morbidly obese children and adolescents (28 girls and 19 boys, aged 1-18 years) who presented during a one-year period. Inclusion criterion was a body mass index (BMI) ?120% of the 95th percentile or ?35 kg/m2. Patients with chronic diseases, Cushing syndrome, hypothyroidism, or suspected syndromes that could cause obesity were excluded. Onset of obesity was before age 10 years in all subjects.
Results: Mean age was 13.2±4.1 years, age at onset of obesity 5.1±2.1 years, height standard deviation (SD) score 1.21±0.93, BMI 40.0±8.8 kg/m2, and BMI SD score was 2.72±0.37. One novel (c.870delG) and two previously reported (c.496 G>A, c.346_347delAG) mutations were found in four (8.5%) obese children and adolescents. The novel mutation (c.870delG) was predicted to be a disease-causing frame-shift mutation using in silico analyses. Fasting glucose and lipid levels of the patients with MC4R mutation were normal, but insulin resistance was present in two of the subjects. Six more individuals with MC4R mutation (1 child, 5 adults) were detected following analyses of the family members of affected children.
Conclusion: MC4R mutations are frequently found in morbid obese Turkish children and adolescents.

7.Management of Childhood Thyroid Nodules: Surgical and Endocrinological Findings in a Large Group of Cases
Emre Divarcı, Ülgen Çeltik, Zafer Dökümcü, Orkan Ergün, Geylani Özok, Samim Özen, Damla Gökşen Şimşek, Şükran Darcan, Nazan Çetingül, Aylin Oral, Yeşim Ertan, Bengü Demirağ, Ahmet Çelik
doi: 10.4274/jcrpe.4272  Pages 222 - 228
Objective: The management of childhood thyroid nodules is still a big challenge for clinicians. In this study, we aimed to present our surgical and endocrinological experience in more than one hundred pediatric cases.
Methods: A retrospective analysis of patients admitted with a thyroid nodule between 2006 and 2014 was performed. Detailed ultrasonography and fine-needle aspiration biopsy (FNAB) were the cornerstones of the diagnostic approach.
Results: One hundred-three children (72 female, 31 male) with a mean age of 13.1±3.6 years (3-18 years) were admitted to our center. Management strategy was surgery in 58 patients and follow-up in 45 patients. Mean nodule size was 17±12.7 mm (2-45 mm). The diagnoses were listed as benign solitary nodule (48 patients), thyroid carcinoma (26 patients), multinodular goiter (23 patients), Hashimoto thyroiditis (4 patients), and Graves’ disease (2 patients). Surgical procedures were nodulectomy/lobectomy (32 patients), total thyroidectomy (TT) (13 patients), or TT+ neck dissection (13 patients). The rate of malignancy was 25% in the total group and 44% in the surgery group. The malignancy rate was higher in patients younger than 12 years compared to older children (41% vs. 17%, p=0.040). Metastasis was seen in 38% of the malignant nodules. Postoperative complications were transient hypocalcemia (8%), permanent hypocalcemia (1.7%), and unilateral vocal cord paralysis (1.7%). Recurrence or mortality was not encountered in the 5.4±1.2-year follow-up period.
Conclusion: Thyroid nodule in a child requires an aggressive diagnostic approach due to increased risk of malignancy and metastasis. Intraoperative frozen section examination must be done as a useful adjunct to determine the surgical strategy. Incidence of complications is small in thyroid surgery when performed by experienced surgeons.

8.Clinical and Genetic Findings of Turkish Hypophosphatasia Cases
Halil Sağlam, Şahin Erdöl, Sevil Dorum
doi: 10.4274/jcrpe.4549  Pages 229 - 236
Objective: Hypophosphatasia (HPP) is a rare, commonly unrecognized hereditary mineralization defect with a dramatically poor prognosis in severe cases. This study is the first to examine the detailed clinical and laboratory characteristics of patients with HPP and healthy carriers in Turkey.
Methods: The study data were obtained retrospectively from the files of 10 healthy carriers and of 16 cases with HPP (12 children and 4 adults) who were followed in our center from 2012 to 2016.
Results: The annual incidence of perinatal lethal hypophosphatasia (PLH) was estimated to be approximately 1 case per 435,517 live births, which is the first report from Turkey. The clinical courses of the cases differed depending on the type of HPP. All of the seven cases (58.3% of all cases) with perinatal lethal form of HPP died. A need for respiratory support (p=0.001), a history of pyridoxine-dependent seizures (p=0.001), a low chest circumference measurement (p=0.017), younger age at diagnosis (p=0.029), a small head circumference at the time of presentation (p=0.042), a low arm span to height ratio (p=0.048), and a low serum alkaline phosphatase (ALP) level (p=0.042) seemed to be predicting factors for mortality. The mean height standard deviation score of the patients and those of the healthy carriers did not differ significantly (p=0.173). Different mutations were detected in nine of 14 cases (64.2%) in whom an ALPL gene mutation analysis could be performed, and five of these cases (35.7%) had novel mutations. The most common mutations were c746G>T (five alleles), c346G>A (three alleles), and c.140C>T (three alleles). In addition, the most frequently observed genotype in Turkish HPP cases was autosomal-dominant c.346G>A (p.A116T) mutations which were detected in three cases in two different families.
Conclusion: Because of the respiratory problems, especially the lung hypoplasia, the clinical course is poor in cases with the perinatal lethal form of HPP. Some minor abnormalities such as mild short stature and osteopenia could be observed in asymptomatic heterozygote carriers. Laboratory findings were normal in these cases.

9.The Relationship of Disordered Eating Attitudes with Stress Level, Bone Turnover Markers, and Bone Mineral Density in Obese Adolescents
Aslı Okbay Güneş, Müjgan Alikaşifoğlu, Ezgi Şen Demirdöğen, Ethem Erginöz, Türkay Demir, Mine Kucur, Oya Ercan
doi: 10.4274/jcrpe.3794  Pages 237 - 245
Objective: To investigate the effect of stress caused by disordered eating attitudes on bone health in obese adolescents.
Methods: A cross-sectional study comprising 80 obese adolescents was performed from November 2013 to September 2014. Twenty-four-hour urinary free cortisol levels were measured as a biological marker of stress. Bone turnover was evaluated using bone-specific alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide concentrations. Bone mineral density was measured using dual-energy X-ray absorptiometry. The Eating Disorder Examination Questionnaire, Dutch Eating Behavior Questionnaire, Children’s Depression Inventory, and the State-Trait Anxiety Inventory for Children were used to assess eating disorders, depression, and anxiety. Psychiatric examinations were performed for binge eating disorders.
Results: In the Pearson’s correlation test, a positive correlation was found between the 24-hour urinary cortisol level and Dutch Eating Behavior Questionnaire total and restrained eating subscale scores (p<0.05 for both). In linear regression analyses, the Dutch Eating Behavior Questionnaire total and restrained eating subscale scores were found to be significant contributors for urinary cortisol level (ß=1.008, p=0.035; ß=2.296, p=0.014, respectively). The femoral neck areal bone mineral density was found to be significantly higher in subjects who had binge eating disorder compared with those without binge eating disorder (p=0.049).
Conclusion: Despite the lack of apparent effects on bone turnover and bone mineral density in our obese adolescents at the time of the study, our results suggest that disordered eating attitudes, and especially restrained eating attitudes, might be a source of stress. Therefore, studies in this area should continue.

10.Phenotype Heterogeneity in Glucokinase–Maturity-Onset Diabetes of the Young (GCK-MODY) Patients
Anna Wedrychowicz, Ewa Tobór, Magdalena Wilk, Ewa Ziólkowska-Ledwith, Anna Rams, Katarzyna Wzorek, Barbara Sabal, Malgorzata Stelmach, Jerzy B. Starzyk
doi: 10.4274/jcrpe.4461  Pages 246 - 252
Objective: The aim of the study was to evaluate the clinical phenotypes of glucokinase-maturity-onset diabetes of the young (GCK-MODY) pediatric patients from Southwest Poland and to search for phenotype-genotype correlations.
Methods: We conducted a retrospective analysis of data on 37 CGK-MODY patients consisting of 21 girls and 16 boys of ages 1.9-20.1 (mean 12.5±5.2) years, treated in our centre in the time period between 2002 and 2013.
Results: GCK-MODY carriers were found in a frequency of 3% among 1043 diabetes mellitus (DM) patients and constituted the second most numerous group of DM patients, following type 1 DM, in our centre. The mean age of GCK-MODY diagnosis was 10.4±4.5 years. The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37). Mean fasting blood glucose level was 6.67±1.64 mmol/L. In the sample, there were patients with normal values (4/37), those with DM (10/37), and IFG (23/37). In OGTT, 120 min glucose level was normal in 8, diabetic in 2, and characteristic for glucose intolerance in 27 of the 37 cases. Twelve of the 37 cases (32%) were identified as GCK-MODY carriers. In the total group, mean C-peptide level was 2.13±0.65 ng/mL and HbA1c was 6.26±0.45% (44.9±-18 mmol/mol). Thirty-two patients had a family history of DM. DM autoantibodies were detected in two patients. The most common mutations were p.Gly318Arg (11/37) and p.Val302Leu (8/37). There was no correlation between type of mutations and plasma glucose levels.
Conclusion: The phenotype of GCK-MODY patients may vary from those characteristic for other DM types to an asymptomatic state with normal FG with no correlation with genotype.

11.The Relationship Between Perceived Family Climate and Glycemic Control in Type 1 Diabetes Mellitus Adolescent Patients
Şafak Eray, Halit Necmi Uçar, Fatma Çetinkaya, Erdal Eren, Pınar Vural
doi: 10.4274/jcrpe.3825  Pages 253 - 259
Objective: Type 1 diabetes mellitus (T1DM) is a chronic disease which ranks third in children under age 16 years. Expressed emotion (EE) is a term that indicates a specific family climate including lack of emotional support (LES), irritability, and emotional over-involvement. It is known that the family environment is highly important for glycemic control in diabetic adolescents. In this study, the relationship between perceived EE and glycemic control in adolescents diagnosed with T1DM not accompanied by psychopathology were investigated.
Methods: The study included 49 adolescents with T1DM and 50 adolescents as a control group. Adolescents with psychopathology and intellectual disability were excluded from the study. Perceived EE was measured by the Shortened Level of Expressed Emotion Scale (SLEES) and blood sugar regulation was assessed by HbA1c levels.
Results: The adolescents with T1DM showed a significant difference in perceived EE (p=0.020) and LES (p=0.014) when compared with the control group. When diabetic adolescents were compared among themselves, the diabetic adolescents with poor glycemic control perceived greater EE (p=0.033) and less emotional support (p=0.049). In regression analyses, the predictive power of mother’s educational level, the employment status of mothers and the subscale “LES” of SLEES combined to explain HbA1c level was determined to be 37.8%.
Conclusion: The strong relationship between perceived EE and glycemic control showed us that perceived EE can hinder treatment compliance without causing psychopathology. For this reason, it is recommended that not only patients with psychopathology, but all diabetic adolescents receive psychosocial support and family interventions.

SHORT COMMUNICATION
12.An ABCC8 Nonsense Mutation Causing Neonatal Diabetes Through Altered Transcript Expression
Sarah E. Flanagan, Vu Chí Dung, Jayne A. L. Houghton, Elisa De Franco, Can Thi Bich Ngoc, Annet Damhuis, Frances M. Ashcroft, Lorna W. Harries, Sian Ellard
doi: 10.4274/jcrpe.4624  Pages 260 - 264
The pancreatic ATP-sensitive K+ (K-ATP) channel is a key regulator of insulin secretion. Gain-of-function mutations in the genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the channel cause neonatal diabetes, whilst loss-of-function mutations in these genes result in congenital hyperinsulinism. We report two patients with neonatal diabetes in whom we unexpectedly identified recessively inherited loss-of-function mutations. The aim of this study was to investigate how a homozygous nonsense mutation in ABCC8 could result in neonatal diabetes. The ABCC8 p.Glu747* was identified in two unrelated Vietnamese patients. This mutation is located within the in-frame exon 17 and RNA studies confirmed (a) the absence of full length SUR1 mRNA and (b) the presence of the alternatively spliced transcript lacking exon 17. Successful transfer of both patients to sulphonylurea treatment suggests that the altered transcript expression enhances the sensitivity of the K-ATP channel to Mg-ADP/ATP. This is the first report of an ABCC8 nonsense mutation causing a gain-of-channel function and these findings extend the spectrum of K-ATP channel mutations observed in patients with neonatal diabetes.

CASE REPORT
13.Pituitary Adenoma Apoplexy in an Adolescent: A Case Report and Review of the Literature
Hero Zijlker, Sebastian Schagen, Jan Maarten Wit, Nienke Biermasz, Wouter van Furth, Wilma Oostdijk
doi: 10.4274/jcrpe.4420  Pages 265 - 273
We present a 13-year-old boy who was admitted with complaints of a state of progressive sleepiness and a sudden headache with vomiting and fever. Laboratory testing showed hypoglycemia, multiple pituitary hormonal deficiencies, and an elevated C-reactive protein level. A cranial magnetic resonance imaging (MRI) showed an opaque sphenoid sinus and an intrasellar mass suggesting hemorrhage, so that we suspected pituitary apoplexy (PA) originating from a non-functioning adenoma, although a pituitary abscess could not completely be excluded. The boy was treated with antibiotics, hydrocortisone, and levothyroxine. Due to his rapid clinical improvement, no surgery was performed and we considered the diagnosis of PA as confirmed. At follow-up, the MRI scan showed a small residual lesion. Pituitary deficiencies of growth hormone, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, and vasopressin persisted. A literature search of all well-documented cases of PA in children or adolescents (n=30, 13 boys and 17 girls) indicated that this condition is rare below 20 years of age but must be considered when a patient experiences headache with or without visual disturbances, even in the presence of clinical and laboratory signals suggestive of pituitary abscess. MRI neuroimaging is helpful in the differential diagnosis. In both conditions, the possibility of ACTH deficiency should always be considered, investigated, and treated. In cases without severe neuro-ophthalmological deficits and/or with a rapid and positive response to acute medical management, one can abstain from surgical treatment.

14.Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene
Monica Gabbay, Sian Ellard, Elisa De Franco, Regina S. Moisés
doi: 10.4274/jcrpe.4494  Pages 274 - 277
Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis.

15.Congenital Central Hypothyroidism Caused by a Novel Thyroid-Stimulating Hormone-Beta Subunit Gene Mutation in Two Siblings
Bayram Özhan, Özlem Boz Anlaş, Bilge Sarıkepe, Burcu Albuz, Nur Semerci Gündüz
doi: 10.4274/jcrpe.4595  Pages 278 - 282
Congenital central hypothyroidism (CCH) is a very rare disease. Alterations in pituitary development genes as well as mutations of immunoglobulin superfamily member 1 and transducin ß-like protein 1 can result in CCH and multiple pituitary hormone deficiencies. However, mutations of the thyrotropin-releasing hormone receptor or thyroid-stimulating hormone-beta (TSHB) gene are responsible for isolated CCH. In this paper, we present the cases of two siblings with a novel mutation of TSHB. Direct sequencing of the coding regions and exon/intron boundaries of the TSHB gene revealed two homozygous nucleotides changes. One of them was c.40A>G (rs10776792) which is a very common variation that is also seen in healthy individuals, the other was c.94G>A at codon 32 of exon 2 which resulted in a change from glutamic acid to lysine (p.E32K). Both patients were homozygous and the parents were heterozygous.

16.Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy
E. Nazlı Gönç, Alev Özön, Ayfer Alikaşifoğlu, Nurgün Kandemir
doi: 10.4274/jcrpe.3986  Pages 283 - 287
Proprotein convertase 1/3 (PC1/3) deficiency is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later. Diabetes mellitus requiring insulin treatment and diabetic ketoacidosis have not been reported in this disorder. We herein present a girl with PC1/3 deficiency who has been followed from birth to 17 years of age. She developed deficiencies of all pituitary hormones over time as well as diabetes mellitus while receiving growth hormone (GH) therapy. She was complicated with diabetic ketoacidosis during dietary management of diabetes mellitus, thus insulin treatment was initiated. Insulin requirement to regulate hyperglycemia was short-lived. Repeat oral glucose tolerance test five years later was normal. The findings of this patient show that diabetes mellitus can develop at any time during follow-up of cases with proportein convertase 1/3 deficiency especially under GH therapy.

17.Tolvaptan Treatment in Children with Chronic Hyponatremia due to Inappropriate Antidiuretic Hormone Secretion: A Report of Three Cases
Gerdi Tuli, Daniele Tessaris, Silvia Einaudi, Luisa De Sanctis, Patrizia Matarazzo
doi: 10.4274/jcrpe.4531  Pages 288 - 292
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment consists of fluid restriction in presence of euvolemia or hypervolemia; loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic solutions are administered in hypovolemic conditions. The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance. Recently, a new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans. Tolvaptan is the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are so far available in paediatric patients, since only one trial has been registered in Europe which includes children and adolescents, but this trial is still ongoing. Here, we report three children with chronic hyponatremia due to SIADH in which tolvaptan has been used successfully.

LookUs & Online Makale