ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 15 Issue : 1 Year : 2023

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Volume: 15  Issue: 1 - 2023

Pages I - XI

2.Specific Functions of Melanocortin 3 Receptor (MC3R)
Tulin Yanik, Seyda Tugce Durhan
doi: 10.4274/jcrpe.galenos.2022.2022-5-21  Pages 1 - 6
Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor which has been defined mostly as a regulator of the appetite/hunger balance mechanisms to date. In addition to its function regarding the weight gain and appetite control mechanisms of MC3R, recent studies have shown that MC3R controls growth, puberty, and circadian rhythms as well. Despite the drastic effects of MC3R deficiency in humans and other mammals, its cellular mechanisms are still under investigation. In this review paper, we aimed to point out the importance of MC3R regulations in three main areas: 1) its impact on weight and appetite control, 2) its role in the control of growth, puberty, and the circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms.

3.Factors Affecting Thyroid Elastography in Healthy Children and Patients with Hashimoto’s Thyroiditis
Serkan Bilge Koca, Turgut Seber
doi: 10.4274/jcrpe.galenos.2022.2022-4-5  Pages 7 - 15
INTRODUCTION: Hashimoto’s thyroiditis (HT) is the most common form of thyroiditis in childhood. In addition to thyroid ultrasonography, shear-wave elastography (SWE) can evaluate thyroid parenchyma tissue stiffness, and more detailed findings can be obtained with this method. We aimed to evaluate the relationship between SWE values and clinical, biochemical and hormonal parameters of patients with HT and in healthy individuals.
METHODS: We compared 46 newly diagnosed HT cases with 46 healthy controls. We examined the effect of all metabolic parameters and thyroid-related markers on SWE values.
RESULTS: The mean SWE values in those patients with euthyroid HT were 12.5±5.1 kilopascal (kPa), whereas it was 8.2±2.82 kPa in healthy controls (p<0.001). Although the clinical [age, gender and body mass index (BMI)] and laboratory parameters (such as thyroid function tests, homeostasis model assessment of insulin resistance, insulin-like growth factor-1 values, which we think may affect SWE scores) of those children with HT and the healthy controls were statistically similar (p>0.05), except for their thyroid autoantibodies and thyroglobulin, SWE values and thyroid volume were significantly higher in those individuals with HT (p<0.001). Multiple linear regression analysis was performed to evaluate the direction and degree of the effect of the variables on thyroid elasticity scores. It was observed that age (p=0.002), BMI standard deviation score (SDS) (p=0.04) and anti-thyroid peroxidase (p=0.008) levels were effective on the thyroid elasticity score in the regression model. We detected a SWE cut-off value of 9.68 kPa with 68% sensitivity and 72% specificity, a 70% positive predictive value, and a 69% negative predictive value in thyroid elastography when differentiating between cases with HT and healthy controls.
DISCUSSION AND CONCLUSION: Our results show that no metabolic factor other than BMI SDS has any effect on SWE scores, especially in healthy children. There was a positive correlation between BMI SDS and SWE in healthy children (r=0.353; p=0.02), but not in those patients with HT (r=0.196; p=0.19). Likewise, age is another factor affecting SWE only in healthy children. We do not recommend routine evaluation of any laboratory parameters other than thyroid functions before thyroid elastography.

4.Endocrine Abnormalities and Growth Characterization in Colombian Pediatric Patients with 22q11 Deletion Syndrome
Juan Lasprilla Tovar, Nora Alejandra Zuluaga, Adriana Carolina Forero Torres, Oscar Correa-Jimenez, Javier Mauricio Sierra
doi: 10.4274/jcrpe.galenos.2022.2022-4-12  Pages 16 - 24
INTRODUCTION: Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition.
METHODS: A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted.
RESULTS: Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate.
DISCUSSION AND CONCLUSION: As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate.

5.Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal Dysgenesis
Rjiba Khouloud, Wafa Slimani, Meriem Gaddas, Ikbel Hadj hassine, Afef Jelloul, Hela Ben Khelifa, Fethi El Amri, Monia Zaouali, Kenneth Mcelreavey, Ali Saad, Soumaya Mougou-Zerelli
doi: 10.4274/jcrpe.galenos.2022.2022-3-15  Pages 25 - 34
INTRODUCTION: Disorders of sexual development (DSD) are a heterogeneous group of genital defects affecting chromosomal, gonadal and anatomical sex. 46,XY DSD is a subset of DSD which covers a wide range of phenotypes in which 46,XY gonadal dysgenesis (GD) is the most severe form. In this study, we report on the clinical and molecular cytogenetic findings of a study on a Tunisian girl with the syndromic form of 46,XY DSD.
METHODS: This case was a phenotypic female patient having several congenital anomalies including growth retardation. Karyotype, fluorescence in situ hybridization and array Comparative Genome Hybridization (array CGH) were performed.
RESULTS: The proband exhibited a de-novo 46,X,der(Y) karyotype. Array CGH revealed a pathogenic 27.5Mb gain of an Xp21.2 chromosome segment leading to Xp functional disomy. No deletion was observed in the Y-chromosome. The duplicated region encompassed the NR0B1 (DAX1) and MAGEB genes, located within the dosage sensitive sex (DSS) reversal locus, known as promote genes responsible for human sex reversal and testis repression. The extra-dosage and interactions of these genes with different specific genes could result in the impairment of the male sex pathway. Over-dosage of KAL1 and IL1RAPL1 genes fall within the somatic features observed in the patient.
DISCUSSION AND CONCLUSION: To the best of our knowledge, we report on the fourth case of Xp21.2-pter duplication within Xp;Yp translocation associated with XY GD. Our findings suggest that when duplicated, the NR0B1 and MAGEB genes could be a major cause of XY GD. Therefore, we emphasize the usefulness of a combined cytogenetic approach in order to provide an accurate genetic diagnosis for those patients having syndromic XY DSD in a clinical setting.

6.Clinical Utility and Outcome Prediction of Early ZnT8-IgG Testing and Titer in Type 1 Diabetes
Amanda Dahl, Sarah Jenkins M., Siobhan J. Pittock, Siobhan T. Pittock
doi: 10.4274/jcrpe.galenos.2022.2022-4-16  Pages 35 - 41
INTRODUCTION: Type 1 diabetes autoantibodies are directed against multiple antigens including: glutamic acid decarboxylase, protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence or titer of ZnT8 antibodies (Ab) was predictive for clinical presentation at diagnosis or for the subsequent disease course.
METHODS: Between January, 2003 and May, 2019, 105 patients aged ≤21 years with a clinical diagnosis of type 1 diabetes mellitus had at least 1 autoantibody measured. A retrospective chart review was completed. At diagnosis, we evaluated the body mass index z-score, hemoglobin (HbA1c), and the presence of diabetic ketoacidosis (DKA). Complications analyzed post-diagnosis included episodes of DKA, the diagnosis of autoimmune disease, and the presence of vascular complications. We evaluated cumulative lifetime excess glucose as HbA1c area under the curve (AUC) >6%.
RESULTS: Seventy-one patients were ZnT8-Ab(+) (68%), with 19 having low titer ZnT8-Ab and 52 with high titer ZnT8-Ab. Follow-up ranged from 10 days to 15.7 years (median 2.08 years). There were no differences in the characteristics at disease onset or in the subsequent follow-up between those with and those without ZnT8-Ab or those with high or low titers of ZnT8 Ab, except for a small but statistically significant difference in cumulative excess glucose (HbA1c AUC >6%) between those with low and high titers (p=0.0095).
DISCUSSION AND CONCLUSION: Our study adds to the limited literature on the effect of the presence and titer of ZnT8-Ab in pediatric diabetes. The small effect of ZnT8-Ab titer on glucose excess as measured by HbA1c AUC warrants further study.

7.Comparison of Commonly Used Methods to Predict the Final Height in Constitutional Tall Stature
Alma Kamar Matias, Evgenia Nizkorodov, Gilad Twig, Lilos Pearl, Zvi Laron
doi: 10.4274/jcrpe.galenos.2022.2022-1-12  Pages 42 - 45
INTRODUCTION: To determine the accuracy of adult height prediction in children with constitutional tall stature.
METHODS: The medical records of 138 non-syndromatic prepubertal and early pubertal children (52 male, 86 female) with a height of ≥90th percentile born between the years 1975 and 1988 were included in this study. Using the Bayley-Pinneau (BP) and Tanner- Whitehouse I (TWI) prediction methods, their height standard deviation score (SDS) at referral was compared with their height SDS at age 17 years when measured at the IDF conscription center.
RESULTS: While remaining tall, the height SDS at age 17 years was lower than that at referral decreasing from 2.13±1 to 1.65±1.21 in boys and from 2.48±1 to 2.15±1 in girls.
DISCUSSION AND CONCLUSION: The prediction by the BP and TWI methods can be useful for estimating adult height in constitutional tall stature even in the prepubertal and early pubertal period. However, the fallibility of these methods should be kept in mind during clinical practice. We think that this study will shed light on these issues.

8.Frequency, Clinical Characteristics and Predictors of Ketoacidosis at Diagnosis of Type One Diabetes Mellitus in Children and Adolescents from Jordan
Rasha Odeh, Lobna Gharaibeh, Amirah Daher, Jumana Albaramki, Bahaa Ashour, Fatima Al Barakat, Dina Dahabreh, Hiba Hadadin, Tala Melhem, Abeer Alassaf
doi: 10.4274/jcrpe.galenos.2022.2022-5-8  Pages 46 - 54
INTRODUCTION: Data regarding diabetic ketoacidosis (DKA) at diagnosis of type one diabetes (T1D) in developing countries are scarce. The aim of this study was to describe the frequency of DKA at the onset of T1D in children and adolescents in Jordan and to compare the clinical and biochemical characteristics between the group that presented with DKA and the group that did not.
METHODS: The records of 341 children and adolescents, less than sixteen years of age, who were diagnosed with T1D between 2015 and 2019 were evaluated retrospectively.
RESULTS: Of all the children diagnosed with T1D, 108 (31.7%) presented with DKA. The majority had mild or moderate DKA (38% and 33.3% respectively). Higher paternal education levels were associated with a lower probability of presenting with DKA (p=0.043). A family history of T1D had a protective effect on the occurrence of DKA (Odds ratio=2.138; 95% confidence interval=1.167-3.917, p=0.014). Patients with celiac disease and higher HbA1c levels were more likely to experience recurrent episodes of DKA, (p=0.004 and 0.011, respectively).
DISCUSSION AND CONCLUSION: In Jordan, the rate of DKA at presentation of T1D remains high. Prevention campaigns are needed to increase diabetes awareness among the public and healthcare providers.

9.The Relationship Between Premature Adrenarche and Platelet Aggregation
Ahmet Bolat, Cengiz Zeybek, Orhan Gürsel, Onur Akın, Mehmet Emre Taşçılar
doi: 10.4274/jcrpe.galenos.2022.2022-6-13  Pages 55 - 61
INTRODUCTION: Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients.
METHODS: The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method.
RESULTS: There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001).
DISCUSSION AND CONCLUSION: Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.

10.Factors Associated with Low Bone Mineral Density at the Time of Diagnosis in Children with Celiac Disease
Emine Çamtosun, Fatma İlknur Varol, Şükrü Güngör, Mukadder Ayşe Selimoğlu
doi: 10.4274/jcrpe.galenos.2022.2022-5-18  Pages 62 - 68
INTRODUCTION: It has been reported that bone mineral density (BMD) is decreased in children with Celiac disease (CD) compared to their healthy peers. The aim of this study was to reveal possible risk factors for low BMD in Turkish children newly diagnosed with CD.
METHODS: Eighty-six patients (2-18 years old) with CD were included in this retrospective study. The relationship between their lumbar BMD z-scores calculated according to their chronological age (CA) and height age (HA) and their clinical, laboratory [biochemical parameters, tissue transglutaminase antibody-IgA (TTGA) levels, human leukocyte antigen (HLA) types] and histopathological parameters were evaluated.
RESULTS: The mean age of the patients at diagnosis was 8.06±4.08 years. The BMD z-score CA was ≤-2 standard deviation (SD) in 26.7% of the patients. The BMD z-score HA was ≤-2 SD in 12.8% of the patients. The BMD z-score HA only correlated with their age at diagnosis of CD (rs value 0.269). However, there was no statistically difference between the BMD z-score HA >-2 SD and ≤-2 SD subgroups regarding their clinical, laboratory and histopathological parameters.
DISCUSSION AND CONCLUSION: Low BMD is common in children with newly diagnosed CD. Age at diagnosis, gender, body size, Celiac symptoms, biochemical parameters, TTGA level, HLA type, and histopathological stage had no predictive values in terms of low BMD in this patient group.

11.Increased Carotid Intima-media Thickness and Its Association with Carbohydrate Metabolism and Adipocytokines in Children Treated with Recombinant Growth Hormone
Seha Saygılı, Mehmet Kocaağa, Gamze Kaya, Mine Şükür, Firdevs Baş, Şükran Poyrazoğlu, Rüveyde Bundak, Feyza Darendeliler
doi: 10.4274/jcrpe.galenos.2022.2022-8-19  Pages 69 - 80
INTRODUCTION: Reports on the association between growth hormone (GH) therapy and cardiovascular risk factors in children are limited. This study aimed to evaluate carotid intima-media thickness (cIMT) in children treated with recombinant human GH (rhGH) and assess the effects of rhGH therapy and changes in serum carbohydrate metabolism, lipid profile and adipocytokines on cIMT.
METHODS: Seventy-one isolated idiopathic GH deficiency (GHD) children and 44 age- and sex-matched healthy controls were enrolled in this study. The study group was divided into two subgroups according to insulin resistance (IR) on oral glucose tolerance tests. Insulin secretion [homeostatic model assessment (HOMA) B, total insulin] and sensitivity (HOMA-IR, QUICKI, Matsuda) indices were calculated. cIMT was measured and the standard deviation scores (SDS) were calculated. Associations between cIMT-SDS and insulin secretion and sensitivity indices, serum lipid levels, adipocytokines (leptin, resistin, ghrelin), and other rhGH treatment-related factors were evaluated.
RESULTS: cIMT-SDS was increased in GHD children treated with rhGH compared to the controls [0.02 (2.27) vs. -1.01 (1.63), p=0.003]. cIMT-SDS did not differ between those children on rhGH treatment with or without IR. High cIMT-SDS was significantly associated with higher serum ghrelin levels and lower serum high density lipoprotein (HDL) levels (β=0.491, p=0.001 and β=-0.027, p=0.017), but not with BMI-SDS, blood pressure, insulin secretion and sensitivity indices, or the dose and duration of rhGH therapy.
DISCUSSION AND CONCLUSION: Our findings showed that GHD children treated with rhGH have increased cIMT. Alterations in carbohydrate metabolism were not associated with cIMT in children treated with rhGH. GH therapy per se appears to be associated with this increased cIMT but causality should be elucidated in further studies. cIMT also appears to be associated with higher ghrelin and lower HDL levels.

12.Weight Loss During Topiramate Treatment in a Severely Obese Adolescent with Congenital Adrenal Hyperplasia and Migraine
Amy Seagroves, Heather M. Ross, Alaina P. Vidmar, Mitchell E. Geffner, William S. Kim, Darryl Hwang, Claudia Borzutzky, Nicole R. Fraga, Mimi S. Kim
doi: 10.4274/jcrpe.galenos.2021.2020.0310  Pages 81 - 85
Youth with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity, early adiposity rebound, and increased abdominal adiposity compared to unaffected youth. Current obesity management in CAH largely focuses on lifestyle modifications. There is evidence that topiramate therapy is effective in reducing body mass index (BMI), as well as visceral adipose tissue (VAT), in unaffected adolescents with exogenous obesity. However, little is known about the efficacy of topiramate in patients with classical CAH. We report on a 17-year-old female with severe obesity and salt-wasting CAH due to 21-hydroxylase deficiency, who demonstrated reductions in BMI, as well as abdominal visceral and subcutaneous adipose tissue (SAT) while on topiramate therapy. The patient was diagnosed with classical CAH as a newborn with a 17-hydroxyprogesterone 11,000 ng/dL. She had a BMI over the 95th percentile at 3 years of age, followed by unremitting obesity. At 17 years old, she was started on topiramate to treat chronic migraines. Following three years of topiramate therapy, her BMI z-score decreased from +2.6 to +2.1. After four years of therapy, her waist circumference decreased from 110 to 101 cm, abdominal VAT decreased substantially by 34.2%, and abdominal SAT decreased by 25.6%. Topiramate therapy was associated with effective weight loss and reduced central adiposity in an adolescent with classical CAH and severe obesity, without any side effects. Further study is warranted regarding topiramate therapy in obese youth with classical CAH and increased central adiposity, who are at higher risk for significant morbidity.

13.Rare Coexistence of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency and Turner Syndrome: A Case Report and Brief Literature Review
Isabel Inácio, Joana Serra-Caetano, Rita Cardoso, Isabel Dinis, Alice Mirante
doi: 10.4274/jcrpe.galenos.2021.2021.0174  Pages 86 - 89
The coexistence of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Turner syndrome (TS) is rare. We report on a 6-year-old Portuguese girl with mosaic TS [45,XO(39)/47,XXX(21)] presenting with premature pubarche at the age of 5 years. Laboratory findings showed elevated 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione and total testosterone, and her sex-determining region Y (SRY) was negative. CYP21A2 gene analysis revealed two mutations (c.[844G>T]; [CYP21A2del]), consistent with the non-classical form of CAH. Complete deletion of CYP21A2 allele occurred de novo. At 6 years and 4 months, she presented with accelerated growth velocity and hydrocortisone at a dose of 5 mg/m2/day was initiated. This case highlights the need to perform global examinations looking for virilization signs in TS patients’ follow-ups. It also supports the reported genetic combination of TS and CAH. Therefore, CAH should be kept in mind in TS patients with SRY negative and virilization signs, even in the absence of short stature.

14.Expanding the Phenotype of TRMT10A Mutations: Case Report and a Review of the Existing Cases
Zeynep Şıklar, Tuğba Kontbay, Kevin Colclough, Kashyap A. Patel, Merih Berberoğlu
doi: 10.4274/jcrpe.galenos.2021.2021.0110  Pages 90 - 96
The tRNA methyltransferase 10 homologue A (TRMT10A) gene encodes tRNA methyl transferase, and biallelic loss of function mutations cause a recessive syndrome of intellectual disability, microcephaly, short stature and diabetes. A case with intellectual disability and distinctive features including microcephaly was admitted. She was diagnosed with epilepsy at 2.5 years old. At 3.6 years of age, severe short stature related to growth hormone (GH) deficiency was detected. She had an incidental diagnosis of diabetes at age 11.4 years which was negative for diabetes antibodies with persistent C-peptide level and she was treated with metformin. Spontaneous puberty did not begin until 15.7 years of age and she was found to have primary ovarian failure. A homozygous p.Arg127* mutation in TRMT10A was detected. In addition to the typical clinical features which characterize TRMT10A syndrome, we observed an unusual form of impaired glucose metabolism which presented in early childhood with hypoglycemia followed by diabetes in late childhood. GH deficiency and primary ovarian failure may also be additional findings of this syndrome. Patients with slow onset diabetes who are negative for autoantibodies and have extra-pancreatic features should be tested for all known subtypes of monogenic diabetes.

15.Compound Heterozygous Variants in FAM111A Cause Autosomal Recessive Kenny-Caffey Syndrome Type 2
Erdal Eren, Havva Tezcan Ünlü, Serdar Ceylaner, Ömer Tarım
doi: 10.4274/jcrpe.galenos.2021.2020.0315  Pages 97 - 102
Kenny-Caffey syndrome (KCS) is a rare autosomal recessive (AR)/dominant disease characterized by hypoparathyroidism, skeletal dysplasia, dwarfism, and dysmorphism. FAM111A or TBCE gene mutations are responsible for this syndrome. Osteocraniostenosis (OCS) is a lethal syndrome with similar features to KCS, and it can be a severe form of KCS type 2 which results from the FAM111A gene mutation. The FAM111A mutation is generally characterized by the autosomal dominant transition. We present a male case having compound heterozygous variants (c.976T>A and c.1714_1716del) in the FAM111A gene with an AR inheritance pattern. Hypocalcemia developed on the second day of life. The patient and his older sister had a dysmorphic face, skeletal dysplasia, and they were diagnosed with hypoparathyroidism. Both siblings died due to septicemia. He is the first reported patient with the FAM111A mutation in Turkey. The phenotype of the patient is compatible with OCS, and the detected variants may explain the disease genetically.

16.Maltodextrin May Be a Promising Treatment Modality After Near-total Pancreatectomy in Infants Younger Than Six Months with Persistent Hyperinsulinism: A Case Report
Yasemin Denkboy Öngen, Erdal Eren, Halil Sağlam
doi: 10.4274/jcrpe.galenos.2021.2021.0121  Pages 103 - 107
Persistent hypoglycemia in infants with congenital hyperinsulinism (CHI) can be challenging in approximately half of these cases, even after undergoing a near-total pancreatectomy. While maltodextrin has been recommended in the nutritional management of CHI cases younger than six months, information regarding its efficacy in managing hypoglycemia are not yet clear. Here, we present a male infant with CHI who experienced persistent hypoglycemia even after undergoing a near-total pancreatectomy and despite multiple medical treatments. The infant’s hypoglycemic episodes were successfully controlled by adding maltodextrin to his diet.

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