Ayça Altıncık

Growth of Children with Type 1 Diabetes Mellitus

Objective: To retrospectively evaluate the effect of type 1 diabetes on growth. Methods: Patients with Type 1 diabetes mellitus (T1DM) followed for at least one year after diagnosis, and without coexisting disorder that could affect growth, were included in this retrospective analysis. Height and body mass index (BMI) values were recorded. According to the data obtained at the end of each year of disease, the patients were divided into two groups: Group 1 (patients whose height standard deviation score (SDS) did not change or showed improvement) and Group 2 (patients whose height SDS showed a decline). The two groups were compared with respect to clinical and laboratory variables. Results: Among the 248 patients followed, 101 (M/F:55/46) fulfilled the inclusion criteria. Overall, the mean height SDS of the patients did not change significantly during the follow−up period. BMI SDS showed no change during the course of the disease, except for a significant rise observed at the end of the first year compared to the value at diagnosis. Height SDS of the patients in Group 1 was higher compared to those in Group 2 from the 2nd year of disease onwards (2nd year, p=0.03; 3rd year, p=0.02; 4th year, p=0.01; 5th year, p=0.03). The ratio of patients presenting with diabetic ketoacidosis at onset was significantly higher in Group 1 at the 4th year of diagnosis (p=0.03). Additionally, the mean HbA1c level showed a modest negative correlation with Δ height SDS at the 3rd year of diagnosis (r=−0.3, p=0.03). Conclusions: No significant deteriorative effect of T1DM on auxological parameters was observed at short term. Some clinical and laboratory variables related with metabolic control were found to correlate with growth. Conflict of interest:None declared.

Evaluation of the relationship between serum adropin levels and blood pressure in obese children.

Abstract Background: The prevalence of obesity and related cardiovascular comorbodities is increasing rapidly. Adipokines play a major role in the pathogenesis of obesity-related inflammation and hypertension. Aim: The aim of this study was to evaluate the serum adropin levels in obese children and to determine the relationship between adropin levels and blood pressure (BP) in the pediatric age group. Methods: Forty obese children (mean age: 12.5±2.5 years; male/female ratio: 18/22) and 15 healthy controls (mean age: 15±3.14 years; male/female ratio: 5/15) were included in the study. Serum adropin levels, and a number of laboratory and clinical variables were compared. Ambulatory blood pressure monitoring was performed on obese subjects. Relationship between adropin levels and BP variables was examined. Results: Serum adropin levels were significantly lower in obese subjects than in healthy controls (193.56±94 vs. 289±187 pg/mL, p=0.03). Adropin levels were correlated negatively with body mass index z-score (r=−0.56; p=0.034). There was no correlation between serum adropin levels and laboratory variables in obese subjects. Five of the patients (12.5%) were nondipper, and nine of the patients (22.5%) had hypertension. There was no significant correlation between serum adropin levels and BP variables. Conclusion: Serum adropin levels were significantly lower in obese children; however, there was no correlation between serum adropin levels and BP variables. Further studies are needed to determine the role of adipokines on BP.

Hyperprolactinemia in children: clinical features and long-term results

Abstract Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2±1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

A novel mutation in a mother and a son with Aarskog-Scott syndrome.

Abstract Aarskog-Scott syndrome, also termed as faciogenital dysplasia, is an X-linked disorder consisting of short stature, craniofacial dysmorphism, shawl scrotum, cryptorchidism, and interdigital webbing. Cardiac and central nervous system abnormalities and behavioral disorders can also be detected. The gene responsible for the syndrome is called FGD1, located at Xp11.21. A 7-year-old boy was admitted to our hospital due to short stature. He was born to non-consanguineous parents after an uneventful term pregnancy. Orchiopexy for bilateral cryptorchidism was performed when he was 2 years old. At physical examination, his height was under 3 percentile, and he had broad nasal bridge, hypertelorism, wide philtrum, brachydactyly, and interdigital webbing. Cranial magnetic resonance imaging and echocardiography revealed normal findings. An eye examination showed amblyopia and astigmatism. The mother had short stature and interdigital webbing as well. Mutational analyses revealed a novel mutation (c.308-2G), hemizygous in the boy and heterozygous in the mother. Aarskog syndrome (faciogenital dysplasia) should be kept in mind in children with short stature and interdigital webbing.

Fine-Needle Aspiration Biopsy in the Diagnosis and Follow-Up of Thyroid Nodules in Childhood

Objective: To assess the role of fine−needle aspiration biopsy (FNAB) in the management of pediatric thyroid nodules. Methods: Results of 30 FNABs performed in our clinic were retrospectively reviewed. Clinical and surgical follow−up data were obtained from the patient files, and clinical correlation and accuracy of FNAB were evaluated. Results: The results of 30 FNABs were reported as benign in 24 (80%), insufficient in 4 (13.3%) patients, malignant in 1 (3.3%), and suspicious in 1 (3.3%) patient. One patient with a FNAB result of malignancy underwent surgery and the histological diagnosis was papillary carcinoma. FNAB was repeated in two of the insufficient biopsies, and reported as benign; in one of these patients, the thyroid nodule disappeared and in one, remained stable at clinical follow−up. Four of the patients with benign FNAB results underwent surgery at clinical follow−up because of an increase in the size of the nodules and one patient was found to have papillary carcinoma. The remaining patients were clinically followed. In this study, the malignancy prevalence was 6.6% in patients with thyroid nodules. There was only one falsenegative case. Conclusion: FNAB is a reliable diagnostic tool in the management of pediatric thyroid nodules. Conflict of interest:None declared.

Evaluation of neutrophil gelatinase-associated lipocalin in normoalbuminuric normotensive type 1 diabetic adolescents.

Abstract Aims: The aims of this study were to determine neutrophil gelatinase-associated lipocalin (NGAL) levels in normoalbuminuric and normotensive adolescents with type 1 diabetes and to assess the relationship between NGAL and clinical and laboratory variables. Methods: Forty-six adolescents with type 1 diabetes [male/female (M/F) ratio, 24/22; median age, 14.5 years; range, 12.2–16 years; diabetes duration, 4.8 years; range, 2.6–6.7 years; hemoglobin A1c (HbA1c), 7.9%; range, 7.2%–9.2%] and 21 healthy controls (M/F, 7/14; median age, 14.8 years; range, 13.6–15.5 years) were compared regarding clinical, laboratory, and ambulatory blood pressure monitoring variables. Results: Median blood and urine glucose, HbA1c, urine NGAL/creatinine ratio [13.2 (range, 8.3–43.1) vs. 4.8 (range, 2.9–20.2), p=0.015], and daytime systolic and diastolic blood pressure (BP) standard deviation score and BP loads were found higher in diabetic adolescents. Urine NGAL levels were found to be correlated with albumin/creatinine ratio (r=0.452, p=0.002), whereas plasma NGAL levels were correlated with nighttime systolic BP load (r=0.309, p=0.037). Patients with high-normal albuminuria (n=6) had higher urine NGAL levels [48.7 ng/mL (range, 27.9–149.1 ng/mL) vs. 14.3 ng/mL (range, 3.5–41 ng/mL), p=0.014] and urine NGAL/creatinine ratio [39.3 ng/mg (range, 21.1–126.3 ng/mg) vs. 11.8 ng/mg (range, 6.3–40.9 ng/mg), p=0.03] compared with those of controls and higher urine NGAL levels compared with that of diabetic adolescents with low-normal albuminuria [n=40, 11.2 ng/mL (range, 6–23.4 ng/mL), p=0.004]. Conclusions: Normoalbuminuric and normotensive adolescents with type 1 diabetes have elevated urinary NGAL values, which might indicate kidney injury.

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey

Abstract Aim: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). Methods: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4±5.6 years (range, 0.08–16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9±4.5 years. Results: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke’s cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p=0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p=0.021). Conclusions: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

A Novel Homozygous Mutation in the Transient Receptor Potential Melastatin 6 Gene: A Case Report

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease caused by mutations in the transient receptor potential melastatin 6 (TRPM6) gene. Affected individuals present in early infancy with seizures caused by the severe hypocalcemia and hypomagnesemia. By presenting this case report, we also aimed to highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia. A Turkish inbred girl, now aged six years, had presented to another hospital at age two months with seizures diagnosed to be due to hypomagnesemia. She was on magnesium replacement therapy when she was admitted to our clinic with complaints of chronic diarrhea at age 3.6 years. During her follow-up in our clinic, she showed an age-appropriate physical and neurological development. In molecular genetic analysis, a novel homozygous frame-shift mutation (c.3447delT>p.F1149fs) was identified in the TRPM6 gene. This mutation leads to a truncation of the TRPM6 protein, thereby complete loss of function. We present the clinical follow-up findings of a pediatric HSH case due to a novel mutation in the TRPM6 gene and highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia.

Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing.

Abstract Aim: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship. Methods: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses. Results: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations – three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic. Conclusion: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.

Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation

Abstract 3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score –5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score –5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8–10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.