Papers by Dragan Zdravković
Paediatrics Today, May 9, 2010
![Research paper thumbnail of [Causes of ambiguous external genitalia in neonates]](https://attachments.academia-assets.com/118749891/thumbnails/1.jpg)
Srpski arhiv za celokupno lekarstvo
The classification of disorders such as ambiguous genitalia in newborns is difficult because simi... more The classification of disorders such as ambiguous genitalia in newborns is difficult because similar or identical phenotypes could have several different aetiologies. In most cases it was impossible to correlate the aetiology of the disorder and the appearance of the external genitalia [1-3]. A newborn with ambiguous genitalia needs prompt evaluation that will permit gender assignment and detection of life-threatening conditions (salt-losing crisis due to congenital adrenal hyperplasia or Wilms' tumour). We studied the causes and characteristics of ambiguous genitalia in newborn infants over the period from 1990 to 1999. The following genital phenotypes are considered as ambiguous: 1. Hypospadias with no palpable gonads; 2. Hypospadias with micropenis and no palpable gonads or one palpable gonad; 3. Newborn with female external genitalia and a gonadal mass in labia or labial fusion and/or clitoral enlargement [1, 4]. The diagnostic evaluation of newborns with ambiguous genitalia...
European Journal of Pediatrics, 2010
Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTHre... more Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTHresistant adrenal insufficiency, autonomic dysfunction, and neurodegeneration. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Over the period 1977-2008 we evaluated ten subjects with the clinical diagnosis of triple A syndrome. Molecular analysis was performed in seven patients and revealed that all except one are compound heterozygotes for two mutations in the AAAS gene. Two novel mutations were detected: c.123+2T>C resulted in splice defect while c.1261_1262insG mutation resulted in a truncated protein (p.V421fs), which most probably is not functional. Genotype-phenotype correlation could not be established. In all our patients, except one sibling of previously diagnosed brother and sister, genetic analysis was performed when at least two symptoms were present, usually alacrima and achalasia. Based on our experience, we recommend that in case of the presence of alacrima and at least one more symptom of triple A syndrome, adrenal function testing and molecular analysis should be performed. In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted.
Digestive and Liver Disease, 2013
Biochemical Definitions and Insulin Sensitivity Plasma glucose, insulin and lipid levels were mea... more Biochemical Definitions and Insulin Sensitivity Plasma glucose, insulin and lipid levels were measured in blood samples obtained in the morning by venipuncture after an overnight fast. Homeostasis model assessment-insulin resistance (HOMA
![Research paper thumbnail of Endocrine Consequences of Cancer Treatment [Article in Serbian]](https://attachments.academia-assets.com/114163001/thumbnails/1.jpg)
The Central European Journal of Paediatrics, 2009
Over the past 30 years, there has been a striking improvement in the number of children who survi... more Over the past 30 years, there has been a striking improvement in the number of children who survive five or more years after malignancies. The current five year overall survival rate for childhood cancers exceeds 70%, and greater than 90% for children diagnosed with Hodgkin’s disease. It is estimated that by the year 2010, one in 250 adults will be a survivor of childhood cancer. Because of the remarkable improvement in survival, approximately two thirds of cancer survivors develop late complications. Endocrine disturbances have been documented in 20% to 65% of survivors and frequently occur as late effects of cancer therapy. Endocrine disorders are presented as hypothalamic-pituitary dysfunction, thyroid disorders and gonadal dysfunction. The damage is often subtle and abnormalities may remain subclinical for years. A variety of clinical presentations may result from complications of treatment including short stature, precocious or delayed puberty, thyroid dysfunction or tumour o...
An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by n... more An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index 490th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n ¼ 1) and impaired glucose regulation in 15.9% (n ¼ 48) of the subjects. Isolated IFG was detected in 4.3% (n ¼ 13), isolated IGT in 8.3% (n ¼ 25) and combined IFG and IGT in 3.3% (n ¼ 10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.
New England Journal of Medicine, 2004
Journal of Epidemiology & Community Health, 1995
Balkan Journal of Medical Genetics, 2011
Ring Y chromosome is a very rare chromosomal aberration. The published mixed gonadal dysgenesis (... more Ring Y chromosome is a very rare chromosomal aberration. The published mixed gonadal dysgenesis (MGD) patients with a ring Y chromosome are short in stature, but are not growth hormone (GH) deficient. We present the molecular cytogenetic and molecular characterization of ring Y chromosome mosaicism in a 10-year-old boy with MGD whose short stature could be explained by the high percentage of cells monosomic for the X-chromosome, but also by the presence of severe GH deficiency. The ring Y chromosome in our patient is a de novo structural aberration. The father's karyotype was normal.
… Specijalna bolnica za …, 2010
The assessment of thyroid function is the most frequently applied endocrine investigation in chil... more The assessment of thyroid function is the most frequently applied endocrine investigation in children and adolescents. Thyroid function tests are usually performed in order to exclude hypothyroidism as a possible cause of growth disorders, obesity, mental retardation or ...
Vojnosanitetski pregled, 2011
Background/Aim. Balancing strict glycemic control with setting realistic goals for each individua... more Background/Aim. Balancing strict glycemic control with setting realistic goals for each individual child and family can optimize growth, ensure normal pubertal development and emotional maturation, and control long term complications in children with type 1 diabetes (T1DM). The aim of this study was to evaluate the efficacy of short-term continuous glucose monitoring system (CGMS) application in improvement of glycemic control in pediatric type 1 diabetes mellitus (T1DM) patients. Methods. A total of 80 pediatric T1DM patients were randomly assigned into the experimental and the control group. The experimental group wore CGMS sensor for 72 hours at the beginning of the study. Self-monitored blood glucose (SMBG) levels and hemoglobin A1c (HbA1c) levels were obtained for both groups at baseline, and at 3 and 6 months. Results. There was a significant improvement in HbA1c (p < 0.001), in both the experimental and the control group, without a significant difference between the groups...
Primary adrenal insufficiency is an endocrine disorder characterized by cortisol and aldosterone ... more Primary adrenal insufficiency is an endocrine disorder characterized by cortisol and aldosterone deficiency caused by destruction of the adrenal cortex. Adrenal crisis is a medical emergency with acute symptoms: nausea, vomiting, abdominal pain, fever, hypoglycemia, seizures, hypovolemic shock, and cardiovascular failure. It occurs in patients with chronic adrenal insufficiency who are exposed to additional stress, such as infection, trauma, or surgical procedures. Dental infection is a possible cause of adrenal crisis in patients with chronic adrenal insufficiency, so pediatric endocrinologists and pediatric dentists should be aware of this risk. The purpose of this report was to present a 6-year-old patient in whom Addison disease was diagnosed through adrenal crisis provoked by dental infection. The patient was treated with intravenous rehydration, intravenous hydrocortisone and antibiotics, and extraction of the infected primary tooth. Multidisciplinary approach and collaboration between the pediatric endocrinologist and the pediatric dentist are necessary to enable adequate medical and dental treatment in children with primary adrenal insufficiency.
European Journal of Pediatrics, 2015
Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, pu... more Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (≥2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13-2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA-IR cutoff point of ≥2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion. Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children. What is Known: • Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. • Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children. What is New: • Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. • Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in order to maintain glucose homeostasis.
Medicinski glasnik Specijalna bolnica za bolesti stitaste zlezde i bolesti metabolizma Zlatibor, 2012
Known data suggest the need for a different approach in the treatment of obesity in the subpopula... more Known data suggest the need for a different approach in the treatment of obesity in the subpopulation of the metabolically healthy obese. Due to differences in terms of complications and treatment, these individuals should also be regarded as a separate entity in further research.
Vojnosanitetski pregled, 2014
Background/Aim. An ideal insulin regimen for children and adolescents with type 1 diabetes mellit... more Background/Aim. An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurrence of hypoglycaemic episodes in children and adolescents with T1DM. Methods. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.3%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin ...
European Journal of Pediatrics, 2008
The triple A syndrome is an autosomal recessive disorder characterized by adrenal insufficiency, ... more The triple A syndrome is an autosomal recessive disorder characterized by adrenal insufficiency, alacrima, achalasia, and impairment of the central, peripheral, and autonomic nervous system functions. The disease is caused by mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. In the present study, we report three siblings with triple A syndrome caused by a compound heterozygous mutation consisting of a novel Val421 frameshift mutation in exon 14 and a previously described Ser236Pro (T&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C transition) missense mutation in exon 8. The second mutation is one of the most frequent mutations in the AAAS gene, occurring in 17 independent patients from different countries. With haplotype analysis, we demonstrate a founder effect for at least 13 of the 17 patients. We conclude that, although very helpful in establishing the final diagnosis of triple A syndrome, DNA analysis is not useful for the prediction of the clinical expression and outcome of the disorder. Further investigations are necessary to evaluate the correlation between genotype and clinical phenotype in the triple A syndrome.
The Journal of Clinical Endocrinology & Metabolism, 2009
The aim of the study was to examine clinical characteristics, biochemical parameters, and TSH-R g... more The aim of the study was to examine clinical characteristics, biochemical parameters, and TSH-R gene variations in children and adolescents with subclinical hypothyroidism (SH) in order to evaluate their pattern of distribution in SH. Patients: We enrolled 88 patients, each having at least two TSH measurements above the upper limit of the reference range with normal free thyroid hormones and negative thyroid autoantibodies. Main Outcome Measures: Clinical characteristics included height, weight, family history of thyroid diseases, thyroid volume, and echogenicity at ultrasonography. Biochemical parameters included TSH, free thyroid hormones, thyroid autoantibodies, and adjusted daily urinary iodine excretion (UIE). Genetic variations in the TSH-R gene were assessed. Results: The prevalence of overweight/obesity, positive family history of thyroid diseases, and thyroid hypoechogenicity was 28.4, 45.5, and 22.7%, respectively. Median TSH was higher in overweight/obese patients than in normal-weight ones (7.4 vs. 5.7 IU/ml; P ϭ 0.04) and in overweight/ obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs. 6.8 IU/ml; P ϭ 0.04). Adjusted daily UIE was lower in subjects without than in those with a positive family history of thyroid diseases (81 vs. 120 g/d; P ϭ 0.001). The prevalence of a positive family history of thyroid diseases was 1.9-fold higher in patients with nonsynonymous mutations in the TSH-R gene than in patients without any mutation (80 vs. 42%; P ϭ 0.03). A novel mutation at position 1559 in exon 10 (W520X) was detected in one child. Conclusions: Overweight/obesity, thyroid hypoechogenicity, and nonsynonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.
Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Beograd KRATAK SADRŽAJ Uv... more Institut za zdravstvenu zaštitu majke i deteta Srbije "Dr Vukan Čupić", Beograd KRATAK SADRŽAJ Uvod Prerani pubertet kod devojčica obeležava razvoj sekundarnih polnih odlika pre osme, odnosno menarhe pre deve te godine. Uzroka preranog puberteta ima mnogo, a klasifikuju se u gonadotropinzavisne (centralne) i gonadotropinne zavisne (periferne) oblike. Najčešći uzroci izoseksualnog lažnog preranog puberteta su funkcionalne ciste jajnika i juvenilni tumor ćelija granuloze. Ciq rada U radu su ispitivani uzroci i kliničke i hormonske odlike izoseksualnog lažnog preranog puberteta kod de vojčica. Metod rada Ispitivawem su obuhvaćene 34 devojčice prepubertetskog uzrasta (raspon 0,59 godina, prosek 4,5 godina) koje su od 1995. do 2004. godine bolnički lečene zbog izoseksualnog preranog puberteta, odnosno prerane telarhe sa pre ranom menarhom ili bez we. Rezultati Izoseksualni lažni prerani pubertet je utvrđen kod sedam devojčica (20,6%). Uzroci preranog polnog sazre vawa kod ostalih ispitanica bili su: pravi prerani pubertet kod 10 devojčica (29,4%), izolovana prerana telarha kod 11 (32,4%) i izolovana prerana menarha kod šest devojčica (17,6%). Glavne odlike kod devojčica s izoseksualnim lažnim preranim pubertetom su: porast dojki (100%), vaginalno krvavqewe (57%), niski nivoi gonadotropnih hormona u serumu (100%), visoki nivoi estradiola (100%) i ultrazvučni nalaz ciste, odnosno tumora jednog jajnika (100%). Kod šest devojči ca uzrok je bila funkcionalna cista jajnika (kod četiri devojčice zabeleženo je spontano povlačewe, a kod dve je izvrše na ekstirpacija ciste), a kod jedne juvenilni tumor ćelija granuloze. Za razliku od wih, kod devojčica sa pravim prera nim pubertetom, pored porasta dojki (100%), utvrđeni su i: pubična kosmatost (60%), ubrzano rastewe (50%), uznapredova lo sazrevawe kostiju (70%), folikuli u oba jajnika i visoki osnovni i stimulisani (gonadotropnim oslobađajućim hormo nom) nivoi folikulostimulišućeg hormona (FSH) i luteinizirajućeg hormona (LH) (100%). Kod devojčica s izolovanom pre ranom telarhom i izolovanom preranom menarhom telesna visina, kostna zrelost, ultrazvučni nalaz na jajnicima i nivoi FSH i LH bili su u skladu s hronološkim uzrastom. Zakqučak Najčešći uzrok izoseksualnog lažnog preranog puberteta kod devojčica je funkcionalna cista jajnika, koja se često povlači spontano. Učestalost juvenilnog tumora ćelija granuloze, prema našem iskustvu, relativno je mala, a rano otkrivawe omogućava izlečewe bolesti. Diferencijalna dijagnoza obuhvata pravi prerani pubertet, izolovanu preranu telarhu i menarhu.
Medicinski glasnik Specijalna bolnica za bolesti stitaste zlezde i bolesti metabolizma Zlatibor, 2012
Childhood obesity is one of the most important present public health issues. Complications of obe... more Childhood obesity is one of the most important present public health issues. Complications of obesity once observed only in the population of obese adults, like type 2 diabetes and other disturbances in glucose regulation, are emerging in the pediatric population along with the pandemic of obesity. Prevalence of these co-morbidities of obesity varies widely in the populations of children and adults in different regions, with signifi cantly higher observed prevalence in USA compared with European countries. Results of the study performed in Institute for Mother and Child Health Care of Serbia "Dr Vukan Čupić" in a group of 301 obese children and adolescents, discovered prevalence of type 2 diabetes was 0,3%, and of other disturbances in glucose regulation, namely impaired glucose regulation and impaired glucose tolerance 16%. Although these results are not suggestive of pediatric type 2 diabetes epidemic in Serbia, high established prevalence of other disturbances in glucose homeostasis emphasizes the need for prevention and early treatment of obesity in order to avoid a decline in life expectancy in future generations of adults in Serbia.
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Papers by Dragan Zdravković