Browsing by Author "Mitrovic, Katarina (23498072800)"

This is the first report of alpha coma (AC) caused by brain edema in a patient with diabetic ketoacidosis (DKA). A previously healthy 15-year-old girl was admitted to the intensive care unit due to altered state of consciousness during the course of treatment for DKA. Patient was in a coma, intubated and had tachycardia with poor peripheral perfusion. Results of laboratory analyses indicated severe DKA and computed tomography scan indicated diffuse brain edema. The EEG pattern showed uniform alpha activity. Treatment with intravenous fluids, insulin and mannitol was started. Patient’s state of consciousness gradually improved and on the third day she was extubated. On the fifth day, her neurologic status and EEG findings were completely normal with no residual neurological deficits. In conclusion, although AC is associated with a high fatality rate, favorable outcome can be achieved with prompt recognition and treatment of cerebral edema in pediatric patients with DKA. © 2017, Turkish Journal of Pediatrics. All rights reserved.

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients. Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates.What is Known:• Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI).• Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11.What is New:• Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations.• Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

Oxidative stress is implicated in both, the onset and the progression of type 1 diabetes mellitus (T1DM). There is accumulated evidence of increased biomarkers of oxidative stress in newly diagnosed, T1DM patients without complications, and in those with advanced disease. In this cross-sectional study, we investigated factors affecting oxidative stress status in pediatric patients with T1DM. Advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), total sulfhydryl (SH) groups, and superoxide dismutase (SOD) activity were determined in 170 children and adolescents with T1DM. Principal component analysis was used to investigate clustering of clinical and laboratory variables associated with elevated oxidative stress and reduced antioxidative defense biomarkers. Factor analysis extracted five factors, interpreted as (1) "weight status factor" including age, BMI, waist and hip circumferences; (2) "proatherogenic factor" that included LDL-cholesterol, non-HDL-cholesterol, and triglycerides; (3) "metabolic control factor" including glucose and HbA1c; (4) "renal marker factor" with positive loading of urinary albumin excretion rate and negative loading of GFR; and (5) "antiatherogenic factor" that included HDL-cholesterol. High AOPP levels were independently predicted by "proatherogenic" (OR: 2.32; 95% CI: 1.44-3.71; p < 0.001), "metabolic control" (OR: 2.24; 95% CI: 1.35-3.73; p < 0.01), and "renal marker" (OR: 1.65; 95% CI: 1.03-2.65; p < 0.05) factors. "Renal marker factor" was a significant predictor of PAB (OR: 0.52; 95% CI: 0.34-0.81; p < 0.01). Regarding antioxidative defense markers, reduced SH groups were predicted by "proatherogenic factor" (OR: 0.56; 95% CI: 0.34-0.94; p < 0.05), while "weight status factor" predicted lower SOD activity (OR: 1.66; 95% CI: 1.03-2.67; p < 0.05). Cardiometabolic risk factors and renal function are associated with oxidative stress in pediatric T1DM patients. © 2020 2020 Walter de Gruyter GmbH, Berlin/Boston.

Oxidative stress is implicated in both, the onset and the progression of type 1 diabetes mellitus (T1DM). There is accumulated evidence of increased biomarkers of oxidative stress in newly diagnosed, T1DM patients without complications, and in those with advanced disease. In this cross-sectional study, we investigated factors affecting oxidative stress status in pediatric patients with T1DM. Advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), total sulfhydryl (SH) groups, and superoxide dismutase (SOD) activity were determined in 170 children and adolescents with T1DM. Principal component analysis was used to investigate clustering of clinical and laboratory variables associated with elevated oxidative stress and reduced antioxidative defense biomarkers. Factor analysis extracted five factors, interpreted as (1) "weight status factor" including age, BMI, waist and hip circumferences; (2) "proatherogenic factor" that included LDL-cholesterol, non-HDL-cholesterol, and triglycerides; (3) "metabolic control factor" including glucose and HbA1c; (4) "renal marker factor" with positive loading of urinary albumin excretion rate and negative loading of GFR; and (5) "antiatherogenic factor" that included HDL-cholesterol. High AOPP levels were independently predicted by "proatherogenic" (OR: 2.32; 95% CI: 1.44-3.71; p < 0.001), "metabolic control" (OR: 2.24; 95% CI: 1.35-3.73; p < 0.01), and "renal marker" (OR: 1.65; 95% CI: 1.03-2.65; p < 0.05) factors. "Renal marker factor" was a significant predictor of PAB (OR: 0.52; 95% CI: 0.34-0.81; p < 0.01). Regarding antioxidative defense markers, reduced SH groups were predicted by "proatherogenic factor" (OR: 0.56; 95% CI: 0.34-0.94; p < 0.05), while "weight status factor" predicted lower SOD activity (OR: 1.66; 95% CI: 1.03-2.67; p < 0.05). Cardiometabolic risk factors and renal function are associated with oxidative stress in pediatric T1DM patients. © 2020 2020 Walter de Gruyter GmbH, Berlin/Boston.

Most of what is known about the metabolically healthy obese phenomenon is derived from studies in the adult population and no standardized criteria to identify these individuals exist to date. The aim of this study was to determine if the preserved insulin sensitivity evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) index is associated with favorable metabolic profile in the obese children. We studied a group of 248 children and adolescents (150 female, 98 male), aged 5.9-18.9 years with diet-induced obesity (BMI >95th percentile). The entire cohort was divided into quartiles based on levels of insulin resistance determined by HOMA-IR index. Subjects in the lower quartile of HOMA-IR were classified as insulin-sensitive group (ISG), whereas children in the upper quartile were categorized as insulin-resistant group (IRG). The ISG subjects had values of HOMA-IR ≤2.75 while the children from the IRG group had HOMA-IR ≥6.16. Subjects from ISG group had lower basal β-cell activity and were less likely to have impaired fasting glucose or impaired glucose tolerance. Concentrations of LDL and total cholesterol, triglycerides, and transaminases were lower and HDL cholesterol levels were higher in ISG subjects. Findings obtained by the use of Matsuda index correlated well with the findings obtained by the use of HOMA-IR. Conclusion: Lower HOMA-IR values were significantly associated with favorable metabolic profile in studied children, which correlates with findings in the adult population and emphasizes the need for further, longitudinal studies of insulin resistance development in childhood obesity. © 2012 Springer-Verlag Berlin Heidelberg.

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. © 2015 Elsevier Inc.

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients. © 2015 Elsevier Inc.

Objective: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). Design: Single-center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD. © 2021, BioScientifica Ltd. All rights reserved.

Objective: To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP). Design: Single-center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP. Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%). Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD. © 2021, BioScientifica Ltd. All rights reserved.

Objective: To assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia. Subjects and methods: The study group consisted of 254 subjects (148 female and 106 male), aged 4.6-18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices. Results: Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity. Conclusions: High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity. © 2015 by De Gruyter.

Objective: To assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia. Subjects and methods: The study group consisted of 254 subjects (148 female and 106 male), aged 4.6-18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices. Results: Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity. Conclusions: High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity. © 2015 by De Gruyter.

Children with a classic form of congenital adrenal hyperplasia (CCAH) have a potentially increased risk of unfavorable cardiometabolic events due to the interplay of corticosteroid treatment, hyperandrogenism, and other factors. Although readily recognized in adults, these aspects are frequently overlooked in children and youth with CCAH; Aim: To review the evidence available from studies regarding cardiometabolic health outcomes in CCAH patients; Methods: A review of the literature was performed following PRISMA guidelines, including studies published between 2000 and 2024. We included studies reporting cardiometabolic outcomes in children and adolescents (<18 years) with CCAH. Where pediatric data were sparse, additional data were obtained from studies with older adolescents and young adults (15–25 years). Cardiometabolic outcomes included risk factors, such as obesity, insulin resistance, lipids, blood pressure, and vascular markers; Results: Twenty-five studies were analyzed. The prevalence of obesity was found to be higher in children with CCAH, as well as of increased visceral adiposity. Higher indices of insulin resistance were also a frequent finding in children with CCAH. CCAH patients had higher systolic blood pressure and more frequently loss of nocturnal blood pressure dipping, particularly among salt-wasting subtypes and in younger children. Subclinical atherosclerosis was indicated by increased carotid intima–media thickness, elevated hs-CRP, and impaired endothelial function. Other findings suggested changes in lipid profiles, particularly decreased HDL-c and increased triglycerides, although the findings were less consistent; Conclusions: Compared with the general pediatric population, children with CCAH were found to have an increase in multiple cardiometabolic risk factors. It is therefore vital to monitor these risk factors in pediatric CCAH, as well as tailoring treatment with cardiometabolic health in mind, to achieve better long-term cardiovascular and metabolic outcomes. Future research should focus on longitudinal studies of cardiometabolic outcomes and innovative therapeutic approaches to reduce these risks in patients with CCAH. © 2025 by the authors.

Children with a classic form of congenital adrenal hyperplasia (CCAH) have a potentially increased risk of unfavorable cardiometabolic events due to the interplay of corticosteroid treatment, hyperandrogenism, and other factors. Although readily recognized in adults, these aspects are frequently overlooked in children and youth with CCAH; Aim: To review the evidence available from studies regarding cardiometabolic health outcomes in CCAH patients; Methods: A review of the literature was performed following PRISMA guidelines, including studies published between 2000 and 2024. We included studies reporting cardiometabolic outcomes in children and adolescents (<18 years) with CCAH. Where pediatric data were sparse, additional data were obtained from studies with older adolescents and young adults (15–25 years). Cardiometabolic outcomes included risk factors, such as obesity, insulin resistance, lipids, blood pressure, and vascular markers; Results: Twenty-five studies were analyzed. The prevalence of obesity was found to be higher in children with CCAH, as well as of increased visceral adiposity. Higher indices of insulin resistance were also a frequent finding in children with CCAH. CCAH patients had higher systolic blood pressure and more frequently loss of nocturnal blood pressure dipping, particularly among salt-wasting subtypes and in younger children. Subclinical atherosclerosis was indicated by increased carotid intima–media thickness, elevated hs-CRP, and impaired endothelial function. Other findings suggested changes in lipid profiles, particularly decreased HDL-c and increased triglycerides, although the findings were less consistent; Conclusions: Compared with the general pediatric population, children with CCAH were found to have an increase in multiple cardiometabolic risk factors. It is therefore vital to monitor these risk factors in pediatric CCAH, as well as tailoring treatment with cardiometabolic health in mind, to achieve better long-term cardiovascular and metabolic outcomes. Future research should focus on longitudinal studies of cardiometabolic outcomes and innovative therapeutic approaches to reduce these risks in patients with CCAH. © 2025 by the authors.

Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". Case presentation: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. Conclusions: This is the first described case of a child with PHH following esophageal reconstruction. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". Case presentation: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. Conclusions: This is the first described case of a child with PHH following esophageal reconstruction. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

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. Conclusion: 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. © 2015, Springer-Verlag Berlin Heidelberg.

Purpose: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test. Methods: A prospective, case–control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis. Results: Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model. Conclusions: Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Purpose: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test. Methods: A prospective, case–control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis. Results: Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model. Conclusions: Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.