An essential indicator of children's health is weight gain and general growth reflecting development, making the understanding of abnormal growth and maturation patterns crucial for early intervention and long-term health outcomes. The Maturity–Development–Nutrition (MDN) matrix method enables the easy identification of intrauterine growth retardation during the newborn period, which can increase the risk of stillbirth and infant mortality. The main purpose was to examine the birth status (length of prenatal development, body length, body weight, nutritional status) of children with classic growth hormone deficiency treated with growth hormone using the MDN matrix method. We examined the birth status of 98 children (67 boys, 31 girls) with isolated growth hormone deficiency who were treated at the North Buda St. John’s Centre Hospital, between 1975 and 2016. We analysed birth status using data on the children’s gestational age, sex, birth length and birth weight. Centile values for birth length and weight were determined using national reference series corresponding to birth year, gestational age and sex. The MDN matrix was used to assess newborn nutritional status and intrauterine growth retardation type. Children with growth hormone deficiency have a prenatal development length that is similar to the Hungarian reference values. However, their birth length and weight were lower than the domestic reference series. According to the MDN matrix method, their nutritional status was similar to that of children born between 2000 and 2012. However, 34.69% of the children were growth-retarded according to their birth developmental status, which was significantly higher than the frequency observed in the children included in the reference series. The results confirm that the MDN method may be appropriate for identifying newborns who would benefit from early investigations to diagnose growth hormone deficiency.

Regular monitoring of children's nutritional status is essential to prevent micronutrient deficiencies, nutritional status abnormalities as stunting, wasting, overweight and obesity. Nutritional status assessment is usually performed by paediatricians by using anthropometry (body mass index, weight to height indices) and/or by body fat-mass measurement (bioimpedance analysis, dual-energy x-ray absorptiometry, computer tomography, etc.). Parents are also interested in but usually fail to evaluate their child's nutritional status. To help the sufficient collaboration between the physician and parents a new nutritional status monitoring method is developed for families. The new monitoring system was developed under a paediatrician's supervision by considering national and international recommendations, references as well as the anthropometric measurement possibilities at home. The model requires age, sex, body mass, height, waist circumference and hand circumference as predictor (input) variables of nutritional status, while (1) the centile values of the measured body dimensions, (2) body fat percentage and the centile of body fat percentage, (3) the nutritional status category (undernutrition, normal nutritional status, overfat/obese) can be predicted (outcome variables) by the new method. The predictive accuracy of the model for nutritional status category was 94.88% in boys and 98.66% in girls. The new model was developed for nutritional status assessment in school-aged children and will be incorporated in the healthy lifestyle module of 'Teenage Survival Guide' educational package to be developed by the Health Promotion and Education Research Team, Hungarian Academy of Sciences, Hungary. The new monitoring system could help the families to identify the early signs of malnutrition in children. Nutritional status assessment in children at home is suggested twice a year, and in case of suspicious nutritional status abnormality it is recommended to visit the general practitioner.

Graves’-Basedow’s disease (GD) is a well-defined hyperthyroid disorder caused by circulating antibodies that results the overproduction of thyroid hormones. All but a few children present with some degree of thyroid gland enlargement and most have two or more signs of excessive thyroid activity, such as tremor, irritability/nervousness, tachycardia etc. Fully developed clinical picture is easy to recognize while often the onset is insidious. Thyroid hormones affect many body systems, so signs and symptoms of Graves’ disease can be wide ranging. A survey on PubMed literature was conducted to gather all published pediatric Graves-Basedow’s cases with unusual presentation at the time of diagnosis. We found all together 70 manuscripts with relevant information from 1978 to 2020 but mainly adult cases. One third of them were found to meet the criteria we focused on and were included in this paper, though in some situation the unusual findings do not consist part of hyperthyroidism, the rare manifestation is only a coexistence, or the serious disease even precedes the GD. Dermatopathy, hepatic dysfunction, impaired fluid balance, concomitant disorders in thyrotoxicosis, tricky laboratory findings, a phenomenon of metamorphic thyroid autoimmunity, peculiarities of thyroid dysfunction in children with Down syndrome, apparent associations, and reconstitution GD are highlighted in this chapter. Awareness about the relation of these remote findings to GD, or frequent coexistence with GD is important for early diagnosis. Finally, a reasonable suspicion for Graves’ disease may ultimately help to prevent unnecessary investigations and treatment.

The health status of an individual is determined not only by their genetic background but also by their physical environment, social environment and access and use of the health care system. The Roma are one of the largest ethnic minority groups in Hungary. The majority of the Roma population live in poor conditions in segregated settlements in Hungary, with most experiencing higher exposure to environmental health hazards. The main aim of this study was to examine the biological health and aging status of Roma women living in low socioeconomic conditions in Hungary.

The frequency of X chromosome loss in women increases with ageing. Numerous cases have linked the numerical reduction of sex chromosomes to the development of malignant tumours, recurrent miscarriages and Alzheimer’s disease. The main aim of the study was to investigate the age pattern and secular trend of the cytological ageing (X chromosome loss), as well as to analyse the relationship between the level of chromosome loss and body and bone structural parameters in adult women. Twenty-one women aged between 20–40 years were enrolled to the present study. Body mass components were estimated by body impedance analysis, bone structure was estimated by quantitative ultrasound technique. Cellular ageing was assessed by X chromosome loss estimation (using FISH probe). The results revealed an increased level of X chromosome loss in women aged between 21–30 compared to their age-peers lived decades before, and women aged between 31–40 and studied in 2021. By considering the body and bone structural profile (another indicator of their biological status) of women in the younger age-group, an increased fat component and a decreased skeletomuscular component could be described in this age-group. The results are rather preliminary, that aimed to explore explanatory components in the changes in the rate of X chromosome loss. In order to establish the findings, further investigations, as well as the increase of the sample size is required.

Abstract Objectives GX-H9 is a long-acting form of recombinant human GH under clinical development for both adults and children with GHD. In this report, 24-month efficacy and safety of once weekly and every other week (EOW) administration of GX-H9 were evaluated, in addition to Genotropin® switch-ability to GX-H9 after 12-month of treatment. Methods Subjects were randomly assigned to receive either one of three doses of GX-H9 (0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week) or 0.03 mg/kg/day of Genotropin®. Treatment duration is 24-month for all patients in GX-H9 arms while patients in Genotropin® arm were re-randomized to one of three doses of GX-H9 at the completion of the first 12-month of treatment. Doses of GX-H9 were adjusted throughout the treatment period whenever necessary, based on IGF-1 levels. Results Out of 56 randomized, 54 received either GX-H9 or Genotropin®. Fifty subjects completed the 12-month treatment period. Of 50, 45 subjects completed the next 12-month, comprising 33 patients from GX-H9 and 12 patients who switched from Genotropin®. First year/second year mean±SD annualized height velocity (aHV) for 0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week of GX-H9 were 10.50±2.54/9.14±1.96, 11.76±1.96/9.88±1.92 and 11.03±2.92/9.72±1.90 cm/year, respectively. First year mean±SD aHV for Genotropin® was 9.14±3.09 cm/year. Patients switched to one of the three doses of GX-H9 in the second year showed comparable aHV in the second year (8.73±2.69/7.60±0.90/9.13±1.07 cm/year for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg/EOW GX-H9, respectively). No significant slow-down of the growth was observed in the second year from patients who received GX-H9 throughout and patients who switched from Genotropin®. Mean change in height SDS after 12 months/24 months of GX-H9 treatment throughout from baseline treatment improved continuously (+1.10/+1.61 and +1.31/+1.89 and +1.15/+1.69 for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg EOW GX-H9, respectively). First year mean change in height SDS for Genotropin® was +0.92 SDS, and showed comparable improvement in height SDS after switching to GX-H9 weekly arms (+0.76 and +0.79 SDS for 0.8 mg/kg/week and 1.2 mg/kg/week, respectively). Most treatment-emergent adverse events were evaluated as unrelated to the study drug and were mild or moderate in severity. No new safety concerns were observed throughout 24 months of long-term GX-H9 treatment or after switching to GX-H9 from Genotropin®.Conclusions Growth response and safety profile of GX-H9 in children with GHD is comparable to those of daily GH, achieving robust growth rates after 24-month treatment. Subjects switched from Genotropin® in the second year, also showed substantial catch-up growth indicated by improvement in height SDS. GX-H9 has a unique potential to be a convenient long-term GH providing not only weekly but also twice-monthly treatment.

Growth hormone deficiency (GHD) in children is a rare, aetiologically diverse condition that results in growth failure and short stature. Inadequate response to two different growth hormone stimulation tests (GHST) is required for the diagnosis of GHD. Macimorelin acetate, a potent, orally administered growth hormone (GH) secretagogue, is approved by the FDA and EMA for the diagnosis of adult GHD. Study AEZS-130-P01 is the first of two studies to investigate macimorelin acetate as a diagnostic test in children with suspected GHD. This was an open-label, group comparison, dose escalation trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single-dose 0.25, 0.5 and 1 mg/kg oral macimorelin acetate in paediatric subjects with suspected GHD. The macimorelin GHST was administered between two standard GHST, conducted as per local clinical practice, with a recovery period of 7-28 days between tests. Blood samples were collected pre-dose (±15 min) and 15, 30, 45, 60, 90, 120 and 360 minutes after macimorelin acetate intake. Overall, 24 paediatric subjects (8 per cohort [C1, C2, C3]) were included in the pharmacokinetic/pharmacodynamic (PK/PD) analysis. Five males and 3 females were observed in C1 and C2, 7 males and 1 female in C3. In all three cohorts, at least 3 subjects represented Tanner stages I or II. All 24 subjects (100%) were white, with a median age of 9.8, 9.0 and 10.5 years (range 4-15 years) and a median body-mass index of 16.1 kg/m2 (12.4-21.4 kg/m2) at screening. Overall, 88 adverse events were reported, many related to the standard GHST; none were considered related to the macimorelin test. Maximum plasma concentrations for macimorelin were mainly observed between 30-45 min. The mean Cmax values were 3.46, 8.13 and 12.87 ng/ml for C1, C2, and C3, respectively. The AUCs increased with dose; the mean AUC0-6 values were 6.69, 18.02 and 30.92 h*ng/mL. The mean elimination half-lives were 1.22, 1.61 and 1.71 h, respectively. PK and PD profiles for all three cohorts were comparable, with peak GH levels mainly observed within 30-60 min following macimorelin intake. Macimorelin acetate was safe and well tolerated in all dosing cohorts. A dose-dependent increase in macimorelin Cmax and AUC in children and adolescents correlated well with data from adult subjects. A robust dose-proportional GH response was also achieved. PD results showed that GH response was comparable in all dose groups, with a slight shift to earlier tmax at higher macimorelin doses.

Objectives: The precise age estimation is of high importance in bone mineral density (BMD) assessment in children, since the bone structure of a studied child is evaluated by using the age and gender dependent references. In addition, the biological age - the bone age in this case - estimation could help this bone structural evaluation process, since the developmental status of the skeletal system can significantly alter from the theoretical developmental status determined by chronological age in healthy, but early or late maturing children. The aims of the study were (1) to check whether volumetric BMD (vBMD) Z-scores estimated by considering chronological age and biological age differ significantly in children aged between 7-18 years, and (2) in the case of significant inaccuracy of Z-score estimation based on chronological age to construct new vBMD standards adjusted for body developmental status. Subjects and methods: Body structural and densitometry data of 476 healthy children aged between 7 and 18 years were used in the analysis. pQCT measurements were performed at the distal radius using Stratec XCT-2000 equipment (Stratec Inc, Germany). The centile curves of vBMD parameters were estimated by using lmsChartMaker Pro 2.3 software. Ulnar length age was used as biological age in the analysis. Results: The total and 'cortical + subcortical' vBMD changed by age in the studied age interval in both genders, while the trabecular vBMD showed significant change by age only in females. Our results confirmed that when the biological age of a child significantly differs from her/his chronological age, vBMD evaluation should be done by considering her/his biological age. Due to the increase in individual variability of rate and timing of pubertal developmental processes, the sensitivity of vBMD evaluation by considering body developmental status was the lowest in the age between 12 and 16 years in the boys and between 10 and 12 years in the girls. Therefore the suggested vBMD adjustments for biological ages are highly recommended to use at least in children with ages outside these age intervals. Conclusion: If the estimation of any biological age cannot be carried out, vBMD references adjusted for height or other body dimensions should be used in the bone health status estimation in children.

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.

Turner-syndrome is a genetic disorder that involves X-chromosome, and affects about 2500–3000 newborn girls around the world. The disease is accompanied by numerous clinical and morphological characteristics, therefore it is very important to study Turner-syndrome patients’ developmental pattern. The main aim of the study was to examine the relationship between the morphological characteristics, the karyotype and the type of treatment of patients with Turner's syndrome. Twenty girls and women with Turner-syndrome were studied. The presence or the absence of the morphological characteristics (cubitus valgus, webbed neck, low hairline, four finger crease, short metacarpals and -tarsals, vision problems, low-set ears, spinal malformations, dental malformations) was recorded. The strength of the relationship between the frequency of the examined morphological features and the type of karyotype or treatment was analysed by Fisher’s exact test. Cubitus valgus, low-set ears, and dental malformations were the most common morphological abnormalities. Webbed neck, four finger crease and short metacarpals and -tarsals showed significant correlation with the karyotype. We didn’t find any correlation of morphological characteristics with the hormone treatment.

Abstract: Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2–15% of patients with idiopathic short stature (ISS), in 50–90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351–1356.

INTRODUCTION The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2-15% of patients with idiopathic short stature (ISS), in 50-90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. AIM The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. METHOD A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. RESULTS 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. CONCLUSIONS The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351-1356.

Absztrakt: Bevezetes: A SHOX gen izolalt haploinsufficientiaja az alacsonynovest okozo monogenes elvaltozasok leggyakoribb oka. A gen heterozigota elterese az idiopathias alacsonynovessel (ISS) diagnosztizalt betegek 2–15%-aban, Leri–Weill-dyschondrosteosis szindroma (LWS) 50–90%-aban, valamint a Turner-szindromaban szenvedők csaknem 100%-aban igazolhato. Celkitűzes: A SHOX gen haploinsufficientiaja gyakorisaganak meghatarozasa ISS-sel es LWS-sel diagnosztizalt, valamint Turner-fenotipusu, de normalis karyotypussal rendelkező betegek (TF) koreben, valamint beazonositani a SHOX genelteresre jellemző dysmorphias jeleket. Modszer: Osszesen 144 betegben kerult sor a SHOX gen haploinsufficientia-vizsgalatara multiplex ligatios proba Amplifikacio (MLPA) modszerrel. A betegek klinikai adatai (auxologiai parameterek, csontrendszeri rendellenessegek, dysmorphias tunetek) es a pozitiv genotipus kozotti osszefuggeseket statisztikai modszerekkel elemeztek. Eredmenyek: A vizsgalt 144 betegből 11 (7,6%) eseteben igazolodott SHOX genelteres, női dominanciaval (8/11, 81%). A SHOX-pozitiv betegeknek szignifikansan magasabb volt a testtomegindexe (BMI) (5/11-ből vs. 20/133-bol mutatott emelkedett erteket, p<0,02), es gyakoribbak voltak a dysmorphias tunetek (9/11 vs. 62/133, p = 0,02). A felső vegtagokon megjelenő Madelung-deformitas SHOX-pozitiv betegek kozott szinten szignifikansan gyakrabban fordult elő (4/11, 36% vs. 14/133, 10%, p = 0,0066), mint a SHOX-negativakban, de a vizsgalatkori eletkor, az alacsonynoves merteke, valamint az auxologiai meresek alapjan szamolt testaranyok nem mutattak statisztikailag kimutathato kulonbseget a ket csoport kozott. Kovetkeztetesek: A SHOX gen haploinsufficientiajanak előfordulasi gyakorisaga a vizsgalt betegpopulacionkban megegyezik az irodalmi adatokkal. SHOX-pozitiv esetekben, az idiopathias alacsonynoves mellett, a dysmorphias elvaltozasok pozitiv prediktiv ertekkel birnak a SHOX genelvaltozasok fennallasara. Ugyanakkor a dysmorphias jegyet nem mutato, de genetikailag pozitiv eset arra utal, hogy a SHOX gen vizsgalata indokolt dysmorphias tunetet nem mutato idiopathias alacsonynoves eseten is. Orv Hetil. 2017; 158(34): 1351–1356. | Abstract: Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2–15% of patients with idiopathic short stature (ISS), in 50–90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351–1356.

OBJECTIVES:The estimation of skeletal maturity is a useful tool in pediatric practice to determine the degree of delay or advancement in growth disorders and the effectiveness of treatment in conditions that influence linear growth. Skeletal maturity of children is commonly assessed using either Greulich-Pyle (GP) or Tanner-Whitehouse methods (TW2 and TW3). However, a less invasive ultrasonic method, that does not use ionizing radiation, has been suggested for use in epidemiological studies of skeletal maturity. The main purpose of the present study was to determine the accuracy of an ultrasonic method based on the GP maturity indicators compared to the standard GP radiographic method.METHODS:Skeletal maturity of 1502 healthy children, aged from 6 to 18 years, was estimated by quantitative ultrasound and compared to GP bone ages estimated from left hand and wrist radiographs of a subsample of 47 randomly selected participants.RESULTS:The ultrasonic bone age estimation demonstrated very strong correlations with all the radiological age estimations. The correlation coefficients ranged between 0.895 and 0.958, and the strongest correlation of ultrasonic skeletal maturity estimation was found with the Tanner-Whitehouse RUS method. The ultrasonic bone age estimation is suggested for use between the chronological ages of 8.5-16.0 years in boys and 7.5-15.0 years in girls.CONCLUSIONS:The ultrasonic bone age estimation is suggested for use in epidemiological surveys since the sensitivity for screening for not normal bone development is appropriate, at least within the 8-15 years age interval.

The analysis of bone age estimations performed by radiological and ultrasonic methods in children aged between 7–17 years. In the paediatric practice skeletal development estimation is a useful tool to examine the level of growth abnormality in the diagnosis and the analysis of the medical treatment effectiveness of children with constitutional delay of growth, growth hormone deficiency, hypothyroidism and other severe chronic illnesses that have significant influence on linear growth. Skeletal maturity of living children is commonly is assessed by using Greulich–Pyle (GP) and Tanner–Whitehouse methods (TW) in the clinical practice in the diagnostic radiography. However, an ultrasonic method was suggested to use in the epidemiological studies of skeletal maturity from the beginning of the 2000s. The aim of the study were to analyse the skeletal maturity estimations of GP, TW2 and TW3 methods by a meta-analysis of former bone age studies and by a comparison of radiological bone estimates; as well as to analyse the accuracy of an ultrasonic method (based on the GP estimation) compared to the GP standard radiographic method. Bone age of healthy children (n: 1648, aged between 7 and 17 years) was estimated by a quantitative ultrasonic Sunlight BoneAge device. In addition, TW2, TW3 and GP bone ages were estimated from radiographs taken from the left wrist-hand region in a randomly selected subsample (n: 47) of subjects. Meta-analysis of radiological skeletal age assessments from the late 1950s was done including the present study. The TW2 and TW3 skeletal age estimations differed from the chronological age of 11 years in the boys and from the beginning of studied age interval in the girls. The GP method showed very strong correlation with both the TW3 RUS and TW3 CA bone age estimations. The CA estimates had a significant decreasing tendency with GP estimates by chronological age in both genders due to the special pattern of carpal maturation. The ultrasonic bone age estimation is suggested to use between the chronological ages 8.5–16 years in the boys and 7.5–15 years in the girls. The very strong correlation of radiological and ultrasonic bone age estimates gives us the possibility to use the ultrasonic bone age estimation in epidemiological surveys to assess skeletal maturity in children without the use of ionizing radiation.