A new monitoring system for nutritional status assessment in children at home.

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.

Body structural and cellular aging of women with low socioeconomic status in Hungary: A pilot study.

OBJECTIVES: 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. METHODS: Low SES Roma (n: 20) and high SES non-Roma women (n: 30) aged between 35 and 65 years were enrolled to the present analysis. Body mass components were estimated by body impedance analysis, bone structure was estimated by quantitative ultrasound technique. Cellular aging was assessed by X chromosome loss estimation. Data on health status, lifestyle and socioeconomic factors were collected by questionnaires. RESULTS: The results revealed that low SES women are prone to be more obese, have a higher amount of abdominal body fat, and have worse bone structure than the national reference values. A positive relationship was found between aging and the rate of X chromosome loss was detected only in women with low SES. Waist to hip ratio, existence of cardiovascular diseases and the number of gravidities were predictors of the rate of X chromosome loss in women. CONCLUSIONS: The results suggested that age-adjusted rate of X chromosome loss could be related to the socioeconomic status.

A proposal for the adjustment of bone mineral density for body dimensions in children.

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.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macimorelin in Children with Suspected Growth Hormone Deficiency: An Open-Label, Group Comparison, Dose-Escalation Trial.

BACKGROUND/AIMS: Diagnosis of growth hormone deficiency (GHD) in children requires the use of provocative growth hormone (GH) stimulation tests, which can have limited reliability and are potentially contraindicated in some patients. This is the first paediatric study to test the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of macimorelin, an oral GH secretagogue, approved for diagnosis of adult GHD. METHODS: In this open-label, group comparison, single-dose escalation trial (EudraCT 2018-001988-23), sequential cohorts of patients (C1-C3) received ascending single doses of macimorelin: 0.25 (C1), 0.5 (C2), and 1.0 (C3) mg/kg. Primary endpoints were safety and tolerability, and secondary endpoints were PK/PD. RESULTS: Twenty-four patients aged between 2 and <18 with suspected GHD participated in the study. No macimorelin-related adverse events were reported, and macimorelin was well tolerated. Plasma macimorelin concentrations increased with dose: mean areas under the curve were 6.69 (C1), 18.02 (C2), and 30.92 (C3) h × ng/mL; mean maximum concentrations were 3.46 (C1), 8.13 (C2), and 12.87 (C3) ng/mL. GH concentration increased following macimorelin administration: mean times of maximum measured concentration were 52.5 (C1), 37.5 (C2), and 37.5 (C3) min. CONCLUSION: All 3 doses of macimorelin had excellent safety and tolerability with PK/PD profiles in expected ranges. These results support the use of 1.0 mg/mL macimorelin in a Phase 3 test validation trial in children.

[The prevalence of SHOX gene deletion in children with idiopathic short stature. A multicentric study]. / A SHOX géndeletio elofordulása idiopáthiás alacsonynövésben. Multicentrikus tanulmány.

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.

A comparison of skeletal maturity assessed by radiological and ultrasonic methods.

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.

[Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism]. / Kombinált l-tiroxin és l-trijód-tironin hormonpótlás congenitalis hypothyreosisban.

INTRODUCTION: L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. AIM: To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. METHOD: Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 µg/kg) once a day. RESULTS: The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 µg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. CONCLUSIONS: According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Congenital disorders of the thyroid: hypo/hyper.

This article summarizes the ontogenesis and genetics of the thyroid with regards to its possible congenital dysfunction and briefly refers to the roles of the mother-placenta-fetal unit, iodine effect, and organic and functional changes of the negative feedback mechanism, as well as maturity and illness, in some forms of congenital hypo- and hyperthyroidism. This article also describes the published literature and the authors' data on the clinical aspects of congenital hypothyroidism, on the alternating hypo- and hyperthyroidism in the neonatal period, and on neonatal hyperthyroidism.

Growth hormone and treatment outcomes: expert review of current clinical practice.

Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient followup every 3-6 months, and that growth and adherence should be monitored at each visit. Growth response is variable, and an accepted definition of good/poor response is lacking. Combined with patient education and regular patient follow-up, a definition of treatment response could lead to improved treatment outcomes. Few experts use prediction models in clinical practice, but all agree that pharmacogenetics might improve prediction, enable early therapy modulation, and promote growth. Poor growth is often due to low adherence. Guidance on optimal management of growth hormone therapy is required, with focus on early diagnosis, dosing, treatment monitoring, adherence, and motivation.

Congenital disorders of the thyroid: hypo/hyper.

This article summarizes the ontogenesis and genetics of the thyroid with regards to its possible congenital dysfunction and briefly refers to the roles of the mother-placenta-fetal unit, iodine effect, and organic and functional changes of the negative feedback mechanism, as well as maturity and illness, in some forms of congenital hypo- and hyperthyroidism. This article also describes the published literature and the authors' data on the clinical aspects of congenital hypothyroidism, on the alternating hypo- and hyperthyroidism in the neonatal period, and on neonatal hyperthyroidism.

High prevalence of PROP1 gene mutations in Hungarian patients with childhood-onset combined anterior pituitary hormone deficiency.

Combined pituitary hormone deficiency is characterized by the impaired production of pituitary hormones, commonly including growth hormone. The pathomechanism of the childhood-onset form of this disorder may involve germline mutations of genes encoding pituitary transcription factors, of which PROP1 gene mutations have been studied most extensively. However, controversy exists about the significance of PROP1 gene mutations, as both low and high frequencies have been reported in these patients. Because the different results may be related to differences in patient populations and/or the variability of clinical phenotypes, we performed the present study to examine the prevalence and spectrum of PROP1 gene mutations in 35 patients with non-acquired childhood-onset growth hormone deficiency combined with at least one other anterior pituitary hormone deficiency. Genetic testing indicated the presence of disease-causing mutations in exons 2 and 3 of the PROP1 gene in 15 patients (43% of all patients; homozygous mutations in 10 patients and compound heterozygous mutations in 5 patients). Comparison of clinical data of patients with and without PROP1 gene mutations failed to show significant differences, except an earlier growth retardation detected in patients with PROP1 gene mutations. In one patient with PROP1 gene mutation, radiologic imaging showed an enlargement of the anterior lobe of the pituitary, whereas the other patients had hypoplastic or normal pituitary gland. All patients with PROP1 gene mutations had normal posterior pituitary lobe by radiologic imaging. These results indicate that using our inclusion criteria for genetic testing, PROP1 gene mutations can be detected in a high proportion of Hungarian patients with non-acquired childhood-onset growth hormone deficiency combined with at least one other anterior pituitary hormone defect.