Search

The statistical distributions of structure parameters and the electron energy level of the preexisting traps in polar liquids have been investigated. The TIPS model of intermolecular interactions has been applied. The numerical computations were performed for methanol and are compared with the earlier Tachiya and Mozumder calculations. [ABSTRACT FROM AUTHOR]

Abstract Background In recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD. The aim of this study was to estimate intracellular INF-γ and IL-4 levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n = 18), Hashimoto's thyroiditis (HT; n = 18) and non-toxic multinodular goiter (NTMG; n = 18). Methods Fresh thyroid tissues were taken on culture medium RPMI -1640, it was mechanically prepared. In next step were added cell activators -12- myristate 13- the acetate (PMA) and Ionomycin as well as the inhibitor of transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml flasks at 37°C in a 5-95% CO2-air water-saturated atmosphere. After that, thyrocytes were identified by mouse mAb directed against human TPO epitope 64 conjugated with rabbit anti-mouse antibodies IgG (Fab')2 labeled by FITC. After incubation at room temperature to each of samples added reagent A fixative the cellular membrane. In next step into the cell suspensions were added reagent B to permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-γ-PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter EPICS XL). Results In examined group of patients with GD we observed statistically significant higher mean percentage of cells with phenotype CD4+IL-4 (p < 0.05; p < 0.025), CD8+IL-4 (p < 0.033; p < 0.01) and TFCs-IL-4+ (p < 0.05; p < 0.01) in comparison to patients with HT and NTMG. The analysis of mean percentages of positive TILs and TFCs with intracellular INF-g levels in patients with HT revealed statistically significant increase percentage of CD4+INF-γ (p < 0.04; p < 0.001), CD8+ INF-γ (NS; p < 0.025), TFCs+INF-γ (p < 0.03; p < 0.001) cells in comparison to the percentage of positive cells from patients with GD and NTMG. Conclusions We conclude that human thyrocytes in autoimmune thyroid disorders could be a source of cytokine production and that their activation influences local interaction with T lymphocytes inflowing to the thyroid gland.

Abstract Background The diagnosis of growth hormone (GH) deficiency (GHD) in short children seems unquestionable when both GH peak in stimulating tests (GHST) and IGF-I concentration are decreased. However, the discrepancies between the results of GHST and IGF-I secretion are observed. It seems purposeful to determine the significance of GHST and IGF-I assessment in diagnosing GHD. The relationship between GH secretion and thyroid function, as well as GH influence on the peripheral thyroxine (T4) to triiodothyronine (T3) deiodination, mediated by IGF-I, were identified. Thus, clear differences in thyroid function between GH-deficient and non-GH-deficient subjects should exist. Methods Analysis comprised 800 children (541 boys), age 11.6 ± 3.1 years (mean ± SD), with short stature, in whom two (2) standard GHST (with clonidine and with glucagon) were performed and IGF-I, free T4 (FT4), free T3 (FT3) and TSH serum concentrations were assessed. The patients were qualified to the following groups: GHD - decreased GH peak in GHST and IGF-I SDS (n = 81), ISS - normal GH peak and IGF-I SDS (n = 347), low GH - normal IGF-I SDS, and decreased GH peak (n = 212), low IGF - decreased IGF-I SDS, and normal GH peak (n = 160). The relationships among the results of particular tests were evaluated. Results In the groups with decreased IGF-I concentrations (GHD Group and low IGF Group), the more severe deficit of height was observed, together with higher TSH and FT4 but lower FT3 levels than in groups with normal IGF-I concentrations (ISS Group and low GH Group), independently of the results of GHST. TSH, FT4 and FT3 concentrations were - respectively - similar in two groups with decreased IGF-I secretion, as well as in two groups with normal IGF-I levels. Significant correlations were found between patients' height SDS and IGF-I SDS, between FT3 and IGF-I SDS (positive), and between FT4 and IGF-I SDS (negative), with no correlation between GH peak and any of the parameters analyzed. Conclusion The assessment of thyroid function in children with short stature provides the evidence that measurement of IGF-I concentration may be a procedure reliable at least to the some degree in diagnosing GHD as the results of GHST.

Abstract Background Normal thyroid hormone secretion or appropriate L-thyroxine (L-T4) substitution is necessary for the optimal effect of the growth hormone (GH) administration on growth rate. The decrease of free thyroxine (FT4) levels at recombinant human GH (rhGH) therapy onset has been reported in several studies. The aim of the present study was to evaluate the effect of rhGH administration on thyrotropin (TSH) and FT4 serum concentrations in children with GH deficiency (GHD) during the 1st year of therapy, as well as to assess potential indications to thyroid hormone supplementation in them. Patients and methods The analysis involved data of 75 children (59 boys, 16 girls) with disorders of GH secretion (GHD, neurosecretory dysfunction - NSD) and partial GH inactivity (inactGH), who were treated with rhGH for - at least - one year. In all the children, body height and height velocity (HV) were assessed before and after 1 year of therapy, while TSH, FT4, IGF-I and IGFBP-3 before treatment and after 3-6 months and 1 year of treatment. In the patients, who revealed hypothyroidism (HypoT), an appropriate L-T4 substitution was introduced immediately. The incidence of HypoT, occurring during the initial phase of rhGH therapy, was assessed, as well as its influence on the therapy effectiveness. Results Before rhGH substitution, there were no significant differences in either auxological indices or TSH and FT4 secretion, or IGF-I concentration and its bioavailability among the groups of patients. During the initial 3-6 months of rhGH administration, a significant decrease of FT4 serum concentration, together with a significant increase of IGF-I SDS and IGF-I/IGFBP-3 molar ratio was observed in all the studied groups. In 17 children, HypoT was diagnosed and L-T4 substitution was administered. Despite similar IGF-I secretion increase, the improvement of HV presented significantly lower in children with HypoT than in those who remained euthyroid all the time. Conclusions The incidence of HypoT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on the growth rate should be taken into account.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

The aim of the study was to investigate the effects of seasonal variability of insolation, the implementation of new recommendations for vitamin D supplementation (2018), and the SARS-CoV-2 pandemic lockdown (2020) on 25(OH)D concentrations in children from central Poland. The retrospective analysis of variability of 25(OH)D concentrations during the last 8 years was performed in a group of 1440 children with short stature, aged 3.0-18.0 years. Significant differences in 25(OH)D concentrations were found between the periods from mid-2014 to mid-2018, from mid-2018 to mid-2020, and from mid-2020 to mid-2022 (medians: 22.9, 26.0, and 29.9 ng/mL, respectively). Time series models created on the grounds of data from 6 years of the pre-pandemic period and used for prediction for the pandemic period explained over 80% of the seasonal variability of 25(OH)D concentrations, with overprediction for the first year of the pandemic and underprediction for the second year. A significant increase in 25(OH)D concentrations was observed both after the introduction of new vitamin D supplementation guidelines and during the SARS-CoV-2 pandemic; however, the scale of vitamin D deficiency and insufficiency was still too high. Time series models are useful in analyzing the impact of health policy interventions and pandemic restrictions on the seasonal variability of vitamin D concentrations.

Not required for Clinical Vignette.

Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5 th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5 th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32 nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32 nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5 th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stawerska, Nowak-Bednarek, Talar, Kolasa-Kicińska, Łupińska, Hilczer, Gulczyńska and Lewiński.)

Short stature is characteristic for Turner syndrome (TS) patients, and particular karyotype abnormalities of the X chromosome may be associated with different responsiveness to recombinant human GH (rhGH) therapy. The aim of the study was to analyze the effect of different types of TS karyotype abnormalities on the response to rhGH therapy. A total of 57 prepubertal patients with TS treated with rhGH with a 3 year follow-up were enrolled in the study and categorized according to their karyotype as X monosomy ( n = 35), isochromosome ( n = 11), marker chromosome ( n = 5), or X-mosaicism ( n = 6). Height and height velocity (HV) were evaluated annually. In the first year, all groups responded well to the therapy. In the second year, HV deteriorated significantly in X-monosomy and isochromosome in comparison to the remaining two groups ( p = 0.0007). After 3 years of therapy, all patients improved the score in comparison to their target height, but better outcomes were achieved in patients with marker chromosome and X-mosaicism ( p = 0.0072). X-monosomy or isochromosome determined a poorer response during the second and third year of rhGH therapy. The results of the study indicate that the effects of rhGH therapy in patients with TS may depend on the type of TS karyotype causing the syndrome.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) ( p = 0.00) and lower body mass index (BMI) SDS ( p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 ( p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

Genotype-phenotype correlation in patients with Prader-Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start ( p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID ( p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 ( p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age-group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start ( p = 0.00), with lower body mass index (BMI) SDS ( p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 ( p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Introduction: Apart from growth promotion, growth hormone (GH) has important metabolic effects. Patients with severe GH deficiency (GHD) should be treated with GH throughout life. Current criteria for growth promoting therapy withdrawal in Poland differ from the latest recommendations. Aim of the study To assess cost-effectiveness and safety of continuation of GH therapy in growth promoting doses in patients with isolated GHD after the attainment of near-final height (near-FH) and the incidence of persistent GHD after the therapy withdrawal., Material and Methods: 160 children with isolated GHD (height < 3 centile, GH peak < 10.0 µg/l), who continued GH therapy for growth promotion after the attainment of near-FH (height velocity   2.0) at near-FH and incidence of severe GHD in retesting (performed in 62 patients)., Results: Height gain after near-FH was 1.1 ±0.8 cm in boys and 1.0 ±0.8 in girls. Increase of height by 1.0 cm required on average 487 mg of GH (264 injections). IGF-1 concentrations at near-FH were increased in 39 patients, with no clinical side effects. None of the patients retested had GH peak   10.0 µg/l., Conclusions: There is no rationale to continue GH therapy in growth promoting doses in the patients with isolated GHD after fulfilling the criteria of near-FH.

Ghrelin - a growth hormone (GH) secretagogue - presents a circadian rhythm with higher nocturnal than diurnal concentration (similar to GH). However, daily ghrelin production depends on food intake and nutritional state; it is increased in the fasting state and decreased after a meal. Since most past research concerning short stature children has relied on the morning ghrelin concentration for analyses, we decided to assess ghrelin concentration at the 60 th and 90 th minute after falling asleep and in the morning at 06:00 h, shortly after waking up from nighttime sleep (after 12 h of fasting). We compared these ghrelin concentrations to determine differences between nocturnal and morning ghrelin release in short children, both with idiopathic short stature (ISS) and growth hormone deficiency (GHD). We also analyzed the correlation between the nocturnal and morning ghrelin concentrations with nocturnal GH concentrations, measured at the same time points, as well as with maximal GH concentration, achieved by stimulation tests, and with the insulin-like growth factor I (IGF-I). The ghrelin and GH concentration 60 th and 90 th minute after falling asleep, as well as fasting morning ghrelin and IGF-I concentrations, were measured in 19 (n = 10 ISS and n = 9 GHD) prepubertal short children (7 girls and 12 boys), aged 10.36 ± 3.06 y. Differences between the nocturnal and morning ghrelin concentrations were analyzed by the Wilcoxon matched-pairs signed-rank test. Typical regression and correlation analyses were used to assess relationships among parametric data for other analyses. The Wilcoxon test showed ghrelin concentration is significantly higher in the morning than both at the 60 th and 90 th minute after falling asleep time points (in ISS and GHD). A significant correlation was observed: a) positive - between nocturnal ghrelin (both at the 60 th and 90 th minute) and morning ghrelin concentrations; b) positive - between ghrelin at the 60 th minute and nocturnal GH concentrations (both at the 60 th and 90 th minute); c) negative - between ghrelin at the 60 th minute and IGF-I concentrations; and d) negative - between body mass index and ghrelin concentrations at the 60 th and 90 th minute. We conclude: 1) in short children, both with GHD and with ISS, morning ghrelin level reflects its nocturnal concentration; however, it is significantly higher than the nocturnal ones. There is no significant difference between the measurement of ghrelin concentration at night at the 60 th or 90 th minute after falling asleep; 2) morning ghrelin concentration is affected by the hunger and satiety; therefore, it appears that nocturnal measurements better reflect the pool of hormone responsible for stimulation of GH and IGF-I secretion, especially since positive correlation between nocturnal ghrelin and nocturnal GH secretion was noted; 3) it seems that a higher body mass index is an additional independent factor, associated mainly with lower nocturnal (but not morning) ghrelin secretion.

Introduction: There is a discussion about growth hormone therapy in idiopathic short stature (ISS) children. To diagnose ISS, it is necessary to exclude other diseases; gastrointestinal tract diseases (GIDs) are among them. However, GID symptoms may be scarce. The aim of the study was to evaluate the frequency of unexpected oligosymptomatic GIDs in ISS and assess their influence on auxological parameters and insulin-like growth factor I (IGF-I) concentration., Material and Methods: The analysis included 101 children with ISS and 95 controls. All patients were tested for celiac disease (CD), inflammatory bowel disease (IBD), lactose malabsorption (LM), cystic fibrosis (CF), Helicobacter pylori (HP) and Ascaris sp. (Asc) infections, as well as Candida albicans (Calb) colonization, by applying simple blood and stool tests and gastrofiberoscopy., Results: In 75.2% of short children, one or more than one GIDs listed above were diagnosed, with the highest frequency of: Calb (46.5%), LM (33.7%), HP (24.7%) and/or Asc (21.8%). The incidence of GIDs was significantly higher than in the control group. The GID frequency increases with the age of children. In most ISS children, the IGF-I SDS was below -1.0 and it was the lowest in children with HP ( p < 0.05)., Conclusions: High frequency of unexpected oligosymptomatic GIDs in children diagnosed with ISS indicates the need to search for gastrointestinal (GI) causes in each case of short stature in children. The pathomechanisms responsible for short stature in these cases may vary, although it seems that reduced production of IGF-I plays an important role., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)