Adolescent boys with constitutional delay of growth and puberty grow faster than patients with organic growth hormone deficiency.

OBJECTIVE: Constitutional delay of growth and puberty (CDGP) is a tempo variant with a good prognosis. Healthy late-maturing adolescents grow slower than postulated by age-related references, and therefore, CDGP is frequently confused with growth hormone deficiency (GHD). For differential diagnosis, height velocity references for CDGP are needed. DESIGN AND PATIENTS: Here, we provide height velocity data for late-maturing boys based on mixed longitudinal and cross-sectional observations in a group of 38 German adolescents with proven CDGP and compare them with cross-sectional observations in a group of 164 adolescents with organic GHD from the National Cooperative Growth Study registry. RESULTS: In the critical age interval from 13.4 to 14.9 years, the growth of prepubertal adolescents with CDGP was faster (mean/median height velocity, 5.2/5.4 cm/years; quartiles, 4.4-6.2 cm/years) than that of prepubertal adolescents with organic GHD (3.5/3.2 cm/years; quartiles, 2.0-4.4 cm/years) in the cross-sectional analysis (p < .0001). Based on our mixed longitudinal and cross-sectional analysis, the height velocity of adolescent boys with CDGP exceeded previous model calculations on average by 1.0 cm. CONCLUSIONS: In conclusion, prepubertal adolescents with CDGP grow faster than patients with organic GHD. Previous model estimates underestimated height velocity of boys with CDGP.

Feel Safe and Money is Less Important! Hypnotic Suggestions of Safety Decrease Brain Responses to Monetary Rewards in a Risk Game.

When a stimulus is important, the corresponding brain responses increase, especially the P300 brain response. This is true for all kinds of important stimuli, also monetary rewards. In our study, we developed a hypnotic suggestion to reduce the subjective importance of monetary rewards. As successful suggestions do not contain negations, we suggested participants to feel safe during hypnosis instead of suggesting that money is not important anymore. We predicted lower P300 amplitudes when participants feel safe during hypnosis. We tested 24 highly suggestible participants playing a risk game in 2 conditions with monetary rewards while we measured their EEG brain responses. In the safety condition, we induced a hypnotic state and suggested that participants feel safe. In the control condition, participants played the risk game without hypnosis. Here we show that participants felt significantly safer in the safety condition and showed significantly lower P300 amplitudes to monetary rewards. Risk behavior did not differ significantly between conditions. Our results are important for substance use disorders, as decreased P300 responses to substance-related stimuli are associated with less craving and better abstinence. Therefore, we conclude that suggestions to feel safe during hypnosis might work as a treatment for individuals with substance use disorders.

Characteristic dynamics of height and weight in preschool boys with constitutional delay of growth and puberty or hypogonadotropic hypogonadism.

OBJECTIVE: Constitutional delay of growth and puberty (CDGP) is a frequent variant of the normal leading to short stature and/or pubertal delay. To distinguish CDGP from hypogonadotropic hypogonadism (HH), we evaluated height, growth and weight pattern of CDGP and HH in the first 5 years of life. DESIGN AND PATIENTS: We studied retrospectively height and weight in the first 5 years (y) of life in 54 boys with CDGP and 8 boys with HH. RESULTS: In boys with CDGP, height-SDS decreased (change -0.94 (interquartile range [IQR] -1.69 to -0.05); P < 0.001) between birth and 2 years. BMI-SDS decreased (change -0.38 (IQR -1.21-0.16); P < 0.001) in the same time period. There were no significant changes in height-SDS or BMI-SDS between 2 years and 5 years, while height-SDS (change + 1.49 (IQR 1.02-1.95); P < 0.001) and BMI-SDS (change + 0.91 (IQR 0.12-1.69); P < 0.001) increased between pubertal and adult age. In boys with HH, height-SDS and BMI-SDS did not change significantly in the first 5 years of life. Height-SDS decreased (change -1.39 (IQR -1.96 to -0.67); P = 0.018) significantly between 5 years of life and puberty, while there were no significant changes in BMI-SDS in this time period. At pubertal age, BMI-SDS was significantly (P = 0.001) higher in boys with HH compared with boys with CDGP. CONCLUSION: Height deflection and weight deflection in CDGP occur already during the first two years of life in contrast to HH. This different pattern of growth and weight might be helpful to distinguish CDGP from HH.

A New Model of Adult Height Prediction Validated in Boys with Constitutional Delay of Growth and Puberty.

BACKGROUND: For children with retarded bone ages such as in constitutional delay of growth and puberty (CDGP) there are no specific methods to predict adult height based on bone age. Widely used methods such as Bayley-Pinneau (BP) tend to overestimate adult height in CDGP. OBJECTIVE: We aimed to develop a specific adult height prediction model for teenage boys with retarded bone ages >1 year. METHODS: Based on the adult heights of 68 males (median age 22.5 years) a new height prediction model was calculated based on 105 height measurements and bone age determinations at a median age of 14.0 years. The new model was adapted for the degree of bone age retardation and validated in an independent cohort of 32 boys with CDGP. RESULTS: The BP method overestimated adult height (median +1.2 cm; p = 0.282), especially in boys with a bone age retardation ≥2 years (median +1.6 cm; p = 0.027). In the validation study, there was no significant difference between adult height and predicted adult height based on the new model (p = 0.196), while the BP model led to a significant overestimation of predicted adult height (median +4.1 cm; p = 0.009). CONCLUSIONS: The new model to predict adult height in boys with CDGP provides novel indices for height predictions in bone ages >13 years and is adapted to different degrees of bone age retardation. The new prediction model has a good predictive capability and overcomes some of the shortcomings of the BP model.

A PRDX1-p38α heterodimer amplifies MET-driven invasion of IDH-wildtype and IDH-mutant gliomas.

The Peroxiredoxin 1 (PRDX1) gene maps to chromosome arm 1p and is hemizygously deleted and epigenetically silenced in isocitrate dehydrogenase 1 or 2 (IDH)-mutant and 1p/19q-codeleted oligodendroglial tumors. In contrast, IDH-wildtype astrocytic gliomas including glioblastomas mostly lack epigenetic silencing and express PRDX1 protein. In our study, we investigated how PRDX1 contributes to the infiltrative growth of IDH-wildtype gliomas. Focusing on p38α-dependent pathways, we analyzed clinical data from 133 patients of the NOA-04 trial cohort to look for differences in the gene expression profiles of gliomas with wildtype or mutant IDH. Biochemical interaction studies as well as in vitro and ex vivo migration studies were used to establish a biological role of PRDX1 in maintaining pathway activity. Whole-brain high-resolution ultramicroscopy and survival analyses of pre-clinical mouse models for IDH-wildtype gliomas were then used for in vivo confirmation. Based on clinical data, we found that the absence of PRDX1 is associated with changes in the expression of MET/HGF signaling components. PRDX1 forms a heterodimer with p38α mitogen-activated protein kinase 14 (MAPK14), stabilizing phospho-p38α in glioma cells. This process amplifies hepatocyte growth factor (HGF)-mediated signaling and stimulates actin cytoskeleton dynamics that promote glioma cell migration. Whole-brain high-resolution ultramicroscopy confirms these findings, indicating that PRDX1 promotes glioma brain invasion in vivo. Finally, reduced expression of PRDX1 increased survival in mouse glioma models. Thus, our preclinical findings suggest that PRDX1 expression levels may serve as a molecular marker for patients who could benefit from targeted inhibition of MET/HGF signaling.