Titel Deelnemers "Korte inhoud" "Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty" "Slawomir Wojniusz, Nina Callens, Stefan Sütterlin, Stein Andersson, Jean De Schepper, Inge Gies, Jesse Vanbesien, Kathleen De Waele, Sara Van Aken, Margarita Craen, Claus Vögele, Martine Cools, Ira R Haraldsen" "Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate-Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children's parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen's d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen's d = 1.03); lower heart rate was associated with longer treatment duration (r = -0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health." "Peripheral precocious puberty in Li-Fraumeni syndrome" "Sofie Ryckx, Jean De Schepper, Philippe Giron, Ken Maes, Freya Vaeyens, Kaat Wilgenhof, Pierre Lefesvre, Caroline Ernst, Kim Vanderlinden, Daniel Klink, Frederik Jan Hes, Jesse Vanbesien, Inge Gies, Willem Staels" "INTRODUCTION: Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty.CASE PRESENTATION: Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li-Fraumeni syndrome.DISCUSSION: Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li-Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li-Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation.CONCLUSION: In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension." "Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees" "Verena Behringer, T. Deschner, C. Deimel, Jeroen Stevens, G. Hohmann" "Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees." "Early puberty suppression and gender-affirming hormones do not alter final height in transgender adolescents" "Silvia Ciancia, Daniel Klink, Margarita Craen, Martine Cools" "Background Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with growth and may impact final height (FH).Aim To investigate the impact of ePS and GAH on FH in trans boys and trans girls.Methods Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau's tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG).Results The age at the start of PS was 12.37 & PLUSMN; 0.74 years in trans boys and 13.10 & PLUSMN; 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 & PLUSMN; 4.08 cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 & PLUSMN; 7.66 cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57 cm & PLUSMN; 3.1 (P = .168) and -0.98 cm & PLUSMN; 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62 cm & PLUSMN; 3.79, P = .056 and -2.35 cm & PLUSMN; 5.2, P = .051, respectively).Conclusion Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG." "Human evolution and variation in puberty onset" "Charles Susanne, M. Vercauteren, Roland Hauspie" "Human evolution and variation in puberty onset" "Conventional and computational flow cytometry analyses reveal sustained human intrathymic T cell development from birth until puberty" "Marieke Lavaert, Bart Vandekerckhove, Georges Leclercq, Kai Ling Liang, Tom Taghon" "The thymus is the organ where subsets of mature T cells are generated which subsequently egress to function as central mediators in the immune system. While continuously generating T cells even into adulthood, the thymus does undergo involution during life. This is characterized by an initial rapid decrease in thymic cellularity during early life and by a second age-dependent decline in adulthood. The thymic cellularity of neonates remains low during the first month after birth and the tissue reaches a maximum in cellularity at 6 months of age. In order to study the effect that this first phase of thymic involution has on thymic immune subset frequencies, we performed multi-color flow cytometry on thymic samples collected from birth to 14 years of age. In consideration of the inherent limitations posed by conventional flow cytometry analysis, we established a novel computational analysis pipeline that is adapted from single-cell transcriptome sequencing data analysis. This allowed us to overcome technical effects by batch correction, analyze multiple samples simultaneously, limit computational cost by subsampling, and to rely on KNN-graphs for graph-based clustering. As a result, we successfully identified rare, distinct and gradually developing immune subsets within the human thymus tissues. Although the thymus undergoes early involution from infanthood onwards, our data suggests that this does not affect human T-cell development as we did not observe significant alterations in the proportions of T-lineage developmental intermediates from birth to puberty. Thus, in addition to providing an interesting novel strategy to analyze conventional flow cytometry data for the thymus, our work shows that the early phase of human thymic involution mainly limits the overall T cell output since no obvious changes in thymocyte subsets could be observed." "Estrogen receptor alpha signaling in extrahypothalamic neurons during late puberty decreases bone size and strength in female but not in male mice" "Na Ri Kim, Ferran Jardi, Rougin Khalil, Leen Antonio, Dieter Schollaert, Ludo Deboel, G. Harry van Lenthe, Brigitte Decallonne, Geert Carmeliet, Jan-Ake Gustafsson, Frank Claessens, Claes Ohlsson, Marie K. Lagerquist, Vanessa Dubois, Dirk Vanderschueren" "Growth, puberty and testicular function in boys born small for gestational age with a nonspecific disorder of sex development" "Lloyd Tack, Saskia van der Straaten, Stefan Riedl, Alexander Springer, PaulU+2010Martin Holterhus, Nadine C. Hornig, Zofia Kolesinska, Marek Niedziela, Federico Baronio, Antonio Balsamo, Sabine E. Hannema, Anna Nordenström, Sukran Poyrazoglu, Fatma F. Darendeliler, Romina Grinspon, Rodolfo Rey, Fahad Aljuraibah, Jillian Bryce, Faisal Ahmed, Rieko TadokoroU+2010Cuccaro, Ieuan Hughes, Guilherme GuaragnaU+2010Filho, Andrea T. MacielU+2010Guerra, Gil GuerraU+2010Junior, Martine Cools" "Testosterone restores body composition, bone mass, and bone strength following early puberty suppression in a mouse model mimicking the clinical strategy in trans boys" "Vanessa Dubois, Silvia Ciancia, Stefanie Doms, Sarah El Kharraz, Vera Sommers, Na Ri Kim, Karel David, Jolien Van Dijck, Roger Valle Tenney, Christa Maes, Leen Antonio, Brigitte Decallonne, Geert Carmeliet, Frank Claessens, Martine Cools, Dirk Vanderschueren" "Transgender youth increasingly present at pediatric gender services. Some of them receive long-term puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) before starting gender-affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4-week-old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa-treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa-treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. (c) 2023 American Society for Bone and Mineral Research (ASBMR)." "Low BMI, but not high BMI, influences the timing of puberty in boys" "Mathieu Roelants" "BACKGROUND: Previous studies investigating the association between weight status and onset of puberty in boys have been equivocal. It is currently unclear to what extent weight class influences puberty onset and progression. OBJECTIVES: To explore the relationship between degree of sexual maturation and anthropometric measures in Norwegian boys. METHODS: The following endpoints were collected in a Norwegian cross-sectional study of 324 healthy boys aged 9-16: ultrasound-determined testicular volume (USTV), total serum testosterone, Tanner pubic hair stage, height, weight, waist circumference (WC), subscapular skinfolds (SSF), and body fat percentage (%BF). Testicular volume-for-age z-scores were used to classify ""early,"" ""average,"" or ""late"" maturing boys. Ordinal logistic regression analyses with a proportional odds model were applied to analyze the association between anthropometric variables and age-adjusted degree of pubertal development, with results expressed as age-adjusted odds ratios (AOR). Cumulative incidence curves for reaching pubertal milestones were stratified by BMI. RESULTS: Boys with a low BMI for age (BMIz   1) exhibited a comparable timing as normal weight boys. The same was found for WC. Pubertal markers were not associated with SSF or %BF. CONCLUSION: By examining the association between puberty and weight status classified as low, average, or high, we found that a low BMI or WC for age were associated with a less advanced pubertal development and delayed timing of puberty in boys. No significant association was observed for a high BMI or WC. Moreover, no significant effects of SSF or %BF were observed. A low weight status should also be considered when assessing pubertal development in boys."