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Background—Central precocious puberty (CPP) is characterized by clinical, biochemical, and ra-diological features similar to those of normal puberty, but CPP occurs before the age of eight in girls and before the age of nine in boys, subsequently leading to a reduction in the final body height in adulthood due to premature fusion of growth plates. The diagnosis of CPP is confirmed with a gonadotropin-releasing hormone (GnRH) stimulation test, which can lead to different interpreta-tions because the diagnostic peak levels of luteinizing hormone (LH) can vary. Patients and methods—This was a single-center, retrospective observational study investigating the possible correlation between gonadotropin peaks on the GnRH test and auxological, metabolic, and radi-ological parameters of patients evaluated for CPP. We collected and analyzed data from the medical records of children with suspected CPP over a period from January 2019 to July 2022 who underwent a GnRH test at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, It-aly. Results—Our correlation analysis revealed no statistically significant differences in any aux-ological and radiological parameters. Among laboratory parameters, baseline levels of LH, folli-cle-stimulating hormone, sex hormone-binding globulin, and 17-beta estradiol were higher in children with a definitive diagnosis of CPP than in those with a negative GnRH test. In particular, the levels of LH at baseline and after the GnRH test were statistically significant in the group of CPP patients, consistent with the interpretation of the test. In the multivariate analysis, using a cut-off value of 4.1 IU/L, LH peaks showed both very high sensitivity (94%) and very high speci-ficity (95%); all other variables showed high specificity (90%) but unsatisfactory sensitivity. Con-clusion—Basal hormone dosages and, especially, basal levels of LH should be considered

The paper discusses relevant issues related to GnRH test for diagnosing central precocious puberty

Introduction: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels. Methods: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH (R)(100 mu g/m(2)) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels. Results: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 +/- 257.1 vs. 247.6 +/- 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5-115.7] vs. 143.5 [71.4-285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = -0.73, p = 0.005, and r = -0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = -0.57, p = 0.041). Conclusion: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels. (C) 2022 The Author(s). Published by S. Karger AG, Basel, Funding agencies:Research Committee and ALF funding, Region Örebro County, SwedenRegional Research Council Mid Sweden

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 function

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 function

The onset of puberty in girls has been occurring each time at a younger age, generating concern among parents and seeking healthcare for possible precocious puberty. Nowadays diagnosis of central precocious puberty (CPP) and early puberty onset have chronological cutoff points established over five years ago and despite secular changes described in various populations of the world. The importance of differentiating a physiological event from a pathogenic one is mainly because of the need of timely decision to begin treatment in order to prevent height compromise, reproductive system alterations and risk of future diseases like cardiovascular disease and breast cancer in adulthood. Limits for puberty onset based on biostatistics in normal population should not be applied only to establish limits of chronological age because the risk of a wrong diagnosis. In this article physiological and pathological events of puberty in girls will be reviewed; agreements and disputes described in scientific literature will be presented., Se ha observado que el inicio de la pubertad en las niñas se viene produciendo cada vez a edad más temprana, motivando la preocupación de los padres y la búsqueda de atención ante la posibilidad de pubertad precoz. A la actualidad, el diagnóstico de pubertad precoz central (PPC) y pubertad normal de inicio temprano, mantienen puntos de corte cronológicos establecidos hace más de un lustro; esto, a pesar de los cambios seculares descritos en diversas poblaciones del orbe. La importancia de diferenciar un evento fisiológico de uno patológico se enmarca en la necesidad de adoptar una decisión oportuna para iniciar tratamiento con la finalidad de evitar compromiso de la talla final, alteraciones en la vida reproductiva y riesgo de enfermedades a futuro, como las enfermedades cardiovasculares y cáncer de mama en la vida adulta. Por lo tanto, los límites para el inicio de la pubertad, basados en normalidad bioestadística poblacional, no deberían traducirse únicamente en el establecimiento de límites de edad cronológico, debido al riesgo de diagnósticos erróneos. En el presente artículo haremos una revisión de los acontecimientos relacionados a la pubertad en sus formas fisiológicas y patológicas en niñas; presentando los acuerdos y controversias que al respecto se describen en la literatura científica.

Over the last 10 years, several children, fetuses and women have been reported to be virilized through interpersonal transfer of testosterone (T) gel used by fathers or partners. Long-term exposure to androgens in children, such as in poorly controlled congenital adrenal hyperplasia, is known to promote central precocious puberty., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Over the last 10 years, several children, fetuses and women have been reported to be virilized through interpersonal transfer of testosterone (T) gel used by fathers or partners. Long-term exposure to androgens in children, such as in poorly controlled congenital adrenal hyperplasia, is known to promote central precocious puberty., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Background/Aim: In children with central precocious puberty (CPP), gonadotropin-releasing hormone (GnRH) analogue treatment has been associated with an increase in body mass index (BMI). We evaluated BMI and body composition in adolescents treated with GnRH analogue at their near final height to assess the long-term effects of therapy on these parameters. Patients and Methods: We studied 20 patients (14.8 ± 1.6 years; 17 females) previously treated with triptorelin depot for CPP (3.75 mg/28 days) from 8.1 ± 0.8 to 11.5 ± 0.8 years. 23 healthy adolescents with normal onset of puberty (14.7 ± 2.1 years, 19 females) were the controls. BMI and body composition (dual-energy x-ray absorptiometry) were assessed. Results: Patients reached their near adult height (-0.5 ± 1.1 standard deviation score (SDS)); the girls were menstruating and the majority (15/17) had regular cycles, the boys showed normal testicular function. BMI was unchanged from the start of GnRH analogue therapy (0.4 ± 1.0 SDS) to near adult height (0.2 ± 1.0 SDS, p = NS vs. 0). Total fat mass (TFM) was significantly increased (16,144 ± 8,065 g; controls 10,712.1 ± 4,120.4 g, p < 0.02); glucose homeostasis and lipid profile corresponded to reference ranges. Conclusions: GnRH analogue therapy did not show long-term detrimental effects on BMI, but it may increase TFM, suggesting that body composition should be monitored till adulthood.

Central precocious puberty (CPP) is treated with GnRH analogues to stabilize secondary sexual characteristics and to prevent loss of final height (FH) due to accelerated bone maturation. However, some studies suggest that FH is not always improved and that treatment may induce excessive weight gain. We analysed data from 19 girls treated for CPP with monthly injections of 3.75 mg triptorelin. Pubertal development, bone age, height, weight and body mass index (BMI) were evaluated at start (chronological age: 7.8 ± 1.8 yrs, mean ±SD), at the end of treatment (10.6 ± 1.1 yrs) and at FH (14.9 ± 2.5 yrs). At start of treatment, breast (B) development was B3 (from 2 to 4), bone age 10.6 ± 1.7 yrs, height 2.1 ± 1.1 SDS and BMI 1.3 ± 0.8 SDS. Treatment stabilized or reduced breast development and decreased bone maturation. Final height was 162.3 ± 6.6 cm (0.0 ± 1.1 SDS) and was comparable to predicted adult height at the start of treatment and to corrected mid-parental height. BMI SDS at the start, the end of treatment and at final evaluation were 1.3 ± 0.8, 1.6 ± 0.8 and 1.4 ± 0.9 SDS. In conclusion, in our girls with central precocious puberty, treatment with GnRH agonist stabilized or decreased breast development and stabilized bone maturation, but did not increase neither final height nor weight. Aspects other than height should also be taken into account when considering treatment of children with precocious puberty., SCOPUS: ar.j, info:eu-repo/semantics/published

Central precocious puberty (CPP) is treated with GnRH analogues to stabilize secondary sexual characteristics and to prevent loss of final height (FH) due to accelerated bone maturation. However, some studies suggest that FH is not always improved and that treatment may induce excessive weight gain. We analysed data from 19 girls treated for CPP with monthly injections of 3.75 mg triptorelin. Pubertal development, bone age, height, weight and body mass index (BMI) were evaluated at start (chronological age: 7.8 ± 1.8 yrs, mean ±SD), at the end of treatment (10.6 ± 1.1 yrs) and at FH (14.9 ± 2.5 yrs). At start of treatment, breast (B) development was B3 (from 2 to 4), bone age 10.6 ± 1.7 yrs, height 2.1 ± 1.1 SDS and BMI 1.3 ± 0.8 SDS. Treatment stabilized or reduced breast development and decreased bone maturation. Final height was 162.3 ± 6.6 cm (0.0 ± 1.1 SDS) and was comparable to predicted adult height at the start of treatment and to corrected mid-parental height. BMI SDS at the start, the end of treatment and at final evaluation were 1.3 ± 0.8, 1.6 ± 0.8 and 1.4 ± 0.9 SDS. In conclusion, in our girls with central precocious puberty, treatment with GnRH agonist stabilized or decreased breast development and stabilized bone maturation, but did not increase neither final height nor weight. Aspects other than height should also be taken into account when considering treatment of children with precocious puberty., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective. To establish the prevalence of endocrinologic disorders in children with neurofibromatosis type 1 (NF1) and the relationship between these disorders and cerebral abnormalities on magnetic resonance imaging. Design. A prospective follow-up study. Setting. A multidisciplinary neurofibromatosis clinic. Patients. A total of 122 children diagnosed with NF1 according to diagnostic criteria set by the National Institutes of Health. Results. Central precocious puberty (CPP) was diagnosed in 3 children and growth hormone deficiency (GHD) in 3 children. Optic pathway gliomas were observed in 15 children; in 9 of the 15 cases, the optic chiasm was involved. Of the 3 children with CPP, only 1 showed a chiasma glioma on magnetic resonance imaging. In 1 case with GHD, an optic chiasm glioma was detected on neuroimaging. Two of the 9 children with an optic chiasm glioma presented with CPP or GHD. Conclusions. It has been suggested that CPP in children with NF1 is found exclusively in the presence of a chiasma glioma. We conclude that chiasma glioma may not be obligatory in children with NF1 and CPP or GHD. Moreover, we report a prevalence of GHD in children with NF1 of 2.5%, which has not been established earlier.

In order to understand the processes occurring during precocious puberty, one needs to specify what is currently known about normal pubertal development. Puberty can be defined as a maturational process of the hypothalamic-pituitarygonadal axis, which results in the development of the gonads and, concomitantly, in the physical and physiological processes which constitute adulthood and the capacity to reproduce. The regulation of puberty is a very complex process, involving the hormonal interaction of the cells in the hypothalamus, pituitary and gonads. A central role in this process is played by the Gonadotropin Releasing Hormone (GnRH or LHRH: Luteinizing Hormone Releasing Hormone) which is produced and secreted by the hypothalamus.