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The Journal of Clinical Endocrinology... Jun 2024The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding... (Review)
Review
CONTEXT
The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)-insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth.
EVIDENCE ACQUISITION
Extensive literature review through PubMed and other search engines.
EVIDENCE SYNTHESIS
Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments.
CONCLUSION
The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized.
Topics: Humans; Child; Growth Disorders; Human Growth Hormone; Puberty; Body Height; Male; Female; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Insulin-Like Growth Factor I; Adolescent
PubMed: 38181434
DOI: 10.1210/clinem/dgae011 -
Reproductive Biology and Endocrinology... Oct 2023Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL.
METHODS
Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data.
RESULTS
Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649--0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674-3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281-6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510-2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521-3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675-2.421).
CONCLUSION
Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.
Topics: Adult; Humans; Child; Puberty, Precocious; Overweight; Endocrine System Diseases; Survivors; Metabolic Diseases; Obesity; Hypothyroidism; Hypogonadism
PubMed: 37794442
DOI: 10.1186/s12958-023-01137-y -
Breast Cancer Research : BCR Mar 2024Breast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its...
BACKGROUND
Breast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast.
METHODS
This is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset).
RESULTS
In the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R = 44%) and time since menarche (R = 42%), respectively.
CONCLUSION
We characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.
Topics: Female; Humans; Child, Preschool; Child; Cohort Studies; Breast Neoplasms; Chile; Puberty; Menarche; Obesity
PubMed: 38475816
DOI: 10.1186/s13058-024-01793-x -
Nature Communications Feb 2024We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable...
We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable regression, Mendelian randomization and negative control (parity only). Older age of menarche is related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, which is largely attenuated when accounting for adult body mass index. In multivariable regression, higher parity relates to more particles and lipids in VLDL, which are not observed in male negative controls. In multivariable regression and Mendelian randomization, older age at natural menopause is related to lower concentrations of inflammation markers, but we observe inconsistent results for LDL-related traits due to chronological age-specific effects. For example, older age at menopause is related to lower LDL-cholesterol in younger women but slightly higher in older women. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.
Topics: Adult; Humans; Male; Female; Aged; Menarche; Menopause; Reproduction; Body Mass Index; Metabolome; Risk Factors; Age Factors
PubMed: 38320991
DOI: 10.1038/s41467-023-44459-6 -
The Journal of Clinical Endocrinology... Oct 2023Prepubertal adiposity is associated with earlier puberty. It is unclear when this association starts, if all adiposity markers are similarly associated, and whether all...
CONTEXT
Prepubertal adiposity is associated with earlier puberty. It is unclear when this association starts, if all adiposity markers are similarly associated, and whether all pubertal milestones are similarly affected.
OBJECTIVE
To evaluate the association between different adiposity markers during childhood and the timing of different pubertal milestones in Latino girls.
DESIGN, SETTING, AND PARTICIPANTS
Longitudinal follow-up of 539 female participants of the Chilean Growth and Obesity Cohort recruited from childcare centers (mean age 3.5 years) from the southeast area of Santiago, Chile. Participants were singletons born between 2002 and 2003 within the normal birthweight range. Since 2006, a trained dietitian measured weight, height, waist circumference (WC) and skinfolds to estimate body mass index (BMI) Centers for Disease Control and Prevention percentiles, central obesity, percentage of fat mass (%FM), and fat mass index (FMI, fat mass/height2).
MAIN OUTCOME
Since 2009, sexual maturation was assessed every 6 months to assess age at (1) thelarche, (2) pubarche, (3) menarche, and (4) peak height velocity (PHV).
RESULTS
At thelarche, 12.5% were obese and 2% had central obesity. The median age of pubarche, menarche, and PHV were all associated with markers of adiposity at different time points during childhood whereas thelarche only with %FM and FMI. Adiposity clusters models showed that children with trajectories of high WC, %FM, and FMI during childhood were related with earlier thelarche, pubarche, menarche, and PHV but BMI trajectories only with menarche and PHV.
CONCLUSIONS
Higher WC, %FM, and FMI were associated with earlier age at thelarche, pubarche, menarche, and PHV. The effect of BMI was less consistent.
Topics: Child; Child, Preschool; Female; Humans; Adiposity; Body Mass Index; Hispanic or Latino; Menarche; Obesity; Obesity, Abdominal; Puberty; Chile
PubMed: 37226986
DOI: 10.1210/clinem/dgad294 -
Proceedings of the National Academy of... Oct 2023Anxiety disorders are a major public health concern and current treatments are inadequate for many individuals. Anxiety is more common in women than men and this...
Anxiety disorders are a major public health concern and current treatments are inadequate for many individuals. Anxiety is more common in women than men and this difference arises during puberty. Sex differences in physiological stress responses may contribute to this variability. During puberty, gonadal hormones shape brain structure and function, but the extent to which these changes affect stress sensitivity is unknown. We examined how pubertal androgens shape behavioral and neural responses to social stress in California mice (), a model species for studying sex differences in stress responses. In adults, social defeat reduces social approach and increases social vigilance in females but not males. We show this sex difference is absent in juveniles, and that prepubertal castration sensitizes adult males to social defeat. Adult gonadectomy does not alter behavioral responses to defeat, indicating that gonadal hormones act during puberty to program behavioral responses to stress in adulthood. Calcium imaging in the medioventral bed nucleus of the stria terminalis (BNST) showed that social threats increased neural activity and that prepubertal castration generalized these responses to less threatening social contexts. These results support recent hypotheses that the BNST responds to immediate threats. Prepubertal treatment with the nonaromatizable androgen dihydrotestosterone acts in males and females to reduce the effects of defeat on social approach and vigilance in adults. These data indicate that activation of androgen receptors during puberty is critical for programming behavioral responses to stress in adulthood.
Topics: Adult; Humans; Male; Female; Sex Differentiation; Septal Nuclei; Androgens; Gonadal Hormones; Puberty
PubMed: 37847733
DOI: 10.1073/pnas.2306475120 -
Nigerian Journal of Clinical Practice Oct 2023Delayed puberty (DP) affects approximately 2% of adolescents. In most patients of both genders, delayed puberty is due to constitutional delay in growth and puberty...
BACKGROUND
Delayed puberty (DP) affects approximately 2% of adolescents. In most patients of both genders, delayed puberty is due to constitutional delay in growth and puberty (CDGP); it is a self-limiting condition starting later than usual during puberty but progressing normally. Other causes of DP include permanent hypogonadotropic hypogonadism, functional hypogonadotropic hypogonadism, and gonadal insufficiency.
METHODS
Nine patients admitted to the Ankara Atatürk Sanatoryum Training and Research Hospital Pediatric Endocrinology Department with hypogonadotropic hypogonadism between January 2012 and December 2022 were analyzed.
RESULTS
Nine patients who applied to our pediatric endocrinology clinic with delayed puberty were analyzed. These nine patients were diagnosed and reported as hypogonadotropic hypogonadism with molecular methods. We aimed to determine the status of these cases from a molecular point of view, to emphasize the importance of hypogonadotropic hypogonadism in patients with delayed puberty, and to reveal the rarely encountered delayed puberty together with the clinical and laboratory data set of the patients.
CONCLUSIONS
To emphasize the importance of hypogonadotropic hypogonadism, which is a rare cause of delayed puberty, the molecular predispositions of our patients followed in our clinic are reviewed, and the data we have provided will contribute to the accumulation of data in this area.
Topics: Adolescent; Female; Humans; Male; Diagnosis, Differential; Growth Disorders; Hypogonadism; Puberty; Puberty, Delayed
PubMed: 37929534
DOI: 10.4103/njcp.njcp_244_23 -
The Journal of Clinical Endocrinology... Feb 2024
Topics: Humans; Prevalence; Puberty; Puberty, Delayed; Receptor, Melanocortin, Type 3
PubMed: 37589951
DOI: 10.1210/clinem/dgad486 -
The Journal of Clinical Endocrinology... Aug 2023Age of pubertal onset has been decreasing in many countries but there have been no data on pubertal development in Chinese children over the last decade.
CONTEXT
Age of pubertal onset has been decreasing in many countries but there have been no data on pubertal development in Chinese children over the last decade.
OBJECTIVE
The primary objective of the study was to evaluate the current status of sexual maturation in Chinese children and adolescents. Secondary objectives were to examine socioeconomic, lifestyle, and auxological associations with pubertal onset.
METHODS
In this national, cross-sectional, community-based health survey, a multistage, stratified cluster random sampling method was used to select a nationally representative sample, consisting of 231 575 children and adolescents (123 232 boys and 108 343 girls) between 2017 and 2019. Growth parameters and pubertal staging were assessed by physical examination.
RESULTS
Compared to 10 years previously, the median age of Tanner 2 breast development and menarche were similar at 9.65 years and 12.39 years respectively. However, male puberty occurred earlier with a median age of testicular volume ≥4 mL of 10.65 years. Pubertal onset did occur earlier at the extremes, with 3.3% of the girls with breast development at 6.5-6.99 years old, increasing to 5.8% by 7.5-7.99 years old. Early pubertal onset was also noted in boys, with a testicular volume ≥ 4 mL noted in 1.5% at 7.5-7.99 years, increasing to 3.5% at 8.5-8.99 years old. Obesity and overweight increased risk of developing earlier puberty relative to normal weight in both boys and girls.
CONCLUSION
Over the past decade, pubertal development is occurring earlier in Chinese children. While the cause is multifactorial, overweight and obesity are associated with earlier puberty onset. The currently used normative pubertal data of precocious puberty may not be applicable to diagnose precocious puberty.
Topics: Child; Female; Humans; Male; Cross-Sectional Studies; East Asian People; Menarche; Obesity; Overweight; Puberty; Puberty, Precocious; Sexual Maturation
PubMed: 36881937
DOI: 10.1210/clinem/dgad102 -
Journal of the American Academy of... Apr 2024Transgender and gender diverse (TGD) adolescents are those whose gender identity is incongruent with societal expectations based on their sex assigned at birth. Some TGD...
Transgender and gender diverse (TGD) adolescents are those whose gender identity is incongruent with societal expectations based on their sex assigned at birth. Some TGD adolescents may meet criteria for gender dysphoria, which requires at least 6 months of psychological distress related to gender incongruence. Such adolescents may seek pubertal suppression with a gonadotropin-releasing hormone agonist (GnRHa). GnRHa temporarily and reversibly suppress endogenous puberty, allowing adolescents to engage with care without puberty-related psychological distress. Most patients treated with GnRHa proceed to treatment with gender-affirming hormones (eg, estrogen or testosterone to induce puberty that aligns with their gender identity), whereas a small number choose to stop GnRHa treatment, allowing endogenous puberty to proceed. Longitudinal cohort and cross-sectional studies link GnRHa treatment to improved mental health outcomes, when provided in accordance with clinical guidelines..
PubMed: 38582366
DOI: 10.1016/j.jaac.2024.03.016