Growth variations with opposite clinical outcomes and the emerging role of IGF-1

Normal growth pattern variations [i.e., constitutional advancement and constitutional delay of growth and puberty (CAGP and CDGP)] are the mirror image of each other and are associated with early puberty (EP) and delayed puberty (DP), respectively. Differences between CAGP and CDGP relate not only to auxological characteristics (height, weight) but also to insulin-like growth factor-1 (IGF-1). IGF-1 levels in CAGP are above average whereas in CDGP they are below average, suggesting a role for IGF-1 in the induction of these growth patterns. Herein, we provide data suggesting that early activation of the growth hormone (GH)/IGF-1 axis induces the growth pattern of CAGP. Moreover, we suggest that IGF-1 is a decisive factor for the release of the gonadotropin-releasing hormone (GnRH) inhibition brake that occurs in prepuberty. It is therefore crucial for puberty onset. © 2022 Elsevier Lt

L-Dopa Stimulates Cortisol Secretion through Adrenocorticotropic Hormone Release in Short Children

We recently showed that L-Dopa administration is a potent stimulator of cortisol secretion in children with short stature. Herein, we examined whether adrenocorticotropic hormone (ACTH) is implicated in the mechanism by which cortisol is stimulated during the L-Dopa test. Methods: Nineteen children with short stature who fulfilled the auxological criteria for growth hormone (GH) deficiency and had a subnormal GH response to glucagon stimulation underwent a second GH stimulation test ( L-Dopa test). Serum GH, cortisol and plasma ACTH were determined at baseline and every 30 min up to 120 min after oral L-Dopa administration. Peak values of GH >10 ng/ml, cortisol >18 μg/dl and ACTH >52 pg/ml were considered as normal response. Results: Normal response rates were 10.5% (2/19) for GH, 94.7% (18/19) for cortisol and 68.4% (13/19) for ACTH. Among the children with a normal response in ACTH, its concentration increased from a basal value (mean ± standard deviation) of 23.3 ± 9.6 to 290.3 ± 221 pg/ml, almost always 90-120 min after L-Dopa administration. Mean peak cortisol was 36.2 ± 9.1 μg/dl, and it peaked almost simultaneously with ACTH. Conclusion: Our data suggest a stimulatory effect of the dopaminergic system on the hypothalamic-pituitary-adrenal axis. © 2015 S. Karger AG, Basel

Early Adiposity Rebound and Premature Adrenarche

Objectives To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls). Study design In this cross-sectional study of 82 prepubertal children with PA and 63 controls, the main outcome measures were height and body mass index SDS progression, from birth to presentation at the clinic, baseline biochemical and hormonal evaluation, bone age determination, and age at AR. Results Children with PA were significantly taller and more adipose than controls from the first years of life. 33% of children with PA presented the growth pattern of constitutional advancement of growth (ie, early growth acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs 4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45 (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese girls with PA were taller and had earlier age at AR compared with nonobese controls. Conclusions Early AR and constitutional advancement of growth may be triggering factors for adrenal androgen production and PA. © 2017 Elsevier Inc

Increased symptoms of anxiety and depression in prepubertal girls, but not boys, with premature adrenarche: associations with serum DHEAS and daily salivary cortisol concentrations

Concerns over anxiety and depressive symptoms in children with premature adrenarche (PA) have been recently raised. However, to date, most relevant studies are on a small number of girls. In this cross-sectional study, 82 pre-pubertal children (66 girls and 16 boys) diagnosed with PA, were compared to 63 control children regarding their psychological characteristics and hypothalamic–pituitary–adrenal (HPA) axis function, as assessed by salivary cortisol measurement. Symptoms of anxiety and depression were assessed by child self-report (Spence Children’s Anxiety Scale (SCAS) and Depression self-rating scale for Children (DSRS)) and parent-report (Child Behaviour Checklist (CBCL)) tests validated for the Greek population. Salivary cortisol levels were determined directly after awakening (approximately 7am) and evening (8pm) of the same day. Morning serum DHEAS levels were assessed in PA children. Girls with PA scored significantly higher on anxiety (p =.016) and depression (p =.039) scales than controls. No group differences were noted for parent reports and children’s salivary cortisol concentrations. Boys with PA did not demonstrate significant differences in any of the aforementioned parameters. Our findings suggest that girls with PA may be at higher risk for reporting symptoms of anxiety and depression than their non-PA peers. HPA axis dysregulation in this population was not documented. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS

Background: Adiposity rebound (AR), the second BMI rise in childhood at around the age of 6 years, is associated with obesity and metabolic alteration in later life. Given that polycystic ovary syndrome (PCOS) has a strong metabolic component, early life growth patterns could reveal a risk of PCOS. Thus, we aimed to investigate the associations between age at AR and PCOS diagnosis and BMI later in life. Materials and methods: This study is part of a prospective, population-based longitudinal study, where women with PCOS diagnosis by age 46 (n = 280) were compared with asymptomatic women (CTRLs, n = 1573). Weight and height data from birth to age 13 years, at age at menarche, and at ages 31 and 46 years were analyzed Results: Women with PCOS had lower birth weight (3357 +/- 477 vs. 3 445 +/- 505 g, p <0.001), earlier age at AR (5.2 +/- 1.0 vs. 5.6 +/- 0.90 years, p <0.001) and higher BMI from AR onwards compared with controls. Early timing of AR was associated with PCOS diagnosis independently of BMI (OR 1.62, 95% CI 1.37-1.92). Women with PCOS and early AR had higher BMI at 31 and 46 years when compared to controls with early AR. The age at AR did not associate with T levels at ages 31 or 46 years. Conclusions: Early AR was associated with PCOS diagnosis and high BMI in adulthood. Adolescent girls with early AR and persisting obesity should be screened for PCOS symptoms, such as persistent irregular cycles and hirsutism.Peer reviewe

Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS

Abstract Background: Adiposity rebound (AR), the second BMI rise in childhood at around the age of 6 years, is associated with obesity and metabolic alteration in later life. Given that polycystic ovary syndrome (PCOS) has a strong metabolic component, early life growth patterns could reveal a risk of PCOS. Thus, we aimed to investigate the associations between age at AR and PCOS diagnosis and BMI later in life. Materials and methods: This study is part of a prospective, population-based longitudinal study, where women with PCOS diagnosis by age 46 (n = 280) were compared with asymptomatic women (CTRLs, n = 1573). Weight and height data from birth to age 13 years, at age at menarche, and at ages 31 and 46 years were analyzed. Results: Women with PCOS had lower birth weight (3357 ± 477 vs. 3 445 ± 505 g, p < 0.001), earlier age at AR (5.2 ± 1.0 vs. 5.6 ± 0.90 years, p < 0.001) and higher BMI from AR onwards compared with controls. Early timing of AR was associated with PCOS diagnosis independently of BMI (OR 1.62, 95% Cl 1.37–1.92). Women with PCOS and early AR had higher BMI at 31 and 46 years when compared to controls with early AR. The age at AR did not associate with T levels at ages 31 or 46 years. Conclusions: Early AR was associated with PCOS diagnosis and high BMI in adulthood. Adolescent girls with early AR and persisting obesity should be screened for PCOS symptoms, such as persistent irregular cycles and hirsutism