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      Trajectories of Growth and Serum DHEAS and IGF-1 Concentrations in Girls With a History of Premature Adrenarche: Attenuation of the Phenotype by Adulthood

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          Abstract

          Background: It has been speculated that premature adrenarche (PA) could lead to unfavorable outcome, including shorter adult stature, but longitudinal follow-up data are insufficient.

          Methods: This prospective case-control study included 30 PA and 42 control females who were born mostly full-term and appropriate for gestational age. They were examined first at the median age of 7.6 years and now at 18.1 years. Main outcome measures were height, body mass index (BMI), age at menarche, and serum dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor 1 (IGF-1) concentrations.

          Results: The PA and control females had comparable mean (standard deviation) adult height [167.2 (6.8) vs. 164.5 (5.1) cm, P = 0.059] and median (25th–75th percentiles) BMI [22.8 (21.1–28.9) vs. 21.6 (19.8–24.3) kg/m 2, P = 0.068, respectively]. Adult heights were comparable with the mid-parental heights in both study groups. The PA females were taller than the controls until the age of 12 years and they lacked a distinct pubertal growth spurt. Serum DHEAS and IGF-1 concentrations did not differ between the PA and control groups at the age of 18 years. Median (range) age at menarche was significantly lower in the PA than control females [11.5 (9.5–15.0) vs. 13.0 (10.0–15.0), P = 0.001].

          Conclusions: Although PA girls have advanced growth and earlier pubertal development together with a tendency to be more overweight, their height, BMI, and serum DHEAS and IGF-1 concentrations are comparable to those of their peers at the age of 18 years. Our findings indicate a benign outcome of PA in appropriate for gestational age -born females concerning adult height and adrenal androgen secretion.

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          Most cited references31

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          Standards for children's height at ages 2-9 years allowing for heights of parents.

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            New population-based references for birth weight, length, and head circumference in singletons and twins from 23 to 43 gestation weeks.

            Birth size curves are needed for clinical and epidemiological purposes. We constructed birth weight (BW), length (BL), and head circumference (BHC) references, assessed effects of twinness and parity, and defined cut-off points for small, appropriate, and large for gestational age. Birth register data of all 753,036 infants born in 1996-2008 in Finland were cleaned to create references reflecting optimal intrauterine growth. The final data included 533,666 singletons and 15,033 twins (median gestation weeks (gws) 40.0 and 37.1, respectively, 41.6% primiparous). Sex-specific BW, BL, and BHC references were constructed from 23 to 43 gws separately for singletons and twins born to primiparous or multiparous mothers. GAMLSS method was used for modelling. In singletons from 36 gws onwards, increased BW and BL were observed in comparison to previous reference from 1979-1983. Twins diverged from singletons from 30 gws onwards. At 37.0 gws, mean BW was 400 g lower and mean BL 1.2 cm shorter than in singletons. From 30 gws onwards, birth size was larger in infants of multiparous than primiparous mothers. Population-based birth size references are available for the evaluation of birth size. Accounting for plurality and parity improves the accuracy of birth size evaluation.
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              Premature adrenarche: etiology, clinical findings, and consequences.

              Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood, typically at around 5-8 years of age in humans. The AAPs dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH secretion and action are needed for adrenarche, but additional inherent and exogenous factors regulate AA secretion. Inter-individual variation in the timing of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood are remarkable. Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action (pubic/axillary hair, adult type body odor, oily skin or hair, comedones, acne, accelerated statural growth) before the age of 8 years in girls or 9 years in boys associated with AAP concentrations high for the prepubertal chronological age. To accept the diagnosis of PA, central puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital adrenal hyperplasia, and exogenous source of androgens need to be excluded. The individually variable peripheral conversion of circulating AAPs to biologically more active androgens (testosterone, dihydrotestosterone) and the androgen receptor activity in the target tissues are as important as the circulating AAP concentrations as determinants of androgen action. PA has gained much attention during the last decades, as it has been associated with small birth size, the metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk for type 2 diabetes and cardiovascular diseases in later life. The aim of this review is to describe the known hormonal changes and their possible regulators in on-time and premature adrenarche, and the clinical features and possible later health problems associating with PA.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                10 July 2018
                2018
                : 9
                : 375
                Affiliations
                Department of Pediatrics, University of Eastern Finland and Kuopio University Hospital , Kuopio, Finland
                Author notes

                Edited by: Indraneel Banerjee, University of Manchester, United Kingdom

                Reviewed by: Laura Audí, Vall d'Hebron Research Institute, Spain; Maurizio Delvecchio, Ospedale Madonna Delle Grazie, Italy

                *Correspondence: Jani Liimatta jani.liimatta@ 123456kuh.fi

                This article was submitted to Pediatric Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2018.00375
                6048846
                71624e9c-b1a4-43c1-9802-3bab35b5ce70
                Copyright © 2018 Liimatta, Utriainen, Voutilainen and Jääskeläinen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 May 2018
                : 22 June 2018
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 36, Pages: 8, Words: 6321
                Funding
                Funded by: Kuopion Yliopistollinen Sairaala 10.13039/501100004092
                Funded by: Lastentautien Tutkimussäätiö 10.13039/501100005744
                Funded by: Suomen Lääketieteen Säätiö 10.13039/100008723
                Funded by: Päivikki ja Sakari Sohlbergin Säätiö 10.13039/501100004212
                Funded by: Emil Aaltosen Säätiö 10.13039/501100004756
                Funded by: Sigrid Juséliuksen Säätiö 10.13039/501100006306
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                dehydroepiandrosterone sulfate,growth,insulin-like growth factor 1,menarche,pubarche

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