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      Girls with a History of Premature Adrenarche Have Advanced Growth and Pubertal Development at the Age of 12 Years

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          Abstract

          Background

          Premature adrenarche (PA) has been linked to early thelarche and menarche, but longitudinal data on growth and pubertal development after PA are insufficient.

          Methods

          Growth and pubertal development of mostly full-term and appropriate for gestational age-born 43 PA (36 girls) and 63 control children (52 girls) were analyzed prospectively. Children examined first at the mean age of 7.6 years were reexamined at the mean age of 12.0 years.

          Results

          The PA girls but not the boys were taller and had higher body mass index (BMI) than the controls. A higher proportion of the PA than control girls had reached menarche, while the same percentage of the PA and control boys were at Tanner genital stage ≥2. The PA girls with premature pubarche (PP) were taller but not heavier and had more often reached menarche by the age of 12 years than the PA girls without PP. The PA girls with menarche had lower birth length (BL) and higher prepubertal insulin-like growth factor 1 (IGF-1) concentrations compared with non-menarcheal PA girls. In logistic regression analyses for all girls, lower BL standard deviation score, earlier maternal menarche, and higher prepubertal IGF-1 were independently associated with menarche.

          Conclusion

          At 12 years of age, the PA girls had higher BMI, advanced linear growth, and accelerated pubertal development with earlier menarche than the control girls. The PA girls with PP were taller and had earlier menarche than the PA girls without PP. Lower BL and higher prepubertal IGF-1 concentration were predictive factors for menarche by the age of 12 years.

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          Most cited references32

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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
                URI : http://frontiersin.org/people/u/470593
                URI : http://frontiersin.org/people/u/487603
                URI : http://frontiersin.org/people/u/9470
                URI : http://frontiersin.org/people/u/13818
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                31 October 2017
                2017
                : 8
                : 291
                Affiliations
                [1] 1Department of Pediatrics, University of Eastern Finland and Kuopio University Hospital , Kuopio, Finland
                Author notes

                Edited by: Mohamad Maghnie, Università di Genova, Italy

                Reviewed by: Laura Audí, Vall d’Hebron Research Institute, Spain; Hugo Fideleff, Universidad de Buenos Aires, Argentina; Luigi R. Garibaldi, University of Pittsburgh-Children’s Hospital, United States

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

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

                Article
                10.3389/fendo.2017.00291
                5671637
                29163361
                a5439224-e0de-4f53-aa42-19f02ee65d1f
                Copyright © 2017 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) or licensor 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
                : 25 August 2017
                : 12 October 2017
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 37, Pages: 8, Words: 6487
                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: Sigrid Juséliuksen Säätiö 10.13039/501100006306
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                premature adrenarche,dehydroepiandrosterone sulfate,insulin-like growth factor i,growth,puberty,menarche

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