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      Adrenarche and pubarche in girls with turner syndrome during growth-promoting therapy with human growth hormone

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          Abstract

          Background

          Data on adrenarche and pubarche in girls with Turner syndrome (TS) are inconsistent in the literature.

          Methods

          The cohort consisted of 94 girls and young women with TS born between 1971 and 2001 (age range: 3.1–23.2 yrs.), who were treated with human growth hormone and regularly presented at our outpatient clinic every 4 to 6 months.The longitudinal data of all patients were ascertained retrospectively from patient charts. The data collection ended in January 2016. Adrenarche was assessed by serum DHEAS levels and pubertal status by Tanner stages. Pubarche was defined as the appearance of pubic hair (PH2), whereas spontaneous puberty was defined as Tanner stage B2. The patients were retrospectively subdivided in two groups with regard to pubertal development: group 1 ( n = 21) with spontaneous puberty and group 2 ( n = 70) with induced puberty. Since blood samples were not taken at every visit, we generated seven groups according to the age of the children at which the blood samples were taken: 3–5, 5–7, 7–9, 9–11, 11–13, 13–15, and 15–17 yrs. Serum DHEAS and follicle-stimulating hormone (FSH) levels were measured by chemiluminescence immunoassay and compared with those of a control group of healthy girls.

          Results

          Adrenarche started in TS girls between 5 and 7 years. TS girls had higher DHEAS levels than the control group, with statistically significant differences in the age groups 7 to 17 years. No differences were determined between the TS girls with spontaneous puberty and those with POI. TS girls in group 2 reached the Tanner stages PH2 ( p < 0.04), PH3 ( p < 0.01), PH4 and PH5 ( p < 0.001) markedly later than TS girls in group 1.

          Conclusions

          The onset of adrenarche in girls with TS undergoing GH therapy does not differ from that in healthy girls. However, adrenarche is more pronounced in girls with TS. There is no difference in DHEAS levels between the TS girls with spontaneous puberty and the TS girls with primary ovarian insufficiency (POI), while the tempo of pubarche is markedly slower in the girls with POI.

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          Most cited references27

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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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            Spontaneous pubertal development in Turner's syndrome. Italian Study Group for Turner's Syndrome.

            The incidence of spontaneous puberty in Turner's syndrome is reported to be between 5-10% and, more recently in some series, as high as 20%. In an Italian retrospective multicenter study, of 522 patients older than 12 yr with Turner's syndrome, 84 patients (16, 1%) presented spontaneous pubertal development with menarche that occurred at a chronological age of 13.2 +/- 1.5 yr (mean +/- SD) and a bone age of 12.9 +/- 1.9 yr. Karyotype distribution in the whole group was as follows: 52.1% (272 patients) X-monosomy (45,X), 13.2% (69 patients) mosaicism characterized by X-monosomy and cellular line with no structural abnormalities of the second X, 19.9% (104 patients) mosaicism characterized by X-monosomy and cellular line with structural abnormalities of the second X, and 14.8% (77 patients) structural abnormalities of the second X. Menstrual cycles were still regular in 30 patients at 9.2 +/- 5.0 yr after menarche, 12 developed secondary amenorrhea 1.6 +/- 2.0 yr after menarche, and 19 had irregular menstrual cycles 0.9 +/- 1.8 yr after menarche. As signs of spontaneous puberty developed in 14.0% of X-monosomic patients and in 32.0% of patients with cell lines with more than one X, the presence of the second X seems to have a cardinal influence on the appearance of spontaneous puberty. Spontaneous pregnancy occurred in 3 patients (3.6%). The presence of chromosomal abnormalities and malformations in 2 of 3 pregnancies led us to agree with other investigators in discouraging unassisted pregnancies. Treatment with GH does not seem to exert any influence on either the age of onset or the prevalence of spontaneous pubertal development in Turner's syndrome. The increased percentage of spontaneous menarche is Turner's syndrome reported in the recent literature might be due to increased ascertainment by diligent screening for Turner's syndrome in girls with short stature and mild or no Turner's syndrome stigmata, even though they may be menstruating.
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              Turner's syndrome.

              P Saenger (1996)
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                Author and article information

                Contributors
                +49 (0) 9131-853-6151 , helmuth-guenther.doerr@uk-erlangen.de
                Journal
                BMC Endocr Disord
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central (London )
                1472-6823
                18 January 2019
                18 January 2019
                2019
                : 19
                : 9
                Affiliations
                [1 ]ISNI 0000 0000 9935 6525, GRID grid.411668.c, Paediatric Endocrinology, , University Hospital of Erlangen, ; Loschgestr. 15, 91054 Erlangen, Germany
                [2 ]ISNI 0000 0000 9935 6525, GRID grid.411668.c, Laboratory Medicine, , University Hospital of Erlangen, ; Loschgestr. 15, 91054 Erlangen, Germany
                [3 ]ISNI 0000 0000 9935 6525, GRID grid.411668.c, Department of Paediatrics, and Paediatric Gynaecology, , University Hospital of Erlangen, ; Loschgestr. 15, 91054 Erlangen, Germany
                [4 ]ISNI 0000 0000 9935 6525, GRID grid.411668.c, Department of Gynaecology and Obstetrics, , University Hospital of Erlangen, ; Loschgestr. 15, 91054 Erlangen, Germany
                Author information
                http://orcid.org/0000-0002-4838-6737
                Article
                333
                10.1186/s12902-019-0333-z
                6339350
                30658614
                a023b87c-0ab8-47fa-9f52-8ca8d0342797
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 September 2018
                : 8 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Endocrinology & Diabetes
                turner syndrome,dheas,adrenarche,primary ovarian insufficiency
                Endocrinology & Diabetes
                turner syndrome, dheas, adrenarche, primary ovarian insufficiency

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