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Published in: BMC Endocrine Disorders 1/2019

Open Access 01-12-2019 | Turner's Syndrome | Research article

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

Authors: Helmuth G. Dörr, Theresa Penger, Michaela Marx, Manfred Rauh, Patricia G. Oppelt, Thomas K. M. Völkl

Published in: BMC Endocrine Disorders | Issue 1/2019

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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.
Literature
1.
go back to reference Gonzalez L, Witchel SF. The patient with turner syndrome: puberty and medical management concerns. Fertil Steril. 2012;98(4):780–6.CrossRef Gonzalez L, Witchel SF. The patient with turner syndrome: puberty and medical management concerns. Fertil Steril. 2012;98(4):780–6.CrossRef
2.
4.
go back to reference Hankus M, Soltysik K, Szeliga K, Antosz A, Drosdzol-Cop A, Wilk K, et al. Prediction of spontaneous puberty in turner syndrome based on mid-childhood gonadotropin concentrations, karyotype, and ovary visualization: a longitudinal study. Horm Res Paediatr. 2018;89(2):90–7.CrossRef Hankus M, Soltysik K, Szeliga K, Antosz A, Drosdzol-Cop A, Wilk K, et al. Prediction of spontaneous puberty in turner syndrome based on mid-childhood gonadotropin concentrations, karyotype, and ovary visualization: a longitudinal study. Horm Res Paediatr. 2018;89(2):90–7.CrossRef
5.
go back to reference Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G. Spontaneous pubertal development in Turner's syndrome. Italian study Group for Turner's syndrome. J Clin Endocrinol Metab. 1997;82(6):1810–3.PubMed Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G. Spontaneous pubertal development in Turner's syndrome. Italian study Group for Turner's syndrome. J Clin Endocrinol Metab. 1997;82(6):1810–3.PubMed
6.
go back to reference Belgorosky A, Baquedano MS, Guercio G, Rivarola MA. Adrenarche: postnatal adrenal zonation and hormonal and metabolic regulation. Horm Res. 2008;70(5):257–67.CrossRef Belgorosky A, Baquedano MS, Guercio G, Rivarola MA. Adrenarche: postnatal adrenal zonation and hormonal and metabolic regulation. Horm Res. 2008;70(5):257–67.CrossRef
7.
go back to reference Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child. 2012;97(3):250–4.CrossRef Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child. 2012;97(3):250–4.CrossRef
8.
go back to reference Voutilainen R, Jaaskelainen J. Premature adrenarche: etiology, clinical findings, and consequences. J Steroid Biochem Mol Biol. 2015;145:226–36.CrossRef Voutilainen R, Jaaskelainen J. Premature adrenarche: etiology, clinical findings, and consequences. J Steroid Biochem Mol Biol. 2015;145:226–36.CrossRef
9.
go back to reference Guercio G, Rivarola MA, Chaler E, Maceiras M, Belgorosky A. Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls. J Clin Endocrinol Metab. 2003;88(3):1389–93.CrossRef Guercio G, Rivarola MA, Chaler E, Maceiras M, Belgorosky A. Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls. J Clin Endocrinol Metab. 2003;88(3):1389–93.CrossRef
10.
go back to reference Iwatani N, Kodama M, Seto H. A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche? Endocrinologia japonica. 1992;39(3):251–7.CrossRef Iwatani N, Kodama M, Seto H. A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche? Endocrinologia japonica. 1992;39(3):251–7.CrossRef
11.
go back to reference Sklar CA, Ulstrom RA. Effect of human growth hormone on adrenal androgens in children with growth hormone deficiency. Horm Res. 1984;20(3):166–71.CrossRef Sklar CA, Ulstrom RA. Effect of human growth hormone on adrenal androgens in children with growth hormone deficiency. Horm Res. 1984;20(3):166–71.CrossRef
12.
go back to reference Leschek EW, Troendle JF, Yanovski JA, Rose SR, Bernstein DB, Cutler GB Jr, et al. Effect of growth hormone treatment on testicular function, puberty, and adrenarche in boys with non-growth hormone-deficient short stature: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2001;138(3):406–10.CrossRef Leschek EW, Troendle JF, Yanovski JA, Rose SR, Bernstein DB, Cutler GB Jr, et al. Effect of growth hormone treatment on testicular function, puberty, and adrenarche in boys with non-growth hormone-deficient short stature: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2001;138(3):406–10.CrossRef
13.
go back to reference Counts DR, Pescovitz OH, Barnes KM, Hench KD, Chrousos GP, Sherins RJ, et al. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1987;64(6):1174–8.CrossRef Counts DR, Pescovitz OH, Barnes KM, Hench KD, Chrousos GP, Sherins RJ, et al. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1987;64(6):1174–8.CrossRef
14.
go back to reference Tung YC, Lee JS, Tsai WY, Hsiao PH. Physiological changes of adrenal androgens in childhood. J Formos Med Assoc. 2004;103(12):921–4.PubMed Tung YC, Lee JS, Tsai WY, Hsiao PH. Physiological changes of adrenal androgens in childhood. J Formos Med Assoc. 2004;103(12):921–4.PubMed
15.
go back to reference Sklar CA, Kaplan SL, Grumbach MM. Evidence for dissociation between adrenarche and gonadarche: studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency, and constitutionally delayed growth and adolescence. J Clin Endocrinol Metab. 1980;51(3):548–56.CrossRef Sklar CA, Kaplan SL, Grumbach MM. Evidence for dissociation between adrenarche and gonadarche: studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency, and constitutionally delayed growth and adolescence. J Clin Endocrinol Metab. 1980;51(3):548–56.CrossRef
16.
go back to reference Teller WM, Homoki J, Wudy S, Schlickenrieder JH. Adrenarche is dissociated from gonadarche--studies in patients with Turner's syndrome. Acta Endocrinol Suppl (Copenh). 1986;279:232–40.CrossRef Teller WM, Homoki J, Wudy S, Schlickenrieder JH. Adrenarche is dissociated from gonadarche--studies in patients with Turner's syndrome. Acta Endocrinol Suppl (Copenh). 1986;279:232–40.CrossRef
17.
go back to reference Lee PA, Kowarski A, Migeon CJ, Blizzard RM. Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children. J Clin Endocrinol Metab. 1975;40(4):664–9.CrossRef Lee PA, Kowarski A, Migeon CJ, Blizzard RM. Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children. J Clin Endocrinol Metab. 1975;40(4):664–9.CrossRef
18.
go back to reference Martin DD, Schweizer R, Schwarze CP, Elmlinger MW, Ranke MB, Binder G. The early dehydroepiandrosterone sulfate rise of adrenarche and the delay of pubarche indicate primary ovarian failure in turner syndrome. J Clin Endocrinol Metab. 2004;89(3):1164–8.CrossRef Martin DD, Schweizer R, Schwarze CP, Elmlinger MW, Ranke MB, Binder G. The early dehydroepiandrosterone sulfate rise of adrenarche and the delay of pubarche indicate primary ovarian failure in turner syndrome. J Clin Endocrinol Metab. 2004;89(3):1164–8.CrossRef
19.
go back to reference Kromeyer-Hauschild K, Wabitsch M, Kunze D, Geller F, Geiß HC, Hesse V, von Hippel A, Jaeger U, Johnsen D, Korte W, Menner K, Müller G, Müller JM, Niemann-Pilatus A, Remer T, Schaefer F, Wittchen H-U, Zabransky S, Zellner K, Ziegler A, Hebebrand J. Perzentile für den Body-mass-Index für das Kinder- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift Kinderheilkunde. 2001;149:807–18.CrossRef Kromeyer-Hauschild K, Wabitsch M, Kunze D, Geller F, Geiß HC, Hesse V, von Hippel A, Jaeger U, Johnsen D, Korte W, Menner K, Müller G, Müller JM, Niemann-Pilatus A, Remer T, Schaefer F, Wittchen H-U, Zabransky S, Zellner K, Ziegler A, Hebebrand J. Perzentile für den Body-mass-Index für das Kinder- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift Kinderheilkunde. 2001;149:807–18.CrossRef
20.
go back to reference Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291–303.CrossRef Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291–303.CrossRef
21.
go back to reference Kahl H, Schaffrath RA, Schlaud M. Sexual maturation of children and adolescents in Germany. Results of the German health interview and examination survey for children and adolescents (KiGGS). BundesgesundheitsblattGesundheitsforschungGesundheitsschutz. 2007;50(5–6):677–85. Kahl H, Schaffrath RA, Schlaud M. Sexual maturation of children and adolescents in Germany. Results of the German health interview and examination survey for children and adolescents (KiGGS). BundesgesundheitsblattGesundheitsforschungGesundheitsschutz. 2007;50(5–6):677–85.
22.
go back to reference Frenzel S, Biskupek-Sigwart J, Breuning U, Dörr HG. Dehydroepiandrosteronsulfat (DHEAS) im Serum bei gesunden Kindern und Jugendichen. Monatsschrift Kinderheilkunde. 1997;145(Suppl. 1):100. Frenzel S, Biskupek-Sigwart J, Breuning U, Dörr HG. Dehydroepiandrosteronsulfat (DHEAS) im Serum bei gesunden Kindern und Jugendichen. Monatsschrift Kinderheilkunde. 1997;145(Suppl. 1):100.
23.
go back to reference Hagen CP, Main KM, Kjaergaard S, Juul A. FSH, LH, inhibin B and estradiol levels in turner syndrome depend on age and karyotype: longitudinal study of 70 turner girls with or without spontaneous puberty. Hum Reprod. 2010;25(12):3134–41.CrossRef Hagen CP, Main KM, Kjaergaard S, Juul A. FSH, LH, inhibin B and estradiol levels in turner syndrome depend on age and karyotype: longitudinal study of 70 turner girls with or without spontaneous puberty. Hum Reprod. 2010;25(12):3134–41.CrossRef
24.
go back to reference Hosoda A, Fujieda K, Matsuura N, Okuno A, Yuri K. Age-related change of pulsatile gonadotropin secretion in turner syndrome. PediatrRes. 1991;29(2):196–200. Hosoda A, Fujieda K, Matsuura N, Okuno A, Yuri K. Age-related change of pulsatile gonadotropin secretion in turner syndrome. PediatrRes. 1991;29(2):196–200.
25.
go back to reference Conte FA, Grumbach MM, Kaplan SL. A diphasic pattern of gonadotropin secretion in patients with the syndrome of gonadal dysgenesis. J Clin Endocrinol Metab. 1975;40(4):670–4.CrossRef Conte FA, Grumbach MM, Kaplan SL. A diphasic pattern of gonadotropin secretion in patients with the syndrome of gonadal dysgenesis. J Clin Endocrinol Metab. 1975;40(4):670–4.CrossRef
26.
go back to reference Chrysis D, Spiliotis BE, Stene M, Cacciari E, Davenport ML. Gonadotropin secretion in girls with turner syndrome measured by an ultrasensitive immunochemiluminometric assay. Horm Res. 2006;65(5):261–6.PubMed Chrysis D, Spiliotis BE, Stene M, Cacciari E, Davenport ML. Gonadotropin secretion in girls with turner syndrome measured by an ultrasensitive immunochemiluminometric assay. Horm Res. 2006;65(5):261–6.PubMed
27.
go back to reference Hagen CP, Aksglaede L, Sorensen K, Mouritsen A, Andersson AM, Petersen JH, et al. Individual serum levels of anti-Mullerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study. Hum Reprod. 2012;27(3):861–6.CrossRef Hagen CP, Aksglaede L, Sorensen K, Mouritsen A, Andersson AM, Petersen JH, et al. Individual serum levels of anti-Mullerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study. Hum Reprod. 2012;27(3):861–6.CrossRef
28.
go back to reference Balducci R, Toscano V, Larizza D, Mangiantini A, Galasso C, Municchi G, et al. Effects of long-term growth hormone therapy on adrenal steroidogenesis in turner syndrome. Horm Res. 1998;49(5):210–5.PubMed Balducci R, Toscano V, Larizza D, Mangiantini A, Galasso C, Municchi G, et al. Effects of long-term growth hormone therapy on adrenal steroidogenesis in turner syndrome. Horm Res. 1998;49(5):210–5.PubMed
29.
go back to reference Mesiano S, Katz SL, Lee JY, Jaffe RB. Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. J Clin Endocrinol Metab. 1997;82(5):1390–6.PubMed Mesiano S, Katz SL, Lee JY, Jaffe RB. Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. J Clin Endocrinol Metab. 1997;82(5):1390–6.PubMed
30.
go back to reference Buckler JM. A longitudinal study of adolescent growth. London: Springer; 1990.CrossRef Buckler JM. A longitudinal study of adolescent growth. London: Springer; 1990.CrossRef
31.
go back to reference Largo RH, Prader A. Pubertal development in Swiss girls. Helv Paediatr Acta. 1983;38(3):229–43.PubMed Largo RH, Prader A. Pubertal development in Swiss girls. Helv Paediatr Acta. 1983;38(3):229–43.PubMed
Metadata
Title
Adrenarche and pubarche in girls with turner syndrome during growth-promoting therapy with human growth hormone
Authors
Helmuth G. Dörr
Theresa Penger
Michaela Marx
Manfred Rauh
Patricia G. Oppelt
Thomas K. M. Völkl
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2019
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-019-0333-z

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