Pubertätsentwicklung und Adipositas

ZUSAMMENFASSUNG

Die Beurteilung der Pubertätsentwicklung sowie Übergewicht und Adipositas sind tagtäglicher Bestandteil der pädiatrischen Praxis. Dabei beeinflussen sich Pubertätsentwicklung und Adipositas wechselseitig. Während Mädchen mit Adipositas häufig eine Pubertätsakzeleration aufweisen, sind die Daten bei Jungen weniger eindeutig. Möglicherweise verursacht Übergewicht hier eine Pubertätsbeschleunigung und Adipositas eine Pubertätsverzögerung. Leicht erhöhte Androgenspiegel bei Mädchen sowie leicht erhöhte Östrogenspiegel bei Jungen und eine präpubertäre Wachstumsakzeleration bei beiden Geschlechtern sind häufige Phänomene bei Kindern mit Adipositas. Die Ursachen sind multifaktoriell. Hierbei spielt das Fettgewebe eine entscheidende Rolle, sowohl durch die zentrale Aktivierung der Hypothalamus-Hypophysen-Gonadenachse über Leptin und Kisspeptin als auch durch periphere Effekte, wie beispielweise die Umwandlung von Androgenen zu Östrogen. Syndrome, welche sowohl Störungen der Pubertätsentwicklung als auch Adipositas umfassen, dürfen bei der klinischen Einschätzung nicht übersehen werden. Zur Einschätzung der altersgerechten Pubertätsentwicklung bei Kindern und Jugendlichen mit Adipositas kann in Kenntnis der typischen Veränderungen und Warnzeichen in den meisten Fällen jedoch auf weitere Diagnostik verzichtet und der Verlauf vorerst beobachtet werden.

ABSTRACT

Suspected disorders of pubertal development as well as overweight and obesity belong to every pediatrician’s routine. Hereby, both diseases interfere with each other. Girls with obesity show accelerated pubertal development, on the contrary, this trend is less consistent in boys. Overweight may lead to an earlier pubertal timing in boys, whereas obesity causes pubertal delay. Elevated androgen levels are common in girls with obesity, elevated estradiol levels are common in boys with obesity, both sexes show accelerated growth during the prepubertal period. Causes are multifactorial. Adipose tissue plays a crucial role by mediating central activation of the hypothalamus-pituitary-gonadal axis through leptin and kisspeptin, as well as by peripheral effects through conversion of androgens to estrogen. Syndromes, which comprise altered pubertal development as well as obesity should not be dismissed. To evaluate pubertal timing in adolescents with obesity, further diagnostic testing is often not necessary, if typical alterations and red flags are taken under consideration carefully.

Schlüsselwörter

Pubertätsentwicklung - kindliche Adipositas - Pubertas präcox - Pubertas tarda

Keywords

Pubertal development - childhood obesity - precocious puberty - delayed puberty

Publication History

Article published online:
24 February 2023

• Literatur

• 1 Herman-Giddens ME, Slora EJ, Wasserman RC. et al Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 1997; 99: 505-512 DOI: 10.1542/peds.99.4.505.
• 2 Aksglaede L, Sørensen K, Petersen JH. et al Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics 2009; 123: e932-9 DOI: 10.1542/peds.2008-2491.
• 3 Papadimitriou A, Pantsiotou S, Douros K. et al Timing of pubertal onset in girls: evidence for non-Gaussian distribution. J Clin Endocrinol Metab 2008; 93: 4422-4425 DOI: 10.1210/jc.2008-0661.
• 4 Semiz S, Kurt F, Kurt DT. et al Pubertal development of Turkish children. J Pediatr Endocrinol Metab 2008; 21: 951-961 DOI: 10.1515/jpem.2008.21.10.951.
• 5 Sun SS, Schubert CM, Chumlea WC. et al National estimates of the timing of sexual maturation and racial differences among US children. Pediatrics 2002; 110: 911-919 DOI: 10.1542/peds.110.5.911.
• 6 Herman-Giddens ME, Wang L, Koch G. Secondary sexual characteristics in boys: estimates from the national health and nutrition examination survey III, 1988–1994. Arch Pediatr Adolesc Med 2001; 155: 1022-1028 DOI: 10.1001/archpedi.155.9.1022.
• 7 Sørensen K, Aksglaede L, Petersen JH. et al Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab 2010; 95: 263-270 DOI: 10.1210/jc.2009-1478.
• 8 Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty?. Lancet Child Adolesc Heal 2019; 03: 44-54 DOI: 10.1016/S2352-4642(18)30306-7.
• 9 Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291-303 DOI: 10.1136/adc.44.235.291.
• 10 Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty?. Lancet Child Adolesc Heal 2019; 03: 44-54 DOI: 10.1016/S2352-4642(18)30306-7.
• 11 Tanner JM, Marshall WA. Variations in the Pattern of Pubertal Changes in Boys. Arch Dis Child 1970; 45: 13-24
• 12 Juul A, Magnusdottir S, Scheike T. et al Age at voice break in Danish boys: Effects of pre-pubertal body mass index and secular trend. Int J Androl 2007; 30: 537-542 DOI: 10.1111/j.1365-2605.2007.00751.x.
• 13 Parent A-S, Teilmann G, Juul A. et al The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev 2003; 24: 668-693 DOI: 10.1210/er.2002-0019.
• 14 Keen KL, Burich AJ, Mitsushima D. et al Effects of pulsatile infusion of the GABA(A) receptor blocker bicuculline on the onset of puberty in female rhesus monkeys. Endocrinology 1999; 140: 5257-5266 DOI: 10.1210/endo.140.11.7139.
• 15 Navarro VM, Gottsch ML, Wu M. et al Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 2011; 152: 4265-4275 DOI: 10.1210/en.2011-1143.
• 16 Clarkson J, Boon WC, Simpson ER. et al Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 2009; 150: 3214-3220 DOI: 10.1210/en.2008-1733.
• 17 Kauffman AS, Gottsch ML, Roa J. et al Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology 2007; 148: 1774-1783 DOI: 10.1210/en.2006-1540.
• 18 Casanueva FF, Dieguez C. Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol 1999; 20: 317-363 DOI: 10.1006/frne.1999.0187.
• 19 Kiess W, Muller G, Galler A. et al Body fat mass, leptin and puberty. J Pediatr Endocrinol Metab 2000; 13: 717-722 DOI: 10.1515/jpem.2000.13.s1.717.
• 20 Morris DH, Jones ME, Schoemaker MJ. et al Familial concordance for age at menarche: analyses from the Breakthrough Generations Study. Paediatr Perinat Epidemiol 2011; 25: 306-311 DOI: 10.1111/j.1365-3016.2010.01183.x.
• 21 Lomniczi A, Ojeda SR. The Emerging Role of Epigenetics in the Regulation of Female Puberty. Endocr Dev 2016; 29: 1-16 DOI: 10.1159/000438840.
• 22 Kempf E, Vogel M, Vogel T. et al Dynamic alterations in linear growth and endocrine parameters in children with obesity and height reference values. eClinicalMedicine 2021: 37 DOI: 10.1016/j.eclinm.2021.100977
• 23 Thankamony A, Ong KK, Ahmed ML. et al Higher levels of IGF-I and adrenal androgens at age 8 years are associated with earlier age at menarche in girls. J Clin Endocrinol Metab 2012; 97: E786-90 DOI: 10.1210/jc.2011-3261.
• 24 Reinehr T, Kulle A, Wolters B. et al Steroid hormone profiles in prepubertal obese children before and after weight loss. J Clin Endocrinol Metab 2013; 98: E1022-30 DOI: 10.1210/jc.2013-1173.
• 25 Teede H, Misso M, Costello M. et al International evidence-based guideline for the assessment and management of polycystic ovary syndrome. 2018
• 26 Biro FM, Kiess W. Contemporary trends in onset and completion of puberty, gain in height and adiposity. Endocr Dev 2016; 29: 122-133 DOI: 10.1159/000438881.
• 27 Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty?. Lancet Child Adolesc Heal 2019; 03: 44-54 DOI: 10.1016/S2352-4642(18)30306-7.
• 28 Lee JM, Wasserman R, Kaciroti N. et al Timing of Puberty in Overweight Versus Obese Boys. Pediatrics 2016; 137: e20150164 DOI: 10.1542/peds.2015-0164.
• 29 Juul A, Teilmann G, Scheike T. et al Pubertal development in Danish children: comparison of recent European and US data. Int J Androl 2006; 29: 247-255 discussion 286–90. doi:10.1111/j.1365-2605.2005.00556.x
• 30 Kleber M, Schwarz A, Reinehr T. Obesity in children and adolescents: Relationship to growth, pubarche, menarche, and voice break. J Pediatr Endocrinol Metab 2011; 24: 125-130 DOI: 10.1515/JPEM.2011.089.
• 31 Roemmich JN, Clark PA, Berr SS. et al Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Physiol 1998; 275: E543-51 DOI: 10.1152/ajpendo.1998.275.3.E543.
• 32 Rutters F, Nieuwenhuizen AG, Verhoef SPM. et al The relationship between leptin, gonadotropic hormones, and body composition during puberty in a Dutch children cohort. Eur J Endocrinol 2009; 160: 973-978 DOI: 10.1530/EJE-08-0762.
• 33 Biro FM, Khoury P, Morrison JA. Influence of obesity on timing of puberty. Int J Androl 2006; 29: 272-277 discussion 286–90 DOI: 10.1111/j.1365-2605.2005.00602.x.
• 34 Mathew H, Castracane VD, Mantzoros C. Adipose tissue and reproductive health. Metabolism 2018; 86: 18-32 DOI: 10.1016/j.metabol.2017.11.006.
• 35 Bulun SE, Chen D, Moy I. et al Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab 2012; 23: 83-89 DOI: 10.1016/j.tem.2011.10.003.
• 36 Bagatell J, Bremner J. Mediated by Aromatization to Estradiol to Inhibit absent. Society 1994: 15
• 37 Sørensen K, Aksglaede L, Munch-Andersen T. et al Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty. Diabetes Care 2009; 32: 909-914 DOI: 10.2337/dc08-1618.
• 38 Manfredi-Lozano M, Roa J, Tena-Sempere M. Connecting metabolism and gonadal function: Novel central neuropeptide pathways involved in the metabolic control of puberty and fertility. Front Neuroendocrinol 2018; 48: 37-49 DOI: 10.1016/j.yfrne.2017.07.008.
• 39 Neville KA, Walker JL. Precocious pubarche is associated with SGA, prematurity, weight gain, and obesity. Arch Dis Child 2005; 90: 258-261 DOI: 10.1136/adc.2004.053959.
• 40 Ong KK, Elks CE, Wills AK. et al Associations between the pubertal timing-related variant in LIN28B and BMI vary across the life course. J Clin Endocrinol Metab 2011; 96: E125-9 DOI: 10.1210/jc.2010-0941.
• 41 Bandini LG, Must A, Naumova EN. et al Change in leptin, body composition and other hormones around menarche – a visual representation. Acta Paediatr 2008; 97: 1454-1459 DOI: 10.1111/j.1651-2227.2008.00948.x.
• 42 Round JM, Jones DA, Honour JW. et al Hormonal factors in the development of differences in strength between boys and girls during adolescence: a longitudinal study. Ann Hum Biol 1999; 26: 49-62 DOI: 10.1080/030144699282976.
• 43 Wolters B, Lass N, Reinehr T. Treatment with gonadotropin-releasing hormone analogues: different impact on body weight in normal-weight and overweight children. Horm Res Paediatr 2012; 78: 304-311 DOI: 10.1159/000346145.
• 44 Reinehr T, Wabitsch M, Kleber M. et al Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes. Pediatr Diabetes 2009; 10: 395-400 DOI: 10.1111/j.1399-5448.2008.00492.x.
• 45 Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001; 50: 2444-2450 DOI: 10.2337/diabetes.50.11.2444.
• 46 Freemark MS.. Pediatric Obesity. New York, Heidelberg, London: Springer; 2010. DOI: 10.1007/978-1-60327-874-4
• 47 Prasasya R, Grotheer KV, Siracusa LD. et al Temple syndrome and Kagami-Ogata syndrome: Clinical presentations, genotypes, models and mechanisms. Hum Mol Genet 2020; 29: R107-R116 DOI: 10.1093/hmg/ddaa133.
• 48 Malhotra S, Sivasubramanian R, Srivastava G. Evaluation and Management of Early Onset Genetic Obesity in Childhood. J Pediatr Genet 2021; 10: 194-204 DOI: 10.1055/s-0041-1731035.