Premature adrenarche: Etiology, clinical findings, and consequences

Journal of Steroid Biochemistry and Molecular Biology

Volumn 145, Issue , 2015, Pages 226-236

  Voutilainen, Raimo ^a   Jääskeläinen, Jarmo ^a  

^a KUOPIO UNIVERSITY HOSPITAL   (Finland)

Author keywords

Adrenarche; Birth weight; DHEA; DHEAS; PCOS; Steroid

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; ANDROSTANOLONE; PRASTERONE; PRASTERONE SULFATE; TESTOSTERONE; CYP17A1 PROTEIN, HUMAN; STEROID; STEROID 17ALPHA MONOOXYGENASE;

ADRENAL CORTEX; ADRENARCHE; BODY COMPOSITION; BODY HEIGHT; BONE DENSITY; CHILD GROWTH; CHRONIC INFLAMMATION; CLINICAL FEATURE; FEMALE; GENE MUTATION; GENETIC POLYMORPHISM; HORMONAL REGULATION; HUMAN; HYPERANDROGENISM; MALE; OVARY POLYCYSTIC DISEASE; PRECOCIOUS PUBERTY; PREMATURE ADRENARCHE; PUBERTY; REVIEW; BLOOD; BODY WEIGHT; CHILD; COMPLICATION; GENETICS; HAIR; HYPERINSULINISM; METABOLISM; OBESITY; ODOR; PHOSPHORYLATION; PUBERTY, PRECOCIOUS;

ADRENAL CORTEX; ADRENARCHE; BODY WEIGHT; CHILD; FEMALE; HAIR; HUMANS; HYPERANDROGENISM; HYPERINSULINISM; MALE; ODORS; OVERWEIGHT; PHOSPHORYLATION; PUBERTY, PRECOCIOUS; STEROID 17-ALPHA-HYDROXYLASE; STEROIDS;

EID: 84915784049     PISSN: 09600760     EISSN: 18791220     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2014.06.004     Document Type: Review

References (139)

1. F. Albright Osteoporosis Ann. Intern. Med. 27 1947 861 882
2. G. Dhom The prepubertal and pubertal growth of the adrenal (adrenarche) Beitr. Pathol. 150 1973 357 377
3. G.B. Cutler Jr, M. Glenn, M. Bush, G.D. Hodgen, C.E. Graham, and D.L. Loriaux Adrenarche: a survey of rodents, domestic animals, and primates Endocrinology 103 1978 2112 2118
4. P.J. Smail, C. Faiman, W.C. Hobson, G.B. Fuller, and J.S. Winter Further studies on adrenarche in nonhuman primates Endocrinology 111 1982 844 848
5. A.J. Conley, R.M. Bernstein, and A.D. Nguyen Adrenarche in nonhuman primates: the evidence for it and the need to redefine it J. Endocrinol. 214 2012 121 131
6. S. Silverman, C. Migeon, E. Rosemberg, and L. Wilkins Precocious growth of sexual hair without other secondary sexual development: "premature pubarche" a constitutional variation of adolescence Pediatrics 10 1952 426 432
7. P. Utriainen, R. Voutilainen, and J. Jääskeläinen Continuum of phenotypes and sympathoadrenal function in premature adrenarche Eur. J. Endocrinol. 160 2009 657 665
8. S. Korth-Schutz, L.S. Levine, and M.I. New Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche J. Clin. Endocrinol. Metab. 42 1976 117 124
9. R. Voutilainen, J. Perheentupa, and D. Apter Benign premature adrenarche: clinical features and serum steroid levels Acta Paediatr. Scand. 72 1983 707 711
10. L. Ibanez, R. Virdis, N. Potau, M. Zampolli, L. Ghizzoni, M.A. Albisu, A. Carrascosa, S. Bernasconi, and E. Vicens-Calvet Natural history of premature pubarche: an auxological study J. Clin. Endocrinol. Metab. 74 1992 254 257
11. A. Pere, J. Perheentupa, M. Peter, and R. Voutilainen Follow up of growth and steroids in premature adrenarche Eur. J. Pediatr. 154 1995 346 352
12. P. Utriainen, R. Voutilainen, and J. Jääskeläinen Girls with premature adrenarche have accelerated early childhood growth J. Pediatr. 154 2009 882 887
13. R.M. Williams, C.E. Ward, and I.A. Hughes Premature adrenarche Arch. Dis. Child. 97 2012 250 254
14. R.J. Auchus, and W.E. Rainey Adrenarche - physiology, biochemistry and human disease Clin. Endocrinol. 60 2004 288 296
15. W.L. Miller Androgen synthesis in adrenarche Rev. Endocr. Metab. Disord. 10 2009 3 17
16. P.J. Hornsby Adrenarche a cell biological perspective J. Endocrinol. 214 2012 113 119
17. J. Rege, and W.E. Rainey The steroid metabolome of adrenarche J. Endocrinol. 214 2012 133 143
18. L. Ibanez, J. Dimartino-Nardi, N. Potau, and P. Saenger Premature adrenarche - normal variant or forerunner of adult disease? Endocr. Rev. 21 2000 671 696
19. J. Idkowiak, G.G. Lavery, V. Dhir, T.G. Barrett, P.M. Stewart, N. Krone, and W. Arlt Premature adrenarche: novel lessons from early onset androgen excess Eur. J. Endocrinol. 165 2011 189 207
20. S.E. Oberfield, A.B. Sopher, and A.T. Gerken Approach to the girl with early onset of pubic hair J. Clin. Endocrinol. Metab. 96 2011 1610 1622
21. S. Mesiano, and R.B. Jaffe Developmental and functional biology of the primate fetal adrenal cortex Endocr. Rev. 18 1997 378 403
22. K.M. Doody, B.R. Carr, W.E. Rainey, W. Byrd, B.A. Murry, R.C. Strickler, J.L. Thomas, and J.I. Mason 3 Beta-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland Endocrinology 126 1990 2487 2492
23. R. Voutilainen, V. Ilvesmäki, and P.J. Miettinen Low expression of 3 beta-hydroxy-5-ene steroid dehydrogenase in human fetal adrenals in vivo; adrenocorticotropin and protein kinase C-dependent regulation in adrenocortical cultures J. Clin. Endocrinol. Metab. 72 1991 761 767
24. T. Narasaka, T. Suzuki, T. Moriya, and H. Sasano Temporal and spatial distribution of corticosteroidogenic enzyme immunoreactivity in developing human adrenal Mol. Cell. Endocrinol. 174 2001 111 120
25. M. Goto, K. Piper Hanley, J. Marcos, P.J. Wood, S. Wright, A.D. Postle, I.T. Cameron, J.I. Mason, D.I. Wilson, and N.A. Hanley In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development J. Clin. Invest. 116 2006 953 960
26. R. Voutilainen, A.I. Kahri, and M. Salmenperä The effects of progesterone, pregnenolone, estriol, ACTH and HCG on steroid secretion of cultured human fetal adrenals J. Steroid Biochem. 10 1979 695 700
27. R. Voutilainen, and W.L. Miller Developmental expression of genes for the steroidogenic enzymes P450scc (20,22 desmolase), P450c17 (17-hydroxylase/17,20 lyase) and P450c21 (21-hydroxylase) in the human fetus J. Clin. Endocrinol. Metab. 63 1986 1145 1150
28. V. Ilvesmäki, and R. Voutilainen Interaction of phorbol ester and adrenocorticotropin in the regulation of steroidogenic P450 genes in human fetal and adult adrenal cell cultures Endocrinology 128 1991 1450 1458
29. R.J. Schiebinger, B.D. Albertson, F.G. Cassorla, D.W. Bowyer, G.W. Geelhoed, G.B. Cutler Jr, and D.L. Loriaux The developmental changes in plasma adrenal androgens during infancy and adrenarche are associated with changing activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase J. Clin. Invest. 67 1981 1177 1182
30. B.H. Rich, R.L. Rosenfield, A.W. Lucky, J.C. Helke, and P. Otto Adrenarche: changing response to adrenocorticotropin J. Clin. Endocrinol. Metab. 52 1981 1129 1136
31. E.O. Reiter, V.G. Fuldauer, and A.W. Root Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities J. Pediatr. 90 1977 766 770
32. J.S. Gell, B.R. Carr, H. Sasano, B. Atkins, L. Margraf, J.I. Mason, and W.E. Rainey Adrenarche results from development of a 3beta-hydroxysteroid dehydrogenase-deficient adrenal reticularis J. Clin. Endocrinol. Metab. 83 1998 3695 3701
33. S. Mapes, C.J. Corbin, A. Tarantal, and A. Conley The primate adrenal zona reticularis is defined by expression of cytochrome b5, 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) and NADPH-cytochrome P450 reductase (reductase) but not 3beta-hydroxysteroid dehydrogenase/delta5-4 isomerase (3beta-HSD) J. Clin. Endocrinol. Metab. 84 1999 3382 3385
34. T. Suzuki, H. Sasano, J. Takeyama, C. Kaneko, W.A. Freije, B.R. Carr, and W.E. Rainey Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex: immunohistochemical studies Clin. Endocrinol. 53 2000 739 747
35. L.H. Zhang, H. Rodriguez, S. Ohno, and W.L. Miller Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome Proc. Natl. Acad. Sci. U. S. A. 92 1995 10619 10623
36. M.K. Tee, and W.L. Miller Phosphorylation of human cytochrome P450c17 by p38α selectively increases 17,20 lyase activity and androgen biosynthesis J. Biol. Chem. 288 2013 23903 29313
37. D.C. Anderson The adrenal androgen-stimulating hormone does not exist Lancet 2 8192 1980 454 456
38. A.I. Kahri, R. Voutilainen, and M. Salmenperä Different biological action of corticosteroids, corticosterone and cortisol, as a base of zonal function of adrenal cortex Acta Endocrinol. (Copenh.) 91 1979 329 337
39. L.S. Topor, M. Asai, J. Dunn, and J.A. Majzoub Cortisol stimulates secretion of dehydroepiandrosterone in human adrenocortical cells through inhibition of 3betaHSD2 J. Clin. Endocrinol. Metab. 96 2011 E31 E39
40. Z. Dickerman, D.R. Grant, C. Faiman, and J.S. Winter Intraadrenal steroid concentrations in man: zonal differences and developmental changes J. Clin. Endocrinol. Metab. 59 1984 1031 1036
41. R. Voutilainen, R. Riikonen, O. Simell, and J. Perheentupa The effect of ACTH therapy on serum dehydroepiandrosterone, androstenedione, testosterone and 5α-dihydrotestosterone in infants J. Steroid Biochem. 28 1987 193 196
42. M.R. Palmert, D.L. Hayden, M.J. Mansfield, J.F. Crigler Jr, W.F. Crowley Jr, D.W. Chandler, and P.A. Boepple The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process J. Clin. Endocrinol. Metab. 86 2001 4536 4542
43. T. Remer, K.R. Boye, M.F. Hartmann, and S.A. Wudy Urinary markers of adrenarche: reference values in healthy subjects, aged 3-18 years J. Clin. Endocrinol. Metab. 90 2005 2015 2021
44. G. Lashansky, P. Saenger, K. Fishman, T. Gautier, D. Mayes, G. Berg, J. Di Martino-Nardi, and E. Reiter Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation J. Clin. Endocrinol. Metab. 73 1991 674 686
45. N. Orentreich, J.L. Brind, R.L. Rizer, and J.H. Vogelman Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood J. Clin. Endocrinol. Metab. 59 1984 551 555
46. A. Weber, A.J.L. Clark, L.A. Perry, J.W. Honour, and M.O. Savage Diminished adrenal androgen secretion in familial glucocorticoid deficiency implicates a significant role for ACTH in the induction of adrenarche Clin. Endocrinol. 46 1997 431 437
47. C. Boettcher, M.F. Hartman, J. de Laffolie, K.P. Zimmer, and S.A. Wudy Absent adrenarche in children with hypopituitarism: a study based on urinary steroid metabolomics Horm. Res. Paediatr. 79 2013 356 360
48. S. Kannisto, M. Korppi, K. Remes, and R. Voutilainen Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression in asthmatic children treated with inhaled steroids J. Clin. Endocrinol. Metab. 86 2001 4908 4912
49. S. Kannisto, A. Laatikainen, A. Taivainen, K. Savolainen, H. Tukiainen, and R. Voutilainen Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression during inhaled steroid therapy in adult asthmatic patients Eur. J. Endocrinol. 150 2004 687 690
50. G.C. Lachelin, M. Barnett, B.R. Hopper, G. Brink, and S.S. Yen Adrenal function in normal women and women with the polycystic ovary syndrome J. Clin. Endocrinol. Metab. 49 1979 892 898
51. A.W. Lucky, R.J. Rosenfield, J. McGuire, S. Rudy, and J. Helke Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche J. Clin. Endocrinol. Metab. 62 1986 840 848
52. S. Likitmaskul, C.T. Cowell, K. Donaghue, D.J. Kreutzmann, N.J. Howard, B. Blades, and M. Silink 'Exaggerated adrenarche' in children presenting with premature adrenarche Clin. Endocrinol. 42 1995 265 272
53. L. Ibanez, N. Potau, M.V. Marcos, and F. de Zegher Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age J. Clin. Endocrinol. Metab. 84 1999 4739 4741
54. M. Maliqueo, T. Sir-Petermann, V. Perez, B. Echiburu, A.L. de Guevara, C. Galvez, N. Crisosto, and R. Azziz Adrenal function during childhood and puberty in daughters of women with polycystic ovary syndrome J. Clin. Endocrinol. Metab. 94 2009 3282 3288
55. W.F. Paterson, S.F. Ahmed, L. Bath, M.D. Donaldson, R. Fleming, S.A. Greene, I. Hunter, C.J. Kelnar, A. Mayo, J.S. Schulga, D. Shapiro, P.J. Smail, and A.M. Wallace Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry Clin. Endocrinol. 72 2010 496 501
56. L. Ibanez, N. Potau, I. Francois, and F. de Zegher Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth J. Clin. Endocrinol. Metab. 83 1998 3558 3562
57. N. Potau, L. Ibanez, S. Rique, C. Sanchez-Ufarte, and F. de Zegher Pronounced adrenarche and precocious pubarche in boys Horm. Res. 51 1999 238 241
58. L. Ibanez, R. Jimenez, and F. de Zegher Early puberty-menarche after precocious pubarche: relation to prenatal growth Pediatrics 117 2006 117 121
59. R.L. Rosenfield Identifying children at risk for polycystic ovary syndrome J. Clin. Endocrinol. Metab. 92 2007 787 796
60. L. Ghizzoni, and V. Gasco Premature pubarche Horm. Res. Paediatr. 73 2010 420 422
61. L. Ibanez, K.K. Ong, N. Mongan, J. Jääskeläinen, M.V. Marcos, I.A. Hughes, F. De Zegher, and D.B. Dunger Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism J. Clin. Endocrinol. Metab. 88 2003 3333 3338
62. A. Vottero, M. Capelletti, S. Giuliodori, I. Viani, M. Ziveri, T.M. Neri, S. Bernasconi, and L. Ghizzoni Decreased androgen receptor gene methylation in premature pubarche: a novel pathogenetic mechanism? J. Clin. Endocrinol. Metab. 91 2006 968 972
63. S. Lappalainen, P. Utriainen, T. Kuulasmaa, R. Voutilainen, and J. Jääskeläinen Androgen receptor gene CAG repeat polymorphism and X-chromosome inactivation in children with premature adrenarche J. Clini. Endocrinol. Metab. 93 2008 1304 1309
64. J. Liimatta, S. Laakso, P. Utriainen, R. Voutilainen, J.J. Palvimo, T. Jääskeläinen, and J. Jääskeläinen Serum androgen bioactivity is low in children with premature adrenarche Pediatr. Res. 75 2014 645 650
65. A.B. Sopher, A.M. Jean, S.K. Zwany, D.M. Winston, C.B. Pomeranz, J.J. Bell, D.J. McMahon, A. Hassoun, I. Fennoy, and S.E. Oberfield Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors Obesity 19 2011 1259 1264
66. P. Utriainen, J. Jääskeläinen, and R. Voutilainen Blood erythrocyte and hemoglobin concentrations in premature adrenarche J. Clin. Endocrinol. Metab. 98 2013 E87 E91
67. L. Ibanez, N. Potau, M. Zampolli, S. Rique, P. Saenger, and A. Carrascosa Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche J. Clin. Endocrinol. Metab. 82 1997 2283 2288
68. M.R. Denburg, M.E. Silfen, A.M. Manibo, D. Chin, L.S. Levine, M. Ferin, D.J. McMahon, C. Go, and S.E. Oberfield Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche J. Clin. Endocrinol. Metab. 87 2002 5604 5609
69. M.E. Silfen, A.M. Manibo, M. Ferin, D.J. McMahon, L.S. Levine, and S.E. Oberfield Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity J. Clin. Endocrinol. Metab. 87 2002 398 403
70. P. Utriainen, J. Jääskeläinen, A. Saarinen, E. Vanninen, O. Mäkitie, and R. Voutilainen Body composition and bone mineral density in children with premature adrenarche and the association of LRP5 gene polymorphisms with bone mineral density J. Clin. Endocrinol. Metab. 94 2009 4144 4151
71. L. Ghizzoni, and S. Milani The natural history of premature adrenarche J. Pediatr. Endocrinol. Metab. 13 Suppl. 5 2000 1247 1251
72. T. Oron, Y. Lebenthal, L. de Vries, M. Yackobovitch-Gavan, M. Phillip, and L. Lazar Interrelationship of extent of precocious adrenarche in appropriate for gestational age girls with clinical outcome J. Pediatr. 160 2012 308 313
73. J. von Oettingen, J. Sola Pou, L.L. Levitsky, and M. Misra Clinical presentation of children with premature adrenarche Clin. Pediatr. (Phila.) 51 2012 1140 1149
74. S.E. Oberfield, D.M. Mayes, and L.S. Levine Adrenal steroidogenic function in a black and hispanic population with precocious pubarche J. Clin. Endocrinol. Metab. 70 1990 76 82
75. S.F. Siegel, D.N. Finegold, M.D. Urban, R. McVie, and P.A. Lee Premature pubarche: etiological heterogeneity J. Clin. Endocrinol. Metab. 74 1992 239 247
76. R. Balducci, B. Boscherini, A. Mangiantini, M. Morellini, and V. Toscano Isolated precocious pubarche: an approach J. Clin. Endocrinol. Metab. 79 1994 582 589
77. M.-L. Charkaluk, C. Trivin, and R. Brauner Premature pubarche as an indicator of how body weight influences the onset of adrenarche Eur. J. Pediatr. 163 2004 89 93
78. I. Francois, and F. de Zegher Adrenarche and fetal growth Pediatr. Res. 41 1997 440 442
79. J. Dahlgren, M. Boguszewski, S. Rosberg, and K. Albertsson-Wikland Adrenal steroid hormones in short children born small for gestational age Clin. Endocrinol. 49 1998 353 361
80. P. Ghirri, M. Bernardini, M. Vuerich, A.M. Cuttano, L. Coccoli, I. Merusi, C. Ciulli, L. D'Accavio, U. Bottone, and A. Boldrini Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls Gynecol. Endocrinol. 15 2001 91 97
81. S. Tenhola, A. Martikainen, E. Rahiala, M. Parviainen, P. Halonen, and R. Voutilainen Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age J. Pediatr. 141 2002 477 482
82. K.K. Ong, N. Potau, C.J. Petry, R. Jones, A.R. Ness, J.W. Honour, F. de Zegher, L. Ibanez, and D.B. Dunger Avon longitudinal study of parents and children study team. Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls J. Clin. Endocrinol. Metab. 89 2004 2647 2651
83. D. Jaquet, J. Leger, D. Chevenne, P. Czernichow, and C. Levy-Marchal Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women J. Clin. Endocrinol. Metab. 84 1999 3945 3949
84. K. Allvin, C. Ankarberg-Lindgren, H. Fors, and J. Dahlgren Elevated serum levels of estradiol, dihydrotestosterone, and inhibin B in adult males born small for gestational age J. Clin. Endocrinol. Metab. 93 2008 1464 1469
85. R.B. Jensen, S. Vielwerth, T. Larsen, L. Hilsted, A. Cohen, D.M. Hougaard, L.T. Jensen, G. Greisen, and A. Juul Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence Horm. Res. Paediatr. 75 2011 2 7
86. B. Todorova, M. Salonen, J. Jääskeläinen, A. Tapio, T. Jääskeläinen, J. Palvimo, U. Turpeinen, E. Hämäläinen, M. Räsänen, S. Tenhola, and R. Voutilainen Adrenocortical hormonal activity in 20-year-old subjects born small or appropriate for gestational age Horm. Res. Paediatr. 77 2012 298 304
87. M. Szathmari, B. Vasarhelyi, and T. Tulassay Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood Horm. Res. 55 2001 172 178
88. C.L. Meuwese, A.M. Euser, B.E. Ballieux, H.A. van Vliet, M.J. Finken, F.J. Walther, F.W. Dekker, and J.M. Wit Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life Eur. J. Endocrinol. 163 2010 681 689
89. T. Meas, D. Chevenne, E. Thibaud, J. Leger, S. Cabrol, P. Czernichow, and C. Levy-Marchal Endocrine consequences of premature pubarche in post-pubertal Caucasian girls Clin. Endocrinol. 57 2002 101 106
90. P. Utriainen, J. Jääskeläinen, J. Romppanen, and R. Voutilainen Childhood metabolic syndrome and its components in premature adrenarche J. Clin. Endocrinol. Metab. 92 2007 4282 4285
91. K.A. Neville, and J.L. Walker Precocious pubarche is associated with SGA, prematurity, weight gain, and obesity Arch. Dis. Child. 90 2005 258 261
92. V.H. Boonstra, P.G. Mulder, F.H. de Jong, and A.C. Hokken-Koelega Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment J. Clin. Endocrinol. Metab. 89 2004 712 717
93. L. Ibanez, N. Potau, R. Virdis, M. Zampolli, C. Terzi, M. Gussinye, A. Carrascosa, and E. Vicens-Calvet Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism J. Clin. Endocrinol. Metab. 76 1993 1599 1603
94. R.P. Mathew, J.L. Najjar, R.A. Lorenz, D.E. Mayes, and W.E. Russell Premature pubarche in girls is associated with functional adrenal but not ovarian hyperandrogenism J. Pediatr. 141 2002 91 98
95. J.L. Cresswell, D.J. Barker, C. Osmond, P. Egger, D.I. Phillips, and R.B. Fraser Fetal growth, length of gestation, and polycystic ovaries in adult life Lancet 350 1997 1131 1135
96. J. Laitinen, S. Taponen, H. Martikainen, A. Pouta, I. Millwood, A.L. Hartikainen, A. Ruokonen, U. Sovio, M.I. McCarthy, S. Franks, and M.R. Jarvelin Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms Int. J. Obes. Relat. Metab. Disord. 27 2003 710 715
97. H. Mumm, M. Kamper-Jørgensen, A.M. Nybo Andersen, D. Glintborg, and M. Andersen Birth weight and polycystic ovary syndrome in adult life: a register-based study on 523,757 Danish women born 1973-1991 Fertil. Steril. 99 2013 777 782
98. A.A. Bremer Polycystic ovary syndrome in the pediatric population Metab. Syndr. Relat. Disord. 8 2010 375 394
99. L.S. Vilmann, E. Thisted, J.L. Baker, and J.C. Holm Development of obesity and polycystic ovary syndrome in adolescents Horm. Res. Paediatr. 78 2012 269 278
100. D.A. Ehrmann, R.B. Barnes, and R.L. Rosenfield Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion Endocr. Rev. 16 1995 322 353
101. E. Diamanti-Kandarakis, and A. Dunaif Insulin resistance and the polycyctic ovary syndrome revisited: an update on mechanisms and implications Endocr. Rev. 33 2012 981 1030
102. E. Oppenheimer, B. Linder, and J. DiMartino-Nardi Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans J. Clin. Endocrinol. Metab. 80 1995 614 618
103. R.L. Barbieri, A. Makris, and K.J. Ryan Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca Obstet. Gynecol. 64 1984 73S 80S
104. R. Voutilainen, and W.L. Miller Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain-cleavage enzyme, P450scc, in human steroidogenic tissues Proc. Natl. Acad. Sci. U. S. A. 84 1987 1590 1594
105. D. l'Allemand, A. Penhoat, M.-C. Lebrethon, R. Ardevol, V. Baehr, W. Oelkers, and J.M. Saez Insulin-like growth factors enhance steroidogenic enzyme and corticotrophin receptor messenger ribonucleic acid levels and corticotropin steroidogenic responsiveness in cultured human adrenocortical cells J. Clin. Endocrinol. Metab. 81 1996 3892 3897
106. S. Mesiano, S.L. Katz, J.Y. Lee, and R.B. Jaffe 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. 82 1997 1390 1396
107. S.A. Amiel, S. Caprio, R.S. Sherwin, G. Plewe, M.W. Haymond, and W.V. Tamborlane Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism J. Clin. Endocrinol. Metab. 72 1991 277 282
108. A. Moran, D.R. Jacobs Jr, J. Steinberger, C.P. Hong, R. Prineas, R. Luepker, and A.R. Sinaiko Insulin resistance during puberty: results from clamp studies in 357 children Diabetes 48 1999 2039 2044
109. A. Moran, D.R. Jacobs Jr, J. Steinberger, P. Cohen, C.P. Hong, R. Prineas, and A.R. Sinaiko Association between the insulin resistance of puberty and the insulin-like growth factor-I/growth hormone axis J. Clin. Endocrinol. Metab. 87 2002 4817 4820
110. A.R. Genazzani, C. Pintor, and R. Corda Plasma levels of gonadotropins, prolactin, thyroxine, and adrenal and gonadal steroids in obese prepubertal girls J. Clin. Endocrinol. Metab. 47 1978 974 979
111. C. Corvalan, R. Uauy, and V. Mericq Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 year in Chilean children of normal birth weight Am. J. Clin. Nutr. 97 2013 318 325
112. S. Zukauskaite, A. Seibokaite, L. Lasas, D. Lasiene, B. Urbonaite, and J. Kiesylyte Serum hormone levels and anthropometric characteristics in girls with hyperandrogenism Medicina (Kaunas) 41 2005 305 312
113. K. de Ferran, I.A. Paiva, S. Garcia Ldos, P. Gama Mde, and M.M. Guimarães Isolated premature pubarche: report of anthropometric and metabolic profile of a Brazilian cohort of girls Horm. Res. Paediatr. 75 2011 367 373
114. T. Remer, and F. Manz Role of nutritional status in the regulation of adrenarche J. Clin. Endocrinol. Metab. 84 1999 3936 3944
115. C. Pintor, S. Loche, A. Faedda, V. Fanni, A.M. Nurchi, and R. Corda Adrenal androgens in obese boys before and after weight loss Horm. Metab. Res. 16 1984 544 548
116. G.F. Gonzales, A. Villena, C. Gonez, and M. Zevallos Relationship between body mass index, age, and serum adrenal androgen levels in Peruvian children living at high altitude and at sea level Hum. Biol. 66 1994 145 153
117. L. Ibanez, K. Ong, F. de Zegher, M.V. Marcos, L. del Rio, and D.B. Dunger Fat distribution in non-obese girls with and without precocious pubarche: central adiposity related to insulinaemia and androgenaemia from prepuberty to postmenarche Clin. Endocrinol. 58 2003 372 379
118. A.B. Sopher, J.C. Thornton, M.E. Silfen, A. Manibo, S.E. Oberfield, J. Wang, R.N. Pierson Jr, L.S. Levine, and M. Horlick Prepubertal girls with premature adrenarche have greater bone mineral content and density than controls J. Clin. Endocrinol. Metab. 86 2001 5269 5272
119. L. Ibanez, N. Potau, P. Chacon, C. Pascual, and A. Carrascosa Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche Diabetologia 41 1998 1057 1063
120. N. Potau, R. Williams, K. Ong, C. Sanchez-Ufarte, F. de Zegher, L. Ibanez, and D. Dunger Fasting insulin sensitivity and post-oral glucose hyperinsulinaemia related to cardiovascular risk factors in adolescents with precocious pubarche Clin. Endocrinol. 59 2003 756 762
121. A. Güven, P. Cinaz, and A. Bideci Is premature adrenarche a risk factor for atherogenesis? Pediatr. Int. 47 2005 20 25
122. P. Utriainen, J. Jääskeläinen, O. Gröhn, J. Kuusisto, K. Pulkki, and R. Voutilainen Circulating TNF-alpha and IL-6 concentrations and TNF-alpha -308 G > A polymorphism in children with premature adrenarche Front. Endocrinol. (Lausanne) 1 2010 6
123. L. Ibanez, C. Aulesa, N. Potau, K. Ong, D.B. Dunger, and F. de Zegher Plasminogen activator inhibitor-1 in girls with precocious pubarche: a premenarcheal marker for polycystic ovary syndrome? Pediatr. Res. 51 2002 244 248
124. L. Ibanez, A. Fucci, C. Valls, K. Ong, D. Dunger, and F. de Zegher Neutrophil count in small-for-gestational age children: contrasting effects of metformin and growth hormone therapy J. Clin. Endocrinol. Metab. 90 2005 3435 3439
125. G. Zhai, A. Teumer, L. Stolk, J.R. Perry, L. Vandenput, A.D. Coviello, A. Koster, J.T. Bell, S. Bhasin, J. Eriksson, A. Eriksson, F. Ernst, L. Ferrucci, T.M. Frayling, D. Glass, E. Grundberg, R. Haring, A.K. Hedman, A. Hofman, D.P. Kiel, H.K. Kroemer, Y. Liu, K.L. Lunetta, M. Maggio, M. Lorentzon, M. Mangino, D. Melzer, I. Miljkovic, Muther Consortium, A. Nica, B.W. Penninx, R.S. Vasan, F. Rivadeneira, K.S. Small, N. Soranzo, A.G. Uitterlinden, H. Völzke, S.G. Wilson, L. Xi, W.V. Zhuang, T.B. Harris, J.M. Murabito, C. Ohlsson, A. Murray, F.H. de Jong, T.D. Spector, and H. Wallaschofski Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms PLoS Genet. 7 2011 e1002025
126. N. Chaberlain, E. Driver, and R. Miesfeld The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function Nucleic Acids Res. 22 1994 3181 3186
127. S. Lappalainen, P. Utriainen, T. Kuulasmaa, R. Voutilainen, and J. Jääskeläinen ACTH receptor promoter polymorphism associates with severity of premature adrenarche and modulates hypothalamo-pituitary-adrenal axis in children Pediatr. Res. 63 2008 410 414
128. M.B. Roldan, C. White, and S.F. Witchel Association of the GAA1013 → GAG polymorphism of the insulin-like growth factor-1 receptor (IGF1R) gene with premature pubarche Fertil. Steril. 88 2007 410 417
129. L. Ibanez, M.V. Marcos, N. Potau, C. White, C.E. Aston, and S.F. Witchel Increased frequency of the G972R variant of the insulin receptor substrate-1 (irs-1) gene among girls with a history of precocious pubarche Fertil. Steril. 78 2002 1288 1293
130. C. Dacou-Voutetakis, and M. Dracopoulou High incidence of molecular defects of the CYP21 gene in patients with premature adrenarche J. Clin. Endocrinol. Metab. 84 1999 1570 1574
131. J.W. Temeck, S. Pang, C. Nelson, and M. New Genetic defects of steroidogenesis in premature pubarche J. Clin. Endocrinol. Metab. 64 1987 609 617
132. A.H. Morris, E.O. Reiter, M.E. Geffner, B.M. Lippe, R.M. Itami, and D.M. Mayes Absence of nonclassical congenital adrenal hyperplasia in patients with precocious adrenarche J. Clin. Endocrinol. Metab. 69 1989 709 715
133. C.J. Petry, K.K. Ong, K.F. Michelmore, S. Artigas, D.L. Wingate, A.H. Balen, F. de Zegher, L. Ibanez, and D.B. Dunger Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women Hum. Reprod. 20 2005 1837 1843
134. N. Nader, B.E. Bachrach, D.E. Hurt, S. Gajula, A. Pittman, R. Lescher, and T. Kino A novel point mutation in helix 10 of the human glucocorticoid receptor causes generalized glucocorticoid resistance by disrupting the structure of the ligand-binding domain J. Clin. Endocrinol. Metab. 95 2010 2281 2285
135. G.G. Lavery, J. Idkowiak, M. Sherlock, I. Bujalska, J.P. Ride, K. Saqib, M.F. Hartmann, B. Hughes, S.A. Wudy, J. De Schepper, W. Arlt, N. Krone, C.H. Shackleton, E.A. Walker, and P.M. Stewart Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling Eur. J. Endocrinol. 168 2013 K19 K26
136. C. Noordam, V. Dhir, J.C. McNelis, F. Schlereth, N.A. Hanley, N. Krone, J.A. Smeitink, R. Smeets, F.C. Sweep, H.L. Claahsen-van der Grinten, and W. Arlt Inactivating PAPSS2 mutations in a patient with premature pubarche N. Engl. J. Med. 360 2009 2310 2318
137. P. Utriainen, S. Laakso, J. Jääskeläinen, and R. Voutilainen Polymorphism of POR, SULT2A1 and HSD11B1 in children with premature adrenarche Metabolism 61 2012 1215 1219
138. P.C. White Ontogeny of adrenal steroid biosynthesis: why girls will be girls J. Clin. Invest. 116 2006 872 874
139. D. Apter Serum steroids and pituitary hormones in female puberty: a partly longitudinal stydy Clin. Endocrinol. 12 1980 107 120.