Skip to main content
SpringerLink
Log in

Premature adrenarche

  • Review Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Adrenarche is the puberty of the adrenal gland. The descriptive term “pubarche” indicates the appearance of pubic hair, which may be accompanied by axillary hair. This process is considered premature if it occurs before age 8 yr in girls and 9 yr in boys. The chief hormonal products of adrenarche are DHEA and DHEAS. The well-documented evolution of adrenarche in primates and men is incompatible with either a neutral or harmful role for DHEA and implies most likely a positive role for some aspects of young adult pubertal maturation and developmental maturation. Premature adrenarche has no adverse effects on the onset and progression of gonadarche and/or final height. Mechanisms for initiation of adrenal androgen secretion at adrenarche are still not well understood. Maturational increases in 17-hydroxylase and 17,20-lyase are seen together with a lower activity of 3β-hydroxysteroid dehydrogenase (3β-HSD). There is good evidence that the zona reticularis is the source of adrenal androgens. Adrenarche and gonadarche are regulated differently. Although premature adrenarche has been thought to be a benign, normal variant of puberty, our findings indicate that, for certain girls, premature adrenarche represents an early clinical feature of syndrome X (obesity, hypertension, dyslipidemia, insulin resistance). Perhaps the early identification of these patients will permit early therapy, such as lifestyle changes, including dietary and activity level intervention. As insulin resistance is an underlying feature of premature adrenarche, it seems rational to assess the efficacy and safety of using insulin-sensitizing agents to treat these individuals. In the absence of controlled longitudinal studies, the cross-sectional data available from our studies suggest that premature pubarche driven by premature adrenarche and hyperinsulinemia may precede the development of ovarian hyperandrogenism, and this sequence may have an early origin with low birth weight serving as a marker. Premature adrenarche may thus be a forerunner of syndrome X in some girls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parker L.N., Sack J., Fisher D.A., Odell W.D. The adrenarche: prolactin. gonadotropins, adrenal androgens, and cortisol. J. Clin. Endocrinol. Metab. 1978, 46: 396–401.

    Article  CAS  PubMed  Google Scholar 

  2. Sklar C.A., Kaplan S.L., Grumbach M.M. 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: 548–556.

    Article  CAS  PubMed  Google Scholar 

  3. Apter D., Pakarinen A., Hammond G.L., Vihko R. Adrenocortical function in puberty. Acta Paediatr. Scand. 1979, 68: 599–604.

    Article  CAS  PubMed  Google Scholar 

  4. Orentreich N., Brind J.L., Rizer R.L., Vogelman J.H. Age changes and sex differences in serum dehydroepiandrostenedione sulfate concentrations throughout adulthood. J. Clin. Endocrinol. Metab. 1984, 59: 551–555.

    Article  CAS  PubMed  Google Scholar 

  5. Miller W.L. The molecular basis of premature adrenarche: an hypothesis. Acta Paediatr. Suppl. 1999, 433: 60–66.

    Article  Google Scholar 

  6. Cutler Jr. G.B., Loriaux D.L. Adrenarche and its relationship to the onset of puberty. Fed. Proc. 1980, 39: 2384–2392.

    CAS  PubMed  Google Scholar 

  7. Smail P.J., Faiman C., Hobson W.C., Fuller G.B., Winter J.S.D. Further studies on adrenarche in non-human primates. Endocrinology 1982, 111: 844–848.

    Article  CAS  PubMed  Google Scholar 

  8. Meusy-Dessolle N., Dang P.C. Plasma concentrations of testosterone, dihydrotesto-sterone, Δ-androstenedione, dihydroepiandrosterone and oestradiol-17 in the crab-eating monkey (Macaca fascicularis) from birth to adulthood. J. Reprod. Fertil. 1985, 74: 347–359.

    Article  CAS  PubMed  Google Scholar 

  9. Lane M.A., Ingram D.K., Ball S.S., Roth G.S. Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction. J. Clin. Endocrinol. Metab. 1997, 82: 2093–2096.

    Article  CAS  PubMed  Google Scholar 

  10. Hornsby P.J. The biosynthesis of DHEA by the adrenal cortex and its age-related decline. In: Watson R.W. (Ed.), DHEA: health promotion and aging. Academic, Harwood, 1998, p. 1.

    Google Scholar 

  11. Morales A.J., Nolan J.J., Nelson J.C., Yen S.S.C. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J. Clin. Endocrinol. Metab. 1994, 78: 1360–1367.

    CAS  PubMed  Google Scholar 

  12. Baulieu E.E. Dehydroepiandrosterone (DHEA): a fountain of youth? J. Clin. Endocrinol. Metab. 1996, 81: 3147–3151.

    Article  CAS  PubMed  Google Scholar 

  13. Ghizzoni L., Virdis R., Ziveri M., Lamboglini A., Alberini A., Volta C., Bernasconi S. Adrenal steroid, cortisol, adrenocorticotropin and β-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche. J. Clin. Endocrinol. Metab. 1989, 69: 875–880.

    Article  CAS  PubMed  Google Scholar 

  14. Ibáñez L., Potau N., Marcos M.V., DeZegher F. Corticotropin-releasing hormone: a potent androgen secretagogue in girls with hyperandrogenism after precocious pubarche. J. Clin. Endocrinol. Metab. 1999, 84: 4602–4607.

    PubMed  Google Scholar 

  15. Albertson B., Hobson W., Barnett B., Turner P.T., Clark R.V., Schiebinger R.J., Loriaux, D.L., Cutler G.B. Jr. Dissociation of cortisol and adrenal androgen secretion in the hypophysectomized ACTH-replaced chimpanze. J. Clin. Endocrinol. Metab. 1984, 59: 13–18.

    Article  CAS  PubMed  Google Scholar 

  16. Mills I.H., Brooks R.V., Prunty F.T.G. The relationship between the production of cortisol and of androgen by the human adrenal. In: Currie A.R., Symington T., Grank J.K. (Eds.), The human adrenal cortex. Livingstone, London, 1962, p. 20.

    Google Scholar 

  17. Grumbach M.M., Richard S.G.E., Conte F.A., Kaplan S.I. Clinial disorders of adrenal function and puberty: an assessment of the role of the adrenal cortex in normal and abnormal puberty in man and evidence for an ACTH-like pituitary adrenal androgen stimulation hormone. In: James V.H.T., Serio M., Giusti G., Martini L. (Eds.), The endocrine function of the human adrenal cortex. Serono Symposia 18. Academic Press, London, 1978, p. 583.

    Google Scholar 

  18. Hauffa B.P., Kaplan S.L., Grumbach M.M. Dissociation between plasma adrenal androgens and cortisol in Cushing’s disease and ectopic ACTHproducing tumour: relation to adrenarche. Lancet 1984, 1: 1373–1376.

    Article  CAS  PubMed  Google Scholar 

  19. Suda T., Demura H., Demura R., Jibiki K., Tozawa F., Shizuma F. Anterior pituitary hormones in plasma and pituitary from patients with Cushing’s disease. J. Clin. Endocrinol. Metab. 1980, 51: 1048–1053.

    Article  CAS  PubMed  Google Scholar 

  20. Chan J.S.D., Seidah N.G., Chretien M. Measurement of N-terminal (1–76) proopiomelanocortin in human plasma: correlation with adrenocorticotropin. J. Clin. Endocrinol. Metab. 1983, 56: 791–796.

    Article  CAS  PubMed  Google Scholar 

  21. Parker L.N., Lifrak E.T., Odell W.D. A 60,000 molecular weight human pituitary glycopeptide stimulates adrenal androgen secretion. Endocrinology 1983, 113: 2092–2096.

    Article  CAS  PubMed  Google Scholar 

  22. Parker L., Lifrak E., Shively J., Lee T., Kaplan B., Walker P., Calaycacy J., Florsheim W., Soong-Shiong P. Human gland cortical androgen-stimulating hormone (CASH) is identical with a portion of the joint peptide of pituitary proopiomelanocortin (POMC). Program of the 71st Annual Meeting of The Endocrine Society, Seattle, Washington, 1989, p. 97 (Abstract).

    Google Scholar 

  23. Parker L., Lifrak E., Gelfand R., Shively J., Lee T., Kaplan B., Walker P., Calaycay J., Florsheim W., Mason I., Soong-Shiong P. Isolation, purification, synthesis and binding of human adrenal gland cortical androgen stimulating hormone. Endocr. J. 1993, 1: 441–445.

    Google Scholar 

  24. Mellon S.H., Shively J.E., Miller W.L. Human proopiomelanocortin (79–96), a proposed androgen stimulating hormone, does not affect steroidogenesis in cultured human fetal adrenal cells. J. Clin. Endocrinol. Metab. 1991, 72: 19–22.

    Article  CAS  PubMed  Google Scholar 

  25. Penhoat A., Sanchez P., Jaillard C., Langlois D., Begeot M. Human proopiomelanocortin (79–96), a proposed cortisol adrenal-stimulating hormone, does not affect steroidogenesis in cultured human adult adrenal cells. J. Clin. Endocrinol. Metab. 1991, 72: 23–26.

    Article  CAS  PubMed  Google Scholar 

  26. Robinson P., Bateman A., Mulay S., Spenser S.J., Jaffe R.B. Isolation and characterization of three forms of joining peptide from adult human pituitaries: lack of adrenal androgen-stimulating activity. Endocrinology 1991, 129: 859–867.

    Article  CAS  PubMed  Google Scholar 

  27. Miller W.L., Johnson L.K. Synthesis and glycosylation of proopiomelanocortin by a Cushing tumor. J. Clin. Endocrinol. Metab. 1982, 55: 441–446.

    Article  CAS  PubMed  Google Scholar 

  28. Remer T., Marz F. Role of nutritional status in the regulation of adrenarche. J. Clin. Endocrinol. Metab. 1999, 84: 3936–3944.

    CAS  PubMed  Google Scholar 

  29. Schiebinger R.J., Albertson B.D., Cassorla F.G., Bowyer D.W., Geelhoed G.W., Cutler Jr. G.B., Loriaux D.L. 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. 1981, 67: 1177–1182.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Rich B., Rosenfield R., Lucky A., Helke J., Otto P. Adrenarche: changing adrenal response to adrenocorticotropin. J. Clin. Endocrinol. Metab. 1981, 52: 1129–1134.

    Article  CAS  PubMed  Google Scholar 

  31. Kahri A.I., Voutilainen R., Salmenperae M. Different biological action of corticosteroids, corticosterone and cortisol as a basis of zonal function adrenal cortex. Acta Endocrinol. (Copenh.) 1979, 91: 329–337.

    CAS  Google Scholar 

  32. Gell J.S., Carr B.R., Sasano H., Atkins B., Margraf L., Mason J.I., Rainey W.E. Adrenarche results from development of a 3β-hydroxysteroid dehydrogenase-deficient adrenal reticularis. J. Clin. Endocrinol. Metab. 1998, 83: 3695–3709.

    CAS  PubMed  Google Scholar 

  33. L’Allemand D., Penhoat A., Lebrethon M.C., Ardevol R., Baeher V., Oelkers W., Saez J.M. Insulin-like growth factors enhance steroidogenic enzyme and corticotropin receptor messenger ribonucleic acid levels and corticotropin steroidogenic responsiveness in cultured human adrenocortical cells. J. Clin. Endocrinol. Metab. 1996, 81: 392–397.

    Google Scholar 

  34. Lebrethon M.C., Jaillard C., Naville D., Begeot M., Saez J.M. Effects of transforming growth factor-1 on human adrenocortical fasciculata-reticualris cell differentiated functions. J. Clin. Endocrinol. Metab. 1994, 79: 1033–1039.

    CAS  PubMed  Google Scholar 

  35. Wolkersdörfer G.W., Lohmann T., Marx C., Schröder S., Pfeiffer R., Stahl H.-D., Scherbaum W.A., Chrousos G.P., Bornstein S.R. Lympocytes stimulate dehydroepiandrosterone production through direct cellular contract with adrenal zona reticularis cells: a novel mechanism of immuneendocrine interaction. J. Clin. Endocrinol. Metab. 1999, 84: 4220–4227.

    PubMed  Google Scholar 

  36. Yanagibashi K., Hall P.F. Role of electron transport in the regulation of the lyase activity of C32 side-chain cleavage P-450 from porcine adrenal and testicular microsomes. J. Biol. Chem. 1980, 261: 8429–8433.

    Google Scholar 

  37. Lin D., Black S.M., Nagahama Y., Miller W.L. Steroid 17-alpha-hydroxylase and 17,20-lyase activities of P450C17:contributions of serion 106 and P450 reductase. Endocrinology 1993, 132: 2498–2506.

    CAS  PubMed  Google Scholar 

  38. Geller D.J., Auchus R.J., Mendonca B.B., Miller W.L. Molecular mechanism of 17,20-lyase deficiency. Horm. Res. 1997, 48 (Suppl. 2): (Abstract).

  39. Miller W.L., Tyrell J.B, The adrenal cortex. In: Felig P., Baxter J.D., Frohman L.A. (Eds.), Endocrinology and metabolism, ed. 3. McGraw-Hill, New York, 1995, p. 555.

    Google Scholar 

  40. Lashansky G., Saenger P., Fishman K., Gautier T., Mayes D., Berg G., DiMartino-Nardi J., Reiter E. Normative data for adrenal steroidogenesis in a healthy pediatric population: age and sex-related changes after ACTH stimulation. J. Clin. Endocrinol. Metab. 1991, 73: 674–686.

    Article  CAS  PubMed  Google Scholar 

  41. Lashansky G., Saenger P., DiMartino-Nardi J., Gautier T., Mayes D., Berg G., Reiter E. Normative data for the steroidogenic response of mineralocorticoids and their precursors to adrenocorticotropin in a healthy pediatric population. J. Clin. Endocrinol. Metab. 1992, 75: 1491–1496.

    CAS  PubMed  Google Scholar 

  42. Zhang L., Rodriguez H., Ohno S., Miller W.L. Serine phosphorylation of human P450C17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc. Natl. Acad. Sci. USA 1995, 92: 10619–10623.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms for implications for pathogenesis. Endocr. Rev. 1997, 18: 774–800.

    CAS  PubMed  Google Scholar 

  44. Takayama S., White M.F., Kahn C.R. Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. J. Biol. Chem. 1988, 263: 3440–3447.

    CAS  PubMed  Google Scholar 

  45. Chin C.E., Dickens M., Tavare J.M., Roth R.A. Overexpression of protein kinase C isoenzymes a-, b, I, g and e in cells overexpressing the insulin receptor: effects on receptor phosphorylation and signaling. J. Biol. Chem. 1993, 268: 6338–6347.

    CAS  PubMed  Google Scholar 

  46. Saenger P. Turner’s syndrome. N. Engl. J. Med. 1996, 335: 1749–1754.

    Article  CAS  PubMed  Google Scholar 

  47. Counts D.R., Pescovitz O.H., Barnes K.M., Hench K.D., Chrousos G.P., Sherin S.R., Comite F., Loriaux D. L., Cutler G.B. Jr. Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 1987, 64: 1174–1178.

    Article  CAS  PubMed  Google Scholar 

  48. Urban M., Lee P.A., Guta J.P., Migeon C.J. Androgens in pubertal males with Addison’s disease. J. Clin. Endocrinol. Metab. 1980, 5: 925–929.

    Article  Google Scholar 

  49. Silverman S.H., Migeon C.J., Rosenberg E., Wilkins L. Precocious growth of sexual hair without other secondary sexual development: “premature pubarche”, a constitutional variation of adolescence. Pediatrics 1952, 10: 426–432.

    CAS  PubMed  Google Scholar 

  50. Sigurjonsdottir T.J., Hayles A.S. Premature pubarche. Clin. Pediatr. (Phil.) 1968, 7: 29–33.

    Article  CAS  Google Scholar 

  51. Wilkins L. Abnormalities and variations of sexual development during childhood and adolescence. In: Advances in pediatrics. Interscience, New York, 1948, Vol. 3, p. 159.

    Google Scholar 

  52. Talbot N.B., Sobel E.H., McArthur J.W., Crawford J.D. Precocious adrenarche. In: Case J.P., Lockwood A.S., Brainard M. (Eds.), Functional endocrinology from birth through adolescence. Commonwealth Fund, Harvard University, Cambridge, 1952, p. 247.

    Google Scholar 

  53. Liu N., Grumbach M.M., DeNapoli R.A., Morishi-ma A. Prevalence of electro-encephalographic abnormaltiies in idiopathic precocious puberty and premature pubarche: bearing on pathogenesis and neuroendocrine regulation of puberty. J. Clin. Endocrinol. Metab. 1965, 25: 1296–1308.

    Article  CAS  PubMed  Google Scholar 

  54. Thamdrup E. Premature pubarche: a hypothalamic disorder: Report of 17 cases. Acta Endocrinol. (Copenh.) 1955, 18: 564–567.

    CAS  Google Scholar 

  55. Reiter E.O., Kulin H.F. Sexual maturation in the female: normal development and precocious puberty. Pediatr. Clin. North Am. 1972, 19: 581–603.

    CAS  PubMed  Google Scholar 

  56. Rosenbaum M., Leibel R.L. Obesity in Childhood. Pediatr. Rev. 1989, 11: 43–55.

    Article  CAS  PubMed  Google Scholar 

  57. Jabbar M., Pugliese M., Fort P., Becker B., Lifshitz F. Excess weight and precocious pubarche in children: alterations of the adrenocortical hormones. J. Am. Coll. Nutr. 1991, 10: 289–296.

    Article  CAS  PubMed  Google Scholar 

  58. Herman-Giddens M.E., Slora E.J., Wasserman R.C., Bourdony C.J., Bhapkar M.V., Koch G.G., Hasemeier C.M. 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.

    Article  CAS  PubMed  Google Scholar 

  59. Rosenfield R.L., Bachrach L.K., Chernausek S.D., Gertner J.M., Gottschalk G., Hardin D.S., Pescovitz O., Saenger P. Current age of onset of puberty. Pediatrics 2000, 106: 622–623.

    Article  CAS  PubMed  Google Scholar 

  60. Oppenheimer E., Linder B., DiMartino-Nardi J. Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans. J. Clin. Endocrinol. Metab. 1995, 80: 614–618.

    CAS  PubMed  Google Scholar 

  61. DiMartino-Nardi J. Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls. Acta Paediatr. Suppl. 1999, 443: 67–72.

    Article  Google Scholar 

  62. Nestler J.E., Clore J.N., Blackard W.G. The central role of obesity (hyperinsulinemia) in the pathogenesis of polycystic ovary syndrome. Am. J. Obstet. Gynecol. 1989, 161: 1095–1097.

    Article  CAS  PubMed  Google Scholar 

  63. Vuguin P., Linder B., Rosenfeld R.G., Saenger P., DiMartino-Nardi J. The role of insulin sensitivity, insulin-like growth factor and insulin-like growth factor binding proteins 1 and 3 in the hyperandrogenism of African-American and Caribbean-Hispanic girls with premature adrenarche. J. Clin. Endocrinol. Metab. 1999, 84: 2037–2042.

    CAS  PubMed  Google Scholar 

  64. Legro R.S., Finegood D., Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 1998, 83: 2694–2698.

    CAS  PubMed  Google Scholar 

  65. Vuguin P., Saenger P., DiMartino-Nardi J. Fasting glucose:insulin ratio: a useful measure of insulin resistance in girls with premature adrenarche. Pediatr. Res. 1999, 45: 99A.

    Google Scholar 

  66. Francois I., de Zegher F. Adrenarche and fetal growth. Pediatr. Res. 1997, 41: 440–442.

    Article  CAS  PubMed  Google Scholar 

  67. Ibanez L., Potau N., Francois I., de Zegher F. Precocious pubarche, hyperinsulinism and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J. Clin. Endocrinol. Metab. 1998, 83: 3558–3562.

    Article  CAS  PubMed  Google Scholar 

  68. Grinstein G.P., Vuguin P., Saenger P., DiMartino-Nardi J. The relationship between birth weight (BW), body mass index (BMI) and insulin sensitivity (SI) in prepubertal Caribbean Hispanic (CH) and black African-American (BAA) girls with premature adrenarche. Pediatr. Res. 1999, 45: 89 (Abstract).

    Article  Google Scholar 

  69. Ghizzoni L., Mastorakos G., Vottero A. Commentary — Adrenal hyperandrogenism in children. J. Clin. Endocrinol. Metab. 1999, 84: 4431–4435.

    Article  CAS  PubMed  Google Scholar 

  70. Ibáñez L., DiMartino-Nardi J., Potau N., Saenger P. Premature adrenarche — Normal variant or forerunner of adult disease? Endocr. Rev. 2000, 21: 671–696.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Endocrinology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, New York, 10467, USA

    Paul Saenger & J. DiMartino-Nardi

Authors
  1. Paul Saenger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. DiMartino-Nardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Saenger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saenger, P., DiMartino-Nardi, J. Premature adrenarche. J Endocrinol Invest 24, 724–733 (2001). https://doi.org/10.1007/BF03343917

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343917

Key-words

Search

Navigation