Ann Pediatr Endocrinol Metab.  2018 Dec;23(4):210-214. 10.6065/apem.2018.23.4.210.

Interpretation of androgen and anti-Mullerian hormone profiles in a Hispanic cohort of 5- to 8-year-old girls with premature adrenarche

• Brar PC
• Dingle E
• Ovadia D
• Pivo S
• Prasad V
• David R

• KMID: 2432283
• DOI: http://doi.org/10.6065/apem.2018.23.4.210

Abstract

PURPOSE
Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5-8 years) and age and body mass index (BMI) matched controls.
METHODS
Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done.
RESULTS
PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m2 vs. 17.8±2.7 kg/m2). Dehydroepiandrostenedione sulfate (63.3±51.3 μg/dL vs. 29.8±17.3 μg/dL, P < 0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values ( < 14 years: reference range, 0.49-3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups.
CONCLUSIONS
Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed.

Keyword

Anti-mullerian hormone; Adrenarche; Polycystic ovary syndrome; Androge

MeSH Terms

17-alpha-Hydroxyprogesterone
Adrenarche*
Anti-Mullerian Hormone*
Body Mass Index
Child*
Cohort Studies*
Electronic Health Records
Female*
Hispanic Americans*
Humans
Polycystic Ovary Syndrome
Reference Values
Retrospective Studies
Testosterone
17-alpha-Hydroxyprogesterone
Anti-Mullerian Hormone
Testosterone

Figure

• 

  Fig. 1. Pearson correlation (linear regression); P=0.006, r=0.034. DHEAS, dehydroepiandrostenedione sulphate.

Reference

References

1. Leung AK, Robson WL. Premature adrenarche. J Pediatr Health Care. 2008; 22:230–3.

2. Liimatta J, Laakso S, Utriainen P, Voutilainen R, Palvimo JJ, Jääskeläinen T, et al. Serum androgen bioactivity is low in children with premature adrenarche. Pediatr Res. 2014; 75:645–50.

3. Voutilainen R, Jääskeläinen J. Premature adrenarche: etiology, clinical findings, and consequences. J Steroid Biochem Mol Biol. 2015; 145:226–36.

4. Montalto J, Yong AB, Funder JW, Connelly JF. Serum 5-androstene-3 beta,17 beta-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche. J Steroid Biochem. 1989; 33:1149–54.

5. Dorn LD, Rose SR, Rotenstein D, Susman EJ, Huang B, Loucks TL, et al. Differences in endocrine parameters and psychopathology in girls with premature adrenarche versus on-time adrenarche. J Pediatr Endocrinol Metab. 2008; 21:439–48.

6. Ibáñez L, Potau N, Zampolli M, Riqué S, Saenger P, Carrascosa A. 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. 1997; 82:2283–8.

7. Ibáñez L, Potau N, Chacon P, Pascual C, Carrascosa A. Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia. 1998; 41:1057–63.

8. Silfen ME, Manibo AM, Ferin M, McMahon DJ, Levine LS, Oberfield SE. Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity. J Clin Endocrinol Metab. 2002; 87:398–403.

9. Banerjee S, Raghavan S, Wasserman EJ, Linder BL, Saenger P, DiMartino-Nardi J. Hormonal findings in African-American and Caribbean Hispanic girls with premature adrenarche: implications for polycystic ovarian syndrome. Pediatrics. 1998; 102:E36.

10. Kousta E. Premature adrenarche leads to polycystic ovary syndrome? Long-term consequences. Ann N Y Acad Sci. 2006; 1092:148–57.

11. Ibañez L, Potau N, Virdis R, Zampolli M, Terzi C, Gussinyé M, et al. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993; 76:1599–603.

12. Ibáñez L, Jaramillo A, Enríquez G, Miró E, López-Bermejo A, Dunger D, et al. Polycystic ovaries after precocious pubarche: relation to prenatal growth. Hum Reprod. 2007; 22:395–400.

13. Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatrics. 2009; 123:84–8.

14. Gavela-Pérez T, Garcés C, Navarro-Sánchez P, López Villanueva L, Soriano-Guillén L. Earlier menarcheal age in Spanish girls is related with an increase in body mass index between pre-pubertal school age and adolescence. Pediatr Obes. 2015; 10:410–5.

15. Ibáñez L, Potau N, Marcos MV, de Zegher F. Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 1999; 84:4739–41.

16. Hokken-Koèlega AC. Timing of puberty and fetal growth. Best Pract Res Clin Endocrinol Metab. 2002; 16:65–71.

17. Zhang LH, Rodriguez H, Ohno S, Miller WL. 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. 1995; 92:10619–23.

18. Ibáñez L, Bonnin MR, Zampolli M, Prat N, Alia PJ, Navarro MA. Usefulness of an ACTH test in the diagnosis of nonclassical 21-hydroxylase deficiency among children presenting with premature pubarche. Horm Res. 1995; 44:51–6.

19. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003; 88:5957–62.

20. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr. 1952; 40:423–41.

21. Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11. 2002; 1–190.

22. Collins WP, Mansfield MD, Alladina NS, Sommerville IF. Radioimmunoassay of plasma testosterone. J Steroid Biochem. 1972; 3:333–48.

23. Kumar A, Kalra B, Patel A, McDavid L, Roudebush WE. Development of a second generation anti-Müllerian hormone (AMH) ELISA. J Immunol Methods. 2010; 362:51–9.

24. Vaiarelli A, Drakopoulos P, Blockeel C, De Vos M, van de Vijver A, Camus M, et al. Limited ability of circulating anti-Müllerian hormone to predict dominant follicular recruitment in PCOS women treated with clomiphene citrate: a comparison of two different assays. Gynecol Endocrinol. 2016; 32:227–30.

25. Wallace AM, Faye SA, Fleming R, Nelson SM. A multicentre evaluation of the new Beckman Coulter anti-Mullerian hormone immunoassay (AMH Gen II). Ann Clin Biochem. 2011; 48(Pt 4):370–3.

26. Hagen CP, Aksglaede L, Sørensen K, Mouritsen A, Andersson AM, Petersen JH, et al. Individual serum levels of anti-Müllerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study. Hum Reprod. 2012; 27:861–6.

27. Paterson WF, Ahmed SF, Bath L, Donaldson MD, Fleming R, Greene SA, et al. Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry. Clin Endocrinol (Oxf). 2010; 72:496–501.

28. Uçar A, Erol OB, Yekeler E, Yildiz I, Bozlak S, Saka N, et al. Pelvic ultrasound findings in prepubertal girls with precocious adrenarche born appropriate for gestational age. Clin Endocrinol (Oxf). 2014; 80:699–705.

29. Wu T, Mendola P, Buck GM. Ethnic differences in the presence of secondary sex characteristics and menarche among US girls: the Third National Health and Nutrition Examination Survey, 1988-1994. Pediatrics. 2002; 110:752–7.

30. Ankarberg-Lindgren C, Norjavaara E. Sensitive RIA measures testosterone concentrations in prepubertal and pubertal children comparable to tandem mass spectrometry. Scand J Clin Lab Invest. 2015; 75:341–4.

31. Diaz A, Bhandari S, Sison C, Vogiatzi M. Characteristics of children with premature pubarche in the new york metropolitan area. Horm Res. 2008; 70:150–4.

32. Sopher AB, Thornton JC, Silfen ME, Manibo A, Oberfield SE, Wang J, et al. Prepubertal girls with premature adrenarche have greater bone mineral content and density than controls. J Clin Endocrinol Metab. 2001; 86:5269–72.

33. DeSalvo DJ, Mehra R, Vaidyanathan P, Kaplowitz PB. In children with premature adrenarche, bone age advancement by 2 or more years is common and generally benign. J Pediatr Endocrinol Metab. 2013; 26:215–21.

34. Sopher AB, Jean AM, Zwany SK, Winston DM, Pomeranz CB, Bell JJ, et al. Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors. Obesity (Silver Spring). 2011; 19:1259–64.

35. Bhide P, Homburg R. Anti-Müllerian hormone and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016; 37:38–45.

36. Qi X, Pang Y, Qiao J. The role of anti-Müllerian hormone in the pathogenesis and pathophysiological characteristics of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2016; 199:82–7.

37. Łebkowska A, Kowalska I. Anti-Müllerian hormone and polycystic ovary syndrome. Endokrynol Pol. 2017; 68:74–8.

38. Crisosto N, Codner E, Maliqueo M, Echiburú B, Sánchez F, Cassorla F, et al. Anti-Müllerian hormone levels in peripubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007; 92:2739–43.

39. Utriainen P, Jääskeläinen J, Voutilainen R. Serum antimüllerian hormone concentrations in prepubertal girls with and without premature adrenarche: The influence of body mass index. Horm Res Paediatr. 2010; 74:207–11.