Ann Pediatr Endocrinol Metab.  2017 Sep;22(3):183-188. 10.6065/apem.2017.22.3.183.

Diurnal variation of gonadotropin levels in girls with early stages of puberty

• Kang YS
• Yoo DY
• Chung IH
• Yoo EG

• KMID: 2396138
• DOI: http://doi.org/10.6065/apem.2017.22.3.183

Abstract

PURPOSE
Pubertal gonadotropin secretion shows circadian pattern and the luteinizing hormone (LH) levels tend to rise in later stages of puberty in girls. We studied the usefulness of basal LH in the evaluation of central precocious puberty with emphasis on the influence of sampling time.
METHODS
Medical records of 334 girls that underwent gonadotropin-releasing hormone stimulation test (GnRHST) were reviewed. Auxological and laboratory data were compared between those with early morning (EM, before 10 AM) and late morning/afternoon (LM/A, after 10 AM) basal samples.
RESULTS
Among those in sexual maturity rating (SMR) 2, EM samples showed higher basal LH (P=0.004) compare to LM/A samples, whereas those in SMR 3 showed no difference in LH levels between EM and LM/A samples. Among girls with pubertal response, EM group showed higher basal LH (P=0.031) and follicular stimulating hormone (P=0.008) than LM/A group. The EM basal LH was more closely related with the peak stimulated LH than the LM/A basal LH did (rs=0.871 vs. rs=0.524). The optimal basal LH cutoffs to predict a pubertal response to GnRHST were 0.11 IU/L with a sensitivity of 66.7% and a specificity of 78.7% in EM group, and 0.07 IU/L with a sensitivity of 60.0% and a specificity of 78.9% in LM/A group, respectively.
CONCLUSION
In girls with early stages of puberty, EM basal LH is a more sensitive screening tool than the LM/A basal LH. Diurnal variation should be considered in evaluating children with precocious puberty.

Keyword

Precocious puberty; Luteinizing hormone; Gonadotropin-releasing hormone

MeSH Terms

Adolescent
Child
Female*
Gonadotropin-Releasing Hormone
Gonadotropins*
Humans
Luteinizing Hormone
Mass Screening
Medical Records
Puberty*
Puberty, Precocious
Sensitivity and Specificity
Gonadotropin-Releasing Hormone
Gonadotropins
Luteinizing Hormone

Figure

• 

  Fig. 1. Comparison of gonadotropin and estradiol levels in early morning (EM) vs. late morning/afternoon (LM/A) basal samples of the 16 girls in the subgroup analysis. LH, luteinizing hormone; FSH, follicular stimulating hormone; E2, estradiol.

• 

  Fig. 2. Subgroup analysis showing correlations between basal LH and peak stimulated LH in early morning (EM) vs. late morning/afternoon (LM/A) samples. LH, luteinizing hormone; FSH, follicular stimulating hormone.

• 

  Fig. 3. Receiver operating characteristic curves for the optimal cutoff of basal serum LH levels for predicting pubertal response in early morning sample group (EM: area under the curve [AUC], 0.773; 95% confidence interval [CI], 0.704– 0.841) and late morning/afternoon sample group (LM/A: AUC, 0.732; 95% CI, 0.641–0.823). EM, early morning; LM/A, late morning/afternoon; LH, luteinizing hormone.

Reference

References

1. Oerter KE, Uriarte MM, Rose SR, Barnes KM, Cutler GB Jr. Gonadotropin secretory dynamics during puberty in normal girls and boys. J Clin Endocrinol Metab. 1990; 71:1251–8.

2. Jakacki RI, Kelch RP, Sauder SE, Lloyd JS, Hopwood NJ, Marshall JC. Pulsatile secretion of luteinizing hormone in children. J Clin Endocrinol Metab. 1982; 55:453–8.

3. Kulin HE, Moore RG Jr, Santner SJ. Circadian rhythms in gonadotropin excretion in prepubertal and pubertal children. J Clin Endocrinol Metab. 1976; 42:770–3.

4. Corley KP, Valk TW, Kelch RP, Marshall JC. Estimation of GnRH pulse amplitude during pubertal development. Pediatr Res. 1981; 15:157–62.

5. Penny R, Olambiwonnu NO, Frasier SD. Episodic fluctuations of serum gonadotropins in pre- and post-pubertal girls and boys. J Clin Endocrinol Metab. 1977; 45:307–11.

6. Lee PA. Central precocious puberty. An overview of diagnosis, treatment, and outcome. Endocrinol Metab Clin North Am. 1999; 28:901–18, xi.

7. Brito VN, Batista MC, Borges MF, Latronico AC, Kohek MB, Thirone AC, et al. Diagnostic value of fluorometric assays in the evaluation of precocious puberty. J Clin Endocrinol Metab. 1999; 84:3539–44.

8. Lee DS, Ryoo NY, Lee SH, Kim S, Kim JH. Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann Pediatr Endocrinol Metab. 2013; 18:196–201.

9. Mogensen SS, Aksglaede L, Mouritsen A, Sørensen K, Main KM, Gideon P, et al. Diagnostic work-up of 449 consecutive girls who were referred to be evaluated for precocious puberty. J Clin Endocrinol Metab. 2011; 96:1393–401.

10. Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr. 1995; 127:47–52.

11. Pasternak Y, Friger M, Loewenthal N, Haim A, Hershkovitz E. The utility of basal serum LH in prediction of central precocious puberty in girls. Eur J Endocrinol. 2012; 166:295–9.

12. Boyar RM, Wu RH, Roffwarg H, Kapen S, Weitzman ED, Hellman L, et al. Human puberty: 24-hour estradiol in pubertal girls. J Clin Endocrinol Metab. 1976; 43:1418–21.

13. Moon JS, Lee SY, Nam CM, Choi JM, Choe BK, Seo JW, et al. 2007 Korean National Growth Charts: review of developmental process and an outlook. Korean J Pediatr. 2008; 51:1–25.

14. Greulich WW, Pyle SI. Radiologic atlas of skeletal development of the hand and wrist. 2nd ed. Standford (CA): Stanford University Press;1959.

15. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR; ESPE-LWPES GnRH Analogs Consensus Conference Group, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009; 123:e752. –62.

16. Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cutpoint and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology. 2005; 16:73–81.

17. Grumbach M, Kaplan S. The neuroendocrinology of human puberty: an ontogenetic perspective. In : Grumbach M, Sizonenko P, editors. Control of the onset of puberty II. Baltimore: Williams and Wikins;1990. p. 1–68.

18. Mitamura R, Yano K, Suzuki N, Ito Y, Makita Y, Okuno A. Diurnal rhythms of luteinizing hormone, folliclestimulating hormone, testosterone, and estradiol secretion before the onset of female puberty in short children. J Clin Endocrinol Metab. 2000; 85:1074–80.

19. Rosenfield RL, Bordini B, Yu C. Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test. J Clin Endocrinol Metab. 2013; 98:1591–601.

20. Midgley AR Jr, Jaffe RB. Regulation of human gonadotropins. X. Episodic fluctuation of LH during the menstrual cycle. J Clin Endocrinol Metab. 1971; 33:962–9.

21. Nankin HR, Troen P. Repetitive luteinizing hormone elevations in serum of normal men. J Clin Endocrinol Metab. 1971; 33:558–60.

22. Apter D, Pakarinen A, Vihko R. Serum prolactin, FSH and LH during puberty in girls and boys. Acta Paediatr Scand. 1978; 67:417–23.

23. Grumbach M. Onset of puberty. In : Berenberg SR, editor. Puberty, biologic and social components. Leiden: H.E. Stenfert Kroese;1975. p. 1–21.

24. Kaplan SL, Grumbach MM, Aubert ML. The ontogenesis of pituitary hormones and hypothalamic factors in the human fetus: maturation of central nervous system regulation of anterior pituitary function. Recent Prog Horm Res. 1976; 32:161–243.

25. Apter D, Bützow TL, Laughlin GA, Yen SS. Gonadotropinreleasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins. J Clin Endocrinol Metab. 1993; 76:940–9.

26. Schroor EJ, van Weissenbruch MM, Engelbregt M, Martens F, Meurs JM, Wennink JM, et al. Bioactivity of luteinizing hormone during normal puberty in girls and boys. Horm Res. 1999; 51:230–7.

27. Bordini B, Littlejohn E, Rosenfield RL. LH dynamics in overweight girls with premature adrenarche and slowly progressive sexual precocity. Int J Pediatr Endocrinol. 2010; 2010:Article ID 724696.

28. Kaplowitz PB. Link between body fat and the timing of puberty. Pediatrics. 2008; 121(3 Suppl):S208–17.

29. Shaw ND, Seminara SB, Welt CK, Au MG, Plummer L, Hughes VA, et al. Expanding the phenotype and genotype of female GnRH deficiency. J Clin Endocrinol Metab. 2011; 96:E566–76.

30. Davison KK, Susman EJ, Birch LL. Percent body fat at age 5 predicts earlier pubertal development among girls at age 9. Pediatrics. 2003; 111(4 Pt 1):815–21.

31. Lee JM, Appugliese D, Kaciroti N, Corwyn RF, Bradley RH, Lumeng JC. Weight status in young girls and the onset of puberty. Pediatrics. 2007; 119:e624. –30.

32. Fu JF, Liang JF, Zhou XL, Prasad HC, Jin JH, Dong GP, et al. Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty. Obesity (Silver Spring). 2015; 23:637–43.