Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Gonadotropin-releasing Hormone Stimulation Test for Precocious Puberty

  • Kim, Han-Kyul (Department of Pediatrics, Chonnam National University Medical School) ;
  • Kee, Seung-Jung (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Seo, Ji-Yeon (Department of Pediatrics, Chonnam National University Medical School) ;
  • Yang, Eun-Mi (Department of Pediatrics, Chonnam National University Medical School) ;
  • Chane, Hong-Jae (Department of Occupational & Environmental Medicine, Chonnam National University Medical School) ;
  • Kim, Chan-Jong (Department of Pediatrics, Chonnam National University Medical School)
  • Published : 2011.10.30
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Abstract

Background: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard to identify central precocious puberty (CPP). This test requires multiple blood samples at different time points to measure gonadotropin levels, and is therefore expensive, time-consuming, and uncomfortable for patients. We aimed to simplify the GnRH stimulation test to require fewer blood samples. Methods: A study of 166 girls with precocious puberty was undertaken. Blood samples were obtained at 0, 15, 30, 45, 60, 90, and 120 min after GnRH administration, and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated and ROC curves were constructed. Results: One hundred and twenty-eight patients (77.1%) were diagnosed for CPP. Peak LH levels were achieved 30 min after GnRH stimulation in patients with CPP. Further, 98.4% of the 45-min samples were diagnostic for CPP, and the cumulative frequency of LH values of ${\geq}$5 IU/L was 100% at 45 min. Using this cut-off value for LH, the ROC curve for LH at 45 min showed the highest sensitivity (98.4%) and specificity (100%) in the diagnosis of CPP. Conclusions: Values of LH measured from a single blood sample obtained at 45 min in the GnRH stimulation test may be adequate for the diagnosis of CPP. Two samples, taken at 30 and 45 min after stimulation, were able to accurately diagnose CPP in 100% of the patients in this study.

Keywords

References

  1. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. 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;24:668-93. https://doi.org/10.1210/er.2002-0019
  2. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, Antoniazzi F, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:e752-62. https://doi.org/10.1542/peds.2008-1783
  3. Lee PA. Central precocious puberty. An overview of diagnosis, treatment, and outcome. Endocrinol Metab Clin North Am 1999;28: 901-18. https://doi.org/10.1016/S0889-8529(05)70108-0
  4. Partsch CJ, Heger S, Sippell WG. Management and outcome of central precocious puberty. Clin Endocrinol (Oxf) 2002;56:129-48. https://doi.org/10.1046/j.0300-0664.2001.01490.x
  5. 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. https://doi.org/10.1210/jc.84.10.3539
  6. Lee PA. Laboratory monitoring of children with precocious puberty. Arch Pediatr Adolesc Med 1994;148:369-76. https://doi.org/10.1001/archpedi.1994.02170040035006
  7. Poomthavorn P, Khlairit P, Mahachoklertwattana P. Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty. Horm Res 2009;72:114-9. https://doi.org/10.1159/000232164
  8. Pescovitz OH, Hench KD, Barnes KM, Loriaux DL, Cutler GB Jr. Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 1988;67:474-9. https://doi.org/10.1210/jcem-67-3-474
  9. Parker KL, Baens-Bailon RG, Lee PA. Depot leuprolide acetate dosage for sexual precocity. J Clin Endocrinol Metab1991;73:50-2. https://doi.org/10.1210/jcem-73-1-50
  10. Cavallo A, Richards GE, Busey S, Michaels SE. A simplified gonadotrophin-releasing hormone test for precocious puberty. Clin Endocrinol (Oxf) 1995;42:641-6. https://doi.org/10.1111/j.1365-2265.1995.tb02692.x
  11. Toguchi H. Pharmaceutical manipulation of leuprorelin acetate to improve clinical performance. J Int Med Res 1990;18(S1):S35-41. https://doi.org/10.1177/03000605900180S107
  12. Manasco PK, Pescovitz OH, Hill SC, Jones JM, Barnes KM, Hench KD, et al. Six-year results of luteinizing hormone releasing hormone (LHRH) agonist treatment in children with LHRH-dependent precocious puberty. J Pediatr 1989;115:105-8. https://doi.org/10.1016/S0022-3476(89)80341-5
  13. Witchel SF, Baens-Bailon RG, Lee PA. Treatment of central precocious puberty: comparison of urinary gonadotropin excretion and gonadotropin-releasing hormone (GnRH) stimulation tests in monitoring GnRH analog therapy. J Clin Endocrinol Metab 1996;81: 1353-6. https://doi.org/10.1210/jc.81.4.1353
  14. 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. https://doi.org/10.1016/S0022-3476(95)70255-5
  15. Houk CP, Kunselman AR, Lee PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 2009;123:e1059-63. https://doi.org/10.1542/peds.2008-1180
  16. Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab 2008;21:1113-8.
  17. Ibanez L, Potau N, Zampolli M, Virdis R, Gussinye M, Carrascosa A, et al. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab 1994;781:30-5.
  18. Greulich WW and Pyle SI. Eds. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford: Stanford University Press, 1959.
  19. Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, Argente J, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40-6. https://doi.org/10.1016/S0022-3476(95)70254-7
  20. 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. https://doi.org/10.1210/jc.2010-2745
  21. Resende EA, Lara BH, Reis JD, Ferreira BP, Pereira GA, Borges MF. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab 2007;92:1424-9. https://doi.org/10.1210/jc.2006-1569
  22. 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. https://doi.org/10.1210/jcem-71-5-1251
  23. Eckert KL, Wilson DM, Bachrach LK, Anhalt H, Habiby RL, Olney RC, et al. A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty. Pediatrics 1996; 97:517-9.
  24. Cavallo A and Zhou XH. LHRH test in the assessment of puberty in normal children. Horm Res 1994;41:10-5. https://doi.org/10.1159/000183870
  25. Brito VN, Latronico AC, Arnhold IJ, Mendonca BB. A single luteinizing hormone determination 2 hours after depot leuprolide is useful for therapy monitoring of gonadotropin-dependent precocious puberty in girls. J Clin Endocrinol Metab 2004;89:4338-42. https://doi.org/10.1210/jc.2003-031537
  26. Choi JH, Shin YL, Yoo HW. The predictive factors for central nervous system lesion in central precocious puberty and the utility of single timed LH after GnRH administration. J Korean Soc Pediatr Endocrinol 2002;7:206-14.

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