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Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods

  • Amnon Zung EMAIL logo , Ella Burundukov , Mira Ulman , Tamar Glaser and Zvi Zadik
Published/Copyright: March 7, 2015
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 7-8

Abstract

Aim: The objective of this study was to validate basal, post-gonadotropin-releasing hormone analogue (post-GnRHa) and first-voided urinary LH (ULH) as alternatives to an LHRH stimulation test in monitoring treatment efficacy in central precocious puberty (CPP).

Methods: Seventeen girls with CPP were followed over 22.5±9.1 months during GnRHa (triptorelin) treatment. ULH and post-GnRHa LH levels were obtained every 4 months before and 24 h after GnRHa administration, respectively, along with clinical and bone age (BA) evaluation. LHRH stimulation tests were performed annually.

Results: A total of 36 LHRH stimulation tests demonstrated adequate suppression with a peak LH of 0.57±0.33 IU/L. The corresponding basal LH was 0.27±0.16 IU/L. Ninety post-GnRHa LH measurements were similar to LHRH-stimulated LH levels (0.56±0.31 IU/L), whereas 8% of ULH levels were above prepubertal threshold. Fourteen episodes of growth acceleration and ten episodes of BA advancement resolved without treatment modification.

Conclusion: Suppressed basal and post-GnRHa LH levels indicate adequate suppression of puberty. Clinical breakthroughs during treatment are transient and resolved spontaneously.

Keywords: GnRHa; gonadotropins; monitoring; precocious puberty
Corresponding author: Amnon Zung, MD, Pediatric Endocrinology Unit, Kaplan Medical Center, affiliated with the Hebrew University of Jerusalem, Rehovot 76100, Israel, Phone: +972-8-9441260, Fax: +972-8-9441124, E-mail:
aAmnon Zung is ESPE member; membership # 124976

Acknowledgments

We would like to express our gratitude to Dr Sharon Straussman for critical review of the original manuscript.

Conflict of interest: The authors have no conflict of interest to declare.

References

1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:e752–62.10.1542/peds.2008-1783Search in Google Scholar PubMed

2. Lahlou N, Carel JC, Chaussain JL, Roger M. Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab 2000;13(Suppl 1): 723–37.10.1515/JPEM.2000.13.S1.723Search in Google Scholar PubMed

3. Mul D, de Muinck Keizer-Schrama SM, Oostdijk W, Drop SL. Auxological and biochemical evaluation of pubertal suppression with the GnRH agonist leuprolide acetate in early and precocious puberty. Horm Res 1999;51:270–6.10.1159/000023413Search in Google Scholar PubMed

4. Carel JC, Lahlou N, Guazzarotti L, Joubert-Collin M, Roger M, et al. Treatment of central precocious puberty with depot leuprorelin. French Leuprorelin Trial Group. Eur J Endocrinol 1995;132: 699–704.10.1530/eje.0.1320699Search in Google Scholar PubMed

5. Neely EK, Lee PA, Bloch CA, Larsen L, Yang D, et al. Leuprolide acetate 1-month depot for central precocious puberty: hormonal suppression and recovery. Int J Pediatr Endocrinol 2011:2010. Article ID 398639, DOI: 10.1155/2010/398639.10.1155/2010/398639Search in Google Scholar PubMed PubMed Central

6. 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: 4338–42.10.1210/jc.2003-031537Search in Google Scholar PubMed

7. Strich D, Kvatinsky N, Hirsch HJ, Gillis D. Triptorelin depot stimulation test for central precocious puberty. J Pediatr Endocrinol Metab 2013;26:631–4.10.1515/jpem-2012-0015Search in Google Scholar PubMed

8. Lee PA. Laboratory monitoring of children with precocious puberty. Arch Pediatr Adolesc Med 1994;148:369–76.10.1001/archpedi.1994.02170040035006Search in Google Scholar PubMed

9. Bhatia S, Neely EK, Wilson DM. Serum luteinizing hormone rises within minutes after depot leuprolide injection: implications for monitoring therapy. Pediatrics 2002;109:e30.10.1542/peds.109.2.e30Search in Google Scholar PubMed

10. Wilson DM. Regular monitoring of bone age is not useful in children treated with growth hormone. Pediatrics 1999;104:1036–9.10.1542/peds.104.S5.1036Search in Google Scholar

11. Houk CP, Kunselman AR, Lee PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 2009;123:e1059–63.10.1542/peds.2008-1180Search in Google Scholar

12. Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr 1995;127:47–52.10.1016/S0022-3476(95)70255-5Search in Google Scholar

13. Neely EK, Silverman LA, Geffner ME, Danoff TM, Gould E, et al. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy. Int J Pediatr Endocrinol 2013;2013:20.10.1186/1687-9856-2013-20Search in Google Scholar

14. Lewis KA, Eugster EA. Random luteinizing hormone often remains pubertal in children treated with the histrelin implant for central precocious puberty. J Pediatr 2013;162:562–5.10.1016/j.jpeds.2012.08.038Search in Google Scholar

15. Acharya SV, Gopal RA, George J, Bandgar TR, Menon PS, et al. Utility of single luteinizing hormone determination 3 h after depot leuprolide in monitoring therapy of gonadotropin-dependent precocious puberty. Pituitary 2009;12:335–8.10.1007/s11102-009-0184-0Search in Google Scholar

16. Salerno M, Di Mayo S, Gasparini N, Mariano A, Macchia V, et al. Central precocious puberty: a single blood sample after gonadotropin-releasing hormone agonist administration in monitoring treatment. Horm Res 1998;50:205–11.10.1159/000023275Search in Google Scholar

17. 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.Search in Google Scholar

18. Zung A, Burundukov E, Ulman M, Glaser T, Rosenberg M, et al. The diagnostic value of first-voided urinary LH compared with GNRH-stimulated gonadotropins in differentiating slowly progressive from rapidly progressive precocious puberty in girls. Eur J Endocrinol 2014;170:749–58.10.1530/EJE-14-0010Search in Google Scholar

19. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.10.1136/adc.44.235.291Search in Google Scholar

20. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, et al. CDC growth charts: United States. Adv Data 2000;314:1–27.Search in Google Scholar

21. Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr 1985;107:317–29.10.1016/S0022-3476(85)80501-1Search in Google Scholar

22. Greulich W, Pyle S. Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Stanford, CA: Stanford University Press, 1959.10.1097/00000441-195909000-00030Search in Google Scholar

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

24. Resensde EA, Lara BH, Reis JD, Ferreira BP, Pereira GA, et al. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab 2007;92:1424–9.10.1210/jc.2006-1569Search in Google Scholar

25. Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab 2007;92:1697–704.10.1210/jc.2006-2479Search in Google Scholar

26. Roger M, Chaussain JL, Berlier P, Bost M, Canlorbe P, et al. Long term treatment of male and female precocious puberty by periodic administration of a long-acting preparation of D-Trp6-luteinizing hormone-releasing hormone microcapsules. J Clin Endocrinol Metab 1986;62:670–7.10.1210/jcem-62-4-670Search in Google Scholar

27. Ibanez L, Potau N, Zampolli M, Virdis R, Gussinye M, 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;78:30–5.10.1210/jc.78.1.30Search in Google Scholar

28. Degros V, Cortet-Rudelli C, Soudan B, Dewailly D. The human chorionic gonadotropin test is more powerful than the gonadotropin-releasing hormone agonist test to discriminate male isolated hypogonadotropic hypogonadism from constitutional delayed puberty. Eur J Endocrinol 2003;149:23–9.10.1530/eje.0.1490023Search in Google Scholar

29. Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40–6.10.1016/S0022-3476(95)70254-7Search in Google Scholar

30. Lee P, Luce M, Bacher P. Practical considerations for the treatment of central precocious puberty with a 3-month depot leuprolide acetate formulation. Abstract SUN-0172, 16th international congress of endocrinology and 96th endocrine society annual meeting, 2014.Search in Google Scholar

31. Fuld K, Chi C, Neely K. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. J Pediatr 2011;159:982–7.10.1016/j.jpeds.2011.05.036Search in Google Scholar PubMed

32. Cook JS, Doty KL, Conn PM, Hansen JR. Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty. J Clin Endocrinol Metab 1992;74:1206–9.Search in Google Scholar

33. Demir A, Voutilainen R, Juul A, Dunkel L, Alfthan H, et al. Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty. J Clin Endocrinol Metab 1996;81:2963–7.Search in Google Scholar

34. Bay K, Andersson AM, Skakkebaek NE. Estradiol levels in prepubertal boys and girls: analytical challenges. Int J Androl 2004;27:266–73.10.1111/j.1365-2605.2004.00487.xSearch in Google Scholar PubMed

35. Partsch CJ, Sippell WG. Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab 2002;16: 165–89.10.1053/beem.2002.0188Search in Google Scholar PubMed

Received: 2014-11-21
Accepted: 2015-2-2
Published Online: 2015-3-7
Published in Print: 2015-7-1

©2015 by De Gruyter

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  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
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  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
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  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
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  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
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  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
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https://doi.org/10.1515/jpem-2014-0478
Keywords for this article
GnRHa; gonadotropins; monitoring; precocious puberty

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
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