Abstract
Objectives
Basal (unstimulated) LH levels and leuprolide stimulation tests are used to define pubertal status of children presenting with signs of early puberty. The primary aims of this study were to (i) confirm utility of detectable basal LH levels in precluding the need for leuprolide stimulation testing, and, (ii) determine whether duration of testing could be abbreviated from usual 3 h test without compromising sensitivity.
Methods
We reviewed morning basal and leuprolide-stimulated LH levels in 105 children, aged 1–9 years (mean 6.9 years, SD 1.8) who were seen for concerns of precocious puberty and received a leuprolide stimulation test between June 2006 and March 2017.
Results
A pubertal basal LH level had high specificity and poor sensitivity for the following outcome measures: (1) peak stimulated LH≥5 mIU/mL (2) treatment with GnRHa; and (3) a composite outcome of (1) and/or (2). Following leuprolide stimulation, LH response was highest at 180 min in most children (n=78, 74.3%). Using a single cutoff of LH≥5 mIU/mL at any timepoint, 25% of children would have been misdiagnosed with an abbreviated 60 min test. A single sample at 180 min would have correctly identified 97% of patients.
Conclusions
A pubertal basal LH level is sufficient to distinguish children with precocious puberty without stimulation testing. However, prepubertal basal LH had relatively poor negative predictive value to refute CPP, necessitating clinical follow-up and/or a leuprolide stimulation test. For a cutoff of LH≥5 mIU/mL at any timepoint, test duration of 180 min maximizes sensitivity.
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Research funding: None declared.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Competing interests: None declared.
References
1. Harrington, J, Palmert, MR, Hamilton, J. Use of local data to enhance uptake of published recommendations: an example from the diagnostic evaluation of precocious puberty. Arch Dis Child 2014 Jan;99:15–20. https://doi.org/10.1136/archdischild-2013-304414.Search in Google Scholar PubMed
2. Neely, EK, Wilson, DM, Lee, PA, Stene, M, Hintz, RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr 1995 Jul;127:47–52. https://doi.org/10.1016/s0022-3476(95)70255-5.10.1016/S0022-3476(95)70255-5Search in Google Scholar
3. Houk, CP, Kunselman, AR, Lee, PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 2009 Jun;123:e1059–63. https://doi.org/10.1542/peds.2008-1180.10.1542/peds.2008-1180Search in Google Scholar PubMed
4. 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 Dec;21:1113–8. https://doi.org/10.1515/jpem.2008.21.12.1113.10.1515/JPEM.2008.21.12.1113Search in Google Scholar PubMed
5. Chi, CH, Durham, E, Neely, EK. Pharmacodynamics of aqueous leuprolide acetate stimulation testing in girls: correlation between clinical diagnosis and time of peak luteinizing hormone level. J Pediatr 2012 Oct;161:757–9e1. https://doi.org/10.1016/j.jpeds.2012.06.015.10.1016/j.jpeds.2012.06.015Search in Google Scholar PubMed
6. Bordini, B, Littlejohn, E, Rosenfield, RL. Blunted sleep-related luteinizing hormone rise in healthy premenarcheal pubertal girls with elevated body mass index. J Clin Endocrinol Metab 2009 Apr;94:1168–75. https://doi.org/10.1210/jc.2008-1655.10.1210/jc.2008-1655Search in Google Scholar PubMed PubMed Central
7. Kandemir, N, Demirbilek, H, Ozon, ZA, Gonc, N, Alikasifoglu, A. GnRH stimulation test in precocious puberty: single sample is adequate for diagnosis and dose adjustment. J Clin Res Pediatr Endocrinol 2011;3:12–7. https://doi.org/10.4274/jcrpe.v3i1.03.10.4274/jcrpe.v3i1.03Search in Google Scholar PubMed PubMed Central
8. Sathasivam, A, Garibaldi, L, Shapiro, S, Godbold, J, Rapaport, R. Leuprolide stimulation testing for the evaluation of early female sexual maturation. Clin Endocrinol (Oxf). 2010 Sep;73:375–81. https://doi.org/10.1111/j.1365-2265.2010.03796.x.10.1111/j.1365-2265.2010.03796.xSearch in Google Scholar PubMed
9. Yazdani, P, Lin, Y, Raman, V, Haymond, M. A single sample GnRHa stimulation test in the diagnosis of precocious puberty. Int J Pediatr Endocrinol 2012 Jul 18;2012:23. https://doi.org/10.1186/1687-9856-2012-23.10.1186/1687-9856-2012-23Search in Google Scholar PubMed PubMed Central
10. Neely, EK, Hintz, RL, Wilson, DM, Lee, PA, Gautier, T, Argente, J, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995 Jul;127:40–6. https://doi.org/10.1016/s0022-3476(95)70254-7.10.1016/S0022-3476(95)70254-7Search in Google Scholar
11. Carel, JC, Eugster, EA, Rogol, A, Ghizzoni, L, Palmert, MR, Group E-LGACC, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009 Apr;123:e752–62. https://doi.org/10.1542/peds.2008-1783.10.1542/peds.2008-1783Search in Google Scholar PubMed
12. 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 Feb;166:295–9. https://doi.org/10.1530/eje-11-0720.10.1530/EJE-11-0720Search in Google Scholar PubMed
13. Mogensen, SS, Aksglaede, L, Mouritsen, A, Sorensen, 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 May;96:1393–401. https://doi.org/10.1210/jc.2010-2745.10.1210/jc.2010-2745Search in Google Scholar PubMed
14. Garibaldi, LR, Aceto, TJr., Weber, C, Pang, S. The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test. J Clin Endocrinol Metab 1993 Apr;76:851–6. https://doi.org/10.1210/jc.76.4.851.10.1210/jc.76.4.851Search in Google Scholar
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Pharmacological treatment strategies for patients with monogenic obesity
- Original Articles
- Influence of FTO (Fat mass and obesity) gene and parental obesity on Brazilian children and adolescents adiposity
- Developing waist circumference, waist-to-height ratio percentile curves for Pakistani children and adolescents aged 2–18 years using Lambda-Mu-Sigma (LMS) method
- Screening for celiac disease among children with overweight and obesity: toward exploring celiac iceberg
- Relationship between breastfeeding and obesity in high school girls
- Saudi children with celiac disease: are they at risk of developing type-1 diabetes mellitus?
- The relation of serum endocan and soluble endoglin levels with metabolic control in children and adolescents with type 1 diabetes mellitus
- From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus
- Thyroid peroxidase antibodies are common in children with HLA-conferred susceptibility to type 1 diabetes, but are weakly associated with thyroid function
- Individualized dosimetry in children and young adults with differentiated thyroid cancer undergoing iodine-131 therapy
- Association study of DLK1 in girls with idiopathic central precocious puberty
- Clinical, biochemical and genetic characteristics of children with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
- Morning specimen is not representative of metabolic control in Tunisian children with phenylketonuria: a repeated cross-sectional study
- Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults
- Utility and duration of leuprolide stimulation testing in children
- Effect of an interval rehabilitation program with home-based, vibration-assisted training on the development of muscle and bone in children with cerebral palsy – an observational study
- Case Reports
- Metyrapone as treatment in the neonatal McCune–Albright syndrome
- Tumor-induced rickets-osteomalacia: an enigma
- Porto-systemic shunt – a rare cause of hyperandrogenism in children. Two case reports and review of literature
- Hypercalcemia from hypervitaminosis A in a child with autism
Articles in the same Issue
- Frontmatter
- Review Article
- Pharmacological treatment strategies for patients with monogenic obesity
- Original Articles
- Influence of FTO (Fat mass and obesity) gene and parental obesity on Brazilian children and adolescents adiposity
- Developing waist circumference, waist-to-height ratio percentile curves for Pakistani children and adolescents aged 2–18 years using Lambda-Mu-Sigma (LMS) method
- Screening for celiac disease among children with overweight and obesity: toward exploring celiac iceberg
- Relationship between breastfeeding and obesity in high school girls
- Saudi children with celiac disease: are they at risk of developing type-1 diabetes mellitus?
- The relation of serum endocan and soluble endoglin levels with metabolic control in children and adolescents with type 1 diabetes mellitus
- From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus
- Thyroid peroxidase antibodies are common in children with HLA-conferred susceptibility to type 1 diabetes, but are weakly associated with thyroid function
- Individualized dosimetry in children and young adults with differentiated thyroid cancer undergoing iodine-131 therapy
- Association study of DLK1 in girls with idiopathic central precocious puberty
- Clinical, biochemical and genetic characteristics of children with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency
- Morning specimen is not representative of metabolic control in Tunisian children with phenylketonuria: a repeated cross-sectional study
- Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults
- Utility and duration of leuprolide stimulation testing in children
- Effect of an interval rehabilitation program with home-based, vibration-assisted training on the development of muscle and bone in children with cerebral palsy – an observational study
- Case Reports
- Metyrapone as treatment in the neonatal McCune–Albright syndrome
- Tumor-induced rickets-osteomalacia: an enigma
- Porto-systemic shunt – a rare cause of hyperandrogenism in children. Two case reports and review of literature
- Hypercalcemia from hypervitaminosis A in a child with autism