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      A single sample GnRHa stimulation test in the diagnosis of precocious puberty

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          Abstract

          Context

          Gonadotropin-releasing hormone (GnRH) has been the standard test for diagnosing central precocious puberty. Because GnRH is no longer available, GnRH analogues (GnRHa) are now used. Random LH concentration, measured by the third-generation immunochemiluminometric assay, is a useful screening tool for central precocious puberty. However, GnRHa stimulation test should be considered, when a basal LH measurement is inconclusive. However optimal sampling times for luteinizing hormone (LH) have yet to be established.

          Purpose

          To determine the appropriate sampling time for LH post leuprolide challenge.

          Methods

          A retrospective analysis of multi-sample GnRHa stimulation tests performed in 155 children (aged 1–9 years) referred for precocious puberty to Texas Children’s Hospital.

          After 20 mcg/kg of SQ leuprolide acetate, samples were obtained at 0, 1, 3, and 6 hours.

          Results

          Of 71 children with clinical evidence of central precocious puberty, fifty nine children had a peak LH >5 mIU/mL. 52 (88%) of these responders had positive responses at 1 hour (95% CI is 80–96%), whereas all 59 children (100%) had a peak LH response >5 mIU/mL at 3 hours (95% CI is 94-100%), P = 0.005.

          Conclusions

          A single serum LH sample collected 3 hours post GnRHa challenge is the optimal sample to establish the diagnosis of central precocious puberty.

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          Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

          Paola B Lara, Tiago B Ferreira, Samuel A R Pereira … (2007)
          Recently, new methodologies have been applied to commercial immunofluorometric (IFMA) and immunochemiluminometric (ICMA) LH and FSH assays. The objective of the study was to use ICMA to establish basal and GnRH-stimulated LH and FSH reference values in normal subjects of different ages and sexual development, compared with IFMA. We established basal and GnRH-stimulated LH and FSH levels of 315 prepubertal and pubertal children (170 males and 145 females) divided into five groups according to Tanner stage. Of these, 106 subjects (59 males and 47 females) were submitted to GnRH test. The prepubertal upper limit of normal for basal LH, determined by the 95th percentiles of the prepubertal population, were 0.2 IU/liter (ICMA) and 0.6 IU/liter (IFMA) in both genders. No overlap of basal LH levels determined by ICMA was observed between prepubertal and pubertal males, but basal LH determined by IFMA overlapped in 11.8% of subjects. In girls, both methods yielded overlapping values (10.4%, ICMA; and 84.6%, IFMA). The LH peak after GnRH stimulation that defined puberty was 4.1 IU/liter (ICMA) and 3.3 IU/liter (IFMA) in boys and 3.3 IU/liter (ICMA) and 4.2 IU/liter (IFMA) in girls. After GnRH stimulation, values determined by the two methods overlapped in both genders. We conclude that ICMA is more sensitive and precise than IFMA, permitting differentiation of pubertal and prepubertal stage in boys under basal conditions. However, in girls the overlap of basal values was marked, indicating the need for the GnRH test to establish maturity of the hypothalamus-pituitary-gonadal axis.
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            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.

            S Lee, Christopher Houk, Allen R. Kunselman (2008)
            To ascertain the diagnostic value of GnRHa stimulation testing in girls with CPP, single sample 30 minute post-stimulated gonadotropin levels were compared between girls with CPP and prepubertal girls. Serum LH and FSH concentrations were assayed using two third generation gonadotropin assays. Clinical data were reviewed to establish the diagnosis of CPP. GnRHa stimulation testing with one LH measurement obtained 30 minutes after stimulation is adequate for evaluating girls with CPP and as reliable as GnRH stimulation testing.
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              Leuprolide stimulation testing for the evaluation of early female sexual maturation.

              James Godbold, Robert Rapaport, L Garibaldi … (2010)
              Low concentrations of serum LH and/or oestradiol (E(2)) in girls with early physical signs of precocious puberty pose a diagnostic challenge. To assess the diagnostic value of the leuprolide stimulation test in female precocious puberty. Retrospective Chart Review. Outpatient clinic. Thirty-nine girls, 6.9 (1.4) years, with premature stage II-III breast development, with or without pubarche, underwent stimulation testing with subcutaneous leuprolide (20 microg/kg) with the following hormonal measurements in serum: FSH, LH, oestradiol at baseline; FSH and LH at 1 and 2 h; oestradiol at 24 h. Twelve girls with isolated pubarche were also tested with leuprolide. A pubertal hormonal pattern was defined as at least one of the following: a baseline serum level of LH > or = 0.3 U/l, a baseline oestradiol > or = 37 pmol/l (10 ng/l), a stimulated (peak) LH > or = 5.0 U/l, a stimulated oestradiol > or = 184 pmol/l (50 ng/l) to leuprolide. The hormonal response was related to the clinical course during a period of observation of at least 6 months. Following leuprolide stimulation, the hormonal response was concordant with pubertal progression (n = 23) or lack thereof (n = 16) in all children. At baseline, pubertal serum concentrations of LH and/or oestradiol were associated with pubertal progression in all, while serum prepubertal LH and/or oestradiol concentrations were associated with pubertal progression in approximately 50% of the patients. In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Pediatr Endocrinol
                Journal ID (iso-abbrev): Int J Pediatr Endocrinol
                Title: International Journal of Pediatric Endocrinology
                Publisher: BioMed Central
                ISSN (Print): 1687-9848
                ISSN (Electronic): 1687-9856
                Publication date (Print): 2012
                Publication date (Electronic): 18 July 2012
                Volume: 2012
                Issue: 1
                Page: 23
                Affiliations
                [1 ]Pediatric Endocrinology, Baylor College of Medicine, Houston, 77024, TX, USA
                [2 ]University of Utah, Salt Lake City, UT, USA
                [3 ]Baylor College of Medicine, Children’s Nutritional Research Center, Houston, TX, USA
                Article
                Publisher ID: 1687-9856-2012-23
                DOI: 10.1186/1687-9856-2012-23
                PMC ID: 3438042
                PubMed ID: 22809285
                SO-VID: 620ab90a-8289-4331-a6df-bf118d0b191a
                Copyright © Copyright ©2012 Yazdani et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 March 2012
                Date accepted : 23 June 2012
                Categories
                Subject: Research

                ScienceOpen disciplines: Pediatrics
                Keywords: gonadotropin releasing hormone analogue,luteinizing hormone,central precocious puberty
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: gonadotropin releasing hormone analogue, luteinizing hormone, central precocious puberty

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