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      Evaluation of GnRH analogue testing in diagnosis and management of children with pubertal disorders

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          Abstract

          Context:

          Gonadotrophin releasing hormone (GnRH) stimulation test is pivotal in the assessment of children with pubertal disorders. However, lack of availability and high cost often result in the test falling into disfavor. We routinely use the GnRH analogue stimulation test as an alternative at our center.

          Aim:

          To present the data on children with endocrine disorders who underwent GnRH agonist stimulation test in pediatric endocrine clinic of a tertiary care referral hospital.

          Setting and Design:

          Pediatric endocrine clinic of a tertiary care referral hospital. Retrospective analysis of case records.

          Materials and Methods:

          The details pertaining to clinical and radiological parameters and hormonal tests were retrieved from case records of 15 children who underwent GnRH agonist stimulation test from May 2010 to April 2011.

          Results:

          Indications for testing with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious puberty, assessment of hormonal suppression in treatment of precocious puberty and micropenis in two, nine, three and one cases, respectively. The results of the test and clinical and radiological parameters were in concordance. The test was also crucial in diagnosing the onset of central precocious puberty in two children with congenital adrenal hyperplasia.

          Conclusion:

          GnRH agonist test is a convenient, safe test that can be performed on an out-patient basis and can help the clinicians in the correct diagnosis and appropriate treatment of various puberty-related disorders.

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          Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls.

          Allen R. Kunselman, P Lee, Christopher Houk (2009)
          Using basal specimens from original gonadotropin radioimmunoassays, it was not possible to differentiate prepuberty from puberty hence gonadotropin-releasing hormone or gonadotropin-releasing hormone analog (GnRHa) testing was required to make this distinction. Third-generation gonadotropin assays have far greater specificity and sensitivity. Using a group of patients who had the diagnosis of central precocious puberty (CPP) verified or excluded by using GnRHa and traditional diagnostic criteria, the objective of this study was to determine if a single basal gonadotropin measurement was adequate to verify the diagnosis of CPP by using 2 third-generation gonadotropin assays. Girls referred for assessment of early puberty had previously been evaluated for central precocious puberty including gonadotropin-releasing hormone analog stimulation testing with gonadotropin measurements by 2 different chemiluminescent third-generation immunoassays. Diagnosis of central precocious puberty was made on the basis of the response to the gonadotropin-releasing hormone analog, and clinical criteria. Girls with central precocious puberty had luteinizing hormone responses ranging from 9.1 to 67.6 U/L, the prepubertal luteinizing hormone response range was 0.2 to 5.0 U/L. Basal serum luteinizing hormone and follicle-stimulating hormone concentrations from these girls have been assessed to determine the utility of using such a single sample to diagnose central precocious puberty. Basal luteinizing hormone levels using the 2 third-generation gonadotropin assays were sufficient to diagnose central precocious puberty in >90% of the girls. Luteinizing hormone values were undetectable in both assays with different lower limits of detection ( 0.83 U/L, except a single value of 0.46 U/L. The basal follicle-stimulating hormone failed to differentiate prepubertal girls from those with central precocious puberty, whereas luteinizing hormone/follicle-stimulating hormone ratios would seem to have limited discernment. A single basal luteinizing hormone measurement is adequate to document a pubertal hypothalamic-pituitary-ovarian axis in most but not all girls with central precocious puberty.
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            Pituitary-gonadal relations in infancy. I. Patterns of serum gonadotropin concentrations from birth to four years of age in man and chimpanzee.

            Maura W. Hobson, Juan F Reyes, Sandra Winter … (1975)
            Mixed cord sera (27 male, 28 female) and sera from 105 male and 93 female children aged 5 days to 4 yr were assayed for FSH, LH and hCG. Cord hCG was similar in both sexes (median 58 mIU/ml; range 20-9000), and fell to less than 5 mIU/ml by 5 days of life, a value which is below the limit of detectable cross reactivity in the LH radioimmunoassay. Cord FSH was less than 5.5 mug LER-907/100 ml in both sexes. In boys there was a rapid rise of FSH in early postnatal life, with peak levels up to 55 mug/100 ml between 1 week and 3 months, followed by a decline by 4 months reaching the low values seen in older prepubertal subjects. This postnatal FSH rise was both more marked in females with peak values at 2-3 months up to 169 mug/100 ml, and also more sustained with levels staying above those of older prepubertal children until 4 yr of age. Serum LH levels in the boys were in the adolescent range by 1 week of age, peaked at 1 month and then declined to the usual childhood range by 4 months. A similar pattern, though with lower peak LH values, was seen in the female infants. A longitudinal study of serum FSH and LH values in one male and one female chimpanzee from 17 to 456 days of age showed patterns in serum gonadotropins which paralleled those seen in the human cross-sectional study.
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              A single luteinizing hormone determination 2 hours after depot leuprolide is useful for therapy monitoring of gonadotropin-dependent precocious puberty in girls.

              A Latronico, Gilberto Brito, Berenice Mendonca … (2004)
              Long-acting GnRH analogs represent the standard treatment for gonadotropin-dependent precocious puberty. The aim of this study was to determine the hormonal parameters for monitoring the adequacy of depot leuprolide acetate treatment in girls with clinical and hormonal diagnosis of gonadotropin-dependent precocious puberty. Eighteen girls were treated monthly with 3.75 mg depot leuprolide acetate. Adequate hypothalamic-pituitary-gonadal axis suppression during treatment was achieved in 16 of the 18 girls according to the clinical parameters and prepubertal LH levels. In these 16 well-controlled girls, the LH peak after a classical GnRH test was compared with a single LH measurement obtained 2 h after depot leuprolide acetate administration before and during GnRH analog treatment. Before therapy, the mean +/- sd LH peak after a classical GnRH test was 18.4 +/- 11.2 IU/liter (ranging from 7-41.5 IU/liter), and it was 22.6 +/- 8.3 IU/liter 2 h after the first depot leuprolide dose (ranging from 10-35.3 IU/liter). During therapy, the mean +/- sd of LH peak after classical GnRH test was 1.4 +/- 0.6 IU/liter (ranging from <0.6 to 2.3 IU/liter), and it was 2.7 +/- 1.9 IU/liter (ranging from 0.7-6.6 IU/liter) 2 h after depot leuprolide. The LH peak after a classical GnRH test and that 2 h after depot leuprolide administration correlate significantly before and during treatment. In conclusion, we established the LH cut-off values for an adequate depot leuprolide therapy as an LH peak below 2.3 IU/liter after a classical GnRH test or below 6.6 IU/liter 2 h after depot leuprolide. The latter measurement may replace the classical GnRH test as a reliable and convenient tool for monitoring therapy in female gonadotropin-dependent precocious puberty.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Indian J Endocrinol Metab
                Journal ID (iso-abbrev): Indian J Endocrinol Metab
                Journal ID (publisher-id): IJEM
                Title: Indian Journal of Endocrinology and Metabolism
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2230-8210
                ISSN (Electronic): 2230-9500
                Publication date (Print): May-Jun 2012
                Volume: 16
                Issue: 3
                Pages: 400-405
                Affiliations
                [1 ] Department of Pediatrics, Bharati Vidyapeeth University Medical College, Pune, Maharashtra, India
                [2 ] Growth and Pediatric Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India
                Author notes
                Corresponding Author: Dr. Vaman Khadilkar, Growth and Pediatric Endocrine Unit, Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, 32 Sasoon Road, Pune – 411 001, Maharashtra, India. E-mail: vamankhadilkar@ 123456gmail.com
                Article
                Publisher ID: IJEM-16-400
                DOI: 10.4103/2230-8210.95682
                PMC ID: 3354848
                PubMed ID: 22629507
                SO-VID: c193f274-f91b-40ab-8279-643893c7c34c
                Copyright © Copyright: © Indian Journal of Endocrinology and Metabolism
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: puberty,gonadotrophin releasing hormone,analogue
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: puberty, gonadotrophin releasing hormone, analogue

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