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      GnRH Stimulation Test in Precocious Puberty: Single Sample is Adequate for Diagnosis and Dose Adjustment

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          Abstract

          Objective: Gonadotropin stimulation test is the gold standard to document precocious puberty. However, the test is costly, time-consuming and uncomfortable. The aim of this study was to simplify the intravenous gonadotropin-releasing hormone (GnRH) stimulation test in the diagnosis of precocious puberty and in the assessment of pubertal suppression.

          Methods: Data pertaining to 584 GnRH stimulation tests (314 testsfor diagnosis and 270 for assessment of pubertal suppression) were analyzed.

          Results: Forty-minute post-injection samples had the greatest frequency of “peaking luteinizing hormone (LH)” (p<0.001) in the diagnostic tests when the cut-off value was taken as 5 IU/L for LH, 40th minute sample was found to have 98% sensitivity and 100% specificity in the diagnosis of precocious puberty, while the sensitivity and specificity of the 20th minute sample was 100% in the assessment of pubertal suppression.

          Conclusion: LH level at the 40th minute post-injection in the diagnosis of central precocious puberty and at the 20th minute post-injection in the assessment of pubertal suppression is highly sensitive and specific. A single sample at these time points can be used in the diagnosis of early puberty and in the assessment of pubertal suppression.

          Conflict of interest:None declared.

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          Most cited references23

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          Association between bullying and psychosomatic problems: a meta-analysis.

          In the last few years, there has been an increasing amount of research showing the concurrent and long-term consequences of bullying and being bullied by peers. OBJECTIVE. We performed a meta-analysis to quantify the association between involvement in bullying and psychosomatic complaints in the school-aged population. We searched online databases (Embase, Medline, PsychInfo, Scopus) up to March 2008, bibliographies of existing studies, and qualitative reviews for studies that examined the association between involvement in bullying and psychosomatic complaints in children and adolescents. The original search identified 19 studies, of which 11 satisfied prestated inclusion criteria. Three random-effects meta-analyses were performed for the following 3 groups of children aged between 7 and 16 years: victims, bullies, and bully-victims. Bully-victims, victims, and bullies had a significantly higher risk for psychosomatic problems compared with uninvolved peers. The association between involvement in bullying and psychosomatic problems was demonstrated. Given that school bullying is a widespread phenomenon in many countries around the world, the present results suggest that bullying be considered a significant international public health issue.
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            Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children.

            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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              Diagnostic value of fluorometric assays in the evaluation of precocious puberty.

              To establish normative data and determine the value of fluorometric AutoDELFIA assays (Wallac Oy) in the investigation of precocious puberty, we determined serum levels of LH, FSH, testosterone, and estradiol under basal and GnRH-stimulated conditions in 277 normal subjects at various pubertal stages and in 77 patients with precocious puberty. A substantial overlap was observed in basal and GnRH-stimulated gonadotropin levels in normal individuals of both sexes with pubertal Tanner stages 1 and 2. The 95th percentile of the normal prepubertal population was the cut-off limit between prepubertal and pubertal levels. These limits were 0.6 IU/L in both sexes for basal LH, 9.6 IU/L in boys and 6.9 IU/L in girls for peak LH after GnRH stimulation, 19 ng/dL in boys for basal testosterone, and 13.6 pg/mL in girls for basal estradiol. Basal and peak LH exceeding these limits were considered positive tests for the diagnosis of gonadotropin-dependent precocious puberty. According to these criteria, the sensitivities of basal and peak LH for the latter diagnosis were 71.4% and 100% in boys, and 62.7% and 92.2% in girls. The specificity and positive predicted value were 100% in both sexes for basal and peak LH levels. The negative predicted values for basal and peak LH were 62.5% and 100% in boys, and 40.6% and 76.5% in girls. Basal and GnRH-stimulated FSH levels overlapped among the various pubertal stages in normal subjects and were, in general, not helpful in the differential diagnosis of precocious puberty. In conclusion, basal LH levels were sufficient to establish the diagnosis of gonadotropin-dependent precocious puberty in 71.4% of boys and 62.7% of girls. In the remaining patients, a GnRH stimulation test was still necessary to confirm this diagnosis. Finally, suppressed LH and FSH levels after GnRH stimulation indicate gonadotropin-independent sexual steroid production.
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                Author and article information

                Journal
                J Clin Res Pediatr Endocrinol
                JCRPE
                Journal of Clinical Research in Pediatric Endocrinology
                Galenos Publishing
                1308-5727
                1308-5735
                March 2011
                23 February 2011
                : 3
                : 1
                : 12-17
                Affiliations
                [1 ] Hacettepe University Medical School, Division of Pediatric Endocrinology, Ankara, Turkey
                +90 312 305 11 24+90 312 312 18 09 dr_huseyin@ 123456hotmail.com Hacettepe University Medical School, Division of Pediatric Endocrinology, Sıhhiye, Ankara, Turkey
                Article
                88
                10.4274/jcrpe.v3i1.03
                3065310
                21448328
                11d17765-812f-4641-8b3f-a5378e3872e5
                © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

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

                History
                : 30 December 2010
                : 4 February 2011
                Categories
                Original Article

                Pediatrics
                central precocious puberty,luteinizing hormone,gnrh analogue,gnrh stimulation test,hypotalamo-pituitary-gonadal axis,follicle stimulating hormone

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