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      Baseline Inhibin B Levels for Diagnosis of Central Precocious Puberty in Girls

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          Abstract

          Aim: To evaluate the use of baseline inhibin B (INHB) levels to differentiate the progressive form (PF) from the non-progressive form (NPF) of central precocious puberty (CPP). Methods: A total of 62 girls were enrolled, 31 with PF and 31 with NPF. Using receiver operating characteristic (ROC) curves, we analysed the diagnostic performance of INHB in addition to other diagnostic tools used to differentiate the 2 forms of CPP. Results: INHB levels were higher in PF versus NPF (29.1 vs. 13.1 pg/ml; p < 0.001). The ROC area under the curve (AUC) was greatest for luteinizing hormone [LH; 0.807, standard error (SE) 0.069], followed by INHB (0.800, SE 0.067), ovarian volume (OV; 0.782, SE 0.070) and uterine volume (0.723, SE 0.076). In ROCs relative to a combination of such parameters, the AUC was greater for LH + INHB (0.972, SE 0.010), followed by OV + LH (0.841, SE 0.084) and OV + INHB (0.836, SE 0.075). The combination of INHB and LH (with cut-offs of 20 pg/ml and 0.2 IU/l, respectively) results in 98% sensitivity and specificity. Conclusion: Our results suggest that the addition of basal INHB values to baseline LH levels provides a reliable method to identify PF. Further replication studies are needed to definitively prove or disprove the utility and advantages of INHB levels as part of the work-up of CPP.

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          Most cited references15

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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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            Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche.

            To determine if uterine and ovarian measurements can significantly distinguish between precocious puberty (PP) and premature thelarche (PT) and whether ultrasound has any advantage over the gonadotropin-releasing hormone (GnRH) stimulation test. Prospective. One hundred and three girls referred consecutively for evaluation of breast budding before age 8 years underwent physical examination, GnRH stimulation test, bone age assessment, and transabdominal pelvic ultrasound. The diagnosis of PP or PT was based on clinical judgment. The clinical, laboratory, and ultrasound data of the PP and PT groups were compared. Eighty-one girls were diagnosed with PP and 22 with PT. Significant differences in most of the uterine and ovarian measurements were found between the groups. On logistic regression analysis, bone age standard deviation score, uterine transverse diameter, and uterine volume were the most significant variables predicting PP. Comparison of 30 girls with PP and 21 with PT in whom peak luteinizing hormone was <5 mIU/ml on the GnRH stimulation test, using analysis of variance, yielded significant differences in uterine width (P<0.001), fundus diameter (P <0.04), uterine volume (P= 0.006), and ovarian circumference (P <0.02). Increased uterine and ovarian measurements may be an early and sensitive sign of PP. Pelvic ultrasound, a noninvasive, inexpensive, and reliable tool, may give the clinician a complementary indication to the GnRH test in distinguishing isolated PT from early-stage PP in girls with early breast budding.
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              Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls.

              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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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2013
                October 2013
                17 September 2013
                : 80
                : 3
                : 207-212
                Affiliations
                aServizio di Endocrinologia Pediatrica, bUnità Operativa di Fisiopatologia della Riproduzione, cUnità Operativa di Genetica Medica, Azienda Ospedaliera ‘Gaetano Rummo', Benevento, and dDepartment of Clinical Medicine and Surgery, Federico II University, Naples, Italy; eService d'Endocrinologie et Diabétologie Pédiatrique, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
                Author notes
                *Dr. Gianpaolo De Filippo, Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Sergio Pansini, 5, IT-80131 Naples (Italy), E-Mail gianpaolo.defilippo@bct.aphp.fr
                Article
                354682 Horm Res Paediatr 2013;80:207-212
                10.1159/000354682
                24051691
                b5a0f449-c3ae-4f30-a582-71fc220f98c8
                © 2013 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 10 March 2013
                : 25 July 2013
                Page count
                Figures: 2, Tables: 1, Pages: 6
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Central precocious puberty,Inhibin B,Girls

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