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      Pelvic Ultrasound in Diagnosing and Evaluating the Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls With Idiopathic Central Precocious Puberty

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          Abstract

          Background and Objective: Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therapeutic agent. At present, GnRH stimulation test is adopted as a gold standard for the diagnosis of ICPP and the efficacy evaluation of GnRHa therapy. However, it is difficult to operate in practice due to the cumbersome procedures and multiple blood samples required. This study was conducted to establish the value of pelvic ultrasound in diagnosing ICPP and evaluating the efficacy of GnRHa therapy.

          Materials and Methods: One hundred and twenty-two girls with ICPP (ICPP group) were enrolled in the study. Pelvic ultrasound and levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were examined before and after GnRHa therapy for 3 months. Eighty normal prepubertal girls were enrolled as the control group. The difference in pelvic ultrasound parameters between the ICPP group before GnRHa therapy and the control group was compared by independent-sample t-test, while paired t-test for ICPP group before and after GnRHa therapy. Receiver operating characteristic (ROC) curve was used to explore the optimal pelvic ultrasound parameters for diagnosing ICPP. Pearson correlation analysis was performed between the pelvic ultrasound parameters and serum sexual hormone level.

          Results: The pelvic ultrasound parameters (length of the uterine body, anteroposterior diameter of the uterine body, transverse diameter of the uterine body, volume of the uterine body, uterine body-cervix ratio, length of the ovary, transverse diameter of the ovary, anteroposterior diameter of the ovary, volume of the ovary, number of increased follicles and maximum diameter of the follicle) in the ICPP group before GnRHa therapy were significantly larger than those of the control group ( P < 0.05). All the above pelvic ultrasound parameters in the ICPP group were significantly decreased after GnRHa therapy compared with those before treatment ( P < 0.05). The volume of the uterine body had the largest area under the ROC curve in differentiating between patients with ICCP and the control group. Pelvic ultrasound parameters were significantly correlated with serum sexual hormone levels ( P < 0.05).

          Conclusion: This study indicates pelvic ultrasound is a simple and reliable tool to diagnose ICPP and evaluates the efficacy of GnRHa therapy by dynamically observing the morphology of internal genitalia. The volume of uterine body was the best ultrasound parameter to distinguish patients with ICPP from normal girls.

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          Most cited references26

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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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            Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society.

            In 1997 a study from the Pediatric Research in Office Settings network, based on pubertal staging of >17,000 girls between 3 and 12 years of age, indicated that breast and pubic hair development are occurring significantly earlier than suggested by our current guidelines, especially in African-American girls. In response to this article, the Lawson Wilkins Pediatric Endocrine Society undertook a comprehensive review of this topic. The primary conclusions of this review are: 1. The current recommendation that breast development before age 8 is precocious is based on outdated studies. Until 1997, no data were available on pubertal staging in US girls that could have documented a trend to earlier maturation. 2. The 1997 study indicates that stage 2 of breast and pubic hair development is being achieved ~1 year earlier in white girls and 2 years earlier in African-American girls than previous studies have shown. 3. Concerns that girls with moderately precocious puberty will be significantly short adults are overstated; most have adult height within the normal range. 4. Therapy with gonadotropin-releasing hormone agonists has not been proven to have a substantial effect on adult height in most girls whose puberty starts between 6 and 8 years of age. 5. New guidelines propose that girls with either breast development or pubic hair should be evaluated if this occurs before age 7 in white girls and before age 6 in African-American girls. No changes in the current guidelines for evaluating boys (signs of puberty at younger than 9 years) can be made at this time.normal puberty, breast development, pubic hair.
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              Prevalence of polycystic ovary syndrome in young women who had idiopathic central precocious puberty.

              To assess the prevalence of polycystic ovary syndrome (PCOS) in a cohort of young women with previous idiopathic central precocious puberty (ICPP) at least 3 years after menarche, and to look for any predictive factors of PCOS at the time ICPP was diagnosed. Longitudinal study. Pediatrics unit, Verona, Italy. Forty-six young women (18.1 +/- 3.0 years) who had been treated with GnRH analogues during childhood, observed at gynecologic age of 6.23 +/- 3.3 years. Semistructured interview concerning cycles, physical exam, blood sampling, and transabdominal pelvic ultrasound. Oligomenorrhea, LH, FSH, E(2), T, DHEAS, free T, delta4-androstenedione, 17-OHP, P, polycystic ovary morphology (PCOM). Fifteen percent of the young women had oligomenorrhea, 28% clinical hyperandrogenism, 48% biochemical hyperandrogenism, and 37% PCOM. A total of 32% of the patients had PCOS according to the Rotterdam definition and 30% had PCOS according to the Androgen Exess Society. The prevalent phenotype of PCOS was characterized by clinical and/or biochemical hyperandrogenism and PCOM. We did not find any predictive factors for PCOS at the time ICPP was diagnosed. Patients with ICCP are prone to developing PCOS. The prominent phenotype in this cohort was PCOM associated with clinical and/or biochemical hyperandrogenism. Further follow-ups of these young adult patients will clarify whether this phenotype persists and if it will have important long-term implications regarding increased risk of infertility or metabolic complications. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                11 February 2019
                2019
                : 10
                : 104
                Affiliations
                [1] 1Department of Radiology, Zhujiang Hospital, Southern Medical University , Guangzhou, China
                [2] 2Department of Ultrasonography, Shenzhen Children’s Hospital , Shenzhen, China
                Author notes

                Edited by: Xiaobing Wang, Shaanxi Normal University, China

                Reviewed by: Fajin Dong, Shenzhen People’s Hospital, China; Chin Moi Chow, University of Sydney, Australia

                *Correspondence: Xian-yue Quan, quanxianyue2014@ 123456163.com

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.00104
                6378315
                30804790
                524db5cf-05c9-427d-a673-2390dfe03307
                Copyright © 2019 Yu, Liu, Chen, Wang and Quan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 November 2018
                : 25 January 2019
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 29, Pages: 8, Words: 0
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                ultrasonography,uterus,ovary,isosexual precocity,sexual characteristics

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