scholarly journals Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog

2007 ◽  
Vol 156 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Claudio Maffeis ◽  
Roberto Franceschi ◽  
Paolo Moghetti ◽  
Marta Camilot ◽  
Silvana Lauriola ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Serum Levels ◽  
Gnrh Analog ◽  
Therapy Discontinuation ◽  
17Β Estradiol ◽  
Therapy Withdrawal ◽  
Ghrelin Secretion

Decreased levels of ghrelin have been measured in growing children during puberty. No data are available for girls with central precocious puberty (CPP). Aims: To explore ghrelin changes before, during, and after GnRH analog treatment in girls with CPP. Subjects and methods: A sample of 20 Caucasian girls (8.08 ± 0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH, 17β estradiol (E2), and ghrelin were measured before starting treatment with GnRH analog, 18 months after therapy began and again 6 months after therapy discontinuation. Results: LH and E2 serum levels decreased significantly during treatment (2.45 ± 2.03 vs 0.67 ± 0.49 UI/l, P < 0.01 and 28.17 ± 9.7 vs 15 pmol/l, P < 0.01 respectively), returning to baseline levels after the discontinuation of therapy (4.75 ± 1.66 UI/l and 29.23 ± 6.99 pmol/l respectively). LH peaked following LHRH stimulation significantly (P < 0.01) decreased during treatment (24.45 ± 14.17 vs 1.3 ± 0.18 UI/l) and then increased after therapy discontinuation (12.58 ± 6.09, P < 0.01). Ghrelin decreased significantly (P < 0.05) during treatment (1849 ± 322 vs 1207 ± 637 pg/ml), and increased, though not significantly (P = 0.09) after therapy withdrawal (1567 ± 629 pg/ml). Conclusions: Contrary to what is expected in physiologic puberty, where ghrelin is progressively reduced, the prepubertal hormone milieau induced by GnRHa treatment in patients suffering from central precocious puberty (CPP) did not promote an increase in ghrelin circulating levels. Therefore, in CPP, ghrelin secretion seems to be independent from pubertal development per se. Concomitant estrogen suppression during treatment may play a potential role in the regulation of ghrelin secretion in these girls.

MKRN3 Levels in Girls with Central Precocious Puberty during GnRHa Treatment: A Longitudinal Study

2018 ◽  
Vol 90 (3) ◽  
pp. 190-195 ◽  
Author(s):  
Anna Grandone ◽  
Grazia Cirillo ◽  
Marcella Sasso ◽  
Gianluca Tornese ◽  
Caterina Luongo ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Ring Finger ◽  
Central Precocious Puberty ◽  
Serum Levels ◽  
Breast Development ◽  
Control Group ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
17Β Estradiol ◽  
Puberty Onset

Background: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment. Methods: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2–8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17β-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed. Results: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001). Conclusions: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.

scholarly journals CENTRAL PRECOCIOUS PUBERTY IN TWO BOYS WITH PRADER-WILLI SYNDROME ON GROWTH HORMONE TREATMENT

2019 ◽  
Vol 5 (6) ◽  
pp. e352-e356 ◽  
Author(s):  
Elena Monai ◽  
Anders Johansen ◽  
Erik Clasen-Linde ◽  
Ewa Rajpert-De Meyts ◽  
Niels Erik Skakkebæk ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Precocious Puberty ◽  
Growth Hormone Treatment ◽  
Pubertal Timing ◽  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Hormone Treatment ◽  
Prader Willi Syndrome ◽  
Gnrh Analog ◽  
Premature Adrenarche

Objective: Prader-Willi syndrome (PWS) is a rare genetic neuroendocrine disorder characterized by hypotonia, obesity, short stature, and mental retardation. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty is rarely seen. Methods: This study reports the clinical, biochemical, and histologic findings in 2 boys with PWS who developed central precocious puberty. Results: Both boys were started on growth hormone therapy during the first years of life according to the PWS indication. They had both bilateral cryptorchidism at birth and had orchidopexy in early childhood. Retrospective histologic analysis of testicular biopsies demonstrated largely normal tissue architecture and germ cell maturation, but severely decreased number of prespermatogonia in one of the patients. Both boys had premature adrenarche around the age of 6. Precocious puberty was diagnosed in both boys with enlargement of testicular volume (>3 mL), signs of virilization and a pubertal response to a gonadotropin-releasing hormone (GnRH) test and they were both treated with GnRH analog. Conclusion: The cases described here displayed typical characteristics for PWS, a considerable heterogeneity of the hypothalamic-pituitary function, as well as testicular histology. Central precocious puberty is extremely rare in PWS boys, but growth hormone treatment may play a role in the pubertal timing.

scholarly journals Central Precocious Puberty in Boys and Girls: Similarities and Differences

Sexes ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 119-131
Author(s):  
Cristina Mucaria ◽  
Nina Tyutyusheva ◽  
Giampiero I. Baroncelli ◽  
Diego Peroni ◽  
Silvano Bertelloni
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Gnrh Analog ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
The Central Nervous System

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes.

scholarly journals Coexistence of central precocious puberty and intraventricular arachnoid cyst: a brief literature update

2020 ◽  
Vol 3 (1) ◽  
pp. 65-70
Author(s):  
Gonzalo Oliván-Gonzalvo ◽  
◽  
Vicente Calatayud-Maldonado ◽  
Keyword(s):  
Arachnoid Cyst ◽  
Precocious Puberty ◽  
Pubertal Development ◽  
Brain Mri ◽  
Central Precocious Puberty ◽  
Mass Effect ◽  
Ventricular Volume ◽  
Gnrh Analog ◽  
Hypothalamic Pituitary Axis ◽  
Velum Interpositum

Central precocious puberty (CPP) is a rare disease. The mean annual incidence in girls is 0.8-1.1/100,000 and in boys 0-0.1/100,000. Intracranial arachnoid cysts (ICACs) are usually congenital and represent 1% of intracranial masses in newborns. Intraventricular location is rare. The objective of this work is to carry out a literature updated review of the coexistence of CPP and intraventricular arachnoid cyst (IVAC). ICACs are usually asymptomatic but can present with CPP in 10-40% of patients. IVACs represents only 0.3-1.4% of ICACs, and most seemed originate from the velum interpositum cistern. CPP in girls is usually idiopathic, while in 30-70% of boys are due to an intracranial lesion. Therefore, the coexistence of PPC and IVAC is very rare in boys and exceptional in girls. The exact mechanism of a cyst´s influence on the hypothalamic-pituitary axis is not completely understood. Theories include increased ventricular volume, associated mass effect on the hypothalamus, and direct compression of portions of the hypothalamic-pituitary axis. Analysis of LH peaks after GnRH testing is the gold standard for the diagnosis of CPP. Brain MRI should be part of the assessment in boys and also in girls since clinical features, including age and sex, are not helpful in predicting those with underlying brain pathology. In cases of CPP with IVAC, surgery does not have any effect on the course of pubertal development. The indication for surgery is the onset of neurological symptoms. The medical treatment selected, safe and effective, is GnRH analog depot preparations. In conclusion, there seems to be a consensus for the diagnosis and management of the coexistence of CPP and IVAC, but the etiopathogenesis is not yet well recognized.

scholarly journals Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty

2006 ◽  
Vol 154 (1) ◽  
pp. 119-124 ◽  
Author(s):  
Jean-Claude Carel ◽  
Joëlle Blumberg ◽  
Christine Seymour ◽  
Catherine Adamsbaum ◽  
Najiba Lahlou ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Sex Steroids ◽  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Injection Pain ◽  
Open Label ◽  
Clinical Onset ◽  
Serum Lh ◽  
Fold Reduction

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH ≥7 IU/l, advanced bone age >1 year, enlarged uterus (≥36 mm) and testosterone level ≥0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. Results: GnRH-stimulated peak LH ≤3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary–gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Central precocious puberty in a boy with 22q13 deletion syndrome and NOTCH-1 gene duplication

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Aris Giannakopoulos ◽  
Helen Fryssira ◽  
Maria Tzetis ◽  
Athina Xaidara ◽  
Christina Kanaka-Gantenbein
Keyword(s):  
Precocious Puberty ◽  
Chromosomal Region ◽  
Neurodevelopmental Disorder ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Deletion Syndrome ◽  
Comparative Genomic ◽  
Gnrh Analog ◽  
22Q13 Deletion Syndrome ◽  
Accelerated Growth

AbstractThe 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the

Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound

2020 ◽  
Vol 33 (6) ◽  
pp. 785-791
Author(s):  
Valeria Calcaterra ◽  
Catherine Klersy ◽  
Federica Vinci ◽  
Corrado Regalbuto ◽  
Giulia Dobbiani ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Tanner Stage ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Diagnostic Value ◽  
Sex Hormone ◽  
Pelvic Ultrasound ◽  
Predictive Values ◽  
Hormone Levels ◽  
Ultrasound Parameters

AbstractObjectivesData on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing.Patients and methodsWe retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP.ResultsBasal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48–67) and 85% (95%CI 74–92), respectively, with a PPV = 86% (95%CI 76–93) and PPN = 54% (95%CI 43–54); the area under the ROC curve was 0.71 (95%CI 0.65–0.78).ConclusionDespite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence (ECLIA) in girls with precocious puberty and premature thelarche

2021 ◽  
Author(s):  
Kamila Botelho Fernandes de Souza ◽  
Melyna Shayanne Pessôa Veiga ◽  
Gabriela Ráina Ferreira Martins ◽  
Adriana Paula da Silva ◽  
Lívia Grimaldi Abud Fujita ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Gonadotropin Releasing Hormone ◽  
Assay Method ◽  
Premature Thelarche ◽  
Releasing Hormone ◽  
Cutoff Values ◽  
Hormone Analog ◽  
Hormone Analogs

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic–pituitary–gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with the intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration, and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

scholarly journals Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty

2006 ◽  
Vol 134 (7-8) ◽  
pp. 305-309 ◽  
Author(s):  
Katarina Mitrovic ◽  
Dragan Zdravkovic ◽  
Tatjana Milenkovic ◽  
Katarina Sedlecki ◽  
Zoran Stankovic
Keyword(s):  
Luteinizing Hormone ◽  
Granulosa Cell ◽  
Precocious Puberty ◽  
Granulosa Cell Tumor ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Cell Tumor ◽  
Ovarian Cysts ◽  
Pelvic Ultrasound ◽  
Releasing Hormone

Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 ?g/m2 LHRH- Relefact LHRH?, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.

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