AMH levels at central precocious puberty and premature thelarche: is it a parameter?

AbstractThe possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated.By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset.Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study.The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups.The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022).These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

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Thelarche variant: A new syndrome of precocious sexual maturation?

Acta Endocrinologica ◽

10.1530/acta.0.1230481 ◽

1990 ◽

Vol 123 (5) ◽

pp. 481-486 ◽

Cited By ~ 51

Author(s):

Richard Stanhope ◽

Charles C. D. Brook

Keyword(s):

Precocious Puberty ◽

Sexual Maturation ◽

Central Precocious Puberty ◽

Clinical Findings ◽

Breast Development ◽

Gnrh Analogue ◽

Gonadotropin Secretion ◽

Premature Thelarche ◽

Isolated Premature Thelarche ◽

Depot Injections

Abstract. We describe 10 girls (mean age 3.7 years, range 1.9-6.9) with precocious sexual maturation and clinical findings intermediate between those of premature thelarche and central precocious puberty. Studies of spontaneous gonadotropin secretion and ovarian ultrasound morphology also revealed findings intermediate between those of isolated premature thelarche and central precocious puberty. There was no response in 6 of the girls treated with GnRH analogue, whether administered intranasally, sc, or by monthly depot injections. We have called this condition thelarche variant because the gonadotropin independence and cyclical nature of breast development may well be due to a lesion of folliculogenesis.

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An Analysis of Predictive Factors for the Conversion from Premature Thelarche into Complete Central Precocious Puberty

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2008-210607 ◽

2008 ◽

Vol 21 (6) ◽

pp. 533-538

Author(s):

Shun-Ye Zhu ◽

Min-Lian Du ◽

Ting-Ting Huang

Keyword(s):

Precocious Puberty ◽

Predictive Factors ◽

Clinical Laboratory ◽

Central Precocious Puberty ◽

Breast Development ◽

Breast Size ◽

Complete Regression ◽

Premature Thelarche ◽

Estrogen Exposure ◽

Longitudinal Diameter

Abstract Aim: To determine the predictive factors for the conversion of premature thelarche (PT) into complete central precocious puberty (CCPP) in girls. Design: Prospective. Methods: One hundred and fifty-one girls with PT referred consecutively for evaluation of clinical, laboratory, and ultrasound data. Results: Twenty-one and a half percent of girls with PT converted into CCPP at a chronological age of 7.1 ± 0.7 years and bone age of 9.0 ± 1.1 years. Using logistic regression analysis, longitudinal diameter of uterus (OR = 1.215), Tanner breast stage at the time of first physical examination (OR = 3.334) 'and regression of breast development (OR= 3.921) were the most significant variables predicting the conversion from PT into CCPP. Compared with the nonconverted group, the converted groups had larger breast size at the time of diagnosis (z = 2.077, p = 0.038). A total of 69.5% (105/151) of patients experienced complete regression of breast development, 13.2% (14/105) of whom converted into CCPP; 21.5% (31/151) of patients had recurrent breast development, 32.3% (10/31) of whom converted into CCPP; 10% (15/151) of patients had constant breast development, 56.7% (7/15) of whom converted into CCPP, with the highest rate among the three breast development categories (x2 = 12.23, p = 0.002). Conclusion: PT is not often a self-limited condition and may sometimes convert into CCPP. The predictive factors for conversion were related to estrogen exposure including longitudinal diameter of the uterus, Tanner breast stage at the first consultation and the regressive categories of breast development.

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Serum Irisin Levels in Central Precocious Puberty and Its Variants

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa720 ◽

2020 ◽

Vol 106 (1) ◽

pp. e247-e254

Author(s):

Esra Kutlu ◽

İlker Tolga Özgen ◽

Huri Bulut ◽

Abdurrahim Koçyiğit ◽

Hafize Otçu ◽

...

Keyword(s):

Regression Analysis ◽

Linear Regression ◽

Precocious Puberty ◽

Linear Regression Analysis ◽

Central Precocious Puberty ◽

Multivariate Linear Regression ◽

The Other ◽

Multivariate Linear Regression Analysis ◽

Premature Thelarche ◽

The Mean

Abstract Aim The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context. Methods A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels. Results Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ± 62.35 ng/mL; PP variants group: 529.60 ± 39.66 ng/mL; and control group: 325.03 ± 27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS. Conclusions The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.

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The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0343 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Nursel Muratoglu Sahin ◽

H. Nursun Ozcan ◽

Aslihan Arasli Yilmaz ◽

Senay Savas Erdeve ◽

Semra Cetinkaya ◽

...

Keyword(s):

Precocious Puberty ◽

Pubertal Development ◽

Follicle Stimulating Hormone ◽

Central Precocious Puberty ◽

Complex Interaction ◽

Breast Development ◽

Premature Thelarche ◽

Blood Samples ◽

Isolated Premature Thelarche ◽

First Time

Abstract Objectives There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic–pituitary–gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. Methods Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. Results After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group’s basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). Conclusions In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

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

Hormone Research in Paediatrics ◽

10.1159/000521593 ◽

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.

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SUN-725 Clinical and Genetic Features of Families with Maternally Inherited Central Precocious Puberty

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1315 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Flávia Rezende Tinano ◽

Ana Pinheiro Machado Canton ◽

Luciana Ribeiro Montenegro ◽

Andrea de Castro Leal ◽

Carolina Ramos ◽

...

Keyword(s):

Precocious Puberty ◽

Association Studies ◽

Brain Mri ◽

Family Members ◽

Central Precocious Puberty ◽

Breast Development ◽

Female Group ◽

Genome Wide Association Studies ◽

Abnormal Gait ◽

Genetic Features

Abstract Context: The clinical recognition of familial central precocious puberty (CPP) has significantly increased in the last years. This fact can be related to the recent descriptions of genetic causes associated with this pediatric condition, such as loss-of-function mutations of two imprinted genes (MKRN3 and DLK1). Inherited defects in both genes cause paternally inherited CPP. However, no genetic abnormality has been described in families with maternally inherited CPP so far. Objectives: To characterize the clinical and genetic features of several families with maternally inherited CPP. Setting and Participants: We analyzed clinical and genetic features of children with familial CPP. No brain MRI alterations were detected in the selected patients with CPP. MKRN3 and DLK1 pathogenic mutations were excluded. Whole-exome sequencing was performed in selected cases. Results: We studied 177 children from 141 families with familial CPP. Paternal inheritance was evidenced in 44 families (31%), whereas 58 (41%) had maternally inheritance. Indeterminate inheritance was detected in the remaining families. Maternally inherited CPP affected mainly female patients (69 girls and two boys). Thelarche occurred at mean age of 6.1 ± 1.9 years in this female group. Most of girls had Tanner 3 (41%) and Tanner 4 (35%) breast development at first evaluation. One boy had additional syndromic features (macrosomia, autism, bilateral eyelid ptosis, high arcade palate, irregular teeth and abnormal gait). The pedigree analysis of patients with maternally inherited CPP revealed the following affected family members: 42 mothers, 10 grandmothers, 11 sisters, 12 aunts, and 11 female cousins. Most of the families (41) had two affected consecutive generations, while eight families had three affected generations. No consanguinity was referred. Ongoing molecular analysis revealed two rare heterozygous variants in the boy with syndromic CPP and three affected family members with precocious menarche (mother, maternally half-sister, and maternally aunt): a frameshift deletion (p.F144fs) in MKKS; and a missense variant (p.P267L) in UGT2B4, which encodes a protein involved in estrogen hydroxylation and it was related to menarche timing in genome-wide association studies. Conclusions: Maternally inherited CPP was diagnosed mainly in girls, who had thelarche at mean age of 6 years old. Dominant pattern of inheritance was more prevalent, with direct maternal transmission in 72% of the studied families. New candidate genes might be implicated with maternally inherited CPP.

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

Hormone Research in Paediatrics ◽

10.1159/000493134 ◽

2018 ◽

Vol 90 (3) ◽

pp. 190-195 ◽

Cited By ~ 1

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.

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Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0142 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Carolina O. Ramos ◽

Ana P M Canton ◽

Carlos Eduardo Seraphim ◽

Aline Guimarães Faria ◽

Flavia Rezende Tinano ◽

...

Keyword(s):

Precocious Puberty ◽

Adult Height ◽

Central Precocious Puberty ◽

Bone Age ◽

Overweight And Obesity ◽

Leuprorelin Acetate ◽

The Mean ◽

Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

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