SUN-097 Gonadotropins Levels Measurement in First Morning Voided Urine as a Diagnostic Tool for Central Precocious Puberty

Abstract Background: GnRH stimulation test is the gold standard for the diagnosis of central precocious puberty (CPP). However, it is invasive and costly. Previous studies showed that increased urinary gonadotropins (Gn) level in first morning voided (FMV) urine reflected the integration of elevated nocturnal Gn secretions. Therefore, it could be used to diagnose CPP. Nevertheless, its cutoff value for diagnosis of CPP is limited. Objective: To determine the association of Gn levels in FMV urine and serum during pubertal development and establish cutoff value of FMV urinary Gn as an alternative noninvasive method for diagnosis of CPP in girls. Methods: Sixty-one girls who had breast development before 8 years of age with sign of rapid pubertal progression (advanced bone age and/or increased height velocity) underwent subcutaneous GnRH agonist test. FMV urinary Gn were also collected on the same day. Both serum and urinary Gn levels were measured using electrochemiluminescence immunoassay (ECLIA) technique. The definite diagnosis of CPP is based on stimulated serum LH > 5 IU/L. FMV urinary Gn were compared between CPP and premature thelarche (PT) groups. The correlation between serum and urinary Gn were assessed and the cutoff value of urinary Gn to diagnose CPP was established. FMV urinary Gn of 480 Thai school girls (control) were also collected to determine the reference values according to their breast Tanner (BT) stages. Results: FMV ULH level in girls with CPP was significantly higher than that of PT (2.46 VS 0.8 IU/L; median, P <0.001). However, the level of ULH in PT group was not different from control group with BT1. FMV ULH and ULH: UFSH were well correlated with basal serum LH (r=0.63 and 0.73, respectively, Ps<0.001) and peak serum LH (r=0.44 and 0.54, respectively, Ps<0.001). Base on receiver operating characteristics analysis, basal serum LH was the best parameter to differentiate CPP from PT (area under the curve 0.797–0.926). ULH levels at ≥ 1.13 IU/L and ≥ 1.52 provide optimal sensitivity (72.3 and 68.1 %, respectively) and specificity (85.7 and 100 %, respectively). Combined ULH level ≥ 1.13 IU/L with ULH: UFSH ≥ 0.17 increased specificity from 85.7 to 92.9 % for predicting a positive GnRH agonist test. (peak LH ≥ 5 IU/L) Conclusions: First morning voided urinary Gn levels measurement is a highly potential method for the diagnosis of CPP in girls due to its good correlation with GnRH agonist test. Further study in a larger number of patients with close monitoring of clinical outcome is required before recommending as a standard investigation in CPP.

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The utility of basal serum LH in prediction of central precocious puberty in girls

Acta Endocrinologica ◽

10.1530/eje-11-0720 ◽

2012 ◽

Vol 166 (2) ◽

pp. 295-299 ◽

Cited By ~ 36

Author(s):

Yehonatan Pasternak ◽

Michael Friger ◽

Neta Loewenthal ◽

Alon Haim ◽

Eli Hershkovitz

Keyword(s):

Precocious Puberty ◽

Predictive Value ◽

Central Precocious Puberty ◽

Stimulation Test ◽

Breast Development ◽

Basal Serum ◽

Serum Lh ◽

Before And After ◽

Design And Methods ◽

Prepubertal Girls

ObjectiveThe mainstay of distinction between prepubertal girls and girls who are suspected of having central precocious puberty (CPP) is based on gonadotropin measurements after a GnRH stimulation test to evaluate hypothalamic–pituitary–gonadal axis maturity. The objective of this study was to determine whether a single basal gonadotropin measurement carries a useful predictive value in verifying or refuting the diagnosis of CPP.Design and methodsBasal serum LH and FSH were measured by a chemiluminescent immunometric assay in a cohort of girls who had been evaluated for CPP before and after GnRH stimulation test. Peak LH levels higher than 5 IU/l were considered a pubertal response.ResultsEighty girls with suspected breast development before 8 years of age were enrolled to the study, out of whom 42 had CPP.Low basal serum LH (≤0.1 IU/l) was sufficient to rule out the diagnosis of CPP in 94.7% of the 38 prepubertal girls; the sensitivity of basal LH levels for this purpose was only 64%. The basal FSH and the basal LH to FSH ratio achieved less efficient predictive value with 76 and 71% sensitivity and 73 and 86% specificity respectively.ConclusionA single basal LH measurement may be adequate to confirm but not to refute the presence of CPP in most of the girls who are evaluated for early pubertal signs.

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The role of kisspeptin and MKRN3 in the diagnosis of central precocious puberty in girls

Endocrine Connections ◽

10.1530/ec-21-0182 ◽

2021 ◽

Author(s):

Mei Li ◽

Yanfei Chen ◽

Binrong Liao ◽

Jing Tang ◽

Jingzi Zhong ◽

...

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Serum Levels ◽

Premature Thelarche ◽

Physical Measurements ◽

Serum Lh ◽

Sexual Characteristics ◽

Biochemical Measurements ◽

Gonadotrophin Releasing Hormone

Objective: To evaluate the characteristics and significance of serum kisspeptin and MKRN3 levels for the diagnostic of central precocious puberty (CPP) in girls. Method: 34 individuals with CPP, 17 individuals with premature thelarche (PT) and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included of body mass index and tests for breast, bone and sexual characteristics were carried out. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3 and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90 and 120min after injection with triptorelin. Results: Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P=0.020), while serum MKRN3 levels lower in the two groups (P=0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P<0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40nmol/L, with 82.4% sensitivity and 57.1% specificity; while the cut-off value of serum MKRN3 was 0.33pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5. Conclusions: Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.

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LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-125067 ◽

2018 ◽

Vol 127 (04) ◽

pp. 234-239

Author(s):

Hwal Jeong ◽

Hae Lee ◽

Jin Hwang

Keyword(s):

Precocious Puberty ◽

Gnrh Agonist ◽

Clinical Symptoms ◽

In Silico Analysis ◽

Central Precocious Puberty ◽

Stimulation Test ◽

Gene Analysis ◽

Adult Women ◽

Missense Mutations ◽

Serum Lh

Abstract Background Luteinizing hormone (LH) is a useful parameter in diagnosing precocious puberty. The pubertal response of serum LH to a GnRH stimulation test is varied, and clinical symptoms of precocious puberty are sometimes disproportionate with serum LH concentrations. Many patients present in a state of precocious puberty that advances rapidly, but the post-GnRH peak LH remains prepubertal. LH receptor mutations are suspected of involvement in the non-classic type of central precocious puberty (CPP). Objective To examine the association between LHCGR polymorphism and non-classic CPP in subjects exhibiting a peak LH<5 IU/L on a GnRH stimulation test. Methods: In total, 102 girls with non-classic CPP and 100 normal adult women were enrolled. All subjects underwent LHCGR gene analysis by the Sanger method, and patients and controls were compared. Auxological data and gonadotropin concentrations were analyzed in the 102 patients. Of these patients, 75 completed GnRH agonist treatment, and the treatment outcomes were analyzed. Results A total of seven variants were identified, including two missense mutations (g.48698754 G/A and g.48688613 G/A) that were found in the patient group (no patients contained both mutations). In silico analysis of these missense mutations suggested the possibility of damaging the LHCGR. However, no significant association was found between the identified LHCGR variants and non-classic CPP. GnRH agonist treatment decreased bone age advancement and increased predicted adult height. Conclusions LHCGR gene polymorphisms do not appear to be a major causative factor for the relatively low concentration of LH in patients with non-classic CPP. GnRH agonist treatment improved clinical parameters in these patients.

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Basal Serum Neurokinin B Levels in Differentiating Idiopathic Central Precocious Puberty from Premature Thelarche

Journal of Clinical Research in Pediatric Endocrinology ◽

10.4274/jcrpe.3817 ◽

2017 ◽

Vol 9 (2) ◽

pp. 101-105

Author(s):

Mesut Parlak ◽

Doğa Türkkahraman ◽

Hamit Yaşar Ellidağ ◽

Gamze Çelmeli ◽

Ayşe Eda Parlak ◽

...

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Neurokinin B ◽

Premature Thelarche ◽

Idiopathic Central Precocious Puberty ◽

Basal Serum

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Effectiveness of basal LH in monitoring central precocious puberty treatment in girls

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0386 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Valeria Calcaterra ◽

Gianpaolo De Filippo ◽

Riccardo Albertini ◽

Domenico Rendina ◽

Beatrice Messini ◽

...

Keyword(s):

Precocious Puberty ◽

Pubertal Development ◽

Central Precocious Puberty ◽

Reliable Indicator ◽

Gnrh Agonists ◽

Basal Serum ◽

Serum Lh ◽

Before And After ◽

Hypothalamic Pituitary Axis ◽

Efficacy Of Treatment

AbstractObjectivesTreatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis.Patients and methodsSerum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy.ResultsAt diagnosis, peaks of >5 IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1 IU/L in 70% and basal FSH levels of <1 IU/L in 10%. E2 were <20 pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3 IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1 IU/L was detected in 85% (p<0.01) and basal FSH ≤1 IU/L in 40% (p<0.01). Serum E2 ≤20 pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1 IU/L (p<0.01) and 38.3% FSH basal values <1 UI/mL (p<0.01). E2 ≤20 pg/mL was observed in 32.72% (p=NS).ConclusionsBasal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

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Near Final Height after GnRH Agonist Treatment in Central Precocious Puberty

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2000.13.s1.787 ◽

2000 ◽

Vol 13 (Supplement) ◽

Cited By ~ 2

Author(s):

M. Micillo ◽

M. Salerno ◽

A. Officioso ◽

E. Perna ◽

N. Gasparini ◽

...

Keyword(s):

Precocious Puberty ◽

Gnrh Agonist ◽

Final Height ◽

Central Precocious Puberty

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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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Clinical data and basal gonadotropins in the diagnostic of central precocious puberty in girls

Endocrine Connections ◽

10.1530/ec-20-0651 ◽

2021 ◽

Author(s):

Teodoro Durá-Travé ◽

Fidel Gallinas-Victoriano ◽

María Malumbres-Chacon ◽

Lotfi Ahmed-Mohamed ◽

María Jesús Chueca Guindulain ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Age At Onset ◽

Area Under The Curve ◽

High Specificity ◽

Central Precocious Puberty ◽

Bone Age ◽

Height Velocity ◽

Pubertal Status ◽

Serum Lh ◽

Before And After

Objective. The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status. Methods. Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- to 8- years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves. Results. There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (p<0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89% and 82% respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls. Conclusions. Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, eliminating the need for GnRH stimulation testing.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0521 ◽

2015 ◽

Vol 28 (11-12) ◽

Cited By ~ 5

Author(s):

Nursel Muratoglu Sahin ◽

Sibel Tulgar Kinik ◽

Mustafa Agah Tekindal ◽

Nilufer Bayraktar

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Breast Development ◽

Premature Thelarche ◽

Pubertal Onset ◽

Antimullerian Hormone ◽

The Mean ◽

Antimüllerian Hormone

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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