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Journal of Pediatric Endocrinology &... Jul 2022The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study...
Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls.
OBJECTIVES
The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP.
METHODS
Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value.
RESULTS
The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978.
CONCLUSIONS
IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.
Topics: Cross-Sectional Studies; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Luteinizing Hormone; Puberty, Precocious
PubMed: 35635485
DOI: 10.1515/jpem-2022-0161 -
Archives of Disease in Childhood Dec 1980Hypothalamic-pituitary-gonadotropic activity was investigated in 9 girls with premature thelarche, and compared with that in 9 healthy girls and 6 girls with true...
Hypothalamic-pituitary-gonadotropic activity was investigated in 9 girls with premature thelarche, and compared with that in 9 healthy girls and 6 girls with true precocious puberty. The gonadotropin stimulation test with luteinising hormone-releasing hormone was used. Girls with premature thelarche showed luteinising hormone response resembling that of normal girls, and follicle-stimulating hormone (FSH) response quite similar to that of girls with precocious puberty. This suggests that in premature thelarche there is a partial activation of the diencephalic-hypophyseal-gonadal axis, which affects FSH only. Premature thelarche therefore, should be considered as one of the disorders due to altered sensitivity of the hypothalamic receptors which regulate sex maturation.
Topics: Breast; Child; Child, Preschool; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Hypothalamo-Hypophyseal System; Infant; Luteinizing Hormone; Puberty, Precocious
PubMed: 6779715
DOI: 10.1136/adc.55.12.941 -
Frontiers in Endocrinology 2023This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central...
OBJECTIVE
This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP).
METHODS
A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months and were divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP.
RESULTS
Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differences were statistically significant (P < 0.05). When the LH basal value was ≥0.58 IU/L and SHBG was ≤58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%.
CONCLUSION
Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty.
Topics: Child; Female; Humans; Early Diagnosis; Follicle Stimulating Hormone; Luteinizing Hormone; Puberty, Precocious; Sex Hormone-Binding Globulin
PubMed: 38317710
DOI: 10.3389/fendo.2023.1273170 -
Journal of Clinical Research in... Nov 2020Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is...
OBJECTIVE
Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age.
METHODS
A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study.
RESULTS
On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants.
CONCLUSION
Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.
Topics: Breast; Child, Preschool; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Infant; Luteinizing Hormone; Male; Prognosis; Puberty, Precocious
PubMed: 32349465
DOI: 10.4274/jcrpe.galenos.2020.2019.0202 -
Scientific Reports Apr 2023Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated...
Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6-8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (ΣDEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and ΣDEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of ΣDEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and ΣDEHP in urine were independent risk factors for IPT progression, and ΣDEHP may be associated with the progression of IPT to CPP or EP.
Topics: Female; Humans; Puberty, Precocious; Diethylhexyl Phthalate; Cohort Studies; Puberty
PubMed: 37019965
DOI: 10.1038/s41598-023-32768-1 -
Journal of Pediatric Endocrinology &... Mar 2015Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test.
BACKGROUND
Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test.
OBJECTIVE
To determine the best predictive model for detecting puberty in girls.
SUBJECTS
Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15).
METHODS
Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed.
RESULTS
The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%.
CONCLUSIONS
The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.
Topics: Child; Child, Preschool; Diagnostic Techniques, Endocrine; Female; Gonadotropins; Humans; Puberty; Puberty, Precocious; Reference Values; Retrospective Studies; Stimulation, Chemical
PubMed: 25514323
DOI: 10.1515/jpem-2014-0135 -
Turkish Journal of Haematology :... Sep 2013Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of...
OBJECTIVE
Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit.
MATERIALS AND METHODS
Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions.
RESULTS
Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction.
CONCLUSION
We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases.
CONFLICT OF INTEREST
None declared.
PubMed: 24385809
DOI: 10.4274/Tjh.2012.0094 -
Clinical Epigenetics May 2024Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal...
BACKGROUND
Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty.
METHODS
An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR.
RESULTS
The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission.
CONCLUSION
We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.
Topics: Humans; Calcium-Binding Proteins; DNA Methylation; Chromosomes, Human, Pair 14; Intercellular Signaling Peptides and Proteins; Genomic Imprinting; Membrane Proteins; Child; Male; Comparative Genomic Hybridization; Female; Chromosome Deletion; Child, Preschool; Phenotype; Abnormalities, Multiple; Imprinting Disorders; Muscle Hypotonia; Facies
PubMed: 38715103
DOI: 10.1186/s13148-024-01652-8 -
Frontiers in Endocrinology 2021Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple... (Review)
Review
Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies.
Topics: Abnormalities, Multiple; Child; Craniofacial Abnormalities; Female; Humans; Magnetic Resonance Imaging; Pituitary Diseases; Pituitary Gland; Puberty, Precocious; Syndrome; Tomography, X-Ray Computed; Triptorelin Pamoate
PubMed: 34122353
DOI: 10.3389/fendo.2021.685888 -
Hormone Research in Paediatrics 2020Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. Premature activation of GnRH secretion leads to idiopathic/central gonadotropin-dependent precocious puberty (CPP). We aimed to compare the blood KP concentrations in girls with CPP and healthy controls.
METHODS
A systematic review and meta-analysis was performed. We searched MEDLINE, EMBASE, The Cochrane Library, and SciELO. Random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed through I2. Meta-regression considered patient age, KP fraction, and analytical method for KP measurement.
RESULTS
The 11 studies included comprised 316 CPP patients and 251 controls. Higher KP levels in the CPP group were found (SMD 1.53; CI 95% = 0.56-2.51). Subgroup analysis revealed association with patient age (p = 0.048), indicating a positive correlation between elevation in KP concentration and age in CPP group. A group of patients with precocious thelarche (PT) from 5 of the included studies comprising 121 patients showed higher levels of KP (1.10; -0.25-2.45: CI 95%) and high heterogeneity (I2 = 91%). The CPP/PT ratio for KP level indicates KP 36% higher on CPP than PT patients.
CONCLUSIONS
A consistent difference in KP levels between girls with CPP and controls was identified. While there are important limitations in KP assays which argue against its use as a diagnostic tool, the KP levels in CPP versus control and PT children are consistent with the predicted mechanisms and pathophysiology of CPP.
Topics: Case-Control Studies; Child; Female; Humans; Kisspeptins; Puberty, Precocious
PubMed: 33887744
DOI: 10.1159/000515660