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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 -
Gynecological Endocrinology : the... Sep 2020Hyperandrogenism is frequent and under investigated in adolescent girls. A 15-year-6-month-old French girl presented with oligomenorrhea and slowly progressing... (Review)
Review
Hyperandrogenism is frequent and under investigated in adolescent girls. A 15-year-6-month-old French girl presented with oligomenorrhea and slowly progressing virilization 2 years post-menarche. Medical history revealed prenatal pesticide exposure through maternal professional activity and recurrent premature thelarche. Severe hirsutism, mild facial acne and clitoromegaly were noted. Serum androgens (testosterone: 94 ng/dL, 4-androstenedione: 8.23 ng/mL) were high and non-classic 21-hydroxylase deficiency was excluded. Pelvic ultrasonography showed a left ovarian mass, confirmed by computed tomography scan. Tumor markers were negative. Laparoscopic surgery was performed. The pathological diagnosis was benign luteinized thecoma. Postoperatively, the menstrual cycle and serum androgens became normal and hirsutism slowly improved. Hyperandrogenism 2 years after menarche should be systematically investigated, even if slowly progressive, since it may be a symptom of a rare virilizing ovarian tumor, like thecoma.
Topics: Adolescent; Diagnosis, Differential; Disease Progression; Female; France; Humans; Hyperandrogenism; Ovarian Neoplasms; Testosterone; Thecoma; Ultrasonography; Virilism
PubMed: 32174224
DOI: 10.1080/09513590.2020.1739265 -
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 -
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 -
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 -
Journal of Clinical Research in... Aug 2023
Topics: Male; Child; Female; Humans; Animals; Rats; Gynecomastia; Puberty, Precocious; Propolis; Breast; Gonadotropin-Releasing Hormone
PubMed: 37338296
DOI: 10.4274/jcrpe.galenos.2023.2023-5-9 -
World Neurosurgery Sep 2019Herpes simplex encephalitis caused by herpes simplex has an estimated annual prevalence in the order of 1 in 250,000 to 500,000 patients and is considered to be the most... (Review)
Review
BACKGROUND
Herpes simplex encephalitis caused by herpes simplex has an estimated annual prevalence in the order of 1 in 250,000 to 500,000 patients and is considered to be the most usually encountered nonendemic pathogenic cause of lethal encephalitis in well-developed countries. There are a few cases reported in the literature in which a diagnostic dilemma between was raised between herpes simplex encephalitis and brain glioma and a definitive diagnosis was difficult to obtain.
CASE DESCRIPTION
We report the case of a 5-year-old girl with a previous medical history of premature thelarche. As a part of her investigation, magnetic resonance imaging of the brain was performed, which revealed a space-occupying lesion of the posterior fossa. Magnetic resonance spectroscopy was performed, which advocated for the diagnosis of glioma. She was operated on, but the histopathologic analysis failed to verify the imaging findings. Herpes simplex virus (HSV) 1 was detected in cerebrospinal fluid (CSF) samples. Follow-up magnetic resonance imaging scans illustrated the progression of the disease.
CONCLUSIONS
The accumulation of data regarding CSF sample analysis, electroencephalography, brain biopsy, and imaging findings, along with the progression of the clinical picture of our patient, verified the diagnosis of HSV encephalitis. When confronted with confounding data that can pose a diagnostic dilemma between HSV encephalitis and glioma, brain biopsy and polymerase chain reaction of CSF samples could be able to verify the definitive diagnosis. When interpreting our results, we always have to consider the evolution of the clinical picture.
Topics: Cerebellar Neoplasms; Child, Preschool; Diagnostic Errors; Encephalitis, Herpes Simplex; Female; Glioma; Humans
PubMed: 31254700
DOI: 10.1016/j.wneu.2019.06.158 -
Clinical Endocrinology Apr 2024Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW)....
Peak serum luteinising hormone cut-off during gonadotropin-releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight.
OBJECTIVE
Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW). This study aimed to evaluate peak serum LH concentration during gonadotropin-releasing hormone analogue (GnRHa) test in girls with OW/OB and NW who had central precocious puberty (CPP) and to determine peak serum LH cut-off for diagnosing CPP in girls with OW/OB.
DESIGN, PATIENTS AND MEASUREMENTS
Medical records of 971 girls with premature breast development who underwent subcutaneous GnRHa (100 µg of triptorelin acetate) test were reviewed. All girls were classified as either CPP or premature thelarche. All of them were further classified into two groups according to their body mass index as NW and OW/OB groups for each Tanner stage.
RESULTS
There were 634 and 337 girls in NW and OW/OB groups, respectively. CPP was diagnosed in 600 girls (249 had Tanner stage II and 351 had Tanner stage III). There were no differences in peak serum LH concentrations between CPP girls with NW and OW/OB. Peak serum LH cut-off of 5 IU/L (the current widely used cut-off) had a sensitivity and a specificity of 75% and 90%, respectively in NW group. Peak serum LH cut-off for CPP diagnosis was lower at 4 IU/L in the OW/OB group with greater sensitivity and specificity of 86% and 93%, respectively. The results were reproducible for each Tanner stage of breasts.
CONCLUSION
Lower peak serum LH cut-off to 4 IU/L for diagnosing CPP in girls with OW/OB should be considered to avoid underdiagnosis of the condition.
Topics: Female; Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Triptorelin Pamoate; Obesity; Overweight; Follicle Stimulating Hormone
PubMed: 38300440
DOI: 10.1111/cen.15026 -
Clinical Endocrinology Jan 2020To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in...
Basal serum luteinising hormone cut-off, and its utility and cost-effectiveness for aiding the diagnosis of the onset of puberty in girls with early stages of breast development.
OBJECTIVE
To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III).
DESIGN, PATIENTS AND MEASUREMENTS
A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost-effectiveness analysis was performed.
RESULTS
In comparison with basal LH cut-off of 0.3 IU/L, basal LH cut-off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut-off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut-off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost-saving when compared with using the cut-off of 0.3 IU/L. Moreover, using basal LH cut-off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients.
CONCLUSIONS
Basal serum LH cut-off of 0.2 IU/L could be a simple and cost-saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.
Topics: Chemistry Techniques, Analytical; Child; Cost-Benefit Analysis; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty; Puberty, Precocious; Retrospective Studies; Sensitivity and Specificity
PubMed: 31705682
DOI: 10.1111/cen.14124 -
BMC Pediatrics Jul 2022We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency...
BACKGROUND
We report five patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), four of whom presented with precocious puberty and one with growth hormone deficiency (GHD. Our five children add to the growing endocrine data base of MRKHS.
CASE PRESENTATION
We retrospectively reviewed clinical data of 5 MRKHS patients from 2017 to 2020. The clinical features, hormonal profiles, radiological imaging and genetic analyses were collated. The age range of the 5 patients at diagnosis was 6.7-9.1 years. Four presented with premature thelarche, and one presented with short stature. External genitalia were normal in all patients. Gonadotropin-releasing hormone stimulation tests for the 5 patients revealed peak luteinizing hormone and follicular stimulating hormone levels of 3.57, 6.24, 11.5, 4.44 and 4.97 IU/L and 9.41, 16.7, 13.8, 14.2 and 10.3 mIU/mL, respectively. Growth hormone stimulation for one patient with short stature was consistent with GHD with a peak level of GH was 7.30 ng/mL. Imaging disclosed advanced bone age in four patients and no skeletal abnormalities in any of the patients. Ultrasonography of the abdomen revealed bilateral polycystic kidneys in one patient. Pelvic magnetic resonance imaging confirmed no uterus in five patients. All of the patients had a normal karyotype (46, XX). In one patient, whole-exome sequencing detected a deletion of 17q12(chr17:36,046,434-36,105,050, hg19) encompassing the HNF1B gene.
CONCLUSIONS
We report the unusual co-occurrence of precocious puberty and GHD in patients with MRKHS, highlighting that abnormal puberty and growth development may represent initial unexplained manifestations. Whether the deletion of 17q 22 begat GHD is unclear.
Topics: 46, XX Disorders of Sex Development; Child; Child, Preschool; Congenital Abnormalities; Female; Growth Hormone; Humans; Mullerian Ducts; Puberty, Precocious; Retrospective Studies; Vagina
PubMed: 35836205
DOI: 10.1186/s12887-022-03474-0