OBJECTIVES: To establish an efficient and clinically applicable predictive model and scoring system for central precocious puberty (CPP) in girls, and to develop a diagnostic prediction application. METHODS: A total of 342 girls aged 4 to 9 years with precocious puberty were included, comprising 216 cases of CPP and 126 cases of isolated premature thelarche. Lasso regression was used to screen for predictive factors, and logistic regression was employed to establish the predictive model. Additionally, a scoring system was constructed using the evidence weight binning method. Data from 129 girls aged 4 to 9 years with precocious puberty were collected for external validation of the scoring system. RESULTS: The logistic regression model incorporated five predictive factors: age, insulin-like growth factor-1 (IGF-1), serum follicle-stimulating hormone (FSH), the luteinizing hormone (LH)/FSH baseline ratio, and uterine thickness. The calculation formula was: ln(P/1-P)=-8.439 + 0.216 × age (years) + 0.008 × IGF-1 (ng/mL) + 0.159 × FSH (mIU/mL) + 9.779 × LH/FSH baseline ratio + 0.284 × uterine thickness (mm). This model demonstrated good discriminative ability (area under the curve=0.892) and calibration (Hosmer-Lemeshow test P>0.05). The scoring system based on this logistic regression model showed good discrimination in both the prediction model and external validation datasets, with areas under the curve of 0.895 and 0.805, respectively. Based on scoring system scores, the population was stratified into three risk levels: high, medium, and low. In the high-risk group, the prevalence of CPP exceeded 90%, while the proportion was lower in the medium and low-risk groups. CONCLUSIONS The CPP diagnostic predictive model established for girls aged 4 to 9 years exhibits good diagnostic performance. The scoring system can effectively and rapidly stratify the risk of CPP, providing valuable reference for clinical decision-making.
Humans ; Puberty, Precocious/diagnosis* ; Female ; Child, Preschool ; Child ; Follicle Stimulating Hormone/blood* ; Insulin-Like Growth Factor I/analysis* ; Luteinizing Hormone/blood* ; Logistic Models

OBJECTIVETo evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls.

METHODSA total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed.

RESULTSThe CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01).

CONCLUSIONSBaseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Adolescent ; Age Determination by Skeleton ; Child ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Puberty, Precocious ; blood ; diagnosis ; ROC Curve

Biomarkers ; blood ; Child ; Chorionic Gonadotropin ; blood ; Follicle Stimulating Hormone ; blood ; Growth Disorders ; etiology ; Humans ; Klinefelter Syndrome ; complications ; diagnosis ; genetics ; Magnetic Resonance Imaging ; Male ; Mediastinal Neoplasms ; complications ; diagnosis ; surgery ; Puberty, Precocious ; diagnosis ; etiology ; Teratoma ; complications ; diagnosis ; surgery ; Testis ; pathology

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.
17-alpha-Hydroxyprogesterone/blood ; 46, XY Disorders of Sex Development/drug therapy/*genetics ; Adolescent ; Adrenal Hyperplasia, Congenital/drug therapy/*genetics ; Adrenal Insufficiency/*congenital/diagnosis/drug therapy/genetics ; Adrenocorticotropic Hormone/*metabolism ; Bone Development/genetics ; Child ; Child, Preschool ; DAX-1 Orphan Nuclear Receptor/genetics ; Female ; Genetic Diseases, X-Linked/drug therapy/*genetics ; Genotype ; Glucocorticoids/therapeutic use ; Humans ; Intellectual Disability/complications ; Male ; Mineralocorticoids/therapeutic use ; Obesity/complications ; Phosphoproteins/genetics ; Puberty, Precocious/complications ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics

OBJECTIVETo study the value of follicle stimulating hormone (FSH), luteinizing hormone (LH) and LH/FSH ratio in the diagnosis of precocious puberty in girls by ROC curve analysis.

METHODSGonadotropin-releasing hormone (GnRH) stimulation test was performed on 220 girls with pseudo-sexual precocity and 61 girls with true sexual precocity. Blood LH and FSH levels were measured before and after 30 and 60 minutes of taking the GnRH test. The ratio of LH to FSH was calculated. Sensitivity and best point for the diagnosis of precocity according to LH, FSH and LH/FSH ratio were analyzed by ROC curve analysis.

RESULTSThe area under the ROC curve was 0.90 and 0.95 according to LH level and LH/FSH ratio respectively for the diagnosis of precocity. The best point for diagnosis by LH was 10.15 IU/L, with a sensitivity of 0.92 and specificity of 0.89. The best point for diagnosis by LH/FSH ratio was 0.60, with a missed diagnosis rate of 6.0% and specificity of 0.91. When true sexual precocity was diagnosed based on one index between LH>10.15 IU/L and LH/FSH ratio>0.60, sensitivity was 0.97 and specificity was 0.94. When the diagnosis of true sexual precocity was diagnosed based on both LH>10.15 IU/L and LH/FSH>0.60, sensitivity was 0.85 and specificity was 1.00.

CONCLUSIONSTrue sexual precocity can be diagnosed when both LH>10.15 IU/L and LH/FSH ratio>0.60. Only one of the two indexes for the diagnosis of true sexual precocity is presented, further observation is necessary to decrease missed diagnosis and misdiagnosis.

Diagnosis, Differential ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; pharmacology ; Humans ; Luteinizing Hormone ; blood ; Puberty, Precocious ; blood ; diagnosis ; ROC Curve

OBJECTIVETo study the value of basal serum gonadotropin levels in the diagnosis of precocious puberty (PP) in girls.

METHODSA total of 77 girls with PP were divided into central PP (CPP) (n=45) and isolated premature thelarche (IPT) groups (n=32) based on the results of gonadotropin releasing hormone (GnRH) stimulation test, which was considered the gold standard for diagnosis of PP. The two groups were compared with respect to basal serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and LH/FSH ratio. The receiver operating characteristic (ROC) curve was used to analyze the accuracy of basal LH and FSH levels and LH/FSH ratio in the diagnosis of PP.

RESULTSThe basal serum LH and FSH levels and LH/FSH ratio in the CPP group were significantly higher than in the IPT group (P<0.01). The basal serum LH level was positively correlated with peak LH level in the GnRH stimulation test in both groups. For diagnosis of CPP, the area under the ROC curve (AUC) for basal serum LH level was larger than for basal serum FSH level and LH/FSH ratio (P<0.05), and there was no significant difference in the AUC value between basal serum FSH level and LH/FSH ratio. When the basal serum LH level was 0.62 IU/L, there was a maximum Youden index (0.684), with 77.8% sensitivity and 90.6% specificity. When the basal serum LH level reached 1.5 IU/L, the sensitivity decreased to 31.1%, but with the highest specificity (100%).

CONCLUSIONSBasal serum LH level is superior to LH/FSH ratio and basal serum FSH level in the diagnosis of CPP, and can be used for preliminary diagnosis of PP in girls in the out-patient department, but there is some misdiagnosis and missed diagnosis. When basal serum LH level is higher than 1.5 IU/L the diagnosis of CPP can be confirmed in combination with clinical manifestation, without the need for an additional GnRH stimulation test.

Child ; Child, Preschool ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Puberty, Precocious ; blood ; diagnosis ; ROC Curve

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.
Age Determination by Skeleton ; Breast/growth & development ; Child ; Estradiol/blood ; Female ; Follicle Stimulating Hormone/blood ; Follow-Up Studies ; Gonadotropin-Releasing Hormone/*analysis ; Humans ; Logistic Models ; Luteinizing Hormone/blood ; Predictive Value of Tests ; Puberty, Precocious/*diagnosis ; ROC Curve ; Retrospective Studies

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 +/- 1.78 vs 2.15 +/- 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed.
Biological Markers/blood ; Child ; Female ; Follicle Stimulating Hormone/blood ; Humans ; Luteinizing Hormone/blood ; Puberty, Precocious/blood/*diagnosis ; Republic of Korea ; Tumor Suppressor Proteins/*blood

Steroid cell tumor, not otherwise specified (NOS), are rare ovarian tumor, in addition, it is more rare in children. The majority of these tumors produce several steroid hormones, particularly testosterone. Estrogen also secreted by steroid cell tumor, NOS, but it is uncommon. Furthermore, hypertension is an infrequent sign in steroid cell tumor, NOS. An 8.5-yr-old girl with hypertension and frequent vaginal spotting visited at our clinic. On laboratory evaluation, secondary hypertension due to an elevated plasma renin level and isosexual pseudoprecocious puberty was diagnosed. Right solid ovarian mass was detected in radiologic tests. She underwent a right ooporectomy and it revealed renin and progesterone receptor positive steroid cell tumor, NOS. After operation, her blood pressure returned to normal level and vaginal bleeding disappeared. Even though this case is very rare, when hypertension coincides with virilization or feminization, a renin-secreting ovarian steroid cell tumor, NOS, should be considered.
Child ; Female ; Humans ; Hypertension/*etiology ; Ovarian Neoplasms/complications/*diagnosis/pathology ; Puberty, Precocious/enzymology/*etiology ; Receptors, Cell Surface/metabolism ; Receptors, Progesterone/metabolism ; Renin/blood ; Sex Cord-Gonadal Stromal Tumors/complications/*diagnosis/pathology ; Steroids/biosynthesis ; Tomography, X-Ray Computed ; Vacuolar Proton-Translocating ATPases/metabolism

BACKGROUND: Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard to identify central precocious puberty (CPP). This test requires multiple blood samples at different time points to measure gonadotropin levels, and is therefore expensive, time-consuming, and uncomfortable for patients. We aimed to simplify the GnRH stimulation test to require fewer blood samples. METHODS: A study of 166 girls with precocious puberty was undertaken. Blood samples were obtained at 0, 15, 30, 45, 60, 90, and 120 min after GnRH administration, and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated and ROC curves were constructed. RESULTS: One hundred and twenty-eight patients (77.1%) were diagnosed for CPP. Peak LH levels were achieved 30 min after GnRH stimulation in patients with CPP. Further, 98.4% of the 45-min samples were diagnostic for CPP, and the cumulative frequency of LH values of > or =5 IU/L was 100% at 45 min. Using this cut-off value for LH, the ROC curve for LH at 45 min showed the highest sensitivity (98.4%) and specificity (100%) in the diagnosis of CPP. CONCLUSIONS: Values of LH measured from a single blood sample obtained at 45 min in the GnRH stimulation test may be adequate for the diagnosis of CPP. Two samples, taken at 30 and 45 min after stimulation, were able to accurately diagnose CPP in 100% of the patients in this study.
Child ; Female ; Follicle Stimulating Hormone/blood ; Gonadotropin-Releasing Hormone/*diagnostic use ; Humans ; Luteinizing Hormone/blood ; Puberty, Precocious/blood/*diagnosis ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Time Factors