First-morning urinary luteinizing hormone and bone age decomposition for diagnosis of central precocious puberty in girls: a two-step prediction model study.
- 1Shenzhen Maternity and Child Healthcare Hospital, Women's and Children's Medical Center, Southern Medical University, Shenzhen, Guangdong, China.
Abstract
Objective
The diagnosis of central precocious puberty (CPP) in girls relies on the invasive gonadotropin-releasing hormone (GnRH) stimulation test. Urinary luteinizing hormone (LH) is a noninvasive candidate biomarker, but evidence from Chinese populations and its integration into multivariable prediction frameworks remain limited. We evaluated the diagnostic accuracy of first-morning urinary LH for CPP, established sex- and pubertal stage-specific reference intervals, and developed a two-step prediction model based on a bone age decomposition.Methods
In this single-center retrospective diagnostic accuracy study, we enrolled 808 children: 295 girls with early breast development (146 CPP, 149 non-CPP), 271 healthy girls, and 242 healthy boys (reference intervals only). First-morning urine was assayed for LH, follicle-stimulating hormone (FSH), and creatinine. Diagnostic performance was evaluated primarily in the 295 symptomatic girls, with an extended analysis in 566 girls including healthy controls; multivariable logistic regression decomposed bone age into chronological age (CA) and the BA-CA difference as separate predictors.Results
Urinary LH showed moderate accuracy for CPP in the primary symptomatic cohort (AUC 0.692, 95% CI 0.630-0.752), peaking in girls aged 7-8 years (AUC 0.708, 95% CI 0.621-0.785); the extended cohort gave similar results (AUC 0.712; secondary, spectrum-extended estimate). The LH-to-creatinine ratio offered no improvement. Basal serum LH was the superior single marker (AUC 0.868 vs 0.692, P < 0.001). The noninvasive Model 1 (CA + BA-CA + urinary LH + breast Tanner stage + uterine length) achieved a C-statistic of 0.853 (sensitivity 73.3%, specificity 83.2%), with CA, BA-CA, and urinary LH as independent predictors. Adding basal serum LH and FSH (Model 2) improved the C-statistic to 0.909; urinary LH retained independent significance (aOR 1.280, P = 0.024), whereas basal FSH was inversely associated with CPP. Bootstrap-corrected C-statistics were 0.838 (Model 1) and 0.893 (Model 2). Pubertal-onset cutoffs were >1.02 mIU/mL in girls and >0.95 mIU/mL in boys.Conclusions
Decomposing bone age into CA and BA-CA enables tiered CPP risk stratification: the noninvasive model supports initial screening without blood sampling, and the complete model refines risk once serum gonadotropins become available. Urinary LH is a clinically useful component of tiered diagnostic algorithms for CPP.
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BibTeX
@article{huang2026firstmorning,
title = {{First-morning urinary luteinizing hormone and bone age decomposition for diagnosis of central precocious puberty in girls: a two-step prediction model study.}},
author = {Miao Huang and Xiyan Lu and Peipei Liu and Guoqing Dong and Mingzhu Li and Wujin Wang and Jianxu Li},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1948363},
url = {https://europepmc.org/article/MED/42910289},
note = {CC BY},
}
RIS
TY - JOUR
TI - First-morning urinary luteinizing hormone and bone age decomposition for diagnosis of central precocious puberty in girls: a two-step prediction model study.
AU - Miao Huang
AU - Xiyan Lu
AU - Peipei Liu
AU - Guoqing Dong
AU - Mingzhu Li
AU - Wujin Wang
AU - Jianxu Li
PY - 2026
DA - 2026/10/07
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1948363
UR - https://europepmc.org/article/MED/42910289
AB - Objective The diagnosis of central precocious puberty (CPP) in girls relies on the invasive gonadotropin-releasing hormone (GnRH) stimulation test. Urinary luteinizing hormone (LH) is a noninvasive candidate biomarker, but evidence from Chinese populations and its integration into multivariable prediction frameworks remain limited. We evaluated the diagnostic accuracy of first-morning urinary LH for CPP, established sex- and pubertal stage-specific reference intervals, and developed a two-step prediction model based on a bone age decomposition.Methods In this single-center retrospective diagnostic accuracy study, we enrolled 808 children: 295 girls with early breast development (146 CPP, 149 non-CPP), 271 healthy girls, and 242 healthy boys (reference intervals only). First-morning urine was assayed for LH, follicle-stimulating hormone (FSH), and creatinine. Diagnostic performance was evaluated primarily in the 295 symptomatic girls, with an extended analysis in 566 girls including healthy controls; multivariable logistic regression decomposed bone age into chronological age (CA) and the BA-CA difference as separate predictors.Results Urinary LH showed moderate accuracy for CPP in the primary symptomatic cohort (AUC 0.692, 95% CI 0.630-0.752), peaking in girls aged 7-8 years (AUC 0.708, 95% CI 0.621-0.785); the extended cohort gave similar results (AUC 0.712; secondary, spectrum-extended estimate). The LH-to-creatinine ratio offered no improvement. Basal serum LH was the superior single marker (AUC 0.868 vs 0.692, P < 0.001). The noninvasive Model 1 (CA + BA-CA + urinary LH + breast Tanner stage + uterine length) achieved a C-statistic of 0.853 (sensitivity 73.3%, specificity 83.2%), with CA, BA-CA, and urinary LH as independent predictors. Adding basal serum LH and FSH (Model 2) improved the C-statistic to 0.909; urinary LH retained independent significance (aOR 1.280, P = 0.024), whereas basal FSH was inversely associated with CPP. Bootstrap-corrected C-statistics were 0.838 (Model 1) and 0.893 (Model 2). Pubertal-onset cutoffs were >1.02 mIU/mL in girls and >0.95 mIU/mL in boys.Conclusions Decomposing bone age into CA and BA-CA enables tiered CPP risk stratification: the noninvasive model supports initial screening without blood sampling, and the complete model refines risk once serum gonadotropins become available. Urinary LH is a clinically useful component of tiered diagnostic algorithms for CPP.
SN - 1664-2392
ER -