First-morning urinary luteinizing hormone and bone age decomposition for diagnosis of central precocious puberty in girls: a two-step prediction model study

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• Picked for Biochemistry (medical) (top studies of the week, 25 October 2026): Urinary hormone assay accuracy and pediatric reference intervals

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.

Abstract as published, via PubMed.