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Context Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels. Objective We evaluated whether urinary hormones could be potential biomarkers for pre- or post- puberty, aiming to simplify the current diagnosis and prognosis procedure. Design, Setting, and Participants We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a six-month follow up. Main Outcome Measures We measured luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples. Results Their urinary LH levels and the ratios of LH: FSH increased significantly with the advancement in Tanner Stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cut-off value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH≥1.74+uLH: uFSH ratio >0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly. Conclusions uLH could be a reliable biomarker for the initial CPP diagnosis and screening; uLH also could be an effective marker for evaluating the efficacy of clinical treatment.

Twin and family studies indicate that smoking addiction is highly influenced by genetic factors. Variants in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been associated with alcoholism and depression. In this study, we tested five single nucleotide polymorphisms (SNPs) in CRHR1 for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström test for ND (FTND) in 2,037 subjects from 602 families of either European American (EA) or African American (AA) ancestry. Association analysis of the five SNPs revealed a significant association of rs171440 with SQ in the AA sample and with SQ and FTND in the pooled AA and EA samples. Haplotype-based association analysis indicated significant association of haplotypes C-C (56.9%) and T-C (38.9%), formed by SNPs rs171440 and rs1396862, with SQ in the AA sample, C-C-G (47.6%) with SQ, and T-C-G (42.3%), formed by SNPs rs171440, rs1396862, and rs878886, with SQ and FTND in the pooled AA and EA samples. However, none of these associations remained significant after correction for multiple testing. Together, our results provide suggestive evidence for the involvement of CRHR1 in ND, which warrants further investigation using larger independent samples.

Precocious puberty (PP) is defined as onset of secondary sexual characteristics before the age of 9 years in boys and 8 years in girls. 1 It is either due to the premature activation of hypothalamic-pituitarygonadal axis which is defined as central precocious puberty (CPP), or it may be gonadotropin independent. 2 Well-recognized etiological factors for CPP are congenital or acquired brain disorders, genetic and environmental factors, and international adoption. 3,4 A large proportion of the CPP girls are idiopathic (85%-90%), whereas the boys have much higher chance of underlying pathology in central nervous system (CNS). 5 Previous studies showed a diverse prevalence of pathological brain lesions in CPP boys, varying from 25% to 94%. 4,6-10 Thus, it has long been stated that brain lesions must