Madsen A, Bruserud IS, Bertelsen BE, et al. - In this cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years, researchers sought to integrate ultrasound (US) breast staging with hypothalamic-pituitary-gonadal hormone references and examine the predictive value of an endocrine profile to determine thelarche. Clinical and ultrasound breast evaluations have been conducted for all included girls. Blood samples have been analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E₂) and estrone (E₁) from the subpicomolar range. In 14 out of 264 (5.3%) girls with clinically prepubertal presentation, ultrasound detection of nonpalpable glandular tissue was associated with significantly higher median serum levels of E₂ and a distinct endocrine profile. The authors provide the first hormone references for use with US breast staging and illustrate the application of endocrine profiling to enhance the identification of female puberty onset.