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Published on: October 13, 2018
Gonadotropin Suppression During Mini-Puberty as an Early Biomarker of Classic 21-Hydroxylase Deficiency
Ryosei Iemura1,2, Yuri Suzuki1, Maki Gau3
1Department of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Introduction:
Newborn screening (NBS) for congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (21OHD) relies on elevated 17-hydroxyprogesterone (17OHP) levels but is limited by a high false-positive rate and difficulty in distinguishing classic from non-classic forms. To evaluate whether the suppression of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during mini-puberty can serve as an early biomarker of classic 21OHD.
Methods:
We conducted a retrospective cohort study of 37 infants evaluated for suspected 21OHD between 2013 and 2025. Subjects were classified as classic (C), non-classic (NC), or false-positive (FP) based on biochemical and genetic confirmation. Neonatal serum LH and FSH levels were compared among groups, and receiver operating characteristic (ROC) analyses were performed.
Results:
LH and FSH levels were significantly suppressed in classic 21OHD compared with NC and FP cases (p < 0.001). Gonadotropin concentrations demonstrated a stepwise pattern (C
Conclusions:
Suppressed LH and FSH levels during the neonatal period reflect the attenuation of mini-puberty and represent a characteristic endocrine feature of classic 21OHD. Gonadotropin measurement may provide a clinically accessible adjunct to NBS for the early identification of severe disease, particularly in male neonates and in the evaluation of 46,XX disorders/differences in sex development.
