FSH and Sertoli Cell Biomarkers Accurately Distinguish Hypogonadotropic Hypogonadism From Self-limited Delayed Puberty.

Summary

In a prospective nested case-control of 65 adolescent males with delayed puberty, baseline FSH, AMH, and inhibin B outperformed LH and testosterone for distinguishing CHH from SLDP. Products FSH×inhibin B < 92 and FSH×AMH < 537 achieved sensitivity >93%, specificity ≥92%, predictive values >92%, and LR+ >12, retaining high performance even without red flags.

Key Findings

• Baseline FSH, AMH, and inhibin B showed superior diagnostic efficiency versus LH and testosterone.
• FSH (IU/L)×inhibin B (ng/mL) < 92 and FSH (IU/L)×AMH (pmol/L) < 537 achieved sensitivity >93%, specificity ≥92%, predictive values >92%, and LR+ >12 for CHH.
• High diagnostic performance persisted when excluding patients with red flags (micropenis, cryptorchidism, microorchidism).
• Prospective follow-up to definitive diagnosis (age 18 or ≥4 years after reaching testis volume 4 mL).

Clinical Implications

Using FSH×inhibin B or FSH×AMH thresholds at baseline could streamline evaluation, reduce need for stimulation tests, and enable earlier targeted management for CHH versus watchful waiting in SLDP.

Limitations

• Modest sample size (n=65) and need for external validation in diverse populations
• Adolescent males only; generalizability to females or other age groups is unknown

Future Directions

Validate thresholds in multiethnic, larger cohorts; assess cost-effectiveness versus stimulation testing; integrate into diagnostic algorithms and decision-support tools.