Diagnostic Accuracy of Serum Steroids and Peptides in the Evaluation of 46, XY Disorders of Sex Development (DSD).

Abstract

Introduction: Biochemical evaluation of 46, XY disorders of sex development(DSD) remains challenging due to overlapping profiles and limited validation in genetically proven cases. We studied the diagnostic accuracy of serum hormonal parameters in a well-characterized cohort.

Methods: Post-hoc hormonal analysis of a prospective study on genetics of 46, XY DSD(n = 165) was performed. Etiological diagnosis was primarily based on genotypic data. Patients without pathogenic genetic variants but with mullerian structures were classified as having gonadal dysgenesis(GD). Serum hormone levels during mini-pubertal, prepubertal, and pubertal stages were analyzed for diagnostic accuracy across etiological subgroups.

Results: In GD, high serum FSH effectively distinguished others across all stages:mini puberty(AUC 0.896; sensitivity 75%, specificity 94.4% at 5.95 IU/L), prepuberty (AUC 0.860; sensitivity 60%, specificity 92.1% at 3.72 IU/L), and puberty (AUC 0.925; sensitivity 89.3%, specificity 90.6% at 38.15 IU/L). In17βHSD3D,(a gonadal steroidogenesis defect), prepubertal hCG-stimulated androstenedione(AUC = 0.929, cutoff 0.53 ng/ml, sensitivity 80%, specificity 80%) and Testosterone/Androstenedione(T/A) ratio(AUC = 0.898, cutoff 1.66, sensitivity 80%, specificity 94.5%) were diagnostic, while T/A cutoff 0.8 had 20% sensitivity. For SRD5A2,(testosterone metabolism defect), low pubertal LH(AUC = 0.908, cutoff 7.11 IU/L, sensitivity 75%, specificity 87.5%) was discriminatory, while prepubertal T/DHT cutoff 10 had 20% specificity. Androgen sensitivity index(ASI)(AUC = 0.972, cutoff 95.27, sensitivity 93.8%, specificity 93.3%) had highest diagnostic accuracy for androgen insensitivity syndrome(an androgen inaction) in pubertal stage.

Conclusion: This study identifies FSH, stimulated T/A (> 1.6), ASI, and LH as key discriminatory markers for etiological diagnosis in 46, XY DSD, while suggesting that traditional cutoffs like stimulated T/DHT > 10 and T/A < 0.8 may have limited utility emphasizing the need for rapid genetic analysis.