Do serum Inhibin B levels allow a discrimination between constitutional delay of growth and puberty (CDGP) and hypogonadotropic hypogonadism (HH) in boys with delayed puberty?

Aims: In boys ≥14 years of age, the clinical differentiation between CDGP and a permanent developmental arrest due to central disturbances may be challenging. Diagnostic aids are the assessment of basal gonadotropin levels and various stimulation tests. All have limitations in sensitivity and specificity. HH necessitates lifelong hormonal replacement. In CDGP mistakenly assigned as HH, hormonal replacement will suppress pubertal activation of the gonadotropic axis.

Sertoli cells are the most active cell population in the prepubertal testis, secreting the glycol-proteo hormone Inhibin-B, increasing during puberty.

Aim: To assess the diagnostic utility of Inhibin-B in adolescent males with delayed puberty in the differentiation between HH and CDGP.

Material and methods: Clinical data (i.e. hormone profile including inhibin-B, testicular volume) of 52 adolescents were assessed. Sera from 15 prepubertal boys with proven HH (low LH increment in GnRHa-test, absence of pubertal development after priming) were compared with those of 11 prepubertal boys with CGDP (pubertal development after priming with androgens) and with 26 boys who had already entered early puberty (LH level ≥1 U/l or a bitesticular volume ≥8 ml) at the time of referral.

Results: Inhibin-B levels of HH-patients (median [± 95%CI]: 13.4 [12.4 – 23.4] pg/ml) were significantly lower than those of prepubertal patients with CDGP (66.1 [31.8 – 86.2] pg/ml; p = 0.0028) and of early pubertal patients with CDGP (136.7 [115.5 – 162] pg/ml); p < 0.0001). Receiver operating characteristics for diagnosis of CDGP vs. IHH (Inhibin-B ≥29 pg/ml): sensitivity 95%, specificity 80%, positive predictive value 91% (p < 0.001).

Conclusions: Inhibin-B constitutes a biomarker to assess whether a boy with pubertal delay will enter puberty spontaneously or not. Thus, unnecessary treatment of CDGP may be avoided, and for patients with HH the decision for definitive hormonal replacement may be facilitated.