Inhibin B and AMH for Diagnosis of Hypogonadotropic Hypogonadism in Boys Under One Year of Age: A Case-Control Study

Abstract Context Congenital hypogonadotropic hypogonadism (CHH) in infant boys is a rare disorder that can manifest as micropenis and/or cryptorchidism. Mini puberty is considered a window of opportunity for CHH diagnosis and treatment. The lack of testosterone (T) elevation during this period is the gold standard for CHH diagnosis, but hormonal evaluation is not always available at this time. Objectives The aim was to compare inhibin B (INHB), anti-Mullerian hormone (AMH), T, LH, and FSH between infant boys (1 to 365 days) with micropenis and/or cryptorchidism due to isolated CHH (iCHH), CHH as part of combined pituitary hormone deficiency (CPHD), or of idiopathic origin (controls), and to determine discriminating cutoffs for CHH diagnosis based on sensitivity (Se) and specificity (Sp). Methods This multicenter study from seven University Hospitals in France included 138 boys aged 0 to 12 months (58 with iCHH, including 28 with a positive molecular diagnosis, 32 with CPHD, and 48 controls). Four periods of interest were studied: between 1 to 4 days, 15 to 65 days (early mini puberty, corresponding to the T peak), 66 to 179 days (late mini puberty), and 180 to 365 days (post mini puberty). Results Out of mini puberty, the best-discriminating hormones were INHB between 1-4 days (Se/Sp 100%/75% at 150 pg/mL, and 89%/100% at 85 pg/mL), and INHB and AMH after 180 days (INHB, Se/Sp 100%/100% at 100 pg/mL)(AMH, Se/Sp 100%/92% at 600 pmol/L, and 75%/100% at 370 pmol/L). INHB and/or AMH discriminating performances were good (area under the ROC curve > 0.95) across all four periods. Conclusion Inhibin B and/or AMH can be used to diagnose CHH in boys < 1 year of age.