Season 6, Episode 17 — 46,XX Virilization: Follow the Androgen Backward

A virilized 46,XX newborn with a uterus is not primarily a problem of testicular differentiation. It is a problem of prenatal androgen exposure. In this episode of Pediatric Urology Academy, we work backward from the phenotype to reconstruct where the androgen came from, when exposure occurred, and which steroidogenic pathway produced it. We explore: • why a uterus strongly shifts the diagnosis toward androgen exposure rather than fetal testicular development • why 21-hydroxylase deficiency remains the most important adrenal cause • how salt wasting can turn a genital finding into an endocrine emergency • why 11β-hydroxylase deficiency produces a different physiology, often with hypertension and hypokalemia • how HSD3B2 deficiency and POR deficiency alter steroid traffic • how backdoor androgen pathways contribute to 46,XX virilization • why maternal virilization during pregnancy can point toward aromatase deficiency or a maternal androgen source • why a normal postnatal androgen level does not exclude major prenatal androgen exposure • how internal Müllerian anatomy and external virilization record different developmental signals • how blood pressure, electrolytes, steroid precursors, maternal history, and skeletal findings can localize the source • why mass-spectrometry steroid profiling can be more informative than isolated hormone measurements • why endocrine stabilization comes before reconstructive decision-making The central framework: The genitalia show where the androgen ended. Expert diagnosis begins by following it backward. Season 6 — Differences of Sex Development: Reconstruct the Biology Hosted by Amin Afrasiabi, MD Pediatric Urology Academy