Challenges in managing disorders of sex development associated with adrenal dysfunction

INTRODUCTION: Disorders of Sex Development (DSD) associated with adrenal dysfunction occur due to different defects in the proteins involved in gonadal and adrenal steroidogenesis. AREAS COVERED: The deficiencies in 21-hydroxylase and 11β-hydroxylase lead to DSD in 46,XX patients, defects in StAR, P450scc, 17α-hydroxylase and 17,20-lyase lead to 46,XY DSD, and 3β-HSD2 and POR deficiencies cause both 46,XX and 46,XY DSD. Challenges in diagnosis arise from the low prevalence and the variability in serum steroid profiles. Replacement therapy with hydrocortisone and fludrocortisone helps to minimize life-threatening adrenal crises; however, availability is still an unresolved problem in many countries. Adverse health outcomes, due to the disease or its treatment, are common and include adult short stature, hypertension, osteoporosis, obesity, cardiometabolic risk, and reproductive health issues. Potential biomarkers to improve monitoring and novel treatment options that have been developed with the primary aim to decrease adrenal androgen production are promising tools to help improve the health and quality of life of these patients. EXPERT OPINION: Steroid profiling by mass spectrometry and next-generation sequencing technologies represent useful tools for establishing an etiologic diagnosis and drive personalized management. Nonetheless, access to health care still remains an issue requiring urgent solutions in many resource-limited settings.