Abstract
CONTEXT: Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (CAH21) is most often diagnosed by newborn screening. The classic parameter studied is 17-hydroxy-progesterone, but the positive predictive value for the diagnosis of CAH is low in full-term newborns and even lower in preterm newborns. OBJECTIVE: To evaluate the diagnostic utility of simultaneously quantifying a large number of steroids by using liquid chromatography/tandem mass spectrometry (LC-MS/MS) from a small serum volume in patients with CAH, particularly during the neonatal period. SETTING AND PARTICIPANTS: LC-MS/MS was applied to sera from patients with CAH who had a classic form (n = 48) and rare forms (n = 2) of 21-hydroxylase deficiency, normal preterm (n = 10) and normal full-term (n = 20) neonates, and young patients without CAH (non-CAH; n = 149) but with various other diseases (delayed or advanced puberty, hirsutism, pubarche, adrenarche, simple growth retardation). METHODS: Sixteen steroids (glucocorticoids, mineralocorticoids, androgens, Δ5-steroids) were analyzed in 150 µL of serum by LC-MS/MS. RESULTS: An LC-MS/MS serum steroid profile was developed and validated to provide a reliable etiologic diagnosis of CAH. The serum levels of 17OH-progesterone and 21 deoxycortisol in non-CAH are reported, along with the rarely assayed 21-deoxycorticorticosterone and 11β hydroxy Δ4-androstenedione, which will aid in the diagnosis of CAH21. In addition, serum levels of mineralocorticoids, androgens, and Δ5-steroids allowed investigation of other forms of CAH. CONCLUSION: This steroid LC-MS/MS approach on a small serum volume is well suited for pediatrics, particularly neonatal medical practice, to aid in the diagnosis and monitoring of various forms of CAH.