A Liquid Chromatography/Tandem Mass Spectometry Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia

• DOI: 10.1210/js.2016-1048
• Publication Date: 2017-04-03T03:38:21Z
• Authors: Marie-Anne Maubert; Jérôme Guéchot; Jean Fiet; Yves Le Bouc; Yves Le Bouc; Nicolas Hélin; Antonin Lamaziere; Dominique Farabos
• Keywords: 11DF; 17OH pregnenolone; 11b hydroxy D4-androstenedione 11DF; DOC; dehydroepiandrosterone; 0302 clinical medicine; liquid chromatography/tandem mass spectrometry LLOQ; CAH due to steroid 21-hydroxylase deficiency DHEA; D4-androstenedione; D4-androstenedione Aldo; progesterone Preg; DHEA; QC; 11 deoxycorticosterone; pregnenolone; cortisol LC-MS/MS; radioimmunoassay; CAH; T; cortisone; 21 deoxycortisol; P; lower limit of quantitation; 17OH progesterone; 17OH progesterone 17OHPreg; 3. Good health; 11b hydroxy D4-androstenedione; [SDV] Life Sciences [q-bio]; 21 deoxycorticosterone; Preg; 17OH pregnenolone 21DB; cortisone F; 11 deoxycorticosterone E; CAH21; liquid chromatography/tandem mass spectrometry; 11 deoxycortisol; cortisol; progesterone; 03 medical and health sciences; E; F; 21 deoxycorticosterone 21DF; A; B; congenital adrenal hyperplasia; LC-MS/MS; quality control; lower limit of quantitation P; pregnenolone QC; LLOQ; Clinical Research Articles; 17OHPreg; aldosterone; 21DF; congenital adrenal hyperplasia CAH21; radioimmunoassay T; corticosterone; RIA; CAH due to steroid 21-hydroxylase deficiency; Abbreviations: 11bOHA; aldosterone B; corticosterone CAH; quality control RIA; Aldo; 21DB; 21 deoxycortisol A; 17OHP; dehydroepiandrosterone DOC; testosterone; 11 deoxycortisol 17OHP

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.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.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).Sixteen steroids (glucocorticoids, mineralocorticoids, androgens, Δ5-steroids) were analyzed in 150 µL of serum by LC-MS/MS.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.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.