SUN-215 LC-MS-Based Profiling of Adrenal Steroids Reveals Metabolic Signatures of 17á-hydroxylase Deficiency

The comprehensive metabolic signatures of adrenal steroids are necessary to understand their pathophysiological functions in adrenal diseases, such as Cushing’s syndrome (CS) and congenital adrenal hyperplasia (CAH). The 17α-hydroxylase deficiency (17α-OHD) CAH, accounted for <1% of CAH cases, is caused by mutations of CYP17A1 gene leading to impaired production of cortisol and adrenal androgens. It may be under-diagnosed in patients in whom routine screening for the early detection of CAH subtypes. A validated liquid chromatography-mass spectrometry (LC-MS)-based quantitative profiling of 27 adrenal steroids in human serum, therefore, has been developed and employed in patients with CS (n = 7) and 17α-OHD CAH (n = 1). In a patient with 17α-OHD, adrenal androgen levels were significantly decreased, especially DHEA sulfate (~1/1,000 times), while pregnenolone sulfate was increased against both healthy (n =43) and CS subjects (p < 0.001). In addition, increased mineralocorticoids and decreased glucocorticoids as well as DHEA-S/Preg-S were observed in a 17α-OHD patient, which mean DHEA-S, Preg-S, and these metabolic ratios could be good biomarkers for detecting 17α-OHD CAH in part of an overall plan of medical care. The developed LC-MS method can quantitatively profile biologically active adrenal steroids and sulfate conjugates in a single run to be a comprehensive diagnostic tool in adrenal diseases.