Abstract
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.