King's College London

Background: Mass spectrometric-based measurements of the steroid metabolome have been introduced to
diagnose disorders featuring abnormal steroidogenesis. Defined reference intervals are important for interpreting
such data.
Methods: Liquid chromatography–tandem mass spectrometry was used to establish reference intervals for 16
steroids (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-
hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone,
dehydroepiandrosterone-sulfate, androstenedione, testosterone) measured in plasma from 525
volunteers with (n =227) and without (n =298) hypertension, including 68 women on oral contraceptives.
Results: Women showed variable plasma concentrations of several steroids associated with menstrual cycle
phase, menopause and oral contraceptive use. Progesterone was higher in females than males, but most other
steroids were higher in males than females and almost all declined with advancing age. Using models that
corrected for age and gender, body mass index showed weak negative relationships with corticosterone, 21-
deoxycortisol, cortisol, cortisone, testosterone, progesterone, 17-hydroxyprogesterone and 11-deoxycorticosterone,
but a positive relationship with 18-hydroxycortisol. Hypertensives and normotensives showed negligible
differences in plasma concentrations of steroids.
Conclusion: Age and gender are the most important variables for plasma steroid reference intervals, which have
been established here according to those variables for a panel of 16 steroids primarily useful for diagnosis and
subtyping of patients with endocrine hypertension.