Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS/MS: Impact of gender, age, oral contraceptives, body mass index and blood pressure status

Abstract

BackgroundMass 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.MethodsLiquid 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.ResultsWomen 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.ConclusionAge 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.

Diurnal variation of steroid hormones and their reference intervals using mass spectrometric analysis

“…Here, we confirm our prior findings with a far larger cohort of patients to emphasize the importance of this time-dependent bimodal distribution and the need for reference intervals to acknowledge and reflect these findings. In terms of amplitude and timing variability, our results for all steroids tested are consistent with those of previous investigations ( 2 , 3 , 4 , 15 , 16 , 27 ). A drawback of most other steroid reference interval studies ( 15 , 23 , 26 ) is their lack of use of atmospheric pressure photoionization (APPI) as the ionization source and this results in increased levels of ionization inhibition thus making their data less credible ( 28 ).…”

“…Statistical analyses were performed using Statistical Package for the Social Sciences, version 23 and box-and-whisker plots were generated using MedCalc, version 17.8.6. The normality of distribution of variables was tested by the Kolmogorov–Smirnov test and steroid hormone profiles were noted to be log normally distributed ( 15 , 19 ). Reference intervals for two steroid hormones were obtained using the percentile approach.…”

“…The use of high-performance liquid chromatography (HPLC) in conjunction with tandem mass spectrometry (MS) is increasingly becoming the method of choice for clinical testing of hormone levels ( 5 , 6 , 15 , 16 , 17 ). Given its high sensitivity, specificity and precision for the identification and detection of analytes, its use is fundamental to disease diagnosis, management and treatment outcomes.…”

Blood steroid levels predict survival in endometrial cancer and reflect tumor estrogen signaling

“…There was no correlation between storage time and level of any of the hormones (Supplementary Table S2). The distribution of hormone levels in our cohort was comparable to previously published data on LC-MS/MS reference intervals of steroids in healthy postmenopausal women [31] ( Supplementary Fig. S2).…”

Impact of Gut Microbiome on Hypertensive Patients With Low-Salt Intake: Shika Study Results

“…21-deoxycortisol is derived from 21-dehydroxylation of corticosterone or cortisol by intestinal bacteria and most notably the inhibition of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Plasma levels of 21-deoxycortisol are elevated in humans with hypertension compared with that of normotensive controls ( 55 ).…”