Plasma Steroid Profiles in Subclinical Compared With Overt Adrenal Cushing Syndrome

Abstract

Context Diagnosis of subclinical adrenal hypercortisolism is based on several tests of the hypothalamic-pituitary-adrenal axis to establish mild alterations of cortisol secretion and dysregulated cortisol physiology. Objective We assessed whether plasma steroid profiles might assist diagnosis of subclinical Cushing syndrome (SC). Design Retrospective cross-sectional study. Setting Two tertiary medical centers. Patients Of 208 patients tested for hypercortisolism, disease was excluded in 152 and confirmed in 21 with overt adrenal Cushing syndrome (AC) compared to 35 with SC. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for reference. Main Outcome Measures A panel of 15 plasma steroids was measured by mass spectrometry, with classification by discriminant analysis. Results Patients with SC had lower plasma concentrations of dehydroepiandrosterone and dehydroepiandrosterone-sulfate than subjects without SC (P < 0.05). The largest increases (P < 0.001) in plasma steroids among patients with SC were observed for 11-deoxycortisol and 11-deoxycorticosterone. Nevertheless, concentrations of 11-deoxycorticosterone, 11-deoxycortisol, and pregnenolone in patients with AC were higher (P < 0.05) than in those with SC. Patients with SC or AC could be distinguished from subjects without disease using this combination of steroids as precisely as with use of measurements of serum cortisol after administration of dexamethasone. The steroid combination provided superior diagnostic performance compared with each of the other routine biochemical tests. Conclusion Distinct plasma steroid profiles in patients with SC may provide a simple and reliable screening method for establishing the diagnosis.

Glucocorticoid Resistance in Premature Adrenarche and PCOS: From Childhood to Adulthood

“…The lack of ACTH action led to diminished androgen secretion and absence of adrenarche [ 27 ]. Lower DHEA and DHEAS levels were found in patients with adrenal and subclinical Cushing syndrome, supporting previous suggestions that ACTH is a major determinant of their secretion [ 28 ].…”

Glucocorticoid Excess in Patients with Pheochromocytoma Compared with Paraganglioma and Other Forms of Hypertension

“…This study presents novel data establishing increased circulating glucocorticoids in patients with pheochromocytoma but not paraganglioma. Among the steroids that were increased in patients with pheochromocytoma, 11-deoxycortisol, 11-deoxycorticosterone, and corticosterone showed larger relative increases than cortisol; this pattern has also been observed in clinical and subclinical Cushing syndrome where the same steroids provide larger diagnostic signals than cortisol ( 20 , 22 ). Moreover, positive relationships were also observed between several glucocorticoids and plasma and urinary markers of catecholamine excess, thus supporting in a clinical setting the concept advanced from preclinical studies by Ehrhart-Bornstein and Bornstein of bidirectional relationships between catecholaminergic and steroidal systems ( 11 , 23 , 24 ).…”

“…Nevertheless, since sustained suppression of ACTH results in reductions of circulating DHEAS ( 32 ) the low plasma concentrations of DHEAS in patients with pheochromocytoma appear to be inconsistent with an influence in patients with pheochromocytoma mediated by ACTH. Apart from low ACTH and DHEAS in patients with adrenal Cushing syndrome, other forms of glucocorticoid excess such as subclinical Cushing and primary bilateral macronodular hyperplasia are also associated with reduced plasma concentrations of DHEAS ( 20 , 33-35 ). Thus, since DHEAS is responsive to ACTH, the lowered plasma concentrations of DHEAS might reflect lower plasma concentrations of ACTH, which may result from feedback inhibition of steroids on the hypothalamic–pituitary–adrenal axis.…”

“…Multivariate analysis with age and sex as covariates was then carried out to establish significance between groups using the Tukey Honestly significant difference (HSD) post hoc test. Final display of data was achieved from the exponents of least square means to derive geometric means with respective plus and minus standard errors as described elsewhere ( 20 ). Within group changes from pre- to postadrenalectomy were calculated using the Wilcoxon signed rank test.…”

Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS

“…Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been introduced into the clinical routine analysis of steroid hormones (19)(20)(21) due to its higher specificity and is increasingly used for the diagnosis of adrenal diseases (22)(23)(24). Aldosterone concentrations measured with LC-MS/MS are usually lower than those measured by most IAs (15,17,(25)(26)(27)(28).…”