The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk

Abstract

Context Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors. Objectives To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS). Design Cohort study. Setting University hospital. Patients Patients (n = 302) with incidentally discovered adrenal masses, divided into unilateral adenoma and hyperplasia with ACS (n = 46 and n = 52, respectively) and NS (n = 120 and n = 84, respectively). Post–dexamethasone suppression test (DST) cortisol <50 or >50 nmol/L defined NS and ACS, respectively. Intervention Analysis of 10-steroid panel by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and clinical data (mean follow-up 39 months). Main Outcome Measures Difference in baseline and post-DST steroid profiles between groups. Correlation with cardiovascular profile. Results Patients with unilateral adenomas and ACS showed higher cortisol, 11-deoxycortisol, and corticosterone and lower dehydroepiandrosterone than those with NS adenomas. Patients with ACS hyperplasia showed higher cortisol and lower androgens in women than those with NS. Patients with ACS had reduced suppression of post-DST cortisol, 11-deoxycortisol, and corticosterone, irrespective of adrenal morphology. Post-DST cortisol and corticosterone were associated with higher prevalence of severe/resistant hypertension. Patients with ACS unilateral adenomas showed higher incidence of worsening of hypertensive disease and novel cardiovascular events than those with NS, with post-DST cortisol [hazard ratio (HR) 1.02; 95% CI, 1.01 to 1.03; P < 0.001] and baseline corticosterone (HR 1.06; 95% CI, 1.01 to 1.12; P = 0.031) among the main predictors. Conclusions Patients with adrenal incidentalomas showed different steroid profiles, depending on functional status and adrenal morphology, with implications for their cardiovascular status.

High prevalence of smoking in patients with adrenal incidentalomas: causality or case selection?

“…We have identified six studies that have reported the prevalence of smoking in patients with or without ACS/pACS (10,11,12,13,14,15). Only two of these reported an increased prevalence of smoking among patients with ACS/pACS (14,15). However, all these studies were considerably smaller than ours and differences in smoking habits between groups were not adjusted for plausible confounding factors such as gender and age.…”

“…Smoking habits were also linked to cortisol ONDST with smokers having cortisol ONDST ≥50 nmol/L more often, both among patients with unilateral and bilateral adrenal incidentalomas. We have identified six studies that have reported the prevalence of smoking in patients with or without ACS/pACS (10,11,12,13,14,15). Only two of these reported an increased prevalence of smoking among patients with ACS/pACS (14,15).…”

RNA Sequencing and Somatic Mutation Status of Adrenocortical Tumors: Novel Pathogenetic Insights

“…Although patients with MACS-CPA could present comorbidities associated to mild cortisol hypersecretion, such as risk of cardiovascular events, hypertension, dyslipidemia, diabetes mellitus type 2, obesity, osteoporosis (13,(15)(16)(17)(18)(19), the long-term data did not provide evidence for an evolution from MACS-CPA to overt CS (32). Additionally, recent analysis by liquid chromatography tandem mass spectrometry in patients with adrenal incidentalomas showed that the steroid profiling of subjects with EIA showed some similarities with those having MACS-CPA (33,34).…”

Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

“…However, again in these patients, measuring cortisol and its metabolites by immunoassay could be more representative of real glucocorticoid (GC) secretion and, possibly more predictive of clinical outcomes, than measuring only pure cortisol levels by LC-MS/MS. Therefore, the use of LC-MS/MS measurement of a comprehensive steroid profile, rather than cortisol alone, could be proposed for the detection of subtle excess GC in patients with incidentally discovered adrenal masses (42,43). In addition, 11-deoxycortisol in serum or urine could become a sensitive marker of residual adrenal function in the future.…”