Plasma steroid profiling in patients with adrenal incidentaloma

Abstract

CONTEXT: Most patients with adrenal incidentaloma have non-functional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need.

OBJECTIVE: Establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for differential diagnosis of patients with adrenal incidentaloma.

DESIGN: Retrospective cross-sectional study.

SETTING: European tertiary-care centers.

PARTICIPANTS: 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma, primary aldosteronism (PA), autonomous cortisol secretion (ACS) and non-functional adrenal incidentaloma (NFAI).

OUTCOME MEASURES: Measures of diagnostic performance (with [95% confidence intervals]) for discriminating different subgroups of patients with adrenal incidentaloma.

RESULTS: Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxprogesterone, androstenedione and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA and pheochromocytoma at respective sensitivities of 83.3[66.1-100]%, 90.8[83.7-97.8]% and 94.8[89.8-99.8]% and specificities of 98.0[96-9-99.2]%, 92.0[89.6-94.3]% and 98.6[97.6-99.6]%. With addition of tumor size, discrimination improved further, particularly for ACC (100[100-100]% sensitivity, 99.5[98.9-100]% specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70-71% sensitivity, 89-90% specificity).

CONCLUSIONS: Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate identification of almost all clinically relevant adrenal tumors.