ACTH Stimulation Maximizes the Accuracy of Peripheral Steroid Profiling in Primary Aldosteronism Subtyping

Abstract

Context: Adrenocorticotropic hormone (ACTH) can contribute to aldosterone excess in primary aldosteronism (PA) via increased melanocortin type 2 receptor expression. Dynamic manipulation of the hypothalamic-pituitary-adrenal (HPA) axis could assist PA subtyping, but a direct comparison of dynamic tests is lacking.

Objective: To investigate plasma steroid differences between aldosterone-producing adenoma (APA) and bilateral PA (BPA) relative to ACTH variations.

Methods: We conducted comprehensive dynamic testing in 80 patients: 40 with APA and 40 with BPA. Peripheral plasma was collected from each patient at 6 time points: morning; midnight; after 1 mg dexamethasone suppression; and 15, 30, and 60 minutes after ACTH stimulation. We quantified 17 steroids by mass spectrometry in response to ACTH variations in all patients and compared their discriminative power between the 2 PA subtypes.

Results: Patients with APA had higher morning and midnight concentrations of 18-hydroxycortisol, 18-oxocortisol, aldosterone, and 18-hydroxycorticosterone than those with BPA (P < 0.001 for all). In response to cosyntropin stimulation, the APA group had larger increments of aldosterone, 18-oxocortisol, 11-deoxycorticosterone, corticosterone, and 11-deoxycortisol (P < 0.05 for all). Following dexamethasone suppression, the APA group had larger decrements of aldosterone, 18-hydroxycortisol, and 18-oxocortisol (P < 0.05 for all), but their concentrations remained higher than in the BPA group (P < 0.01 for all). The highest discriminatory performance between the PA subtypes was achieved using steroids measured 15 minutes post-ACTH stimulation (area under receiver operating characteristic curve 0.957).

Conclusion: Steroid differences between APA and BPA are enhanced by dynamic HPA testing; such noninvasive tests could circumvent the need for adrenal vein sampling in a subset of patients with PA.

Keywords: ACTH; adrenal cortex; aldosterone; hypertension; mass spectrometry; primary aldosteronism.