Endocrine Abstracts

Background: Primary aldosteronism (PA) is mainly caused by unilateral (unilateral PA) or bilateral aldosterone-producing lesions of adrenals (bilateral PA). Accumulating findings suggest distinct metabolic profiles between patients with unilateral and bilateral PA. However, the link between the metabolic features and histopathologic findings of adrenals from patients with PA remains largely unknown.

Objective: To characterize metabolic profiles with a focus on the lipid parameters, adiposity and fatty acid alterations in patients with PA with distinct histopathologic findings and subtypes.

Methods: Patient data were retrospectively collected from a single center and analyzed in 76 patients with bilateral PA and 105 with unilateral PA who were categorized into 71 of classical and 34 of nonclassical histopathology according to HISTALDO consensus. Fatty acid abundances in peripheral serum and adrenal specimens were measured by gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry, respectively, with human adrenocortical HAC15 cells as an in vitro functional validation model.

Findings: Patients of classical histopathology displayed the highest baseline serum omentin-1 levels (classical vs nonclassical vs bilateral PA: 36.13[19.95–191.45] vs 19.63[13.67–37.33] vs 13.46[9.90–29.31] ng/ml, P <0.001), and the lowest leptin levels (classical vs nonclassical vs bilateral PA: 6.40[2.88–10.68] vs 13.43[4.63–21.32] vs 10.06[5.17–18.46] ng/ml, P=0.005). Compared with the nonclassical group, patients of classical histopathology showed lower BMIs (25.17±3.58 vs 27.03±3.06 kg/m², P=0.031) and smaller visceral adipose tissue areas (120.69[74.79-171.16] vs 155.29[127.81-197.46] cm², P=0.020). No differences in lipid profiles and adiposity were detected between the nonclassical and bilateral PA groups. In contrast, patients of classical histopathology displayed the highest peripheral serum polyunsaturated fatty acids (PUFAs) especially ω6-PUFAs concentrations relative to the other two groups. Linear discriminant analysis demonstrated fatty acid signatures classified patients with distinct histopathology and subtypes with an accuracy of 98.7%. Combing with the findings of fatty acid abundance comparisons in aldosterone-producing adenomas vs paired adjacent cortex that identified four distinct PUFAs, C20:4 n-6 (arachidonic acid, ARA) in peripheral serum and adrenals showed a strong association with histopathology and subtypes of PA. Functional experiments demonstrated ARA decreases HAC15 cell viability via reactive oxygen species-induced apoptosis and promotes aldosterone synthase expression and aldosterone production via calcium signaling.

Interpretation: Patients with unilateral PA of classical histopathology display the least severe lipid profiles and adiposity, while showing the highest peripheral serum PUFA levels which is likely associated with their in situ productions in adrenal lesions, with ARA as a potential biomarker for aldosterone-producing lesions of PA.