Radiological characterization across the spectrum of primary aldosteronism

PURPOSE: To define adrenal imaging phenotypes across primary aldosteronism (PA), low-renin hypertension (LRH), normal-renin hypertension (NRH) and controls. METHODS: This retrospective study included 196 patients evaluated for suspected PA between January 2024 and February 2025. Plasma aldosterone concentration (PAC) was measured by LC-MS/MS. Diagnosis and subtype evaluation of PA was conducted according to Endocrine Society Guidelines (n=95). Individuals who did not meet predefined criteria for PA were further categorized as LRH (n=59) or NRH (n=42) based on the direct renin concentration and aldosterone-to-renin-ratio. Age- and sex-matched individuals without known hypertension served as controls (n=50). Imaging features on CT and MRI, independently and blindly segmented by two radiologists, were categorized in diffuse adrenal enlargement, micronodules (< 10 mm), adenoma/indeterminate lesions (≥ 10 mm), and nodular hyperplasia. RESULTS: Median age was highest in PA (50.0 years), followed by LRH (48.0), and NRH (44.0) (p = 0.049). Sex distribution showed female predominance in NRH (81.0%) and LRH (78.0%) compared to PA (49.5%) (p <0.001). Imaging pathologies were rare in controls (2.0%) and increasingly prevalent from NRH (14.3%) to LRH (35.6%) and PA (42.1%) (p < 0.001). The same difference held for lesions ≥10 mm (p < 0.001). Bilateral lesions and nodular hyperplasia occurred exclusively in PA and LRH. Multivariable logistic regression demonstrated that the association between diagnostic group and adrenal imaging pathologies was independent of age, sex, BMI, and imaging modality. CONCLUSION: These exploratory findings support LRH as a potential intermediate phenotype within the spectrum of aldosterone excess despite not fulfilling classical PA criteria.