Bilateral adrenal adenomas presenting with ACTH-independent Cushing's syndrome and primary aldosteronism: diagnostic insights from multi-steroid adrenal venous sampling.

BACKGROUND: Primary aldosteronism (PA) is the most prevalent cause of secondary hypertension (HTN), and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) represents a distinct form of adrenal-derived secondary HTN. Their coexistence resulting from aldosterone- and cortisol-producing adenomas (A/CPAs) is an extremely rare clinical entity. This is particularly true for the subtype characterized by bilateral adrenocortical adenomas, in which one adenoma predominantly secretes aldosterone (ALD) and the other predominantly secretes cortisol (COR), for which only limited clinical reports have been published to date. CASE DESCRIPTION: Both female patients were diagnosed with PA and concurrent ACTH-independent CS. Abdominal computed tomography (CT) revealed bilateral adrenal space-occupying lesions. Adrenal venous sampling (AVS) was subsequently performed using 17α-hydroxyprogesterone (17-OHP), androstenedione (ASD), dehydroepiandrosterone (DHEA) as the reference hormone, which demonstrated lateralized dominance of COR and ALD secretion from opposite adrenal glands. Corresponding clinical features confirmed the diagnosis of A/CPAs in both cases. One patient underwent laparoscopic left adrenal CPA resection, while the other underwent laparoscopic right adrenal CPA resection. Following laparoscopic resection of the CPA in both patients, postoperative COR levels declined, consistent with surgical remission. Spironolactone therapy was initiated. Pathological examination confirmed adrenocortical adenoma. Immunohistochemistry (IHC) showed strong positive expression of CYP11B1 (11β-hydroxylase) and weak expression of CYP11B2 (ALD synthase). Their conditions have remained well controlled to date. CONCLUSIONS: In patients with bilateral adrenal adenomas and concurrent PA and ACTH-independent COR excess, imaging alone may fail to identify the functional source of hormone excess. Multi-steroid adrenal venous sampling demonstrated opposing ALD and COR dominance from contralateral adrenal glands, guiding targeted resection of the COR-dominant lesion and postoperative medical control of residual ALD excess. These cases support multi-steroid AVS for individualized adrenal-sparing management.