Primary AldosteronismOne Picture Is Not Worth a Thousand Words

Physicians often rely on imaging to guide clinical decision making. When computed tomography (CT) or magnetic resonance imaging (MRI) is used to demonstrate adrenal morphologic appearance in patients with primary aldosteronism, the images may lead to errors in clinical management. In this issue, Kempers and colleagues (1) report a systematic review of the diagnostic procedures to distinguish between unilateral and bilateral adrenal disease in patients with primary aldosteronism. Their key finding, based on 950 patients with primary aldosteronism from 38 studies, is that the adrenal morphologic appearance on CT or MRI does not accurately identify the source of aldosterone excess (1). Primary aldosteronism, first described by Conn in 1955 (2), is caused by renin-independent adrenal hypersecretion of aldosterone. Conn's first case was a 34-year-old woman with hypertension and hypokalemia caused by a unilateral adrenal aldosterone-producing adenoma. Hypertension and hypokalemia were cured with right adrenalectomy. In addition to aldosterone-producing adenomas, 6 other subtypes of primary aldosteronism were described over the subsequent 4 decades (3). Aldosterone-producing adenoma and bilateral idiopathic hyperaldosteronism are the 2 most common subtypes of primary aldosteronismaldosterone-producing adenomas account for approximately 35% of cases, and bilateral idiopathic hyperaldosteronism accounts for approximately 60% of cases (3). In patients with an aldosterone-producing adenoma, unilateral adrenalectomy results in normalization of potassium levels in patients with hypokalemia on presentation, improvement of blood pressure in all patients, and normalization of blood pressure in approximately 30% to 60% of patients (36). In patients with idiopathic hyperaldosteronism, unilateral or bilateral adrenalectomy seldom corrects hypertension (7); thus, they should be treated with a mineralocorticoid-receptor antagonist. In addition, lifelong treatment with a mineralocorticoid-receptor antagonist is a reasonable alternative treatment strategy in patients with aldosterone-producing adenomas who are unwilling to have surgery, are elderly, or have comorbid conditions that preclude surgery (8, 9). The treatment goals are to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage from aldosterone excess (10). Thus, a key diagnostic step in patients who want to pursue a surgical cure for primary aldosteronism is to distinguish between a unilateral aldosterone-producing adenoma and bilateral idiopathic hyperaldosteronism. In order for an adrenal cortisol-producing adenoma to produce enough glucocorticoids to cause the Cushing syndrome, a sizeable factory (for example, an adenoma >2.5 cm in diameter) is needed (11). However, because of the efficient mineralocorticoid synthetic processes, aldosterone-producing adenomas can be small (for example, <1 cm in diameter) and still cause clinical hyperaldosteronism (7, 12). Because of their small size, the adenomas may not be morphologically detectable on adrenal-directed CT or MRI. In addition, adrenal glands in a patient with bilateral idiopathic hyperaldosteronism may appear normal on CT or show nodular changes. To confuse the picture even more, the development of adrenocortical nodularity is common in healthy individuals and is, in part, a function of aging (13, 14). Thus, it is impossible for a clinician to know whether a solitary adrenal nodule observed on CT in a patient older than 40 years with primary aldosteronism has any role in the pathogenesis of the aldosterone excessit may be an aldosterone-producing adenoma or a nonfunctioning cortical nodule (15). If such a patient wants to pursue a surgical cure of primary aldosteronism, additional testing is required to determine the source of excess aldosterone secretion. Kempers and colleagues (1) have documented that adrenal CT or MRI is not very accurate in distinguishing between aldosterone-producing adenomas and bilateral idiopathic hyperaldosteronism and can lead to serious and irreversible treatment errors (15). Therefore, adrenal vein sampling (AVS) is essential to direct appropriate therapy in many patients with primary aldosteronism who have a high probability of having an aldosterone-producing adenoma (3) and who seek a potential surgical cure (1, 3, 4, 15). Although AVS, which has been in clinical use for more than 40 years (16), is the criterion standard to distinguish between unilateral and bilateral adrenal disease in patients with primary aldosteronism (4), the indications to perform AVS, the lack of a standardized protocol, and the successful cannulation of both adrenal veins continue to be challenging clinical issues (17). The 5 keys to a successful AVS program are appropriate patient selection, careful patient preparation, focused technical expertise, defined protocol, and accurate data interpretation (17). The use of AVS should be based on patient preferences, patient age, clinical comorbid conditions, and clinical probability of finding an aldosterone-producing adenoma (3). It is an intricate procedure because the right adrenal vein is small and may be difficult to locatethe success rate depends on the proficiency of the angiographer. The key factors that determine the successful catheterization of both adrenal veins are experience, dedication, and repetition. With experience and by focusing the expertise to 1 or 2 radiologists at a referral center, the AVS success rate can be as high as 96% (15, 18). A center-specific, written protocol is mandatory (17). The protocol should be developed by an interested group of endocrinologists, hypertension specialists, internists, surgeons, radiologists, and laboratory personnel. Safeguards should be in place to prevent mislabeling of the blood tubes in the radiology suite and to prevent sample mix-up in the laboratory. At centers that report their experience with AVS, the complication rate is 2.5% or less (15, 1820). The most common complication is symptomatic groin hematoma, and very rarely does adrenal hemorrhage or dissection of an adrenal vein complicate the procedure. A recent clinical practice guideline (4) recommended that AVS be performed in all patients who have primary aldosteronism and want to pursue surgical management. A more practical approach is selective use of AVS based on patient preferences, patient age, adrenal morphologic appearance on CT, clinical comorbid conditions, and clinical probability of finding an aldosterone-producing adenoma (3). It should be performed only in patients with confirmed primary aldosteronism who want to pursue the surgical option in the management of their hypertension (3, 4). When AVS is performed correctly, the standardized AVS laboratory report (17) is worth more than any number of pictures.