Adrenal histopathology in primary aldosteronism: is it time for a change?

Abstract

Primary aldosteronism (PA) entails a group of disorders characterized by excess aldosterone production, relatively independent from the renin–angiotensin system.1 Because PA is the most common form of secondary hypertension and patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential hypertension and the same degree of blood pressure elevation,2–5 early recognition of PA is of utmost importance to cure the high blood pressure and prevent deleterious cardiovascular effects. The 2 major PA subgroups are the unilateral forms, mainly aldosterone-producing adenoma (APA), and bilateral forms, mostly adrenal zona glomerulosa (ZG) hyperplasia, which require surgical or medical treatment, respectively. Adrenal vein sampling (AVS) is the best available method to distinguish between unilateral and bilateral aldosterone hypersecretion.6–8 In medical centers where AVS is available and strict cutoff values for the lateralization index are used,9 almost two thirds of PA cases are attributed to an APA, whereas one third remain classified as bilateral idiopathic forms. The opposite is seen when AVS is unavailable.10 Hence, the availability of AVS greatly affects the recognition of unilateral forms of PA that can be successfully treated with adrenalectomy. After surgery, demonstration of an adenoma at pathology is needed to reach a conclusive diagnosis of the only PA subtype that can be unequivocally diagnosed, eg, APA. After the introduction of the 4 corner criteria,10 an APA can be diagnosed when (1) there is evidence of PA at the screening tests, with an inappropriately high aldosterone/renin ratio and confirmation as needed; (2) aldosterone secretion is lateralized at AVS; (3) an adenoma is detected at pathology; and crucially important, (4) PA is corrected by adrenalectomy. However, at pathology, the identification of an APA may be challenging …