Discordance Between Imaging and Immunohistochemistry in Unilateral Primary Aldosteronism

Aya T. Nanba; Kazutaka Nanba; James B. Byrd; James J. Shields; Thomas J. Giordano; Barbara S. Miller; William E. Rainey; Richard J. Auchus; Adina F. Turcu


Clin Endocrinol. 2017;87(6):665-672. 

In This Article

Abstract and Introduction


Objective Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures.

Patients and Design We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α-hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation.

Results Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT-detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2-negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava.

Conclusions Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA.


Primary aldosteronism (PA) is the most common identifiable form of secondary hypertension.[1] PA is highly prevalent among patients with resistant hypertension and is diagnosed in over 10% of the patients referred to specialized centres.[2–4] PA is associated with increased cardiovascular morbidity and mortality as compared to equivalent degrees of essential hypertension,[5–7] and hence, early recognition and treatment of PA is imperative.[8] PA is traditionally subclassified as either bilateral hyperaldosteronism (BHA) or aldosterone producing adenomas (APA),[1] although some patients have features of both subtypes. Correct subclassification of PA is essential, as patients with unilateral PA can benefit from surgical treatment. Immunostaining for aldosterone synthase (CYP11B2), the key enzyme in aldosterone production, is not widely available; consequently, when postoperative clinical assessment demonstrates surgical cure of hyperaldosteronism, it is assumed that a histologically identified macroscopic adrenal tumour was the primary source of aldosterone. Since the development of highly specific CYP11B2 antibodies, it has been demonstrated that the subclassification of PA spans a continuum, ranging from single or multiple APA, to small aldosterone producing cell clusters (APCC), to zona glomerulosa hyperplasia.[9–12] The variable immunohistochemistry findings in resected adrenals from patients with PA underscore the limitations of adrenal imaging in identifying the source(s) of aldosterone excess.

Adrenal vein sampling (AVS) is considered the most accurate method for determining whether one or both adrenals produce excess aldosterone.[8] Aside from patients younger than 35 years with unequivocal PA,[13,14] cross-sectional adrenal imaging findings are frequently discordant with the aldosterone source as lateralized by AVS.[15–19] Nevertheless, resolution of PA after unilateral adrenalectomy is not always achieved, even if the decision is based on AVS lateralization,[9,13,20] in part because AVS technique and interpretation vary widely between centres.[21] Moreover, AVS results might be influenced by several antihypertensive agents and by autonomous adrenal cortisol synthesis.[1,8] For these reasons, the supremacy of AVS in PA subclassification has been questioned.[20]

Several studies have focused on outcomes after adrenalectomy in PA, but the emphasis has been on success rates rather than on causes of treatment failure. While clinical improvement is achieved in the majority of PA cases treated surgically,[9,13,22–24] data regarding contributors to surgical treatment failure have been scarce. In the present study, we aimed to identify the pitfalls in PA subclassification, leading to the absence of PA improvement after surgical treatment.