Diverse pathological lesions of primary aldosteronism and their clinical significance

Koshiro Nishimoto,Yoshihiro Ogawa,Michio Otsuki,Masakatsu Sone,Hirotaka Shibata,Shozo Miyauchi,Shoichiro Izawa,Hironobu Umakoshi,Shintaro Okamura,Ryuichiro Araki,Takanobu Yoshimoto,Mika Tsuiki,Tsugio Seki,Mitsuhide Naruse,Takuyuki Katabami,Masanori Yasuda,Norio Wada

doi:10.1038/s41440-020-00579-w

Abstract

Primary aldosteronism (PA) is mainly clinically classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (n = 85), partial success (n = 19), and absent success (n = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2–6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.

Highlights

Primary aldosteronism (PA) is the most common cause of endocrine hypertension, which significantly increases cardiovascular complications due to autonomous aldosteroneMembers of the Japan Research Projects for Rare/Intractable Adrenal Diseases (JRAS) Study Group are listed below Acknowledgements
Initial pathological analyses revealed diverse types of putative aldosterone-producing lesions (Fig. 1 and Supplementary Table 1): aldosterone-producing adenoma (APA) that strongly (e.g., Case 148, asterisk in Fig. 1A, B) or unevenly/weakly expressed CYP11B2, APCCs (e.g., Case 214, yellow arrowheads in Fig. 1E, F), and possible APCCto-APA transitional lesions (pAATLs) (e.g., Case 1, Fig. 1G, H) (Supplementary Table 1 and Supplementary Fig. 1; all original images may be downloaded from https:// humandbs.biosciencedbc.jp/en/hum0185-v1-st1 [Supplementary Data 1])
Case 214 was classified into the small PA lesion group for all threshold values because the largest lesion was smaller than 2 mm (Fig. 1E, F)

Summary

Introduction

Primary aldosteronism (PA) is the most common cause of endocrine hypertension, which significantly increases cardiovascular complications due to autonomous aldosteroneMembers of the JRAS Study Group are listed below Acknowledgements. PA is diagnosed by confirmatory tests [2] and is primarily classified as unilateral PA, aldosteroneproducing adenoma (APA, generally unilateral), or bilateral PA ( called idiopathic hyperaldosteronism) [3]. The former is often curable by unilateral adrenalectomy, whereas the latter is mostly treated by lifelong mineralocorticoid receptor antagonists [4]. Immunohistochemistry reveals that APA consists of CYP11B2-positive cells, CYP11B1-positive cells, and Diverse pathological lesions of primary aldosteronism and their clinical significance double negative cells, whereas non-functional adenomas only comprise CYP11B1-positive cells and double negative cells and did not harbor CYP11B2-positive cells. Immunohistochemistry enables pathological discrimination between APA and incidentaloma through the detection of CYP11B2-positive cells [5]

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Conclusion