Endocrine Abstracts

Background: The cure of unilateral primary aldosteronism (PA) after adrenalectomy can result in complete, partial or absent biochemical and clinical improvement¹. Histological findings from HE samples are of little assistance in determining if adenoma or hyperplastic adrenal tissue is hormonally overactive. Our aim in the present study was to compare immunohistochemical (IHC) CYP11B1 and CYP11B2 staining in adrenal slices to histological diagnosis based on H&E staining.

Methods: We identified prospectively 34 patients with confirmed PA². Surgery was based on lateralization of aldosterone concentration in AVS in 33 patients and on lateralization of ¹¹C-metomidate PET and CT findings in one patient. Postoperatively, clinical and biochemical cure were evaluated at about 3 months. Both H&E and immunohistochemical expression of CYP11B1 and CYP11B2 (rat monoclonal anti-human CYP11B1–80–ndash;7 and mouse monoclonal anti-human CYP11B2–41–17 primary antibodies³) were analyzed in 3.5 μm thick adrenal slices in one representative slide from each case. In addition to IHC analysis of aldosterone-producing adenomas (APAs) and hyperplasia, small extranodular CYP11B2 positive cell clusters, so-called aldosterone-producing cell clusters (APCCs) were identified.

Results: After adrenalectomy, 32/34 showed clinical partial or complete cure and 31/32 (data missing for two) biochemical partial or complete cure. The mean aldosterone concentrations, ARR, BP and potassium concentration improved significantly (P<0.001 for all). The number of antihypertensive agents used decreased from 2.5 to 1.0 and DDD decreased by 50% (P<.001 for both). In H&E staining, 22/34 (65%) subjects were diagnosed with APA and 11/34 (32%) with hyperplasia. One subject did not reveal pathologic findings in H&E. All adrenal samples showed CYP11B2 positivity and most some CYP11B1 positivity. The IHC diagnosis was APA in 16/34 (47%), hyperplastic leading nodule 13/34 (38%) and hyperplasia presenting as APCCs in only 6/34 (18%) subjects. IHC staining with CYP11B2 changed the diagnosis from APA to hyperplasia in 6/34 (18%) and from no pathologic findings to APA in 1/34 (3%). One subject with cortical hyperplasia showed CYP11B1 but not CYP11B2 positivity in main nodule together with multiple CYP11B2 positive APCCs. The degree of biochemical cure did not differ between hyperplasia and APA subgroups.

Conclusions: With IHC staining for CYP11B2, the proportion of histological APA diagnoses decrease. APCCs may be significant source of aldosterone excess in some subjects with PA. IHC staining of adrenal tissue improves subtype diagnostics of PA.

References: 1. Williams TA. Lancet Diabetes Endocrinol 2017;5:689

2. Funder JW. JCEM 2016;101:1889

3. Gomez-Sanchez CE. Mol Cell Endocrinol 2014; 5: 111