Immunohistochemical characterization of normal feline adrenal tissue and adrenal tumors secreting aldosterone

Watson, A; Allan, F; Harrington, N; Mahony, O; Brown, M; Syme, H

Abstract

It is suggested that primary hyperaldosteronism (PHA) is an under-diagnosed cause of systemic hypertension in cats. No immunohistochemical markers of aldosterone synthesizing tissues have been identified, meaning that endocrine function cannot be inferred from examining feline tissues. In humans, expression of CYP11B2 (aldosterone synthase) is used for this purpose, but cats have a single CYP11B enzyme responsible for the terminal steps in synthesis of both aldosterone and cortisol, precluding its use as an indicator of steroidogenic function. This study aimed to identify immunohistochemical markers of aldosterone producing tissues. In addition, since there are no existing guidelines for classification of feline adrenal tumors as benign or malignant, this study aimed to investigate potential markers of adrenal tumor malignancy in PHA. Normal adrenals (n = 9) and adrenal tumors secreting aldosterone (n = 31) or cortisol (n = 4) were immunolabeled for steroidogenic enzymes (CYP11B, CYP17A1, and CYB5A), the zona glomerulosa (including KCNJ5 visinin-like 1 (VSNL1), and neuron-specific enolase (NSE)), and proliferation markers (Ki67). Histochemical staining for reticulin was also performed. Transcriptomes of normal (n = 4) and aldosterone secreting tumors (n = 5) were compared. Weak or absent CYP17A1 in conjunction with strong KCNJ5 or VSNL1 immunolabeling was present in aldosterone producing tissues from normal and tumorous cat adrenals. CYP17A1 RNA expression was lower in aldosterone producing tumors compared with normal adrenals (P < .0001). VSNL1 and NSE were not specific markers of aldosterone producing tissue. CYB5A and CYP17A1 were not expressed within the zona reticularis, suggesting minimal adrenal production of androgens. Ki67 proliferative index and reticulin network disruption were not predictive of malignancy.

Citation

Watson, A., Allan, F., Harrington, N., Mahony, O., Brown, M., & Syme, H. (2025). Immunohistochemical characterization of normal feline adrenal tissue and adrenal tumors secreting aldosterone. Veterinary Pathology, https://doi.org/10.1177/03009858251331146

• Journal Article Type: Article
• Acceptance Date: Apr 7, 2025
• Online Publication Date: Apr 21, 2025
• Publication Date: 2025
• Deposit Date: May 20, 2025
• Print ISSN: 0300-9858
• Electronic ISSN: 1544-2217
• Publisher: American College of Veterinary Pathologists
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1177/03009858251331146
• Keywords: adrenal glands; cats; hyperaldosteronism; hypercortisolism; immunohistochemistry; neoplasia; PRIMARY HYPERALDOSTERONISM; ADRENOCORTICAL TUMORS; GENE-EXPRESSION; KCNJ5 MUTATIONS; CAT; 11-BETA-HYDROXYLASE; STEROIDOGENESIS; HISTOPATHOLOGY; SUPPRESSION; CARCINOMA