Intérêt de l'immunomarquage de la protéine GIRK4 dans la confirmation de l’origine glomérulée des lésions surrénaliennes observées chez des chats atteints d'hyperaldostéronisme primaire

Primary hyperaldosteronism (PHA) is an increasingly recognized endocrine disorder in ageing cats, characterized by autonomous aldosterone secretion by the adrenal cortex, leading to systemic hypertension and hypokalaemia. Diagnosis relies on a combination of clinical, biochemical, and imaging findings, but characterization of the underlying histological lesions remains challenging, particularly in the absence of formal histological criteria for zona glomerulosa hyperplasia. In this context, the objective of this study was to evaluate the relevance of GIRK4 immunolabeling (a potassium channel encoded by the KCNJ5 gene), physiologically expressed in zona glomerulosa cells, as a marker of glomerulosa cell identity in adrenal lesions associated with PHA. Adrenal tissues from 10 cats with PHA and 7 control cats were analysed using conventional histology combined with immunolabeling for GIRK4 and CYP17 (an enzyme absent from the zona glomerulosa and specific to the zona fasciculata). In control cats, GIRK4 expression was restricted to the zona glomerulosa, confirming its physiological localization. In PHA cats, GIRK4 expression varied according to lesion type: GIRK4- positive and CYP17-negative formations were interpreted as being of glomerulosa origin, whereas four lesions—including three adenocarcinomas—were negative for GIRK4. For three cases, including two adenocarcinomas, an incorrect diagnosis of PHA was excluded. Thus, the absence of GIRK4 labeling raises two main hypotheses: insufficient sensitivity of the antibody, or possible KCNJ5 mutations. The latter warrants investigation through targeted sequencing. Additionally, the use of complementary markers such as DAB2 could improve the detection of glomerulosa-derived cells when GIRK4 expression is weak or absent. We also observed variability in the organization of the zona glomerulosa according to age in healthy cats, suggesting age-related cortical remodeling with potential implications for the diagnosis of bilateral hyperplasia. Finally, although a GIRK4+/CYP17- immunophenotype is suggestive of a glomerulosa origin, it does not constitute formal evidence of aldosterone secretion. A better understanding of the interplay between CYP17 and CYP11B would be required to confirm the endocrine function of the identified lesions.