Endocrine Abstracts

Primary Hyperaldosteronism (PA) is caused by adrenal tumours or bilateral adrenal hyperplasia (Djajadiningrat-Laanen et al., 2011) causing constitutive aldosterone production. Both germline and somatic mutations have been identified in human PA (Scholl, 2022). The commonest somatic mutations in benign tumours causing PA in humans include KCNJ5, CACNA1D, ATP1A1 and ATP2B3 (Williams et al., 2015). It is hypothesized that analogous somatic mutations arise in feline adrenal tumours. DNA was extracted from adrenal tumours and normal tissue (adjacent adrenal, blood, or pancreas) from eight cats diagnosed with primary hyperaldosteronism. Four cases underwent whole genome sequencing (WGS), with one sample having paired normal and tumour tissue. Variant calling was used to identify single nucleotide substitutions arising within the tumours, these were filtered using SIFT to leave variants with a predicted effect on protein function. Variants of interest were confirmed using Sanger sequencing. All cases underwent polymerase chain reactions followed by targeted Sanger sequencing for CTNNB1, KCNJ5, ATP1A1, ATP2B3, GNA11, PCHD15, SLC35F1. WGS revealed numerous variants with predicted significant effects on protein function. In the case with paired germline DNA, somatic single-nucleotide substitutions were identified in PCDH15 and exon 3 of CTNNB1. A different exon 3 mutation of CTNNB1 was identified in a tumour that did not undergo WGS. GNA11 pg48V was identified in a single tumour. No mutations were identified in KCNJ5, CACNA1D, ATP1A1 or ATP2B3. WGS on 4 further paired samples is pending. The genes most commonly mutated in human aldosterone producing adenomas were not mutated in feline PA. Functional exon 3 mutations of CTNNB1 are however common both in human adrenal adenocarcinomas, and a distinctive subset of APAs alongside pQ209 mutations of GNA11 (Zhou et al., 2021). Protocadherin-related-15 (PCDH15) is one of several plasma membrane proteins essential to hearing and vision, expressed in cochlear, retinal and adrenal aldosterone-producing cells.