The inclusion criteria for patients in this study are based on the pathogenicity of the APC variants they carry, in contrast to other international studies where a clinical definition of FAP was used (> 100 adenomatous polyps in endoscopic studies). In our cohort, some patients presented with polyposis on colonoscopy but had VUS or benign APC variants. These patients were excluded from the study to limit the heterogeneity of the studied population. Patients with pathogenic APC variants who did not strictly fulfil the classic clinical criteria of FAP in endoscopic studies were included as per our criteria. Rather than regarding adrenal tumours as an extraintestinal manifestation of FAP, we focus on whether the pathogenicity of APC variants would affect the formation of adrenal tumours.

There is no Australian data on the prevalence of adrenal tumours in FAP. From recent international studies, the prevalence of adrenal tumours is 3–10% in the general population [10,11,12,13,14] and 7.4–26% among FAP patients defined phenotypically [4, 6,7,8]. The prevalence of adrenal tumours among patients with pathogenic or likely pathogenic APC mutations in this study (26.7%) is so far the highest.

There was no significant correlation between genotype and the presence of adrenal tumours among those with pathogenic variants. This result is consistent with the Canadian study [4]. Most of the variants in our patients with adrenal tumours involve frameshift or premature stop codons, typical of pathogenic variants described in APC in the literature and on the LOVD and ClinVar databases.

No malignant features of adrenal glands were detected among the cohort based on CT or MRI scans. This is consistent with the four previous retrospective studies where only two cases of malignancy were found among them, and it was hypothesised that the prevalence of malignant adrenal tumours among FAP is similar to that in the general population [4, 6,7,8].

There are some limitations identified in this study. This study is retrospective in nature and a control group was not included. Also, the prevalence of adrenal tumours in the general Australian population is unavailable. Therefore, we were unable to directly compare the prevalence of adrenal tumours in our cohort against the Australian population.

The CT or MRI scans were conducted at no specific patient age. Rather, they were done for various reasons, including screening for desmoid tumours, staging for malignancy, and investigating abdominal pain. The percentage of the patients who received the scans due to presentation with gastrointestinal symptoms was similar between those with and without adrenal tumours (41.7% vs. 43.9%) supporting the likelihood that the findings from this study were representative of all patients with FAP. No initial CT or MRI scans of the patients in our cohort were conducted related to clinical suspicion of adrenal tumours (like symptoms of hormonal disturbance). All adrenal lesions we found were considered to be adrenal incidentalomas.

No routine adrenal hormonal testing was conducted for adrenal incidentalomas. Only four patients in this study had adrenal hormonal testing due to secondary hypertension screening and constitutional symptoms of weight loss and fatigue in the context of the adrenal tumours. Thus, it is difficult to assess the pattern of hormonal function for patients with pathogenic APC variants and adrenal tumours. In the general population, isolated or combined subclinical hormonal abnormalities can occur in 37.4% of patients with adrenal tumours [15]. However, no studies in the literature systematically investigate hormonal abnormalities among FAP patients with adrenal tumours. Given the increased prevalence of adrenal tumours among those with pathogenic APC variants, future research can investigate the functional consequences of these adrenal tumours. This will provide meaningful information on whether routine hormonal testing on this cohort will be beneficial.