Serendipitous Adrenal Hyperplasia in Patients Admitted to the Emergency Department for Suspected SARS-CoV-2 Infection is Linked to Increased Mortality.

BACKGROUND: Few data are available on adrenal morphology in patients with acute diseases, although it is known that endogenous glucocorticoids are essential for survival under stress conditions and that an adequate response is driven by activation of the hypothalamic-pituitary-adrenal (HPA) axis. AIMS: The aim of this study was to assess adrenal morphology in patients with acute disease compared with patients with non-acute disease. METHODS: This cross-sectional study included: 402 patients admitted to the emergency department (ED) for suspected SARS-CoV-2 infection (March-May, 2020) [main cohort]; 200 patients admitted to the ED for acute conditions (December 2018-February 2019) [control group A]; 200 outpatients who underwent radiological evaluation of non-acute conditions (January-February 2019) [control group B]. Chest and/or abdominal CT scans were reviewed to identify adrenal nodules or hyperplasia. RESULTS: In the main cohort, altered adrenal morphology was found in 24.9% of the patients (15.4% adrenal hyperplasia; 9.5% adrenal nodules). The frequency of adrenal hyperplasia was higher both in the main cohort (15.4%) and control group A (15.5%) compared to control group B (8.5%; p = 0.02 and p = 0.03, respectively). In the main cohort, 14.9% patients died within 30 d. According to a multivariate analysis, adrenal hyperplasia was an independent risk factor for mortality (p = 0.04), as were older age (p <0.001) and active cancer (p = 0.01). CONCLUSIONS: The notable frequency of adrenal hyperplasia in patients with acute diseases suggests an exaggerated activation of the HPA axis due to stressful conditions. The increased risk of short-term mortality found in patients with adrenal hyperplasia suggests that it may be a possible hallmark of worse prognosis.

Germline NGS targeted analysis in adult patients with sporadic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer that arises sporadically or due to hereditary syndromes. Data on germline variants (GVs) in sporadic ACC are limited. Our aim was to characterize GVs of genes potentially related to adrenal diseases in 150 adult patients with sporadic ACC. METHODS: This was a retrospective analysis of stage I-IV ACC patients with sporadic ACC from two reference centers for ACC in Italy. Patients were included in the analysis if they had confirmed diagnosis of ACC, a frozen peripheral blood sample and complete clinical and follow-up data. Next generation sequencing technology was used to analyze the prevalence of GVs in a custom panel of 17 genes belonging to either cancer-predisposition genes or adrenocortical-differentiation genes categories. RESULTS: We identified 18 GVs based on their frequency, enrichment and predicted functional characteristics. We found six pathogenic (P) or likely pathogenic (LP) variants in ARMC5, CTNNB1, MSH2, PDE11A and TP53 genes; and twelve variants lacking evidence of pathogenicity. New unique P/LP variants were identified in TP53 (p.G105D) and, for the first time, in ARMC5 (p.P731R). The presence of P/LP GVs was associated with reduced survival outcomes and had a significant and independent impact on both progression-free survival and overall survival. CONCLUSIONS: GVs were present in 6.7 % of patients with sporadic ACC, and we identified novel variants of ARMC5 and TP53. These findings may improve understanding of ACC pathogenesis and enable genetic counseling of patients and their families.