Adrenal masses differentiation through the measurement of circulating cell-free DNA concentrations

Lorenzo Tucci; Ana Crastin; Oskar Podstawka; Alessandro Prete; Miriam Asia; Elhassan Yasir S; Vasileios Chortis; Dalmazi Guido Di; Cristina Ronchi

doi:10.1530/endoabs.109.OC2.5

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Endocrine Abstracts (2025) 109 OC2.5 | DOI: 10.1530/endoabs.109.OC2.5

SFEBES2025 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)

Adrenal masses differentiation through the measurement of circulating cell-free DNA concentrations

Lorenzo Tucci ^1,2,3 , Ana Crastin ¹ , Oskar Podstawka ⁴ , Alessandro Prete ^1,5,6 , Miriam Asia ⁶ , Yasir S Elhassan ⁶ , Vasileios Chortis ^1,6 , Guido Di Dalmazi ^2,3 & Cristina Ronchi ^1,6

Author affiliations

¹Department of Metabolism and Systems Science, University of Birmingham, Birmingham, United Kingdom; ²Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy; ³Endocrinology and Diabetes Prevention and Care Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy; ⁴Cancer Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom; ⁵NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom; ⁶Department of Endocrinology, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom

Background: Ruling out malignancy in adrenal masses (AM) is a clinical challenge. We demonstrated that circulating cell-free DNA concentrations (ccfDNA-C) are higher in patients with adrenocortical carcinoma (ACC) compared to healthy subjects (HS). However, ccfDNA-C have not been compared among different types of AM.

Objectives: To assess the potential role of ccfDNA-C for AM differentiation.

Methods: We enrolled 81 patients (45 females) with adrenocortical adenoma (ACA, n=55), other benign AM (OB, n=5), ACC (n=11), pheochromocytoma (n=3) and adrenal metastases from other primary tumours (MET, n=7). Blood samples, clinical, hormonal and radiological data were collected at first referral. AM with heterogeneous radiological appearance and/or size >4 cm or plain Hounsfield Units >10 and not associated with overt adrenal hormone excess were labelled as “undefined AM” (n=36/81, 18 ACA, 5 OB, 6 ACC, 7 MET). ccfDNA was isolated with a commercial kit and ccfDNA-C were measured with fluorometer. Age, sex and tumour size adjusted univariate analysis was conducted to assess ccfDNA-C distribution. We tested the diagnostic performance of our previously published HS-derived cut-off (>0.146 ng/μL) with positive (PPV) and negative predictive value (NPV) for ACC recognition.

Results: ccfDNA-C were higher in ACC than in OB (P=0.001), MET (P<0.001), and ACA (P=0.069) but comparable to PHEO (P=0.402). Our ccfDNA cut-off predicted ACC with PPV=33.33% and NPV=96.3% in the entire cohort. Considering undefined AM, ccfDNA-C were higher in ACC than in each AM group (P<0.001) and our cut-off showed PPV=50.0%, NPV=100.0% in predicting ACC. The same cut-off was confirmed by logistic regression and showed Odds Ratio: 6.515 (95% Confidence of Interval: 1.936-21.911), P<0.001, sensitivity 81.8% and specificity 74.3% with same PPV and NPV.

Conclusions: In undefined AM, high ccfDNA-C seem to be ACC-specific and ccfDNA-C >0.146 ng/μL is useful for ACC discrimination. Further samples are being tested to increase statistical power.