Endocrine Abstracts

JOINT3703

Background: Adrenocortical carcinoma (ACC) is a rare cancer with limited population-based studies. This study aimed to analyze the largest single-center ACC cohort over a 20-year period, investigating prognostic factors for clinical outcomes and the relevance of liquid chromatography tandem mass spectrometry (LC–MS/MS) for hormone measurement.

Methods: We conducted a cohort study of patients treated at our referral center from January 2000 to May 2024. Clinicopathological characteristics, including sex- and age-related differences, were analyzed. Overall survival (OS) was assessed using Kaplan–Meier and Cox regression analyses. Hormone profiling via LC–MS/MS including 15 steroids was performed in a subgroup and compared with standard hormone assays.

Results: 1516 ACC patients (median age 51 years, IQR 39–62; 62% female) were included. Median OS was 59 months (95%CI=50.1–87.9), with ENSAT tumor stage, resection status, Ki67-index confirmed as independent prognostic factors (P<0.001). No significant sex-related differences were found in OS, age at diagnosis, tumor stage, or metastasis patterns. However, men had larger tumors (median 12 (8–16) vs 10 (7–14) cm) that were more frequently incidentally diagnosed (39% vs 26%, P<0.001, χ²=23.06). Young patients (<16 years-old) had significantly longer OS (median not-reached) compared to young/adult (91 months, 95%CI=69.3–122.7), adult (63 months, 95%CI=48.6–77.8) and old patients (35 months, 95%CI 28.7–41.3) at multivariate regression (HR between 0.8 and 0.3, P<0.001). Endocrine-inactive and androgens-secreting tumors were associated with significant better survival (111 months, 95%CI=60.6–161.4, HR=0.56, P>0.001; and 105 months, 95%CI=56.6–153.5, HR=0.63, P=0.01) than other hormone-secreting tumors (36 months, 95%CI=30.3–41.6) at Cox regression. At diagnosis, metastases in liver, lymph nodes, and bone were associated with worse outcomes (P<0.01), while lung metastases had no significant impact. In 78 patients evaluated with LC–MS/MS, a median of 3 (IQR 2–5) elevated steroids per patient was found and only 3 (3.8%) had complete negative hormonal profiles compared to 7 (8.9%) classified as inactive by standard immunoassays. Especially 11-deoxycortisol and 11-deoxycorticosterone were frequently detected (82% and 48%, respectively), also in patients with apparently inactive tumors. Increase of ≥4 steroids were associated with poorer OS (15 months, 95%CI=7.6–22.4) than those with ≤3 increased steroids (31 months, 95%CI=21.9–40.1; HR=1.9, 95%CI=1.1–3.8, P=0.04) at multivariate regression.

Conclusion: While ACC is more frequent in women, our study suggest that sex-dimorphism has no impact on clinical outcome. Younger age, endocrine-inactive, and androgen-secreting tumors are associated with better survival. LC–MS/MS steroid panel diagnostic enhances hormonal detection and demonstrates that virtually all ACCs are endocrine active, improving diagnosis and potentially impacting patient management.