Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and poor prognosis. Lactate dehydrogenase (LDH) is an enzyme of the glycolytic pathway that is associated with tumour progression in several cancers. To date, evidence on the prognostic value of LDH in ACC is limited.

Aims: To assess the impact of LDH in disease-free survival (DFS) in operated ACC.

Materials and methods: Retrospective cohort study of patients with ACC that were followed in a tertiary centre from 1991 to 2023. Cases where adrenalectomy was not performed were excluded. Elevation of baseline (presurgical) LDH was defined according to the laboratory cut-off (≥ 247 U/L). The prognostic value of clinical, biochemical and histopathological variables was assessed by the analysis of Kaplan–Meier curves and Cox proportional hazard regression. A cut-off of LDH was obtained from the analysis of ROC curves.

Results: A total of 33 cases were analysed; 75.8% female, mean age at diagnosis of 49.9±12.7 years, 62.1% functioning tumours, ENSAT stages II in 57.6%, III in 27.3% and IV in 15.2%. Resection was R0 in 69.7%, R1 in 18.2%, R2 in 6.1% and indeterminate in 6.1%. Baseline LDH ranged from 159 to 1848 U/L, with a median of 382.0 (IQR 271.0–621.0). Adjuvant mitotane was performed in 78.1%, chemotherapy in 25.0% and radiotherapy in 28.6%. Disease progression (RECIST 3) occurred in 66.7%; 43.3% with local recurrence and 64.5% with metastasis. Median DFS was 1.0 year, and overall survival 3.9 years (0.0-11.6). Functioning tumours (HR 3.77, CI 1.34–10.63, P=0.012), ENSAT stages III-IV (HR 3.49, CI 1.48–8.27, P=0.004), mitotic grade of >20/50HPF (HR 4.47, CI 1.50–13.30, P=0.007) and elevated baseline LDH (HR 7.84, CI 1.04–59.32, P=0.046) showed lower DFS. Each increase of 100 U/L in LDH predicted an increase of 10.2% on the risk of disease progression (CI 1.01–1.20, P=0.028). LDH was significantly higher in functioning tumours, with a median of 524.0 U/L (IQR 299.0–663.0) vs 242.5 U/L (IQR 173.8–493.8), P=0.036, and showed a correlation with urinary free cortisol (UFC) (r=0.540, P=0.006) and with tumour size (r=0.473, P=0.013). Elevated LDH, unlike functioning tumours or UFC, was associated with the development of metastases after diagnosis (80.0% vs 20%, P=0.023). Baseline LDH ≥ 266.5 U/L predicted disease progression with 95% sensitivity and 71.4% specificity (AUC 90.0%, P=0.002).

Conclusions: Baseline LDH levels were associated with disease progression and poor prognosis in operated ACC. LDH levels may help guiding therapeutic decisions in ACC, along with the other well-established prognostic factors.