What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question

A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence

Adrenal myelolipoma: a comprehensive review

INTRODUCTION: Adrenal myelolipoma is an invariably benign neoplasm of the adrenal gland that is the second most common primary adrenal incidentaloma following adrenocortical adenomas. It is composed of elements of adipose tissue and extramedullary hematopoiesis. Hypotheses on stem cells and hormonal factors have been formulated regarding its pathogenesis that is still obscure. Despite its benign behavior, adrenal myelolipoma is clinically relevant as it might cause significant difficulties in the differential diagnosis of adrenal tumors. METHODS: We have reviewed 420 cases reported between 1957 and 2017 on adrenal myelolipoma retrieved from PubMed and Scopus databases and also 20 of our case series to provide a comprehensive analysis of their pathology, epidemiological and clinical features. RESULTS AND CONCLUSIONS: The average age for its diagnosis was 51 years, and no gender difference was observed. The average size of tumors was 10.2 cm. Congenital adrenal hyperplasia was associated to 10% of all cases analyzed, while other adrenal hypersecretory disorders (cortisol, aldosterone) were found in 7.5% of cases. Computed tomography and magnetic resonance imaging can be reliably used for its differential diagnosis. If the diagnosis of an adrenal myelolipoma is unambiguous, and no associated symptoms or hormonal activity are established, surgical intervention is usually not necessary

Progression of vertebral fractures in patients with adrenocortical carcinoma undergoing mitotane therapy

Context: patients with adrenocortical carcinoma (ACC) are frequently on mitotane therapy for a long-time period. The drug exerts an adrenolytic activity requiring glucocorticoid supplementation, which can be potentially detrimental for bone. Objectives: to explore whether mitotane plus/minus chemotherapy is associated with an increased proportion of morphometric vertebral fractures (VFs) in ACC patients. Secondary objectives were: proportion of patients with VF progression, or worsening of the spinal deformity index (SDI) during mitotane therapy; predictive factors of VF progression and prognostic role of VF progression. Design and setting: multicenter, retrospective cohort study of patients with ACC who received mitotane alone or in association to chemotherapy, recruited from January 2010 to January 2020 in two reference centers in Italy and France. Results: a significant increase in the frequency of VFs before and after mitotane therapy was seen both in Italian (28.3% vs 47.8%, p: 0.04) and French (17.8% vs 35.6%, p 0.04) series. VF progression was observed in 39.1%, and 28.9% of patients, respectively. Baseline VFs and increased patient body mass index, but not the dose of cortisol supplementation, showed an independent association with VF progression at multivariate analysis. Among the 72 advanced ACC patients, progression of VFs was associated with a poorer survival. Conclusions: the administration of mitotane plus/minus chemotherapy in ACC patients impairs bone health independently from cortisol supplementation. Appropriate preventive measures to decrease the fracture risk should be implemented in these patients