Endocrine Abstracts

Introduction: Malignant paraganglioma/pheochromocytoma (MPP) are very rare neuroendocrine tumors with heterogeneous prognostic and no gold-standard treatment. MPP can be associated with germline mutations at SDH-x genes which encode for the succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate. SDH-x mutations lead to inactivation of the enzyme and thus accumulation of succinate.Aim: This project aims to evaluate...

Mitotane (o,p’DDD) represents the most effective treatment of adrenocortical carcinoma (ACC). However, molecular mechanisms of mitotane action remain poorly understood. Mitochondrial (mt) impact of mitotane has previously been suggested but not yet fully validated. We investigated functional consequences of mitotane exposure on mitochondrial steroidogenesis, respiratory chain activity and biogenesis, using human adrenocortical secreting H295R and non-secreting SW13 cells....

Introduction: Adrenocortical carcinoma (ACC) is a rare tumor of the adrenals with poor prognosis (survival rate for metastatic patients <15% at 5 years). Mitotane (o,p′-DDD) is the main therapeutic option with up to 66% objective response rates in patients with serum levels between 14 and 20 mg/l. Its two main metabolites are o,p′-DDA and o,p′-DDE which plasma levels are not correlated to therapeutic response. Mitotane is a lipophilic drug that accumulate...

Background: The benefit to risk ratio of mitotane high starting dose regimen in ACC remains unknown.Methods: To evaluate a high starting dose strategy, we performed a single-center, prospective study with three main objectives: 1) to assess the time taken to reach a mitotane plasma level above 14 mg/l (benefit); 2) to evaluate mitotane tolerance (risk) in the first 3 months of treatment and 3) to analyse the correlation using a regression analysis test b...