Endocrine Abstracts

JOINT596

Introduction: Mitotane is indicated in the treatment of localized, locally advanced and metastatic adrenocortical carcinoma. There are three main mechanisms of action: inhibition of steroidogenesis (CYP11B1 and CYP11A1), increased endoplasmic reticulum stress (increased free cholesterol ester and fatty acid levels by inhibition of SOAT1, an enzyme that promotes the formation of fatty acid-cholesterol esters) and mitochondrial toxicity (membrane alteration and inhibition of respiratory chain) responsible for the apoptosis and necroptosis of adrenal cells. (1)

Observation: A 40mm right adrenal incidentaloma was discovered on abdominal CT in a 62 years old patient. No hormonal excess was found. A laparoscopic right adrenelectomy was performed due to tumor size, high radiodensity on CT and high FDG uptake. The pathological work-up described a 4cm lesion with a focal adrenocortical carcinoma (Weiss 5) developed within an adrenocortical adenoma (Weiss 1) with myxoid reshuffle. An adjuvant therapy by Mitotane was introduced because of an intermediary risk of recurrence (ENSAT 1, R0 and Ki-67 13%). Imaging follow-up every three months (CT scan and 18F-FDG PET/CT). After 9 months of treatment, the plasma mitotane concentration is at the limit superior, 20.3 mg/l (therapeutic range 14 to 20 ng/mL). 18F-FDG PET/CT uptake of the contralateral left adrenal gland appears, SUV max at 8.5 with no nodular lesion or adrenal hyperplasia on the CT scan. Mitotane is stopped because of thyroid adverse effects and hyperlipidemia. 18F-FDG PET/CT three months later: disappearance of the left adrenal gland FDG uptake.

Discussion: Leboulleux et al (2) report that a percentage of 14% to 29% patients under adjuvant therapy by Mitotane following adrenocortical carcinoma surgery have a contralateral uptake: 4% before treatment, 29% between 0 and 6 months after the start of treatment, 26% between 6 and 12 months, 14% between 12 and 24 months and none after 24 months. The uptake was transient and dissapeared in the 24 months after the start of treatment. In this study, there was no FDG uptake in patients with adrenelectomy for pheochromyctoma, invalidating the hypothesis of a compensatory adrenal growth. A hypothesis is that despite hormonal adrenal replacement therapy, ACTH levels remain at the limit superior or slightly above the limit. Adrenal cells might become avid to 18F-FDG following ACTH stimulation.

References1. Claudia Rita Corso et al. Pharmacological profile and effects of mitotane in adrenocortical carcinoma. BJCP;12/20. DOI:10.1111/bcp.147212698.2. S Leboulleux et al. Fluorodesoxyglucose uptake in the remaining adrenal glands during the follow-up of patients with adrenocortical carcinoma;EJE;01/2011. DOI:10.1530/EJE-10-0666.