Paragliola Rosa Maria, Torino Francesco, Papi Giampaolo, Locantore Pietro, Pontecorvi Alfredo, Corsello Salvatore Maria
Unit of Endocrinology, Università Cattolica del Sacro Cuore, Rome, Italy.
Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Eur Endocrinol. 2018 Sep;14(2):62-66. doi: 10.17925/EE.2018.14.2.62. Epub 2018 Sep 10.
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine tumour deriving from the adrenal cortex. A correct therapeutic strategy requires a multidisciplinary approach between endocrinologist, surgeon and oncologist. Surgery is the mainstay treatment in ACC while mitotane, deriving from the insecticide dichloro-diphenyl-trichloro-ethane, is the main base of the medical treatment of ACC in consideration of its adrenocytolitic activity. However, the use of mitotane as adjuvant therapy is still controversial, also in consideration of the retrospective nature of several studies. A prospective randomised trial (ADIUVO), recruiting patients with low-intermediate risk of recurrence, is evaluating the utility of adjuvant treatment with mitotane in this setting. The therapeutic response is observed with plasma levels of mitotane >14 mg/L. However, the major difficulty in the management of mitotane treatment is related to side effects and to the risk of toxicity, which is related to plasmatic levels >20 mg/L, that is considered the upper limit of the therapeutic window. Mitotane therapy results in adrenal insufficiency, and glucocorticoid replacement therapy has to be administered at higher doses than those used in other aetiologies of primary adrenal insufficiency. Furthermore, other endocrine side effects related to mitotane should be considered, in particular on thyroid hormone and testosterone metabolism. Waiting for new medical strategies on molecular targets, it will be mandatory to optimise the current knowledge by prospective trials and, in consideration of the rarity of the disease, collaborative studies between endocrinologists and oncologists are necessary.
肾上腺皮质癌（ACC）是一种罕见且侵袭性强的内分泌肿瘤，起源于肾上腺皮质。正确的治疗策略需要内分泌科医生、外科医生和肿瘤科医生采取多学科方法。手术是ACC的主要治疗手段，而米托坦（源自杀虫剂二氯二苯三氯乙烷）因其肾上腺细胞溶解活性，是ACC药物治疗的主要基础。然而，米托坦作为辅助治疗的应用仍存在争议，这也考虑到了多项研究的回顾性性质。一项前瞻性随机试验（ADIUVO）正在招募复发风险为低至中度的患者，评估在这种情况下米托坦辅助治疗的效用。当米托坦血浆水平>14 mg/L时可观察到治疗反应。然而，米托坦治疗管理中的主要困难与副作用和毒性风险有关，毒性风险与血浆水平>20 mg/L有关，这被认为是治疗窗的上限。米托坦治疗会导致肾上腺功能不全，糖皮质激素替代治疗的剂量必须高于用于其他原发性肾上腺功能不全病因的剂量。此外，应考虑与米托坦相关的其他内分泌副作用，特别是对甲状腺激素和睾酮代谢的影响。在等待针对分子靶点的新治疗策略之际，必须通过前瞻性试验优化现有知识，并且鉴于该疾病的罕见性，内分泌科医生和肿瘤科医生之间的合作研究是必要的。
