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Endocrine Abstracts (2021) 73 PEP1.7 | DOI: 10.1530/endoabs.73.PEP1.7

1University Hospital of Würzburg, Department of Internal Medicine I, Division of Endocrinology, Germany; 2Endocrinology in Charlottenburg, Berlin, Germany; 3University of Florence, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Florence, Italy; 4National and Kapodistrian University of Athens, Department of Pathophysiology, Athens, Greece; 5Institute of Metabolism and System Research, University of Birmingham and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham, UK; 6Catholic University of the Sacred Heart, Division of Endocrinology and Metabolism, Rome, Italy; 7Federico II University, Department of Clinical Medicine and Surgery, Naples, Italy; 8Ludwig-Maximilians-Universität München, Medizinische Klinik und Poliklinik IV, Munich, Germany


Mitotane represents the first-line medical treatment in most patients with adrenocortical carcinoma (ACC). Although adverse effects (AEs) due to mitotane are known to be frequent and may limit treatment, few systematic data are available. Aim of the study was to evaluate the AEs in ACC patients treated with mitotane monotherapy.


A retrospective multicenter study including 311 ACC patients (M:F = 111:200, median age 49 years) treated with mitotane as adjuvant therapy (n = 214, 68.8%) or in advanced disease (n = 97, 31.2%), was performed. Presence and grade of AEs were collected from medical records, retrospectively classified according to the CTCAE 5.0 criteria and correlated with duration of treatment, dosage administered and plasma concentrations of mitotane.


Median duration of mitotane monotherapy was 20 (1–203) months, during which we observed a total of 3004 AEs with a rate per patients of 9.6 (0–30). The number of AEs significantly correlated with AUC of mitotane levels (P = 0.0001, rs = 0.23) and duration of treatment (P = 0.0002, rs = 0.21). Beside glucocorticoid insufficiency, the most frequent AEs were increase of gamma-glutamyl transferase (GGT, 88%), asthenia (68%), nausea (53%), hypercholesterolemia (54%), diarrhea (45%), increased transaminases, anorexia, and vertigo (36%, respectively). Apart from glucocorticoids, specific hormone replace therapy was administrated in 121/172 (70%) patients with hypothyroidism, 44/90 (49%) patients with hypomineralcortisolism, and 20/47 (42.5%) men with hypogonadism secondary to mitotane treatment. Statins and fenofibrate were used in 83/219 (37.9%) and 8/127 (6.3%) of patients with hypercholesterolemia and hypertrygliceridemia. Patients with short-term treatment (≤3 months) had a significantly lower probability to present asthenia (OR = 0.5, P = 0.01), concentration impairment (OR = 0.2, P <0.001), ataxia (OR = 0.1, P = 0.007), increased GGT (OR = 0.4, P = 0.004) and SHBG (OR = 0.2, P <0.001), hypertriglyceridemia (OR = 0.3, P = 0.003), hypothyroidism (OR = 0.4, P = 0.007), hypomineralcortisolism (OR = 0.1, P = 0.01) and gynecomastia (OR = 0.1, P = 0.008) compared to those who received longer treatment (>3 months). Patients with advanced disease were treated for shorter time compared to those adjuvantly treated (median 9 vs 23 months, respectively, P <0.0001) and had a lower risk of aphasia (OR = 0.2, P = 0.04) and dysarthria (OR = 0.5, P = 0.03). Grade 4 AEs were reported in 24 cases (7.7%), including one case of peripheral neuropathy, leukopenia, and sepsis, 3 cases of severe adrenal crisis, and 4, 5, and 9 cases of hypertrygliceridemia, hypercholesterolemia and GTT increase, respectively. Mitotane was permanently discontinued due to AEs in 45 (14.5%) patients.


This is the first comprehensive overview of AEs by mitotane, which will be helpful in the daily clinical practice to prevent and manage toxicity, improving the patient’s quality of life.

Volume 73

European Congress of Endocrinology 2021

22 May 2021 - 26 May 2021

European Society of Endocrinology 

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