Prolonged Adrenal Insufficiency After the Discontinuation of Mitotane Therapy

Author(s): Leonardo Muratori*, Anna Pia, Giuseppe Reimondo, Chiara Pisano, Anna La Salvia, Soraya Puglisi, Giorgio Vittorio Scagliotti, Paola Sperone

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 20 , Issue 3 , 2020

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Graphical Abstract:


Introduction: Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by a high risk of recurrence after radical resection. The role of adjuvant systemic therapy in radically resected patients is unclear. Mitotane, a steroidogenesis inhibitor, is the only drug approved for the systemic treatment of advanced ACC. In 2007, a retrospective case-control study provided the evidence that mitotane, administered for two years after successful surgery, could prolong recurrence-free survival. Adrenal insufficiency (AI), which occurs in almost all patients during the first 12 months of treatment, is an expected side effect of mitotane and requires steroid replacement therapy. Due to its long halflife, mitotane-induced AI persists several months after treatment discontinuation and is managed by cautious tapering of glucocorticoid replacement therapy.

Results: We report a case of symptomatic AI diagnosed after a severe allergic reaction occurring three years after the discontinuation of adjuvant mitotane therapy.

Conclusion: The case suggests that mitotane-induced AI should be monitored for a long time to asses full recovery of adrenal function, in order to prevent adrenal crises.

Keywords: Adrenal cancer, mitotane, adrenal insufficiency, pharmacology, adjuvant, treatment.

Dackiw, Alan PB, et al. "Adrenal cortical carcinoma." World journal of surgery 25.7. 2001, 914.
Schulick, R.D.; Brennan, M.F. Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann. Surg. Oncol., 1999, 6(8), 719-726.
[] [PMID: 10622498]
Veytsman, Irina; Nieman, Lynnette; Fojo, Tito Management of endocrine manifestations and the use of mitotane as a chemotherapeutic agent for adrenocortical carcinoma.Journal of clinical oncology, 2009, 27.27, 4619.
Fassnacht, Martin European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. European journal of endocrinology 1.aop, 2018.
De Francia, S.; Ardito, A.; Daffara, F.; Zaggia, B.; Germano, A.; Berruti, A.; Di Carlo, F. Mitotane treatment for adrenocortical carcinoma: an overview. Minerva Endocrinol., 2012, 37(1), 9-23.
[PMID: 22382612]
Michalakis, K.; Ilias, I. Medical management of adrenal disease: a narrative review. Endocr. Regul., 2009, 43(3), 127-135.
[PMID: 19817507]
Reidy-Lagunes, D.L.; Lung, B.; Untch, B.R.; Raj, N.; Hrabovsky, A.; Kelly, C.; Gerst, S.; Katz, S.; Kampel, L.; Chou, J.; Gopalan, A.; Saltz, L.B. Complete responses to mitotane in metastatic adrenocortical carcinoma—A new look at an old drug. Oncologist, 2017, 22(9), 1102-1106.
[] [PMID: 28559412]
Terzolo, M.; Angeli, A.; Fassnacht, M.; Daffara, F.; Tauchmanova, L.; Conton, P.A.; Rossetto, R.; Buci, L.; Sperone, P.; Grossrubatscher, E.; Reimondo, G.; Bollito, E.; Papotti, M.; Saeger, W.; Hahner, S.; Koschker, A.C.; Arvat, E.; Ambrosi, B.; Loli, P.; Lombardi, G.; Mannelli, M.; Bruzzi, P.; Mantero, F.; Allolio, B.; Dogliotti, L.; Berruti, A. Adjuvant mitotane treatment for adrenocortical carcinoma. N. Engl. J. Med., 2007, 356(23), 2372-2380.
[] [PMID: 17554118]
Hogan, T.F.; Citrin, D.L.; Johnson, B.M.; Nakamura, S.; Davis, T.E.; Borden, E.C. o,p′-DDD (mitotane) therapy of adrenal cortical carcinoma: observations on drug dosage, toxicity, and steroid replacement. Cancer, 1978, 42(5), 2177-2181.
[<2177:AID-CNCR2820420514>3.0.CO;2-X] [PMID: 719602]
Moolenaar, A.J.; van Slooten, H.; van Seters, A.P.; Smeenk, D. Blood levels of o,p′-DDD following administration in various vehicles after a single dose and during long-term treatment. Cancer Chemother. Pharmacol., 1981, 7(1), 51-54.
[] [PMID: 7340988]
Reimondo, G.; Puglisi, S.; Zaggia, B.; Basile, V.; Saba, L.; Perotti, P.; De Francia, S.; Volante, M.; Zatelli, M.C.; Cannavò, S.; Terzolo, M. Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma. Eur. J. Endocrinol., 2017, 177(4), 361-367.
[] [PMID: 28780517]

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Article Details

Year: 2020
Page: [485 - 487]
Pages: 3
DOI: 10.2174/1871530319666190809144620
Price: $65

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