Mitotane is a derivative of DDT.
It directly suppresses the adrenal cortex.
It inhibits steroidgenesis, and long-term use induces atrophy of the adrenal cortex.
Mitotane also alters the peripheral, metabolism, steroids, leading to drug interactions.
Atrophy of the zone fasciculata occurs after several weeks leading to decreased cortisol production and adrenal insufficiency.
Atrophy of the Zona glomerulosa occurs in only some patients, takes longer time to develop, typically months, and results in aldosterone deficiency.
Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing’s syndrome.
Itinduces 3A4 isoform of the cytochrome P450 enzyme, so maintenance doses of glucocorticoids and mineralocorticoids, are several times as high as the usual dose required.
It can decrease levels of free thyroxine and indirectly inhibit the secretion of thyrotropin.
Pregnancy category C
Routes of administration-By mouth
Bioavailability 40%
Protein binding 6%
Elimination half-life 18–159 days
It is an orphan drug for adrenocortical carcinoma.
Its main use is in those patients who have persistent disease despite surgical resection, those who are not surgical candidates, or those who have metastatic disease.
It use showed a significant increase in the recurrence-free interval after radical surgery followed by mitotane when compared to surgery alone.
The drug is also sometimes used in the treatment of Cushing’s syndrome.
The use of mitotane is unfortunately limited by side effects: anorexia and nausea (88%), diarrhea (38%), vomiting (23%), decreased memory and ability to concentrate (50%), rash (23%), gynecomastia (50%), arthralgia (19%), and leukopenia (7%).
It acts as an inhibitor of cholesterol side-chain cleavage enzyme and also of 11β-hydroxylase, 18-hydroxylase, and 3β-hydroxysteroid dehydrogenase to a lesser extent.
Mitotane has direct cytotoxic effects on the adrenal cortex, inducing permanent adrenal atrophy similarly to DDD.