Mitotane: The Adrenal-Destroying Drug for Adrenocortical Carcinoma

Table of Contents

1. A Relative of an Old Insecticide
2. How It Acts on the Adrenal Cortex
3. How the Body Absorbs, Stores and Clears It
4. Results in Advanced Adrenocortical Carcinoma
5. Mitotane After Surgery
6. Reported Use in Cushing's Syndrome
7. The Blood-Level Target of 14 to 20 mg/L
8. What the U.S. Label Says
9. Adrenal Shutdown and Steroid Replacement
10. How It Speeds Up the Breakdown of Other Medicines
11. Brain, Liver, Blood and Other Label Hazards
12. What Is Not Known
13. Key Research Papers
14. Connections
15. Featured Videos

A Relative of an Old Insecticide

Mitotane's chemical name on the U.S. label is (±)-1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane, shortened to o,p'-DDD. The letters DDD place it in the same chemical family as the insecticide DDT. A 2018 review describes mitotane as "deriving from the insecticide" DDT and calls it the main base of medical treatment for adrenocortical carcinoma because of its ability to kill adrenal cortex cells (PubMed PMID: 30349596).

The label calls mitotane "an adrenal cytotoxic agent", meaning a substance that is toxic to adrenal cells. It is sold as 500 mg tablets. The label also classes it as a hazardous drug and states that caregivers wear disposable gloves when they handle the tablets.

Reviews from the main European research groups describe mitotane as the only drug approved for adrenocortical carcinoma (PubMed PMID: 21883349, PubMed PMID: 29452402), and the 2015 Würzburg study notes it has been used clinically for decades despite serious adverse effects (PubMed PMID: 26305886). A 2021 pharmacology review describes it as the only adrenolytic drug, that is, the only drug that breaks down adrenal tissue, approved by the U.S. Food and Drug Administration (FDA) for this cancer (PubMed PMID: 33382119).

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How It Acts on the Adrenal Cortex

The U.S. label states that the mechanism of action is unknown. It describes two observed effects: mitotane changes the way the body breaks down steroids outside the adrenal gland, and it directly suppresses the adrenal cortex.

A blocked fat-handling enzyme in adrenal cancer cells

A 2015 laboratory study from Würzburg, Germany, gave the most detailed explanation so far. Working in an adrenal cancer cell line, the researchers found that mitotane blocks an enzyme called sterol-O-acyl transferase 1 (SOAT1). This enzyme normally packs spare cholesterol into a safe storage form. With the enzyme blocked, free cholesterol, oxysterols and fatty acids built up inside the cancer cells. That build-up stressed the endoplasmic reticulum, the cell's protein-folding workshop, and the cells died. The same stress signals were switched on to a much lesser extent in four cell lines that do not make steroids, which fits the drug's narrow aim at steroid-making tissue (PubMed PMID: 26305886).

In the same study, tumour samples from patients showed variable amounts of sterol-O-acyl transferase 1, and the amount correlated with how the tumours had responded to mitotane. The authors concluded that blocking this enzyme accounts both for the drug's adrenal-specific cell killing and for its fall in steroid output (PubMed PMID: 26305886).

Faster breakdown of cortisol in the liver

Mitotane also raises the liver's breakdown of cortisol. A 2011 review states that a higher replacement dose of steroid hormones is the standard of care during treatment for this reason (PubMed PMID: 21883349). This is the same liver effect that changes the levels of many other medicines (see the interactions section).

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How the Body Absorbs, Stores and Clears It

The label's pharmacology section explains why mitotane behaves so differently from most pills:

• Absorption. About 40% of a swallowed dose is absorbed. The label states that the effect of food on its own tablet is not known, while data from various mitotane formulations suggest that high-fat food increases absorption. The label's instructions are to take the tablets with food, at a consistent time relative to meals.
• Storage in fat. Mitotane is found in most body tissues, but fat is the main place it collects. The label states that blood levels can rise suddenly even on a constant dose, and that fat tissue may keep releasing the drug after it has been stopped. It singles out people who are overweight and people who have recently lost weight for closer blood-level checks.
• Very slow clearance. After the drug is stopped, the time for the blood level to halve ranges from 18 to 159 days, with a median of 53 days. The label states that significant levels can persist for weeks.
• Breakdown products. No unchanged mitotane appears in urine or bile. The main breakdown product in the blood is o,p'-DDA. About 10% of a dose is recovered in urine as a water-soluble breakdown product, and 1% to 17% leaves through the bile.

A 2021 review links these traits, namely heavy first-pass metabolism, build-up in tissue and long elimination, to the high doses needed to reach a working blood level and to the side effects that follow (PubMed PMID: 33382119).

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Results in Advanced Adrenocortical Carcinoma

Mitotane with etoposide, doxorubicin and cisplatin: the FIRM-ACT trial

The FIRM-ACT trial randomly assigned 304 people with advanced adrenocortical carcinoma to mitotane plus one of two chemotherapy combinations. One group received etoposide, doxorubicin and cisplatin every 4 weeks. The trial gave etoposide at 100 mg per square metre of body surface on days 2 to 4, doxorubicin at 40 mg per square metre on day 1, and cisplatin at 40 mg per square metre on days 3 and 4. The other group received streptozocin every 3 weeks (PubMed PMID: 22551107).

• Tumour shrinkage: 23.2% with the etoposide-doxorubicin-cisplatin combination plus mitotane, against 9.2% with streptozocin plus mitotane.
• Time before the cancer grew: a median of 5.0 months against 2.1 months (hazard ratio 0.55).
• Overall survival, the main goal: 14.8 months against 12.0 months, a difference that was not statistically significant (hazard ratio 0.79, P=0.07).
• Second-line switch: people whose cancer grew switched to the other combination. Among the 185 who switched, the median time before further growth was 5.6 months with the etoposide-doxorubicin-cisplatin combination and 2.2 months with streptozocin. Among those who did not switch, median survival was 17.1 months with first-line etoposide-doxorubicin-cisplatin plus mitotane and 4.7 months with streptozocin plus mitotane.
• Serious side effects: rates did not differ significantly between the two arms.

Every person in FIRM-ACT took mitotane, so the trial compared the two chemotherapy partners. It did not test mitotane itself against no mitotane (PubMed PMID: 22551107).

Mitotane on its own

A 2018 study from three German referral centres followed 127 people with advanced adrenocortical carcinoma who took mitotane alone. Twenty-six (20.5%) had an objective tumour response, three of them a complete remission. The median time before the cancer grew was 4.1 months, and median overall survival was 18.5 months. Two features predicted better results: fewer than 10 tumour spots (hazard ratio 0.51 for growth and 0.59 for death) and starting mitotane for a late recurrence rather than early advanced disease (hazard ratio 0.35 and 0.34). Of the people with fewer than 10 tumour spots who started mitotane 360 days or more after diagnosis, 67% had a clinical benefit, defined as stable disease for more than 180 days. People who reached blood levels above 14 mg/L lived significantly longer (hazard ratio 0.42) (PubMed PMID: 29452402).

What the European guideline says

The 2018 European Society of Endocrinology guideline, written with the European Network for the Study of Adrenal Tumors, recommends either mitotane alone or mitotane with etoposide, doxorubicin and cisplatin for advanced disease that cannot be fully removed, with the choice depending on prognostic features (PubMed PMID: 30299884).

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Mitotane After Surgery

Surgery that removes the whole tumour is the main treatment for adrenocortical carcinoma, but the cancer often comes back. Whether mitotane taken after surgery, called adjuvant treatment, holds it off has been argued about for years.

The 2007 Italian-German comparison

A 2007 study looked back at 177 people who had complete surgery at 8 centres in Italy and 47 in Germany between 1985 and 2005. Forty-seven Italian patients took mitotane after surgery. Fifty-five Italian patients and 75 German patients did not. The median time to recurrence was 42 months with mitotane, against 10 months and 25 months in the two comparison groups. The hazard ratios for recurrence without mitotane were 2.91 and 1.97. Side effects were mainly grade 1 or 2, and 13% needed a temporary dose cut. The authors concluded that adjuvant mitotane "may prolong" recurrence-free survival. Because the study looked back at records rather than assigning treatment at random, the groups differed: the German patients were older and had more stage I or II tumours (PubMed PMID: 17554118).

The guideline position for higher-risk people

The 2018 European guideline suggests adjuvant mitotane after complete surgery for people with a perceived high risk of recurrence: ENSAT stage III, a tumour edge that still shows cancer cells under the microscope (R1 resection), or a Ki67 index above 10%. Ki67 is a marker of how many tumour cells are dividing (PubMed PMID: 30299884).

The ADIUVO trial in lower-risk people

ADIUVO was a randomised trial of adjuvant mitotane. It ran in 23 centres across seven countries and enrolled adults whose tumour had been completely removed and who were at low to intermediate risk: stage I to III and Ki67 of 10% or less. Forty-five were assigned to mitotane for 2 years, with the dose adjusted to reach blood levels of 14 to 20 mg/L, and 46 to watchful follow-up alone (PubMed PMID: 37619579).

• Recurrence-free at 5 years: 79% with mitotane and 75% with follow-up alone (hazard ratio 0.74, 95% confidence interval 0.30 to 1.85), not a significant difference.
• Survival at 5 years: 95% and 86%, also not significantly different. Two people died in the mitotane group and five in the follow-up group.
• Side effects: all 42 people who took mitotane had adverse events, and eight (19%) stopped treatment. There were no grade 4 adverse events and no treatment-related deaths.

The authors wrote that adjuvant mitotane "might not be indicated" in low-grade, localised disease, given these patients' relatively good outlook, the lack of a significant gain and the side effects. They also stated the trial's main limit: it was stopped early because recruitment was slow, so it "cannot rule out an efficacy of treatment" (PubMed PMID: 37619579).

Living with long-term adjuvant mitotane

A small Italian study followed 17 people on adjuvant mitotane, with check-ups every 3 months. All reached blood levels above 14 mg/L, and none stopped the drug for good because of side effects. Side effects occurred in every patient and were managed with supportive treatment and adjusted hormone replacement. Fourteen kept high blood levels even as the dose was tapered. The drug lowered cortisol and the adrenal androgen DHEAS more than aldosterone. It also disturbed thyroid tests in a pattern that resembles thyroid failure starting in the pituitary, and in men it lowered testosterone output (PubMed PMID: 18824557).

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Reported Use in Cushing's Syndrome

Cushing's syndrome is the illness caused by long-term excess cortisol. Because mitotane lowers cortisol output, some centres have used it for Cushing's syndrome from causes other than adrenal cancer. A 2011 review notes that mitotane "has also been used for various forms of glucocorticoid excess" (PubMed PMID: 21883349). This use is not among the uses on the U.S. label, which names only adrenocortical carcinoma. The published evidence comes from single-centre records rather than randomised trials.

Pituitary-driven Cushing's disease

A Paris centre reviewed 76 people with Cushing's disease, the form driven by a pituitary tumour, who were treated with mitotane out of 219 diagnosed between 1993 and 2009. Of 67 treated long term, 48 (72%) reached remission, defined as normal 24-hour urine cortisol, after a median of 6.7 months. At remission the mean blood level was 10.5 mg/L, below the cancer target, on a mean daily dose of 2.6 g. Seventeen of 24 people (71%) with lasting remission later relapsed, after a median of 13.2 months. Nineteen (29%) stopped because they could not tolerate the drug. In 12 of 48 people (25%) whose first pituitary scans were normal, a pituitary tumour became visible during treatment, which allowed surgery (PubMed PMID: 22815335).

Cushing's syndrome from hormone-making tumours elsewhere

The same centre reported 23 people whose Cushing's syndrome came from a tumour outside the pituitary that released adrenocorticotropic hormone (ACTH), the signal that drives the adrenal glands. They took a mean of 3.3 g a day for a mean of 1.8 years. Urine cortisol fell from a mean of 2603 to 79 micrograms a day and became normal in 21 of the 23. Twenty developed adrenal insufficiency, alongside improvement in diabetes, high blood pressure and low potassium. Side effects in the first 6 months occurred in seven of 15 people (46%), grade 1 or 2 digestive or nerve effects that resolved with a lower dose or a pause. Controlling the cortisol gave time to find the hidden source tumour in eight of 13 people (PubMed PMID: 20061433).

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The Blood-Level Target of 14 to 20 mg/L

Mitotane is dosed by a measured blood level. The U.S. label gives the target as 14 to 20 mg/L, reached by raising the dose step by step as tolerated.

The lower limit of 14 mg/L

The main evidence is a 2011 European multicentre study that looked back at 91 people taking mitotane for advanced adrenocortical carcinoma. Blood samples taken within 3 months of their best response were analysed (PubMed PMID: 21470991).

• 19% had an objective tumour response.
• The median blood level was higher in people who responded, and more responders were found among people at 14 mg/L or above.
• Survival was significantly longer at 14 mg/L or above (hazard ratio 0.52 in the simple analysis and 0.46 after adjusting for other factors).
• The 14 mg/L cut-off was only moderately accurate at picking out responders: sensitivity 65% and specificity 69%. A level of 20 mg/L or more had a specificity of 90%.

The 2018 German monotherapy study found the same direction: people above 14 mg/L had significantly longer overall survival (hazard ratio 0.42) (PubMed PMID: 29452402).

The upper limit of 20 mg/L

The upper limit rests on toxicity. A 2018 review describes levels above 20 mg/L as the upper limit of the therapeutic window because of the risk of toxicity (PubMed PMID: 30349596). The label states that severe nerve and brain toxicity may occur above 20 mg/L. A 2023 Italian pilot study of five patients found abnormal brain-wave recordings and abnormal thinking tests at levels above 18 mg/L. Some of these changes persisted after the level returned to normal, including in one patient with long-term toxicity (PubMed PMID: 37645432).

How long it takes

The label states the target is usually reached within 3 to 5 months. It describes level checks every 2 weeks after starting and after each dose change, and periodic checks after that, for example monthly. When a level is above 20 mg/L without side effects, the label describes a dose reduction of 50% to 75%.

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What the U.S. Label Says

The current U.S. prescribing information for mitotane tablets, whose latest major changes are dated January 2024, contains these core points:

• Approved use: people with inoperable adrenocortical carcinoma, whether or not the tumour makes hormones. No other use is listed.
• Boxed warning: people taking mitotane are at increased risk of adrenal crisis in the setting of shock, severe trauma or infection, which may lead to death. The label directs that mitotane be stopped temporarily in those situations and that steroids be given.
• Starting dose: the label gives 2000 mg to 6000 mg a day by mouth, split into three or four doses, with food, then raised toward the 14 to 20 mg/L blood level.
• Checks before starting: a pelvic ultrasound in women before menopause, liver tests and a full blood count.
• Contraindications: the label lists none.
• Dose cuts for side effects: the usual cut is 500 to 1000 mg a day. For moderate nerve or brain side effects, the label ties the cut to the blood level: 1000 mg a day if below 14 mg/L, 1500 mg a day if within 14 to 20 mg/L, and a pause if above 20 mg/L.
• Liver and kidney disease: the label advises against use in severe liver impairment or severe kidney impairment and describes more frequent level checks in mild or moderate impairment.

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Adrenal Shutdown and Steroid Replacement

Because mitotane damages the adrenal cortex, most people taking it lose some or all of their own cortisol production. The label states that mitotane can cause adrenal insufficiency or make existing adrenal insufficiency worse, and that both cortisol-type (glucocorticoid) and salt-balancing (mineralocorticoid) deficiency are watched for and replaced.

Two effects push the replacement dose up. Mitotane speeds up the breakdown of steroid hormones, and it raises the blood proteins that bind them. The label states that high-dose replacement may be required and that free cortisol and ACTH are monitored to adjust it. A 2018 review states that steroid replacement during mitotane is given at higher doses than in other causes of primary adrenal insufficiency (PubMed PMID: 30349596).

The rise in binding proteins also distorts hormone tests. The label names sex hormone-binding globulin and corticosteroid-binding globulin, notes that this is taken into account when hormone results are read, and links it to breast enlargement in men. The Italian adjuvant study found gaps between saliva and blood cortisol, and between total and free testosterone, for the same reason (PubMed PMID: 18824557).

The label states that patients are told the signs of adrenal suppression, and it lists shock, trauma and infection as situations in which mitotane is paused. It states that mitotane is paused before planned surgery, and that systemic steroids are given with supportive care until recovery. Hospitals treat adrenal crisis as an emergency.

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How It Speeds Up the Breakdown of Other Medicines

The label calls mitotane a strong inducer of cytochrome P450 3A (CYP3A), a group of liver enzymes, including cytochrome P450 3A4, that break down a large share of prescription drugs. In people taking mitotane, a single dose of the test drug midazolam produced lower blood levels than in people not taking it. The label's interaction section states:

• Other drugs cleared by cytochrome P450 3A: their levels may drop and they may work less well. The label advises against combining mitotane with those where small level changes may lead to serious treatment failure.
• Hormonal contraceptives: mitotane can make some of them ineffective. The label describes effective non-hormonal contraception during treatment and for as long as mitotane remains detectable in the blood.
• Warfarin: mitotane may speed its breakdown and reduce its effect. The label advises against the combination, and where it cannot be avoided describes more frequent INR blood-clotting tests.
• Spironolactone: this diuretic may block mitotane's action. People taking both had significantly lower mitotane levels despite higher mitotane doses.

A 2011 review from Würzburg gathered the clinical evidence. It reported that sunitinib, a targeted cancer drug, was rapidly broken down during mitotane treatment. It noted that standard doses of macrolide antibiotics are unlikely to reach sufficient levels, and that among cholesterol drugs simvastatin is cleared by cytochrome P450 3A4 while pravastatin is not. The authors suggested that several disappointing trials of chemotherapy and targeted drugs in adrenocortical carcinoma may be explained in part by mitotane lowering exposure to those drugs (PubMed PMID: 21883349).

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Brain, Liver, Blood and Other Label Hazards

The current label lists reported adverse reactions without percentages. The most common it names are loss of appetite, upper-stomach discomfort, nausea, vomiting, diarrhoea, dizziness, vertigo, rash, high cholesterol, high triglycerides, low thyroid function and low free testosterone in men. Its warnings section adds:

• Brain and nerve effects: sedation, lethargy and vertigo, with a greater incidence of toxicity above 20 mg/L. The label states that mitotane can impair driving and the use of machinery. Where thinking problems appear, it describes a thyroid check, since mitotane may cause low thyroid function.
• Ovarian cysts: non-cancerous, multiple, two-sided large ovarian cysts in women before menopause. Twisting of the ovary and bleeding cyst rupture have occurred.
• Liver injury: including liver failure. An isolated rise in the liver enzyme GGT may occur.
• Blood counts: low white cells, anaemia and low platelets.
• Bleeding time: mitotane can disturb platelet function. The label states that routine bleeding-time tests do not detect this defect and describes a specific platelet test before surgery or dental work.
• Pregnancy: mitotane can cause harm to an unborn baby. Limited reports after approval describe preterm births and early pregnancy loss. Mitotane passes into breast milk, and the label advises against breastfeeding during treatment and for as long as the drug remains detectable.
• Children: effectiveness in children has not been established. Published case reports describe effects on development such as motor and speech delay and memory problems, along with growth delay and estrogen-like effects.
• Eyes and other organs: the label's list includes maculopathy, blurred and double vision, lens clouding, retinopathy, blood in the urine, protein in the urine, high blood pressure, low blood pressure on standing and opportunistic infection.

The label states that an overdose, meaning levels above 20 mg/L, can cause sedation, lethargy, vertigo, muscle weakness and an unsteady walk, that levels may take weeks to fall, and that mitotane is not likely to be removed by dialysis.

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What Is Not Known

• Whether mitotane lengthens life in advanced disease. No randomised trial has compared mitotane with no mitotane in advanced adrenocortical carcinoma. FIRM-ACT gave mitotane to everyone and found no significant overall survival difference between its two chemotherapy partners (PubMed PMID: 22551107).
• Whether adjuvant mitotane helps after surgery. The supportive 2007 evidence came from records, not randomisation (PubMed PMID: 17554118). The one randomised trial covered only lower-risk people, was stopped early and cannot rule out a benefit (PubMed PMID: 37619579). For higher-risk people, the European guideline gives a suggestion, a weaker grade than a recommendation (PubMed PMID: 30299884).
• Whether the blood-level target is cause or marker. The 14 mg/L evidence is retrospective, and the cut-off had a sensitivity of 65% and a specificity of 69% (PubMed PMID: 21470991). People who tolerate higher doses or have less disease may differ in other ways. The label states that mitotane's exposure-response relationship has not been fully characterised.
• The full mechanism. The label lists the mechanism as unknown. The sterol-O-acyl transferase 1 explanation comes from cell studies and tumour samples (PubMed PMID: 26305886).
• Cancer-causing, gene-damaging and fertility effects. The label states that these are unknown and that no fertility studies have been done.
• The effect of food on absorption of the U.S. tablet. The label lists it as not known.
• The best use in Cushing's syndrome. The data come from single-centre records with high relapse after stopping (PubMed PMID: 22815335, PubMed PMID: 20061433).

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Key Research Papers

1. Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366(23):2189-97. PubMed PMID: 22551107
2. Terzolo M, Fassnacht M, Perotti P, Libé R, Kastelan D, Lacroix A, et al. Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. Lancet Diabetes Endocrinol. 2023;11(10):720-730. PubMed PMID: 37619579
3. Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007;356(23):2372-80. PubMed PMID: 17554118
4. Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, et al. 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. Eur J Endocrinol. 2018;179(4):G1-G46. PubMed PMID: 30299884
5. Hermsen IG, Fassnacht M, Terzolo M, Houterman S, den Hartigh J, Leboulleux S, et al. Plasma concentrations of o,p'DDD, o,p'DDA, and o,p'DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study. J Clin Endocrinol Metab. 2011;96(6):1844-51. PubMed PMID: 21470991
6. Megerle F, Herrmann W, Schloetelburg W, Ronchi CL, Pulzer A, Quinkler M, et al. Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma. J Clin Endocrinol Metab. 2018;103(4):1686-1695. PubMed PMID: 29452402
7. Sbiera S, Leich E, Liebisch G, Sbiera I, Schirbel A, Wiemer L, et al. Mitotane Inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology. 2015;156(11):3895-908. PubMed PMID: 26305886
8. Kroiss M, Quinkler M, Lutz WK, Allolio B, Fassnacht M. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75(5):585-91. PubMed PMID: 21883349
9. Corso CR, Acco A, Bach C, Bonatto SJR, de Figueiredo BC, de Souza LM. Pharmacological profile and effects of mitotane in adrenocortical carcinoma. Br J Clin Pharmacol. 2021;87(7):2698-2710. PubMed PMID: 33382119
10. Paragliola RM, Torino F, Papi G, Locantore P, Pontecorvi A, Corsello SM. Role of Mitotane in Adrenocortical Carcinoma - Review and State of the art. Eur Endocrinol. 2018;14(2):62-66. PubMed PMID: 30349596
11. Daffara F, De Francia S, Reimondo G, Zaggia B, Aroasio E, Porpiglia F, et al. Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly. Endocr Relat Cancer. 2008;15(4):1043-53. PubMed PMID: 18824557
12. Mormando M, Galiè E, Bianchini M, Lauretta R, Puliani G, Tanzilli A, et al. Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study. Front Oncol. 2023;13:1222002. PubMed PMID: 37645432
13. Baudry C, Coste J, Bou Khalil R, Silvera S, Guignat L, Guibourdenche J, et al. Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center. Eur J Endocrinol. 2012;167(4):473-81. PubMed PMID: 22815335
14. Donadille B, Groussin L, Waintrop C, Abbas H, Tenenbaum F, Dugué MA, et al. Management of Cushing's syndrome due to ectopic adrenocorticotropin secretion with 1,ortho-1, para'-dichloro-diphenyl-dichloro-ethane: findings in 23 patients from a single center. J Clin Endocrinol Metab. 2010;95(2):537-44. PubMed PMID: 20061433

Official Sources

1. DailyMed: FDA prescribing information for mitotane tablets (major changes dated January 2024)

PubMed Topic Searches

1. PubMed: mitotane and adrenocortical carcinoma
2. PubMed: adjuvant mitotane after surgery
3. PubMed: mitotane blood-level monitoring
4. PubMed: mitotane and Cushing's syndrome
5. PubMed: mitotane and drug interactions through CYP3A4

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Connections

• Drugs — the parent section
• Adrenocortical Carcinoma — the cancer, its staging, surgery and other treatments
• Cushing's Syndrome — the causes of cortisol excess and the other cortisol-lowering drugs
• Adrenal Incidentaloma — adrenal lumps found by chance and how cancer is told apart
• Li-Fraumeni Syndrome — the inherited TP53 condition linked to childhood adrenal cancer
• Adrenal Insufficiency — the hormone shortfall mitotane causes on purpose
• Cortisol Test — how cortisol is measured, and why binding proteins matter
• ACTH Stimulation Test — the standard test of adrenal reserve

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