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Mitotane

antineoplastic, adrenal cytotoxic (adrenolytic)

Also sold as Lysodren.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Mitotane has a genuine, well-documented nutrient- and mineral-adjacent burden, but it does not look like the classical vitamin-chelation or renal-wasting pattern seen with many chronic medications. Mitotane is a strong CYP3A4 inducer that is directly cytotoxic to the adrenal cortex, and the strongest, most consistent signals in the literature are a reliable rise in cholesterol and triglycerides (an excess, not a deficiency), and a hormonal disturbance of the sodium/potassium axis from the adrenal insufficiency the drug itself causes, which is why glucocorticoid and often mineralocorticoid replacement is mandatory. A small case series also found subnormal vitamin D during mitotane therapy, though the sample is tiny (n=3) and confounded by the glucocorticoid replacement mitotane requires. In vitro work in human adrenocortical tumor cells shows mitotane directly damages mitochondria and impairs the cytochrome c oxidase step of the respiratory chain and generates reactive oxygen species, but this is the drug's own targeted cytotoxic mechanism against tumor tissue, observed only in tumor cell lines, not a demonstrated systemic mitochondrial or oxidative burden in patients.

antineoplastic, adrenal cytotoxic (adrenolytic) · ATC L01XX23 · also sold as Lysodren · reviewed 2026-09-26. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Mitotane in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Cholesterol and triglycerides

Red — Severe

See study details

Mitotane reliably and substantially raises total cholesterol, LDL-C, HDL-C, and triglycerides during therapy. This is an excess/retention effect from increased hepatic synthesis, not a nutrient deficiency, and it calls for lipid-lowering management, not any dietary or supplement change.

Full detail and limits

What the grade means here: Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence. Red

Limits on what this shows

  • Key null findings: Shawa et al. 2013 found gender, BMI, baseline cortisol, and baseline lipid values did not predict the size of the HDL-C rise, arguing against simple confounding by these factors in that cohort.
  • At-risk subgroups: Higher mitotane blood concentrations (within the therapeutic monitoring range) were associated with a larger HDL-C rise in Shawa et al. 2013, suggesting an exposure-response relationship.

Regulatory status

FDA label lists hypercholesterolemia and hypertriglyceridemia among adverse reactions of Lysodren.

Population evidence

Shawa et al. 2013, retrospective cohort, n=38 adrenocortical carcinoma patients on mitotane: mean HDL-C rose from 53.3 to a peak of 86.3 mg/dL (P<0.001); LDL-C rose from 114.4 to 160.1 mg/dL; triglycerides rose from 149 to 216.7 mg/dL (P=0.042); mitotane blood concentration correlated positively with the HDL-C rise. Maher et al. 1992, n=30 patients on o,p'-DDD (mitotane): mean 68% rise in serum cholesterol, predominantly LDL, reversed by simvastatin without stopping mitotane. Bianchini et al. 2021 systematic review: combined LDL-C and HDL-C increase reported in 54.2% of patients pooled across the literature, largely reversible after discontinuation.

Mechanism

Maher et al. 1992 propose that mitotane inhibits cytochrome P450-mediated oxysterol formation, removing the normal oxysterol feedback brake on HMG-CoA reductase and driving increased hepatic cholesterol synthesis (elevated plasma mevalonic acid was observed, and LDL-receptor function in cultured fibroblasts was preserved, arguing against an impaired-clearance explanation).

Counter-evidence held on record

No mitotane cohort in the reviewed literature reported lipids staying normal; three independent groups (Shawa, Maher, and the pooled Bianchini review) all found a rise. A placebo-controlled trial does not exist and would not be ethical for this rare, life-threatening cancer, so all evidence is observational. This is a drug-induced increase, not a deficiency. Never present this entry as a reason to add a supplement; the documented clinical response is statin therapy alongside continued mitotane, under a prescriber's guidance, with routine lipid-panel monitoring.

Sodium and potassium, bounded to inadequate steroid replacement or acute physiologic stress

Orange — Moderate

See study details

Mitotane's cytotoxic destruction of the adrenal cortex removes endogenous aldosterone as well as cortisol, creating a real risk of sodium loss and potassium retention (and, in crisis, hypoglycemia and hypotension). This is bounded to periods of inadequate steroid replacement or acute physiologic stress, not a background dietary mineral deficiency.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

  • Key null findings: None identified; adequately replaced patients on stable glucocorticoid/mineralocorticoid regimens are not reported to run persistently abnormal electrolytes, but no longitudinal electrolyte study in a mitotane cohort was located to confirm this systematically.
  • At-risk subgroups: Patients not yet established on mineralocorticoid replacement, those with intercurrent illness, surgery, or trauma, and anyone who abruptly stops mitotane or steroid replacement.

Regulatory status

FDA label states mitotane produces adrenal cortical suppression/destruction, that glucocorticoid replacement (and mineralocorticoid replacement in many patients) is required, and warns that adrenal crisis can occur during shock, trauma, or infection, requiring immediate exogenous steroid administration.

Population evidence

The label is the only source in this review directly describing this in the mitotane-treated cohort; it does not give a quantified incidence for the resulting electrolyte derangement, which is why this is bounded rather than red.

Mechanism

Direct hormonal disturbance: loss of adrenal cortex output removes aldosterone-driven renal sodium reabsorption and potassium excretion, producing the hyponatremia/hyperkalemia pattern typical of primary adrenal insufficiency, layered on top of cortisol loss.

Counter-evidence held on record

No mitotane-specific study measuring serum sodium/potassium longitudinally across a treated cohort was located in this review; this absence is itself recorded as a literature gap for a future revision rather than assumed to be reassuring. This is a hormone-deficiency retention/loss disturbance, not a dietary mineral deficiency. Potassium supplementation would be dangerous in this context. The treatment is glucocorticoid/mineralocorticoid replacement titrated by an endocrinologist, not dietary sodium loading or potassium restriction undertaken without medical supervision.

Vitamin D, small case series, confounded by required glucocorticoid replacement

Yellow — Low

See study details

A small case series found subnormal total vitamin D during mitotane therapy despite compensatory rises in binding proteins; mechanistically plausible given mitotane's strong CYP3A4 induction, but confirmed in only three patients and confounded by the glucocorticoid replacement mitotane necessitates.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key null findings: None found.
  • At-risk subgroups: Patients on long-term mitotane, particularly those also on chronic glucocorticoid replacement, which independently affects vitamin D and calcium handling and makes attribution to mitotane alone uncertain.

Regulatory status

Not addressed in the FDA label.

Population evidence

van Seters & Moolenaar, 1991 (case series, n=3 adrenocortical carcinoma patients on long-term mitotane): cortisol-binding globulin rose two- to threefold within the first month, paralleled by a rise in sex hormone-binding globulin, with a smaller rise in thyroxine-binding protein; despite these binding-protein increases, "thyroxine and vitamin D remained subnormal"; values normalized within about two years of mitotane discontinuation.

Mechanism

Mitotane is a labeled strong CYP3A4 inducer (Tier A). Potent hepatic enzyme induction is a recognized mechanism for accelerated catabolism of vitamin D by analogy with other strong inducers, though no mitotane-specific vitamin D clearance/kinetics study was located in this review to confirm that analogy directly.

Counter-evidence held on record

The low-vitamin-D signal in van Seters & Moolenaar 1991 cannot be cleanly separated from the confounding effect of the glucocorticoid replacement therapy that mitotane itself necessitates, and n=3 is too small to exclude chance. Theoretical, small-sample signal. No dosing recommendation is made for this entry.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden, the drug's own tumor-cytotoxic mechanism, in vitro only

Yellow — Low

See study details

Mitotane's core cytotoxic mechanism against adrenocortical tumor cells directly damages mitochondria, but this is documented only in human adrenocortical tumor cell lines, as the drug's intended on-target effect, not as an established systemic mitochondrial toxicity in other organs.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key null findings: None of these studies examined non-adrenal, non-tumor tissue; whether mitotane meaningfully burdens mitochondria in muscle, liver, or other organs in treated patients is simply not established either way.
  • At-risk subgroups: Not established outside the tumor-targeted mechanism itself.

Regulatory status

Label describes mitotane as an "adrenal cytotoxic agent" with an overall mechanism of action stated as unknown; it does not name mitochondria specifically.

Population evidence

None in human tissue outside adrenal tumor cell models; all evidence located is in vitro.

Mechanism

Hescot et al. 2013 (Endocr Relat Cancer): in human adrenocortical cells, mitotane at a therapeutic-range concentration (50 µM) inhibited maximal cytochrome c oxidase (respiratory chain complex IV) activity by about 50%, with reduced steady-state COX complex levels, selective for complex IV (complexes II and III unaffected), plus mitochondrial network fragmentation and compensatory increased mitochondrial biogenesis. Poli et al. 2013 reported dose- and time-dependent mitochondrial morphology changes in human adrenocortical cancer cells. Waszut, Szyszka & Dworakowska 2017 (review) state that "the most clear-cut mitotane effects have been observed for mitochondria." Krüger et al. 2025 characterized mitochondria-associated membrane proteomic/lipidomic changes with mitotane treatment (see Overlap map).

Counter-evidence held on record

This is fundamentally the drug's designed pharmacologic action against the tumor; a null systemic-toxicity study was not located, so absence of data is the honest position here, not evidence of absence. Do not present this as a supplement-addressable "mitochondrial support" issue. It is the drug's targeted cytotoxic mechanism against adrenal tumor tissue, observed only in vitro in tumor cell lines.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress, in vitro tumor-cell signal only

Yellow — Low

See study details

In vitro work in human adrenocortical tumor cells shows mitotane triggers reactive oxygen species generation, lipid peroxidation, and endoplasmic reticulum stress signaling as part of its cytotoxic mechanism; whether this represents a meaningful systemic oxidative burden in treated patients is not established.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key null findings: None found for this drug at the human-patient level; no blood oxidative-marker study in mitotane-treated patients was located.
  • At-risk subgroups: Not established.

Regulatory status

Not addressed in the label.

Population evidence

None in human blood or tissue redox markers in treated patients; in vitro only.

Mechanism

Krüger et al. 2025: mitotane treatment of human adrenocortical carcinoma (NCI-H295S) cells triggered reactive oxygen species and lipid peroxidation via the mitochondria-associated-membrane proteins ACSL4 and SOAT1 (mitotane acting as a SOAT1 inhibitor), with upregulation of the endoplasmic-reticulum-stress markers IRE1α and PERK; the authors describe this as resembling, but mechanistically distinct from, canonical ferroptosis. Schiavon et al. 2026 references that mitotane "activates the ER stress pathway" in the same disease model, in a paper primarily about a different investigational agent.

Counter-evidence held on record

None located; this is a genuine gap at the clinical level, with an in vitro signal only. This reflects tumor-cell cytotoxic pharmacology, not a validated claim that mitotane depletes a patient's systemic antioxidant capacity. Do not extrapolate this into a recommendation for antioxidant supplementation.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron, hepcidin trend in a mitotane-specific pilot study, borderline significance

Yellow — Low

See study details

A small pilot study directly measuring hepcidin, the master iron-regulatory hormone, in mitotane-treated adrenocortical carcinoma (ACC) patients found it trending higher than in ACC patients not yet on mitotane, a difference that stopped just short of conventional statistical significance; the direction points toward hormone-mediated iron restriction during mitotane therapy, not a classical dietary or absorptive iron deficiency.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key null findings: Neither between-group hepcidin comparison reported in the abstract crossed the conventional p<0.05 threshold. The authors' own conclusion, that "treatment improve[s] Fe homeostasis," sits in tension with the higher hepcidin their own numbers report in the mitotane-treated versus not-yet-treated subgroup; this review could not resolve that tension without the full-text methods and hematologic-outcome data, which were not accessible, so it is disclosed rather than smoothed over.
  • At-risk subgroups: Patients with active, mitotane-treated adrenocortical carcinoma, per this study's small ACC-t subgroup; not established beyond this single pilot cohort.

Regulatory status

Not addressed in the FDA label; anemia is listed generically among hematologic adverse reactions (see Oxygen delivery / utilization, above) with no iron-specific parameter named.

Population evidence

Krygier et al. 2026, Endocrine 91(1):52 (PMID 41627578, DOI 10.1007/s12020-025-04502-6). Prospective pilot study, n=33 adults with histopathologically confirmed adrenal-gland non-adenoma tumors, subdivided into ACC patients currently on mitotane therapy (ACC-t), ACC patients not yet on mitotane (ACC-nt, pre-treatment), and benign-adrenal-lesion controls (CS). Serum hepcidin was higher in the mitotane-treated group than in the not-yet-treated ACC group: 14.9 (7.6-24.3) vs. 11.1 (8.3-24.3) ng/mL, p=0.053. ACC patients overall also trended higher than benign-lesion controls: 13.9 (7.6-24.3) vs. 12.3 (1.5-20.9) ng/mL, reported as p>0.052. Subgroup sizes were small (roughly 9-13 per arm across the 33 total), consistent with its stated pilot design.

Mechanism

Hepcidin is the principal negative regulator of intestinal iron absorption and macrophage iron release, acting by degrading the iron exporter ferroportin; a hepcidin rise during active malignancy and its treatment is the established mechanism behind iron-restricted, inflammation-pattern anemia in cancer generally, distinct from a dietary or absorptive iron deficiency of the kind classical depletion mechanisms describe.

Counter-evidence held on record

This is the only mitotane-specific iron/hepcidin study located in this review; no null or contradicting mitotane-specific iron study was found to weigh against it. Its own quantitative findings are borderline rather than clearly positive (p=0.053, p>0.052), which is itself recorded here rather than rounded up to a confirmed effect. This describes a hormone-mediated restriction of iron availability tied to active malignancy and its treatment, not a dietary iron deficiency, and the finding is preliminary and not statistically conclusive. Any anemia during mitotane therapy should be worked up clinically (see Oxygen delivery / utilization, above) rather than treated with empiric iron supplementation, which is unlikely to correct a hepcidin-driven functional block and could cause iron overload if given without a confirmed indication.

Copper

Not graded — disclosed evidence gap

See study details

No mechanistic, class-level, or circulating-claim evidence connecting mitotane to copper status was found.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: A direct PubMed search for "mitotane copper" returned zero indexed results (accessed 2026-09-26; the query returned PubMed's own zero-result page, not a bot-check or a rate-limit error, so this reflects a genuine gap in the indexed literature rather than a blocked attempt). No Tier B/C mechanistic evidence and no circulating consumer claim about mitotane and copper were identified to grade or to rebut as white. Both conditions for ungraded are met.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Not graded — disclosed evidence gap

See study details

No study measuring gut microbiome composition or diversity in mitotane-treated patients was located, despite mitotane's labeled gastrointestinal toxicity being a plausible indirect route to disruption.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Direct searches for "mitotane gut microbiome" and "mitotane microbiota" returned no drug-specific results among a combined 200,000-plus indexed records on gut microbiota generally (accessed 2026-09-26). Mitotane's labeled gastrointestinal toxicity (nausea, vomiting, diarrhea) is a plausible indirect mechanism, but no source was located that actually measured microbiome composition or diversity in mitotane-treated patients, so this plausibility was not elevated into a graded claim, per protocol (an absent direct mechanism study is not softened into a possible one). No circulating consumer claim specific to mitotane and the microbiome was identified either, so both conditions for ungraded are met.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery / utilization, labeled anemia and cytopenias, frequency and mechanism not established

Orange — Moderate

See study details

Lysodren's label lists anemia among its hematologic adverse reactions, alongside leukopenia, thrombocytopenia, and prolonged bleeding time, but neither frequency nor mechanism is established in the sources this review could access.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

  • Key null findings: None found; none excluded either, given the access limits described above.
  • At-risk subgroups: Not specified in the label.

Regulatory status

FDA label, adverse reactions section: anemia, leukopenia, thrombocytopenia, prolonged bleeding time.

Population evidence

Label-level only for anemia's frequency. A directly relevant pilot study, Krygier et al. 2026 ("Hepcidin concentration and effect on iron homeostasis in patients with adrenocortical carcinoma and benign adrenal lesions", Endocrine 91(1):52), was opened in a later revision of this dossier and found hepcidin, an iron-restricting hormone, trending higher in mitotane-treated versus not-yet-treated adrenocortical carcinoma patients (see Iron, below, for the full entry and its borderline statistics). That study measured hepcidin only, not hemoglobin, hematocrit, or red-cell indices, so it is a plausible mechanistic contributor to anemia but does not itself establish anemia's frequency or confirm its mechanism in this entry (see Overlap map).

Mechanism

Not established in the label. Elevated hepcidin restricting iron availability for erythropoiesis (see Iron, below) is a plausible partial mechanism, but this has not been directly tested against hematologic outcomes in mitotane-treated patients.

Counter-evidence held on record

None accessible in this review. Anemia is a hematologic clinical outcome, not a diagnosed iron, copper, or B12 deficiency, and must not be reworded as one. Any anemia occurring during mitotane therapy warrants standard clinical workup, not empiric iron or vitamin supplementation.

ATP production, respiratory-chain complex IV inhibition, tumor cells only

Yellow — Low

See study details

The same in vitro respiratory-chain complex IV inhibition that damages tumor-cell mitochondria directly impairs ATP-generating capacity in those cells; there is no direct evidence this extends to a systemic energy-production deficit in patients.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Key null findings: None found; not studied outside tumor cell models.
  • At-risk subgroups: Not established.

Regulatory status

Not addressed in the label. Fatigue/asthenia is a commonly reported clinical symptom during mitotane therapy, but the label attributes this generally to adrenal insufficiency and CNS toxicity, not to a named energy-metabolism deficit.

Population evidence

None in patients directly measuring ATP or cellular energy output.

Mechanism

Hescot et al. 2013 showed approximately 50% reduction in maximal cytochrome c oxidase (complex IV) activity at therapeutic mitotane concentrations in human adrenocortical cells; complex IV is the terminal electron-transport-chain step driving the proton gradient that ATP synthase uses. Krüger et al. 2025 found mitotane treatment reduced ubiquinone (Q10) and heme B in mitochondria-associated membranes and proposed this "may contribute to impaired respiratory chain activity" (see Overlap map: this entry shares its underlying sources with Mitochondrial burden, above).

Counter-evidence held on record

None located. Do not conflate this in vitro, tumor-cell-specific finding with the common clinical complaint of fatigue during mitotane therapy, which has several more established explanations (adrenal insufficiency, hypothyroidism, CNS toxicity) that should be ruled out clinically first.

All references used above
  1. Lysodren (mitotane) tablets, prescribing information. — FDA label via DailyMed (HRA Pharma Rare Diseases; setid f0cd76e9-460c-450e-b094-172e636f340a). Opened and read directly for mechanism of action, metabolism/CYP induction, absorption, elimination, adrenal insufficiency warnings, lipid and hematologic adverse reactions, and drug interactions.
  2. Shawa H, Deniz F, Bazerbashi H, Hernandez M, Vassilopoulou-Sellin R, Jimenez C, Habra MA. Mitotane-induced hyperlipidemia: a retrospective cohort study. — Int J Endocrinol. 2013. n=38 adrenocortical carcinoma patients on mitotane. PMID 24348556.
  3. Maher VM, Trainer PJ, Scoppola A, Anderson JV, Thompson GR, Besser GM. Possible mechanism and treatment of o,p'DDD-induced hypercholesterolaemia. — Q J Med. 1992. n=30 patients on mitotane. PMID 1480741.
  4. Bianchini M, et al. Metabolic and Endocrine Toxicities of Mitotane: A Systematic Review. — Cancers (Basel). 2021;13(19):5001. Systematic review, this drug specifically, pooled data on lipid, thyroid, and gonadal toxicity. PMID 34638485.
  5. van Seters AP, Moolenaar AJ. Mitotane increases the blood levels of hormone-binding proteins. — Eur J Endocrinol (Acta Endocrinol). 1991. Case series, n=3 patients on long-term mitotane. PMID 1903011.
  6. Poirier J, et al. Central Hypothyroidism is Frequent During Mitotane Therapy in Adrenocortical Cancer Patients: Prevalence and Timeline. — J Clin Endocrinol Metab. 2023;108(9):2336-2342. Retrospective, two academic centers, n=66 analyzed (83 screened). Used here for monitoring-panel context only, not as a graded nutrient entry (hypothyroidism is a hormonal, not nutrient, outcome). PMID 36856782.
  7. Hescot S, Slama A, Lombès A, et al. Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells. — Endocr Relat Cancer. 2013;20(3):371-381. In vitro, human adrenocortical carcinoma cells. PMID 23696597.
  8. Krüger AF, Schmitz W, Lamer S, et al. Adrenocortical Mitochondria-Associated Membranes: Isolation, Characterization, and Lipidoproteomic Response to Mitotane. — J Endocr Soc. 2025. In vitro, NCI-H295S human adrenocortical carcinoma cells. PMID 41472891.
  9. Poli G, Guasti D, Rapizzi E, et al. Morphofunctional effects of mitotane on mitochondria in human adrenocortical cancer cells. — 2013. In vitro, human adrenocortical cancer cells. PMID 23722227.Identified by title/snippet in a PubMed listing only; full abstract could not be opened during this review because of rate-limiting. Cited above only for the general morphology finding stated in that snippet, not for numeric detail.
  10. Waszut U, Szyszka P, Dworakowska D. Understanding mitotane mode of action. — 2017. Narrative review. PMID 28456766.Identified by title/snippet in a PubMed listing only; full text could not be opened during this review because of rate-limiting. Quoted above only for the single short phrase captured in that snippet.
  11. Schiavon A, Evaristo C, Saba L, et al. Targeting ER Stress in Adrenocortical Carcinoma: Celastrol as a Novel Therapeutic Candidate. — Biomed Pharmacother. 2026. PMID 41747473.Identified by title/snippet only; full text could not be opened during this review because of rate-limiting. This paper's primary subject is a different investigational agent (celastrol); it is cited above only for its brief comparative reference to mitotane's ER-stress activation.
  12. Krygier A, Filipowicz D, Brominska B, Komarowska H, Szczepanek-Parulska E, Ruchala M. Hepcidin concentration and effect on iron homeostasis in patients with adrenocortical carcinoma and benign adrenal lesions - a pilot study. — Endocrine. 2026;91(1):52. PMID 41627578. Prospective pilot study, n=33 adults with histopathologically confirmed adrenal-gland non-adenoma tumors, subdivided into ACC on mitotane therapy (ACC-t), ACC not yet on mitotane (ACC-nt), and benign-lesion controls (CS); mitotane-treated patients are a named, separated cohort arm in this study. Opened and read (title, authors, and quoted results/conclusion text) in a later revision of this dossier via the Crossref API (DOI/author metadata), the Europe PMC REST API (quoted results text), and the publisher's Springer abstract page; PubMed's own pages for this PMID remained blocked by a bot-verification challenge throughout that revision. Used as the primary supporting source for the Iron entry above.
  13. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index, code L01XX23. — Confirms ATC code L01XX23 = mitotane.
  14. PubMed search listing: "mitotane copper". — Zero results returned, documenting a genuine literature gap (Copper entry above).
  15. PubMed search listings: "mitotane gut microbiome OR microbiota"; "mitotane 25-hydroxyvitamin D". — No mitotane-specific results among the indexed literature returned for either query (Gut microbiome and Vitamin D search-scope context above).