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MyDeficiencies

Osilodrostat

adrenal steroidogenesis inhibitor

Also sold as Isturisa.

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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.

Osilodrostat has no classical absorption-interference or catabolic-depletion mechanism: food changes its exposure only modestly (AUC -11%, Cmax -21%), it is extensively metabolized by CYP3A4, CYP2B6, and CYP2D6 plus UDP-glucuronosyltransferases with no single pathway carrying more than a quarter of clearance, and it is cleared renally, almost entirely as metabolites (90.6% of the dose in urine, only 5.2% unchanged). Critically, osilodrostat is not a CYP450 inducer of any kind; if anything it runs the opposite direction, it is itself an inhibitor of CYP1A2, CYP2C19, CYP2D6, and CYP3A4/5, so the accelerated-catabolism mechanism class that depletes nutrients for many chronic medications does not apply here. As with its sibling steroidogenesis inhibitor metyrapone (see that dossier for class context), the real drug-specific signal is a direct pharmacodynamic consequence of the drug's own mechanism: blocking CYP11B1, the final enzyme in cortisol synthesis, forces upstream buildup of 11-deoxycortisol and 11-deoxycorticosterone (DOC), both of which have real mineralocorticoid-receptor activity. This is labeled, quantified, drug-specific evidence, hypokalemia occurred in 12.4% of patients in the pivotal trial and 18% in the largest independent real-world cohort, an excess/wasting pattern driven by the drug's mechanism, not a dietary deficiency.

adrenal steroidogenesis inhibitor · ATC H02CA02 · also sold as Isturisa · reviewed 2026-09-28. 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 Osilodrostat 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

Potassium/electrolytes - mineralocorticoid-pathway wasting and retention, direction bounded by population and cortisol severity

Orange — Moderate

See study details

Osilodrostat's precursor buildup (11-deoxycorticosterone) has real, quantified mineralocorticoid activity that can newly cause hypokalemia and hypertension as cortisol normalizes in Cushing's disease, but in patients starting from very severe hypercortisolism the net effect on potassium can run the opposite way as the drug lowers cortisol's own mineralocorticoid action.

Full detail, limits and 4 references

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 negative/null findings: Dormoy et al. 2022, retrospective multicenter French study of 33 patients with paraneoplastic (ectopic ACTH) Cushing syndrome and severe baseline hypercortisolism (median pretreatment urinary free cortisol 26 times the upper limit of normal), reported that hypokalemia "resolved substantially" as cortisol fell under osilodrostat treatment, the opposite direction from the pivotal-trial and Tabarin findings (J Clin Endocrinol Metab 2022, PMID 36470583). This is read as cortisol itself, at supraphysiologic levels, being the dominant driver of baseline hypokalemia in that severely hypercortisolemic population, a driver the drug removes faster than its own smaller DOC-mediated effect can newly cause wasting. A 2022 review of adrenal steroidogenesis inhibitors in Cushing's disease similarly frames osilodrostat as a preferred option in patients "without severe or uncontrolled hypokalemia" at baseline, implying clinicians already treat pre-existing, disease-driven hypokalemia as a distinct consideration from the drug's own effect (Pivonello et al., Pituitary 2022, PMID 36036308, title-level and listing-snippet review only, not independently opened in full this session).
  • At-risk subgroups: ACTH-dependent Cushing's disease patients as cortisol approaches or reaches normal range, and during rapid dose titration; patients with pre-existing electrolyte abnormalities or QT risk factors, per the label's pre-treatment correction requirement.
  • Counter-evidence on record: Dormoy et al. 2022 (above), a real, population-bounded reversal, not merely an absence of effect. Also noted for context, not as direct counter-evidence: a 2026 randomized trial of a different Cushing's agent (relacorilant, a different drug class) explicitly contrasted its own safety profile by reporting "no cases of drug-induced hypokalaemia," implicitly treating osilodrostat-class hypokalemia as a known, distinguishing feature of this mechanism (Pivonello et al., GRACE trial, Lancet Diabetes Endocrinol 2026, PMID 41730814, snippet-level only from a PubMed listing page, not independently opened in full).

Regulatory status

Label lists hypokalemia and hypertension among adverse reactions from the pivotal trial (Study 1, 48-week core period, n=137): hypokalemia 12.4%, hypertension 10.2%; edema is among the most common reactions overall (>20%). Label states hypokalemia "respond[s] to potassium supplementation and/or mineralocorticoid antagonists," and that hypokalemia and hypomagnesemia must be corrected before starting therapy and monitored throughout, because both potentiate the drug's QT-prolongation risk.

Population evidence

Label Study 1 (the LINC-3 pivotal trial population), n=137, hypokalemia 12.4%. Independent confirmation: Tabarin et al. 2025, retrospective multicenter French study, n=103 patients with nonpituitary Cushing syndrome (ectopic ACTH, adrenocortical carcinoma, adrenal adenoma, bilateral adrenal nodular hyperplasia), reported hypokalemia in 18% alongside adrenal insufficiency in 28% (J Clin Endocrinol Metab 2025, PMID 41260612). Both are Tier A, drug-in-cohort, with osilodrostat directly administered and outcomes directly measured.

Mechanism

Named: CYP11B1 blockade raises 11-deoxycorticosterone (DOC), a weaker but real mineralocorticoid-receptor agonist than aldosterone, driving renal potassium wasting and sodium/water retention independent of the renin-angiotensin-aldosterone axis. Cross-inhibition of CYP11B2 (aldosterone synthase) by osilodrostat may partially offset this by also lowering aldosterone itself; the net direction in any individual patient depends on the balance of these two opposing effects plus baseline cortisol level.

Counter-evidence held on record

This is an excess-wasting/retention disturbance driven by the drug's own mechanism, with direction dependent on baseline cortisol severity and treatment phase, not a dietary potassium deficiency. It is never a reason to add potassium supplements pre-emptively; potassium (and, per the label, magnesium) should be corrected before starting therapy and monitored by a prescriber throughout, especially during dose titration, with any repletion clinician-directed given the risk of overcorrection. The label's magnesium-correction instruction is a general QT-risk precaution; no evidence was found this session that osilodrostat itself causes magnesium wasting, and no such claim is made here.

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 intended, adrenal-mitochondrial-enzyme mechanism, not generalized toxicity

Yellow — Low

See study details

Osilodrostat's core action is direct inhibition of CYP11B1, a mitochondrial cytochrome P450 enzyme in the adrenal cortex, with measurable cross-inhibition of the equally mitochondrial CYP11B2; this is the drug working as intended, and no evidence of systemic or off-target mitochondrial toxicity was found.

Full detail, limits and 3 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 negative/null findings: Full inhibition-potency (IC50/Ki) values and any off-target mitochondrial-toxicity endpoints from the Valentin-Goyco paper could not be retrieved this session, its abstract text was not indexed in the metadata record reached (abstract_inverted_index returned null); only its enzyme panel and MeSH classification were confirmed. This access gap is disclosed rather than filled with assumption.
  • At-risk subgroups: None identified for generalized mitochondrial effects; the intended, tissue-specific effect applies to anyone taking the drug for its labeled purpose.
  • Counter-evidence on record: None found, and none is needed, no systemic mitochondrial-toxicity claim is being made here (see framing caution).

Regulatory status

Label describes the mechanism as inhibition of 11-beta-hydroxylase (CYP11B1); it does not itself use "mitochondrial" terminology.

Population evidence

Valentin-Goyco et al. 2023, an in vitro study specifically testing osilodrostat's selectivity across the human steroidogenic cytochrome P450 panel, indexed CYP11A1, CYP11B1, and CYP11B2 as mitochondrial enzymes and CYP21A2 as a microsomal comparator (J Steroid Biochem Mol Biol, PMID 37098354, Tier B, drug named in the title). Background reference confirming this enzyme class is mitochondrial, not drug-specific: Hanukoglu, Feuchtwanger and Hanukoglu 1990, "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells," J Biol Chem (DOI 10.1016/s0021-9258(17)30545-8); Schwarz, Chernogolov and Kisselev 1999, "Complex Formation in Vesicle-Reconstituted Mitochondrial Cytochrome P450 Systems (CYP11A1 and CYP11B1)," Biochemistry (DOI 10.1021/bi990584l). Neither 1990/1999 paper studied osilodrostat, which had not yet been developed; both are cited only as enzyme-class background, Tier C for this drug.

Mechanism

Named and specific: competitive inhibition at the heme-thiolate active site of the mitochondrial CYP11B1 enzyme, with measurable cross-reactivity against the structurally related mitochondrial CYP11B2 (aldosterone synthase), and comparatively little activity against microsomal enzymes in the same pathway (for example CYP21A2), per the Valentin-Goyco selectivity panel.

Counter-evidence held on record

Per Hard Rule 2, this entry exists to clarify mechanism, not to claim a mitochondrial-nutrient deficiency: the adrenal-mitochondrial enzyme inhibition is the drug's intended pharmacologic effect, not evidence of systemic mitochondrial harm, and no CoQ10, B-vitamin cofactor, or antioxidant supplementation is implied.

Oxidative Stress

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

Oxidative stress - class-level extrapolation from metyrapone, reverse-direction in rodent models

Yellow — Low

See study details

No osilodrostat-specific oxidative-stress data exist, but metyrapone, the other 11-beta-hydroxylase inhibitor used for the same indication, has verified Tier B rodent evidence that blocking corticosterone synthesis reduces stress- and nicotine-driven oxidative markers rather than raising them. Disclosed here as class-level (Tier C) extrapolation, independently reopened and verified this revision, not as osilodrostat-specific data.

Full detail, limits and 2 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 negative/null findings: In the nicotine-plus-stress model, metyrapone provided only partial protection and did not fully normalize combined stress-plus-nicotine oxidative damage, bounding the effect's magnitude even within the class-level source. No human data, for either drug, were located in any channel.
  • At-risk subgroups: Not applicable; these are rodent CNS-stress models with metyrapone, not a human population, and not drug-specific to osilodrostat.
  • Counter-evidence on record: None found. No osilodrostat-specific oxidative-stress source exists in any channel reached this session to confirm, extend, or contradict this class-level inference.

Regulatory status

Not addressed in the osilodrostat label; no oxidative-stress language appears for osilodrostat or for the drug class.

Population evidence

Tier C, class-level, not osilodrostat-specific. This project's metyrapone dossier cites two rat studies naming metyrapone directly; both were independently reopened this revision via the OpenAlex works API rather than reused on trust. (1) A chronic unpredictable mild stress plus nicotine conditioned-place-preference model in Wistar rats (Mol Neurobiol, 2017, PMID 28484990): the reconstructed abstract, read this session, states that stress "potentiates nicotine's pro-oxidative impacts, though metyrapone reversed certain oxidative changes." (2) A chronic hypobaric hypoxia memory-impairment model in rats, titled "Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment" (Behav Brain Res, 2011, PMID 22137888): reopened this session, but its abstract text remained unindexed (null) in the OpenAlex record reached both this session and previously, so only its title and topic, not any specific lipid-peroxidation or reactive-oxygen-species figures, could be independently confirmed; it is listed here as corroborating title-level context only. No osilodrostat-specific oxidative-stress source was found in any channel reached this session.

Mechanism

Named at the class level: reduced glucocorticoid (cortisol/corticosterone) signaling lowers glucocorticoid-mediated oxidative damage in these rodent models. Osilodrostat and metyrapone both directly inhibit the same enzyme, CYP11B1, and both lower downstream glucocorticoid output, so the same reverse-direction mechanism is biologically plausible for osilodrostat, but it has not been tested directly in any osilodrostat-specific study.

Counter-evidence held on record

This is a class-level extrapolation from a different, though mechanistically closely related, drug (metyrapone), not osilodrostat-specific data, and it runs in the protective direction in rodents. It must never be read as osilodrostat "reducing oxidative stress" in humans, and no antioxidant supplementation is implied.

Copper and Iron Balance

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

Copper

Not graded — disclosed evidence gap

See study details

No biological evidence, at any tier, and no circulating consumer claim, was found linking osilodrostat to copper status in either direction.

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: Both conditions for UNGRADED are met: (1) no Tier A, B, or independently-verified Tier C evidence exists connecting osilodrostat to copper or ceruloplasmin; (2) no consumer or practitioner claim about osilodrostat and copper was located to rebut as white.

Search channels tried

PubMed search-listing page, "osilodrostat copper" (confirmed zero results, page explicitly stated "No results were found"). Crossref works-search API, "osilodrostat copper ceruloplasmin ATP adenosine triphosphate" (explicitly confirmed zero osilodrostat-specific hits, results were generic ATP-biochemistry reference entries only). Europe PMC, Semantic Scholar, and OpenAlex were unavailable (429 or blocked) for targeted follow-up on this specific category. WebSearch was unavailable for the entire review.

Iron

Not graded — disclosed evidence gap

See study details

No biological evidence, at any tier, and no circulating consumer claim, was found linking osilodrostat to iron status in either direction. This is graded independently from the labeled anemia adverse reaction, which is filed above as a clinical outcome, not an iron-deficiency claim.

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: Both conditions for UNGRADED are met, with a genuine access limitation disclosed rather than glossed over: no Tier A, B, or independently-verified Tier C evidence connecting osilodrostat to iron, ferritin, or hepcidin was found, and no consumer claim was located to rebut as white.

Search channels tried

This category received the most persistent renewed effort in this revision, and a clean, unblocked direct PubMed query was still not obtained. PubMed search-listing page, "osilodrostat AND iron" and "osilodrostat iron," attempted three separate times across this revision with waits of roughly 45 to 70 seconds between attempts: every attempt rendered a reCAPTCHA-style "Checking your browser" bot-verification page rather than a results page, a disclosed access limitation, not a confirmed null. PubMed E-utilities (eutils.ncbi.nlm.nih.gov esearch) and the PMC search interface were both attempted as alternate PubMed-family channels; the former was disallowed by robots.txt rules for the fetch tool and separately rejected at the network-proxy layer (policy denial) when tried directly, the latter was also disallowed by robots.txt. Europe PMC REST API returned HTTP 429 on the first attempt this revision, with the proxy explicitly instructing not to retry that endpoint again this session, so it was not retried further. Semantic Scholar API returned HTTP 429 on every attempt. OpenAlex works-search endpoint (combined "osilodrostat iron" and a title/abstract filter variant) returned HTTP 429 on every attempt this revision; OpenAlex's per-PMID lookup endpoint, by contrast, worked reliably for other categories in this same revision, so the failure is specific to its search endpoint, not the API as a whole. Crossref works-search API succeeded once early in this revision ("osilodrostat iron ferritin hepcidin," 7 results returned, all generic iron/ferritin/hepcidin biology in unrelated species and conditions, none mentioning osilodrostat), then returned HTTP 429 on a later repeat attempt seeking a second confirmation. WebSearch was confirmed unavailable again this revision (session-wide budget still exhausted). Net result: no osilodrostat-specific iron evidence was found through any channel that did return content, consistent with the original review, but the core blocker, PubMed's bot-check, persisted across three fresh, spaced-out attempts this revision and was not resolved.

Gut Microbiome Risk

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

Gut microbiome risk - class-level extrapolation from metyrapone, protective in a rat injury model

Yellow — Low

See study details

No osilodrostat-specific gut-microbiome data exist, but metyrapone, the other 11-beta-hydroxylase inhibitor used for the same indication, has verified Tier B rodent evidence that blocking corticosterone reduces stress-driven bacterial translocation across the gut wall. Disclosed here as class-level (Tier C) extrapolation, independently reopened and verified this revision, a barrier-function finding, not microbiome composition or diversity data.

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 negative/null findings: None specific to metyrapone or osilodrostat found. Broader HPA-axis-and-microbiome literature is class-level background at a further remove and was not independently reopened this session, so it is not cited here.
  • At-risk subgroups: Not established for humans; the supporting data are a single rodent trauma model with metyrapone, not osilodrostat.
  • Counter-evidence on record: No microbiome composition, diversity, or sequencing data for osilodrostat or metyrapone in any species were located in any channel this session.

Regulatory status

Not addressed in the osilodrostat label.

Population evidence

Tier C, class-level only. This project's metyrapone dossier's Gut microbiome risk source, Zahs et al., "Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK pathway and promotes bacterial translocation after alcohol and burn injury" (Am J Physiol Regul Integr Comp Physiol, 2005, PMID 15718389, Sprague-Dawley rats given alcohol plus burn injury and metyrapone 25 mg/kg), was independently reopened and read this session via the OpenAlex works API. The reconstructed abstract confirms metyrapone prevented corticosterone-driven suppression of mesenteric lymph node T-cell proliferation and IL-2 production, restoring p38/ERK phosphorylation, and was associated with reduced bacterial translocation after the combined alcohol-and-burn insult. No osilodrostat-specific source was found in any channel reached this session.

Mechanism

Named at the class level: corticosterone suppresses gut-associated lymphoid tissue via p38/ERK pathway inhibition after injury, promoting bacterial translocation; removing the glucocorticoid signal (via a CYP11B1 inhibitor) reversed this specific immune-mediated barrier failure in the tested model. Osilodrostat shares the same CYP11B1-inhibition mechanism as metyrapone, so the same reverse-direction plausibility applies, though it has not been tested directly for osilodrostat.

Counter-evidence held on record

This is narrow, injury-model, barrier-function evidence from a different, though mechanistically closely related, drug, not a general statement about gut microbiome health on osilodrostat. No probiotic or fiber recommendation is implied.

Oxygen and ATP Output

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

Oxygen delivery/utilization - labeled anemia, undefined mechanism and absent from real-world top-line events

Orange — Moderate

See study details

Anemia is a labeled adverse reaction in the pivotal trial (10.2%) with no established mechanism, and it does not appear among the top-line reported adverse events in either of the two independent real-world cohorts located.

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 negative/null findings: Anemia's absence from the top-line adverse-event lists of both independent real-world cohorts (as retrieved at the abstract level) suggests it is not the dominant safety signal outside the pivotal trial, though full-text adverse-event tables for those two cohorts were not accessible through the channels reached this session, so this is a bounded, not a definitive, null finding.
  • At-risk subgroups: Not defined in any source located.
  • Counter-evidence on record: See key negative findings above.

Regulatory status

Label lists anemia among adverse reactions in Study 1's 48-week core period (10.2%, n=137), alongside decreased absolute neutrophil count (observed in 18 of 137 patients, 2 met neutropenia criteria) and postmarketing reports of neutropenia associated with fever and infection.

Population evidence

Label Study 1 is the only source located that quantifies anemia specifically for osilodrostat. Tabarin et al. 2025 (n=103) named adrenal insufficiency (28%) and hypokalemia (18%) as the common adverse events in its retrieved abstract, with no anemia figure given; Dormoy et al. 2022 (n=33) named grade 3 to 4 adrenal insufficiency (8 of 33) as the primary adverse effect, again with no anemia figure in the retrieved abstract.

Mechanism

Not established in the label or in any source located this session. No hemolysis, marrow-suppression, or nutrient-mediated mechanism is named.

Counter-evidence held on record

Anemia is a clinical outcome, not evidence of iron, B12, or copper deficiency, per Hard Rule 2. See the independently graded Iron entry below, which found no drug-specific iron evidence in either direction. A patient developing anemia on osilodrostat should be worked up by a clinician for the underlying disease and for hematinic status, not assumed to reflect a drug-induced nutrient deficiency.

ATP production

Not graded — disclosed evidence gap

See study details

No biological evidence, at any tier, and no circulating consumer claim, was found linking osilodrostat to ATP synthesis or cellular energy output. The Mitochondrial burden entry's in vitro source addresses enzyme target selectivity only, not energy output, and is not extended to this separately graded category.

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: Both conditions for UNGRADED are met: (1) no Tier A, B, or independently-verified Tier C evidence exists connecting osilodrostat to ATP production or mitochondrial energy metabolism; (2) no consumer claim (for example a generic "low energy" claim tied specifically to osilodrostat) was located to rebut as white. Fatigue is a labeled adverse reaction (among the most common, >20%), but per Hard Rule 2 this is a clinical symptom outcome, not a measured ATP or energy-metabolism finding, and is not used to support a grade here.

Search channels tried

PubMed search-listing page, "osilodrostat ATP" (confirmed zero results, page explicitly stated "No results were found"). Crossref works-search API combined query pairing osilodrostat with ATP/adenosine triphosphate and copper (explicitly confirmed zero osilodrostat-specific hits, results were generic ATP-biochemistry reference entries only). Europe PMC and Semantic Scholar were unavailable. WebSearch was unavailable for the entire review.

All references used above
  1. ISTURISA (osilodrostat phosphate) tablets, prescribing information — DailyMed, Recordati Rare Diseases, Inc., SetID f3a5ec24-63c3-4d83-b1c0-6c550fbe7ae2. Opened directly; sections reviewed: mechanism of action, pharmacokinetics, drug interactions, warnings and precautions, adverse reactions, hepatic/renal impairment, pregnancy and pediatric use.
  2. WHO ATC/DDD Index, code H02CA02 (osilodrostat) — Opened directly to confirm ATC classification.
  3. Pivonello R, Fleseriu M, Newell-Price J, et al. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. — Lancet Diabetes Endocrinol, 2020. This is the pivotal trial underlying the label's Study 1 adverse-event data cited throughout this dossier. DOI 10.1016/S2213-8587(20)30240-0.Bibliographic metadata (title, authors, journal, year, DOI) confirmed via Crossref; abstract/full text could not be retrieved through any accessible channel this session (OpenAlex record had no indexed abstract text). Specific adverse-event percentages in this dossier are drawn from the label's own reporting of this same Study 1, not from this paper's text directly.
  4. Tabarin A, Bertherat J, Decoudier B, Lasolle H, Lefebvre H, Drui D, et al. Real-World Osilodrostat Effectiveness and Safety in Nonpituitary Cushing Syndrome. — J Clin Endocrinol Metab, 2025. Retrospective multicenter observational study, n=103. PMID 41260612.Direct PubMed article page returned a bot-verification challenge; abstract retrieved via OpenAlex instead.
  5. Dormoy A, Haissaguerre M, Vitellius G, et al. Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France. — J Clin Endocrinol Metab, 2022. Retrospective multicenter observational study, n=33. PMID 36470583.Direct PubMed article page returned a bot-verification challenge; abstract retrieved via OpenAlex instead.
  6. Valentin-Goyco J, Liu J, Peng HM, Oommen J, Auchus RJ. Selectivity of osilodrostat as an inhibitor of human steroidogenic cytochromes P450. — J Steroid Biochem Mol Biol, 2023. In vitro enzyme-selectivity study naming osilodrostat directly. PMID 37098354.Abstract text was not indexed in the OpenAlex metadata record reached (abstract_inverted_index: null); only title, authors, journal, year, and MeSH-classified enzyme panel (CYP11A1/CYP11B1/CYP11B2 mitochondrial, CYP21A2 microsomal) were confirmed.
  7. Hanukoglu I, Feuchtwanger R, Hanukoglu A. Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells. — J Biol Chem, 1990. Enzyme-class background reference confirming CYP11-family mitochondrial localization; osilodrostat not in this cohort (predates the drug). DOI 10.1016/s0021-9258(17)30545-8.Bibliographic metadata via Crossref only; full text not opened.
  8. Schwarz D, Chernogolov A, Kisselev P. Complex Formation in Vesicle-Reconstituted Mitochondrial Cytochrome P450 Systems (CYP11A1 and CYP11B1). — Biochemistry, 1999. Enzyme-class background reference; osilodrostat not in this cohort. DOI 10.1021/bi990584l.Bibliographic metadata via Crossref only; full text not opened.
  9. Pivonello R, Simeoli C, Di Paola N, Colao A. Cushing's disease: adrenal steroidogenesis inhibitors. — Pituitary, 2022. Class-level review; snippet retrieved from a PubMed search-listing page noted osilodrostat may be preferred "without severe or uncontrolled hypokalemia" at baseline. PMID 36036308.Only the PubMed listing-page title and snippet were reviewed this session, not the full article.
  10. Pivonello R, Arnaldi G, Auchus RJ, et al. Efficacy and safety of relacorilant for the treatment of patients with Cushing's syndrome (GRACE): a multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study. — Lancet Diabetes Endocrinol, 2026. Different drug (relacorilant, a glucocorticoid receptor antagonist, not a steroidogenesis inhibitor); cited only for its listing-page snippet reporting "no cases of drug-induced hypokalaemia," used as class-comparator context for the Potassium/electrolytes entry. PMID 41730814.Only the PubMed listing-page title and snippet were reviewed this session, not the full article; osilodrostat was not in this trial's cohort.
  11. Duggan S. Osilodrostat: First Approval. — Drugs, 2020. Identity/approval-history reference. DOI 10.1007/s40265-020-01277-0.Bibliographic metadata via Crossref only; full text not opened.
  12. Behavioral and Biochemical Impact of Chronic Unpredictable Mild Stress on the Acquisition of Nicotine Conditioned Place Preference in Rats. — Molecular Neurobiology, 2017. Wistar rats, metyrapone 50 mg/kg. Class-level (metyrapone, not osilodrostat) source for the Oxidative stress entry, independently reopened and read this revision via OpenAlex, not reused from this project's metyrapone dossier on trust. PMID 28484990.Metyrapone is not osilodrostat; cited only as disclosed class-level extrapolation. Abstract reconstructed via OpenAlex, direct PubMed page bot-blocked.
  13. Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat. — Behavioural Brain Research, 2011. Male Sprague-Dawley rats. Class-level (metyrapone, not osilodrostat) corroborating source for the Oxidative stress entry, reopened this revision via OpenAlex. PMID 22137888.Metyrapone is not osilodrostat. Abstract text remained unindexed (null) in the OpenAlex record both this revision and previously; only title, journal, and year were independently confirmed, so this source is cited for title-level context only, not for any specific oxidative-marker figure.
  14. Zahs A, et al. Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK pathway and promotes bacterial translocation after alcohol and burn injury. — American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005. Sprague-Dawley rats, metyrapone 25 mg/kg. Class-level (metyrapone, not osilodrostat) source for the Gut microbiome risk entry, independently reopened and read this revision via OpenAlex, not reused from this project's metyrapone dossier on trust. PMID 15718389.Metyrapone is not osilodrostat; cited only as disclosed class-level extrapolation. Abstract reconstructed via OpenAlex, direct PubMed page bot-blocked.