Isturisa (osilodrostat) / Novartis, Recordati - LARVOL DELTA

Millimeter‑segmental analysis of individual equine mane hairs by LC/HRMS for revealing chronological drug distribution in anti‑doping investigations. (PubMed, Forensic Sci Int) - "In silico physicochemical predictions, in which osilodrostat exhibits low molecular weight, moderate lipophilicity, weak basicity, and high permeability, support passive follicular uptake and stable retention, consistent with established biochemical models of drug incorporation into hair. This validated workflow enables high‑resolution reconstruction of drug exposure timing and represents a significant methodological advancement for equine anti‑doping analysis, with potential applicability to other compounds exhibiting suitable physicochemical properties."

Journal

Ectopic Cushing's syndrome. A metastatic hepatic neuroendocrine tumour: case report and literature review. (PubMed, J Surg Case Rep) - "The patient required intensive care stabilization pre-operatively and treatment with osilodrostat, which was then followed by surgical management: left lateral hepatectomy and gastric wedge resection. ACTH levels markedly decreased postoperatively, reflecting successful management. This emphasizes that careful medical management and multidisciplinary collaboration are essential in treating severe, potentially life-threatening ectopic hypercortisolism."

Journal • Critical care • Cushing’s Disease • Endocrine Disorders • Hepatology • Neuroendocrine Tumor • Oncology • Septic Shock • Solid Tumor

Comparative Efficacy of Aldosterone-Related Sodium-Retention Pathway Therapies for Resistant Hypertension: A Drug-Level Network Meta-Analysis of Randomized Controlled Trials. (PubMed, J Clin Hypertens (Greenwich)) - "In the primary drug-level analysis, amiloride, spironolactone, baxdrostat, eplerenone, and lorundrostat significantly reduced office systolic BP compared with placebo, with mean differences (MDs) of -14.08, -10.78, -9.09, -8.14, and -6.80 mmHg, respectively. Osilodrostat showed a statistically uncertain effect, with an MD of -2.61 mmHg...MRAs remain the established reference add-on therapy, whereas newer ASIs and amiloride may represent pathway-based alternatives for selected patients. Trial Registration: INPLASY202670099."

Clinical • Journal • Retrospective data • Cardiovascular • Hypertension

A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement (clinicaltrials.gov) - P=N/A | N=12 | Recruiting | Sponsor: University of Michigan | Trial completion date: Aug 2027 ➔ Jan 2028 | Trial primary completion date: May 2027 ➔ Oct 2027

Trial completion date • Trial primary completion date • Cushing’s Disease • Endocrine Disorders • Nephrology • Renal Disease

LINC 5 European primary analysis: A Phase II study of the pharmacokinetics, pharmacodynamics and tolerability of osilodrostat in paediatric patients with Cushing’s disease (ESPE 2026) - No abstract available

Clinical • P2 data • PK/PD data • Cushing’s Disease • Endocrine Disorders • Pediatrics

Successful use of Osilodrostat for severe reactive hypercortisolism in an 11-year-old boy with a brain empyema (ESPE 2026) - No abstract available

Sustained shrinkage of bilateral adrenal adenomas during long-term osilodrostat therapy. (PubMed, Eur J Endocrinol) - "Osilodrostat showed marked clinical and biochemical efficacy. This case suggests that osilodrostat may contribute to adrenal mass reduction, warranting further investigation."

Journal • Cushing’s Disease • Endocrine Disorders • Hematological Disorders • Nephrology • Renal Disease

Etomidate as a Bridge to Surgery in Ectopic ACTH Syndrome: A Case of Catastrophic Adrenal Suppression and Multiorgan Failure. (ASA 2026) - "After aggressive medical optimization with osilodrostat and etomidate, she underwent left lateral hepatectomy with gastric wedge resection...She recovered and was discharged to long-term care. This case highlights the diagnostic complexity and life-threatening course of EAS."

Clinical • Surgery • Hematological Disorders • Infectious Disease • Neuroendocrine Tumor • Respiratory Diseases • Septic Shock • Solid Tumor

Ectopic ACTH-dependent Cushing syndrome in 3 hospitalized patients: lessons learned from management with osilodrostat. (PubMed, JCEM Case Rep) - "The initial diagnosis of each case was made during hospitalization resulting from complications of CS, implicating severe disease and delayed diagnosis. Our experience suggests that rapid initiation and titration of osilodrostat effectively treats hypercortisolism and improves outcomes."

Journal • Cushing’s Disease • Endocrine Disorders

Is Hypercortisolism Treatable? Which Patients Should Be Treated and How-A Practical Guide for Clinicians. (PubMed, Diabetes Obes Metab) - "As cortisol activity falls, glucose- and blood-pressure medications often require down-titration. Monitoring for adrenal insufficiency, cortisol withdrawal syndrome, and drug-specific adverse effects requires coordinated multidisciplinary follow-up. Through careful evaluation and targeted treatment, hypercortisolism can be recognized and managed as a modifiable contributor to cardiometabolic risk."

Journal • Cardiovascular • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Nephrology • Obesity • Oncology • Renal Disease • Type 2 Diabetes Mellitus

Real-World Effectiveness and Safety of Osilodrostat in Cushing's Syndrome: A Retrospective Phase IV Study. (PubMed, J Clin Endocrinol Metab) - "Osilodrostat is effective, generally well tolerated in routine clinical practice, representing a valuable therapy for CS management, able to achieve rapid and sustained hormonal control, significant metabolic, cardiovascular, clinical and QoL improvements with a well-tolerated safety profile."

Journal • P4 data • Real-world evidence • Retrospective data • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Nephrology • Renal Disease

Individualized osilodrostat treatment for patients with ACTH-dependent Cushing's syndrome: real-world evidence. (PubMed, Front Endocrinol (Lausanne)) - "Adverse events were mild to moderate and included fatigue and nausea (34.6% each), adrenal insufficiency (30.8%), and dizziness (23.1%). In real-world clinical practice, osilodrostat provided rapid and effective biochemical control and clinical improvement in ACTH-dependent CS, with a manageable safety profile and effective doses in the low-to-moderate range."

HEOR • Journal • Real-world evidence • Retrospective data • Cushing’s Disease • Diabetes • Endocrine Disorders • Fatigue • Metabolic Disorders • Nephrology • Renal Disease

Case Report: Continuous block-and-replace strategy with osilodrostat in a patient with cyclic Cushing's syndrome. (PubMed, Front Endocrinol (Lausanne)) - "Imaging failed to identify the ACTH source; therefore inferior petrosal sinus sampling is planned to definitively establish the etiology of CS. This case illustrates the unpredictable nature of cCS and the considerable challenges it poses for both diagnosis and management, emphasizing the need for individualized therapeutic strategies."

Journal • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Hypotension • Infectious Disease • Septic Shock

Protracted osilodrostat-induced pan-adrenal steroidogenic suppression and adrenal size reduction in Cushing disease. (PubMed, JCEM Case Rep) - "Review of 10 previous reports suggests prolonged adrenal insufficiency is uncommon and mineralocorticoid deficiency rarely documented, while persistent androgen suppression has not previously been reported. This case highlights prolonged pan-adrenal steroidogenic suppression with adrenal shrinkage and suggests recovery of adrenal function may take years."

Journal • Cushing’s Disease • Endocrine Disorders • Nephrology • Renal Disease

Efficacy and safety of osilodrostat in patients with ectopic Cushing's syndrome. (PubMed, Hormones (Athens)) - "Based on available real-world reports, osilodrostat appears to be a promising and fast-acting option for controlling severe hypercortisolism in ECS, with a generally acceptable safety profile. However, clinicians should closely monitor for adrenal insufficiency, particularly during dose titration."

Journal • Review • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Nephrology • Renal Disease

Asthma increased the risk of atrial fibrillation: insights from clinical association to genetic and molecular evidence. (PubMed, BMC Pulm Med) - "Our study provides evidence that genetic predisposition to asthma is significantly associated with an increased risk of AF in the European population. Transcriptomic data analyses suggest that CPA3 and its interactions with therapeutic drugs could serve as potential biomarkers, offering new opportunities to improve prognosis in patients with coexisting asthma and AF."

Journal • Asthma • Atrial Fibrillation • Cardiovascular • Immunology • Pulmonary Disease • Respiratory Diseases • CPA3

Dose-Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression. (PubMed, J Clin Med) - "This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose-response relationships of three ASIs-baxdrostat, lorundrostat, and osilodrostat-for the treatment of resistant hypertension. The strong linear dose-response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

Baxdrostat versus Osilodrostat: Steroid Biosynthesis in Human Adrenocortical Cells. (PubMed, Endocr Connect) - "Cells were stimulated with adrenocorticotropic hormone (10 nM) and exposed for 72 h to baxdrostat, osilodrostat, or metyrapone (0-10 μM). Baxdrostat demonstrated greater functional selectivity for CYP11B2, with minimal cortisol-axis impact and smaller upstream precursor accumulation than osilodrostat. These human-tissue data inform dose selection and safety monitoring strategies for selective aldosterone synthase inhibition in aldosterone-mediated and treatment-resistant hypertension."

Journal • Cardiovascular • Hypertension • Oncology • CYP11B1

Successful Use of Osilodrostat as Monotherapy Strategy for Severe Ectopic Cushing'S Syndrome: A Case Report (ENDO 2026) - "She was initiated on ketoconazole (KC) 200 mg BID. Conclusions - Osilodrostat is effective as monotherapy in the treatment of severe EAS by providing effective control of hypercortisolism, resulting in rapid improvement of cortisol-driven metabolic complications. - Osilodorstat should be considered when rapid biochemical control is required, when other steroidogenesis inhibitors are not tolerated, or when patients are poor surgical candidates."

Case report • Clinical • Monotherapy • Cushing’s Disease • Endocrine Disorders • Metabolic Disorders • Musculoskeletal Diseases • Pituitary Gland Carcinoma • Solid Tumor

Osilodrostat Improves Health-Related Quality of Life in Cushing's Disease: Analysis of Patient-Reported Outcomes from the Phase III LINC 3 and LINC 4 Studies (ENDO 2026) - P3 | "Osilodrostat significantly improved HRQoL with clinically meaningful, long-term improvements observed across all reported HRQoL instruments. Including the LINC 3 placebo data may underestimate the treatment effect. The data reinforce evidence of osilodrostat's early and sustained impact on HRQoL in patients with CD."

Clinical • HEOR • P3 data • Patient reported outcomes • CNS Disorders • Cushing’s Disease • Depression • Endocrine Disorders • Mood Disorders • Rare Diseases

Short-Term Pharmacodynamic Effects of Osilodrostat Assessed by Serial Salivary Cortisol Monitoring (ENDO 2026) - "Serial salivary cortisol profiling and AUC revealed sustained and gradual PD effects of osilodrostat during early treatment, with continued reduction in daily cortisol exposure even without dose changes. These findings support weekly rather than daily assessment for dose adjustment and may inform future strategies for early titration."

PK/PD data • Cushing’s Disease • Endocrine Disorders • Nephrology • Renal Disease

Hidden in Plain Sight: Unmasking Cushing Disease after Acute Ischemic Stroke (ENDO 2026) - "He was treated with Tenecteplase and thrombectomy with two stents placement and discharged on aspirin, clopidogrel, and atorvastatin...Patient referred to neurosurgery and due to recent stroke and anticoagulation status, transsphenoidal surgery was postponed for 6 months and osilodrostat started...Underlying undiagnosed CD should be considered in the differential diagnosis as possible etiology, especially in young patients with atypical acute cerebrovascular events. Therefore, it is imperative to adopt heightened clinical hypervigilance of possible CD."

Atherosclerosis • Cardiovascular • Cushing’s Disease • Diabetes • Dyslipidemia • Genetic Disorders • Hematological Disorders • Hypertension • Ischemic stroke • Metabolic Disorders • Neuroendocrine Tumor • Obesity • Solid Tumor • Thrombosis

Short-Term Steroidogenesis Inhibition with High-Dose Metyrapone Therapy to Improve Clinical Outcomes Prior to Surgical Resection of Cortisol-Producing Adrenocortical Carcinoma (ENDO 2026) - "Patient received dexamethasone 0.5 mg orally daily (block and replace therapy) when AM cortisol decreased to < 10 μg/dL. Due to prolonged QT interval of 582 ms (normal QTc < 460) and concurrent amiodarone therapy, osilodrostat was not indicated... This case highlights the critical role of short-term (less than two weeks) preoperative adrenal steroidogenesis inhibition in managing hypercortisolism associated with ACC. High-dose metyrapone rapidly controlled cortisol excess, leading to improvement in clinical and biochemical parameters and optimization prior to surgery in a medically complex patient."

Clinical • Clinical data • Adrenal Cortex Carcinoma • Back Pain • Cardiovascular • Congestive Heart Failure • Cushing’s Disease • Diabetes • Endocrine Disorders • Genetic Disorders • Genito-urinary Cancer • Heart Failure • Hypertension • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • Women's Health

A Rare Etiology of Cushing Syndrome Highlighted by Mifepristone-Related Adverse Effects (ENDO 2026) - "Mifepristone was held, aggressive electrolyte repletion was initiated, and spironolactone was continued, resulting in clinical and biochemical improvement...Prior endocrine evaluation demonstrated elevated late-night salivary cortisol levels (0.218, 0.384, 0.227), normal 24-hour urinary free cortisol (16), incomplete suppression on dexamethasone testing (cortisol 6), and a fasting ACTH of 8 pg/mL... This case highlights bilateral adrenal adenomas as an uncommon cause of Cushing syndrome and illustrates a serious complication of mifepristone therapy. Bilateral adrenalectomy is the standard treatment of choice for overt Cushing's syndrome. Medical management options include osilodrostat, ketoconazole, metyrapone, and mifepristone."

Adverse events • Cardiovascular • Coronary Artery Disease • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

Ectopic Cushing Syndrome with Negative DOTATATE PET: A Diagnostic Challenge. (ENDO 2026) - "Biochemical testing showed urinary free cortisol ~730 μg/24 h (~3× upper limit of normal), elevated ACTH (261 pg/mL), and lack of suppression with high-dose dexamethasone...Ketoconazole was discontinued for hepatotoxicity, and osilodrostat failed to control hypercortisolism... Negative ^68Ga-DOTATATE PET/CT does not exclude ectopic ACTH-secreting tumors. Careful integration of biochemical testing, imaging, and multidisciplinary expertise is essential. Even after partial remission, ongoing surveillance and adjunct medical therapy may be needed to prevent long-term complications of hypercortisolism."

Carcinoid Tumor • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genetic Disorders • Hypertension • Lung Cancer • Metabolic Disorders • Neuroendocrine Tumor • Obesity • Solid Tumor