Isturisa (osilodrostat) / Novartis, Recordati - LARVOL DELTA

MOMACS: Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS) (clinicaltrials.gov) - P4 | N=150 | Recruiting | Sponsor: Laikο General Hospital, Athens

New P4 trial

Successful non-surgical treatment of bilateral macronodular adrenocortical disease with osilodrostat. (PubMed, Endokrynol Pol) - "Not required for Clinical Vignette."

Journal • Cushing’s Disease • Endocrine Disorders

Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. a real-world study in Spain. (PubMed, J Endocrinol Invest) - No abstract available

Journal • Real-world evidence • Cushing’s Disease • Endocrine Disorders

Osilodrostat for Bilateral Adrenal Hypercortisolism in Primary Aldosteronism. (PubMed, N Engl J Med) - No abstract available

Journal • Endocrine Disorders

Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS) (clinicaltrials.gov) - P4 | N=10 | Not yet recruiting | Sponsor: Johns Hopkins University

New P4 trial

LINC CARE: Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing's Syndrome (clinicaltrials.gov) - P4 | N=63 | Not yet recruiting | Sponsor: RECORDATI GROUP

New P4 trial • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Hypertension

Clinical management of ectopic Cushing Syndrome in neuroendocrine neoplasms: a national survey. (PubMed, Front Endocrinol (Lausanne)) - "Regarding diagnostic practices, 56.3% of centers indicated the use of the 1 mg dexamethasone suppression test (DST), followed by the high-dose DST. The desmopressin test was considered outdated or replaceable by 43.8% of respondents...Osilodrostat was the most frequently preferred first-line treatment...The findings underscore the need for a national, more structured referral network to ensure timely diagnosis and access to specialized care. These insights may guide national protocol harmonization in EAS management and better alignment with international standards."

Journal • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Large Cell Carcinoma • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

A Case of Adrenocorticotropin-dependent Cushing Syndrome with Osilodrostat Exposure in Early Pregnancy. (PubMed, JCEM Case Rep) - "After a relapse at 35 years of age, she was initially treated with metyrapone but switched to osilodrostat and hydrocortisone because of nausea, achieving reasonable cortisol control. This case prompts consideration of whether osilodrostat can be used during pregnancy if risks are justified. Pasireotide is rarely used in pregnancy and may have limited effectiveness, but when given, can cause hyperglycemia because of insulin and incretin suppression and should be monitored carefully."

Journal • Cushing’s Disease • Diabetes • Endocrine Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Oncology • Pituitary Gland Carcinoma • Renal Disease

Real-world osilodrostat effectiveness and safety in non-pituitary Cushing syndrome. (PubMed, J Clin Endocrinol Metab) - P | "Osilodrostat is a suitable treatment for endogenous Cushing syndrome of various non-pituitary etiologies."

Journal • Real-world evidence • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor

Liver impairment and medical management of Cushing syndrome and MACS. (PubMed, Front Endocrinol (Lausanne)) - "Normocortisolemic subjects with liver steatosis/metabolic-associated steatohepatitis seem to have higher cortisol concentration than the healthy population...We present two CS cases with baseline liver impairment, which improved on the treatment with steroidogenesis inhibitors. The case reports are followed by literature review regarding liver dysfunction in endogenous hypercortisolemia, impact of hypothalamic-pituitary-adrenal axis on the liver, and liver safety profile of medical treatment used in endogenous hypercortisolemia."

Journal • Review • Cushing’s Disease • Endocrine Disorders • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure

Budget Impact of Metyrapone for the Treatment of Cushing's Syndrome in France (ISPOR-EU 2025) - "Patients who fail surgery, or are ineligible, require pharmacological agents such as steroidogenesis inhibitors (metyrapone, ketoconazole, osilodrostat) to control cortisol levels and reduce associated comorbidities. Treatment of CS patients with metyrapone results in a lower budget impact compared with osilodrostat, driven by lower drug acquisition and AE management costs."

HEOR • Cushing’s Disease • Endocrine Disorders

Real-World Data on the Efficacy and Safety of Osilodrostat in Patients with Cushing's Disease in Spain. (PubMed, J Clin Med) - " Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed."

Journal • Real-world evidence • Cushing’s Disease • Endocrine Disorders • Nephrology • Renal Disease

Severe Cushing Syndrome From Ectopic Adrenocorticotropin Secretion In Metastatic Prostate Cancer Treated With Osilodrostat. (PubMed, JCEM Case Rep) - "In the interim, he developed severe hypokalemia and proximal muscle weakness and was readmitted for potassium repletion and initiation of therapy with osilodrostat in combination with prednisone as part of a block-and-replace strategy. His serum cortisol and 24-hour urine cortisol levels progressively decreased with increasing doses of osilodrostat."

Journal • Cushing’s Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor

Safety and Efficacy of the Aldosterone Synthase Inhibitor Osilodrostat in Primary Hypertension: A Retrospective Cohort Analysis (AHA 2025) - "BackgroundOsilodrostat, the first-generation aldosterone synthase inhibitor, lowered aldosterone and blood pressure in phase II studies, but its real-world safety and efficacy in primary hypertension remain undefined.MethodsWe used the TriNetX Global Collaborative Network to identify adults (≥18 years) initiating osilodrostat between 1 June 2020 and 30 April 2024, requiring a diagnosis of essential hypertension in the prior year and excluding secondary hypertension, spironolactone/eplerenone/finerenone use within 90 days, or pregnancy in the previous 6 months. Kaplan–Meier estimates showed overall survival of 97.5% at both 4 and 8 weeks, 96.2% at 24 weeks, and 90.8% at 52 weeks; freedom from hypokalemia was 91.2% at day 28 and 89% at day 56, AKI-free survival 96.1% at day 168 and 92.1% at day 365, hyperkalemia-free survival 96.2% at day 168, and serious adverse-event-free survival 70.6% at day 168 and 58.6% at day 365.ConclusionIn 80 adults treated with osilodrostat,..."

Retrospective data • Acute Kidney Injury • Cardiovascular • Hypertension • Nephrology • Renal Disease

Evaluating Aldosterone Synthase Inhibitors in Hypertension: A Meta-Analysis of Efficacy, Safety, and Subgroup Outcomes Across Novel Agents (AHA 2025) - "Four different ASIs - lorundrostat, osilodrostat, baxdrostat, and vicadrostat- were evaluated across the included trials. ASIs appear to be effective and well-tolerated antihypertensive agents, offering significant BP reduction across diverse patient groups, with lorundrostat demonstrating the strongest efficacy. These findings support further large-scale head-to-head trials to better define their role in hypertension management."

Retrospective data • Cardiovascular • Chronic Kidney Disease • Hypertension

ADRENOCORTICAL CARCINOMA CRISIS MANAGED WITH STRESS-DOSE STEROIDS (CHEST 2025) - "CASE PRESENTATION: A 48-year-old female with a history of ACC status post-left adrenalectomy with metastasis to lung and liver on pembrolizumab, mitotane, and radiation therapy to the liver presented with fevers, cough, and abdominal pain...Bloodwork revealed an 11-deoxy level of 676 despite mitotane prompting endocrinology to start isturisa... After starting on the stress dose steroids, the patient had a marked improvement leading to a downgrade from ICU. Although not fully understood, ACC is a condition that requires more research to develop treatment plans on an oncologic and endocrine level."

Adrenal Cortex Carcinoma • Cardiovascular • Cough • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Hepatocellular Cancer • Hypertension • Nephrology • Oncology • Renal Disease • Respiratory Diseases • Solid Tumor • IGF2 • PRKAR1A • TP53

WHEN CORTISOL STRIKES: CONCURRENT PNEUMOCYSTIS JIROVECII PNEUMONIA AND COCCIDIOIDOMYCOSIS IN A PATIENT WITH CUSHING DISEASE (CHEST 2025) - "CASE PRESENTATION: A 33-year-old female with a medical history of polycythemia vera (JAK2 V617F positive) complicated by portal vein thrombosis on anticoagulation, cirrhosis with portal hypertension, Cushing's disease secondary to a pituitary adenoma (previously treated with osilodrostat, leading to adrenal insufficiency, later treated and weaned off steroids with plans for surgical resection) presented to the Mayo clinic with dyspnea and pleuritic chest pain...Treatment with trimethoprim-sulfamethoxazole (TMP-SMX), Fluconazole, and Dexamethasone was initiated... This case highlights the critical role of hypercortisolism-induced immunosuppression in predisposing patients to life-threatening opportunistic infections, even in the absence of exogenous corticosteroid use. It underscores the need for heightened clinical awareness, early consideration of PJP prophylaxis in patients with Cushing's disease and other conditions associated with severe hypercortisolism, and..."

Clinical • Cardiovascular • Cushing’s Disease • Endocrine Cancer • Fibrosis • Genitourinary Neuroendocrine Carcinoma • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Kidney Cancer • Nephrology • Neuroendocrine Carcinoma • Pituitary Gland Carcinoma • Pneumonia • Polycythemia Vera • Portal Hypertension • Renal Cell Carcinoma • Renal Disease • Respiratory Diseases • Solid Tumor • Thrombosis • CD4 • CD8 • JAK2

A case of prolonged adrenal insufficiency following osilodrostat discontinuation with a review of the literature. (PubMed, Endocr J) - "Hydrocortisone (intermittently dexamethasone) replacement therapy was initiated, and over time, undetectable morning cortisol levels continued. Factors such as treatment duration, dose, or individual sensitivity may play a role, but other mechanisms, such as an adrenolytic effect, should also be considered. We expect an increase of similar cases, which we believe will lead to further research to better understand the mechanisms behind prolonged adrenocortical blockade after osilodrostat discontinuation."

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

Comparative efficacy and safety of aldosterone synthase inhibitors in hypertension: a Bayesian network meta-analysis of randomised controlled rials. (PubMed, Open Heart) - "ASIs significantly reduce BP with generally favourable tolerability. Osilodrostat and Baxdrostat demonstrated the most consistent efficacy across outcomes, while Lorundrostat also showed potential benefit. This analysis supports the use of ASIs as effective alternatives for BP reduction. Further large-scale and long-term RCTs are needed to validate these findings and guide clinical decision-making."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Hypertension

Enhanced Radiological Detection of a Corticotroph Adenoma Following Treatment With Osilodrostat. (PubMed, JCEM Case Rep) - "She was initially treated with metyrapone, which resulted in partial biochemical control of hypercortisolism. She remains in full clinical and biochemical remission at >2 years postsurgery. This case suggests that a period of eucortisolemia induced by osilodrostat may facilitate localization of corticotroph microadenomas using functional (PET) imaging."

Journal • Cushing’s Disease • Oncology

Osilodrostat-associated Adrenal Gland Shrinkage: a Case Series of Patients with ACTH-Dependent Cushing's Syndrome. (PubMed, J Clin Endocrinol Metab) - "We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients."

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

Osilodrostat dose impact on efficacy/safety in Cushing's disease: Large, pooled analysis of LINC 2, 3 and 4. (PubMed, Eur J Endocrinol) - "In this analysis of the largest and longest prospective interventional studies of an adrenal steroidogenesis inhibitor to date, osilodrostat provided rapid and sustained mUFC control, with dose decreases possible over the long term. AE frequency generally decreased over time, with no relationship with osilodrostat dose. Personalized adjustment of osilodrostat dose is important to optimize outcomes for patients with Cushing's disease."

Journal • Retrospective data • Cushing’s Disease • Endocrine Disorders

Prolonged adrenal suppression after osilodrostat discontinuation in a patient with Cushing's disease with eventual hypercortisolism relapse: Case Report and literature review. (PubMed, Front Med (Lausanne)) - "Following the cessation of osilodrostat, the patient commenced treatment with recombinant human growth hormone due to severe growth hormone deficiency, which revealed an underlying cortisol deficiency, likely caused by a prolonged adrenocortical blockage induced by osilodrostat, requiring the initiation of hydrocortisone replacement therapy. Additionally, it indicates that osilodrostat has the potential to induce prolonged adrenal blockade, even after treatment has ceased. The unexpected persistence of adrenal suppression suggests unknown long-term effects of osilodrostat that require further investigation."

Journal • Cushing’s Disease • Endocrine Disorders • Growth Hormone Deficiency • Nephrology • Renal Disease

A preliminary model to tailor osilodrostat in patients with ACTH-dependent Cushing's syndrome. (PubMed, Eur J Endocrinol) - "Simulations were then performed for different doses of osilodrostat to evaluate the variation in cortisol concentrations. Our results report the first dose-response relationship between osilodrostat dose and cortisol levels, which should be helpful in identifying the optimal dosing regimen in patients with Cushing's syndrome and in individualizing treatment to approximate a nychthemeral rhythm."

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

Osilodrostat Treatment for Cushing's Syndrome: Five Years on Since Regulatory Approval. (PubMed, Endocr Pract) - No abstract available

Journal • Cushing’s Disease • Endocrine Disorders