Metopirone (metyrapone) / Perrigo Company - LARVOL DELTA

Corticosterone regulates the balance between freezing and rearing in defensive responses to predator threat. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Pharmacological inhibition of CORT synthesis using metyrapone reduced freezing and increased rearing during TMT exposure, without impairing threat recognition-evidenced by robust conditioned place aversion and context-specific freezing...These findings suggest that while recognition of TMT's aversiveness remains intact without CORT, this hormone is essential for determining the qualitative and temporal dynamics of defensive responses. Our results reveal a key role for CORT in shaping behavioral flexibility during threat perception."

Journal

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

Real-life data on pasireotide in monotherapy or combined in active Cushing's disease. (PubMed, Front Endocrinol (Lausanne)) - "This is a retrospective monocentric study evaluating the real-life efficacy and safety of pasireotide alone or when combined with cabergoline or metyrapone. This is the first study to report metyrapone add-on to pasireotide, but larger studies are needed to further investigate this association. Pasireotide surely worsens glucose homeostasis, but its positive effects, alone or combined, on blood pressure, lipid profile, and body weight justify its use under careful hyperglycemia management."

Journal • Monotherapy • Retrospective data • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders

Effects of Short- and Long-Term Vortioxetine Administration on Reproductive Function in Female Rats. (PubMed, Pharmaceuticals (Basel)) - " Forty-two female Wistar albino rats were randomized into seven groups (n = 6): healthy control; short-term vortioxetine; long-term vortioxetine; and the same two regimens each combined with metyrosine or metyrapone. Long-term vortioxetine induced infertility in female rats, likely mediated by corticosterone elevation consistent with hypothalamic-pituitary-adrenal axis dysregulation. These findings suggest the need to monitor reproductive risk when considering vortioxetine in women of reproductive age and warrant further mechanistic and translational studies."

Journal • Preclinical • Infertility • Sexual Disorders

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

Impact of glucocorticoid therapy on hypothalamic-pituitary-adrenal axis function in pediatric nephrotic syndrome: A narrative review. (PubMed, World J Clin Pediatr) - "Intermediate values require additional testing, such as the insulin tolerance test, ACTH stimulation test, and metyrapone test...Careful GC management is essential to balance disease control with risks of HPA axis suppression. Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients."

Journal • Review • Asthma • Endocrine Disorders • Glomerulonephritis • Immunology • Nephrology • Pediatrics • Pulmonary Disease • Renal Disease • Respiratory Diseases

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

Rare Case of Dual Paraneoplastic Endocrinopathies in Small Cell Lung Cancer: Triphasic Electrolyte Presentation (KIDNEY WEEK 2025) - "A high-dose dexamethasone suppression test confirmed ectopic Cushing syndrome, so she was started on metyrapone...Tolvaptan was considered, but fluid restriction, salt tablets, and urea normalized her [sodium]...The high cortisol's mineralocorticoid activity, overwhelming 11β-Hydroxysteroid dehydrogenase, likely masked hyponatremia, and then metyrapone-induced cortisol suppression may have unmasked persistent ADH-driven water retention. Anticipating this triphasic course is key to the diagnosis and treatment of a rare dual paraneoplastic syndrome in SCLC."

Clinical • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Heart Failure • Lung Cancer • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma

Chronic Intermittent Cold Stress-induced lipophagy promotes foamy macrophage susceptibility to ferroptosis and exacerbates atherosclerosis. (PubMed, Free Radic Biol Med) - "In vivo, metyrapone (CORT inhibitor) and Ferrostatin-1 (ferroptosis inhibitor) effectively attenuated ferroptosis in foamy macrophages and AS progression. Therefore, targeting ferroptosis or CORT signaling may represent novel therapeutic strategies for AS."

Journal • Atherosclerosis • Cardiovascular • Hematological Disorders • Inflammation • ALOX15 • APOE • GPX4 • KEAP1 • NR3C1

Efficacy and Tolerability of Metyrapone in Mild Autonomous Cortisol Secretion: Real-World Findings From Clinical Practice. (PubMed, Clin Endocrinol (Oxf)) - "Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing adrenal insufficiency, indicating its potential safe clinical utility. A well-powered, controlled, prospective study is needed to validate these findings and comprehensively investigate the broader metabolic outcomes."

Journal • Real-world evidence • Cardiovascular • Diabetes • Dyslipidemia • Endocrine Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

ETOMIDATE AS AN ALTERNATIVE TO ANTIANDROGENIC THERAPY IN A CASE OF HYPERCORTISOLISM (CHEST 2025) - "A number of oral therapies are available to reduce serum cortisol including Ketoconazole, Metyrapone, and Mitotane; however, data regarding intravenous alternatives is limited.In recent years, Etomidate has been studied as an intravenous alternative for antiandrogenic therapy. Without enteral access, conventional oral therapies for hypercortisolism are unavailable. Etomidate should be considered in intubated patients requiring rapid serum cortisol reduction to prevent lapses in antiandrogenic therapy."

Clinical • Adrenal Cortex Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Respiratory Diseases • Solid Tumor

Effects of Metyrapone in Patients with Mild Hypercortisolism. (PubMed, Eur J Endocrinol) - P | "Low-dose evening metyrapone appears to be a safe and potentially effective option for improving BP control in patients with mH, especially those with higher baseline systolic pressure."

Journal • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Myositis • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Ectopic Cushing's syndrome in a patient with DIPNECH and metastatic lung carcinoid. (PubMed, Endocrinol Diabetes Nutr (Engl Ed)) - "Hypercortisolism was managed with octreotide and metyrapone, but the patient succumbed to complications 14 months post-diagnosis. This case suggests DIPNECH's potential to progress to hyperfunctioning, metastatic carcinoids and highlights the necessity for vigilant long-term surveillance and early intervention."

Journal • Review • Carcinoid Tumor • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Lung Cancer • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

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

Cushing's disease in children: a single-centre experience. (PubMed, Childs Nerv Syst) - "CD in children is almost always diagnosed late despite established signs and symptoms, including weight gain and growth failure. TSS is as effective as in adults. A multidisciplinary team is crucial to the safe and effective management of these children."

Journal • Retrospective data • Cushing’s Disease • Endocrine Disorders • Metabolic Disorders • Pediatrics • Pituitary Gland Carcinoma

Prospective study of metyrapone in endogenous Cushing's syndrome (PROMPT). (PubMed, Eur J Endocrinol) - "Metyrapone is a safe and effective treatment for endogenous CS."

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

CEM: Effects of Metyrapone in Patients With Hypercortisolism (clinicaltrials.gov) - P=N/A | N=20 | Active, not recruiting | Sponsor: Istituto Auxologico Italiano | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date

Blood steroid hormone profile and clinical outcomes following switching from metyrapone to osilodrostat in patients with Cushing disease. (PubMed, Endocr J) - "Steroid hormone concentrations, including cortisol, progesterone (Prog), pregnenolone (Preg), deoxycorticosterone, corticosterone, 17-hydroxyprogesterone (17Prog), 17-hydroxypregnenolone (17Preg), and 11-deoxycortisol, were measured using high-performance liquid chromatography-mass spectrometry. Different inhibition patterns of the steroid synthetic enzymes may explain the observed clinical outcomes between these drugs. These data suggest that in patients with Cushing disease receiving metyrapone, switching to osilodrostat may benefit cases with inadequate disease control and complications including hypertension, manifestation of masculinization, and gastric discomfort."

Clinical data • Journal • Cardiovascular • Cushing’s Disease • Hypertension • Otorhinolaryngology

Efficacy and Hepatotoxicity During Rapid Titration of Ketoconazole and/or Metyrapone in Patients With Cushing Syndrome. (PubMed, J Endocr Soc) - "Hypercortisolism can likely be controlled faster with rapid titration of KTZ or MET. LFT abnormalities increased with KTZ but were common with MET treatment, likely reflecting underlying liver pathology in CS."

Journal • Cushing’s Disease • Endocrine Disorders • Hepatology • Liver Failure

Effects of mineralocorticoids on α-Na+/K+ ATPase expression and parasite morphology in T. crassiceps WFU cysticerci. (PubMed, Gen Comp Endocrinol) - "Cysticerci were obtained from the peritoneal cavity of previously infected female mice and cultured in the presence of corticosterone, DOC, spironolactone (a mineralocorticoid receptor antagonist) or metyrapone (a corticosteroid synthesis inhibitor) at different concentrations and for different periods of time. These results suggest a role for mineralocorticoids in salt-water regulation of T. crassiceps WFU. A deep understanding of these mechanisms could contribute to improving therapeutic strategies for cysticercosis."

Journal

Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Mayo Clinic

New P2 trial

Overnight Metyrapone Therapy in Patients with Mild Autonomous Cortisol Secretion (MACS): An Open-Label Phase 2 Clinical Trial (ENDO 2025) - P2 | "MACS was diagnosed based on 1 mg post-dexamethasone suppression test serum cortisol >1.8 mcg/dL. Metyrapone therapy in patients with MACS demonstrated a favorable safety profile with no occurrence of AI. Further investigation into efficacy and MACS-associated outcomes is warranted."

Clinical • P2 data • Acute Kidney Injury • Cardiovascular • Dyslipidemia • Endocrine Disorders • Fatigue • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Obesity • Osteoporosis • Renal Disease • Rheumatology

Increases in cortisol production facilitate the transition to exogenous feeding by larval zebrafish. (PubMed, J Exp Biol) - "Water-borne metyrapone (an 11β-hydroxylase inhibitor) from 3‒5 days post-fertilization (dpf) blocked the 2-fold rise in cortisol levels observed in control larvae during this period...However, these differences dissipated following a two-day washout period. Together, our results indicate that cortisol influences feeding transitions in zebrafish, highlight the plasticity of these processes following perturbations, and suggest that this mechanism is conserved across vertebrates."

Journal

Metyrapone for Mild Autonomous Cortisol Secretion (MACS) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed