Metopirone (metyrapone) / Perrigo Company - LARVOL DELTA

Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management. (PubMed, J Pediatr Endocrinol Metab) - "This case underscores the diagnostic and therapeutic challenges associated with rare pediatric cases of ACTH-independent CS. The treatment course, which included metyrapone, adrenalectomy, and off-label use of osilodrostat, resulted in significant improvement in cortisol control and clinical symptoms. Ongoing genetic analysis is being conducted to explore potential underlying genetic factors contributing to the patient's non-pigmented micronodular adrenal hyperplasia and developmental delay."

Journal • CNS Disorders • Cushing’s Disease • Developmental Disorders • Endocrine Disorders • Nephrology • Oncology • Pediatrics • Sleep Disorder

MTP30. Management of Pituitary Tumors During Pregnancy (ENDO 2025) - "This session will cover the management of micro/macroprolactinomas in pregnancy, the diagnosis and management of Cushing's disease (challenges with test interpretation, timing/risks of transphenoidal surgery in gestation; medical therapy with metyrapone; management peri-delivery), and management of acromegaly pre-conception and during gestation. This topic was previously done as a MTP by Mark Molitch in 2018."

Acromegaly • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Oncology • Pituitary Gland Carcinoma

Identification and Management of Ectopic ACTH Syndrome Secondary to Olfactory Neuroblastoma (ENDO 2025) - "Olfactory neuroblastoma was diagnosed in 2018 status post craniofacial resection, chemotherapy with carboplatin and etoposide, and localized radiation...Hormonal evaluation showed markedly elevated ACTH up to 606 pg/mL (7.2-63.3 pg/mL) and AM cortisol up to 105.1 ug/dL (3.7-19.4 ug/dL) on three separate occasions, all of which were not suppressed despite receiving high-dose dexamethasone (4 mg every six hours) for treatment of cerebral edema...Metyrapone was used to suppress hypercortisolemia before definitive treatment with bilateral adrenalectomy was performed. Following bilateral adrenalectomy, patient was started on stress-dose glucocorticoids before tapering to standard hydrocortisone replacement... Clinicians should consider ectopic production of ACTH from olfactory neuroblastomas in patients who present with cushingoid features. Medical and surgical management for ectopic ACTH-related hypercortisolism can be options for treatment. Medical treatment can be a bridge..."

Ataxia • Cardiovascular • CNS Tumor • Endocrine Disorders • Hypertension • Movement Disorders • Neuroblastoma • Obesity • Oncology • Pituitary Gland Carcinoma • Solid Tumor

Successful Medical Management of Cushing Disease With Metyrapone Throughout Pregnancy: A Report of Two Cases (ENDO 2025) - "One week after delivery, she developed postpartum pre-eclampsia, requiring temporary antihypertensive therapy, including labetalol, nifedipine, and magnesium for three weeks. While not FDA-approved for pregnancy, cortisol synthesis inhibition with metyrapone may be a viable therapeutic option for managing CD during pregnancy when surgical intervention is contraindicated or declined. Careful monitoring, multidisciplinary management, and dose optimization are essential. Particular attention is needed for hypertensive complications, even in the post-partum period."

Clinical • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Gestational Diabetes • Gynecology • Hypertension • Metabolic Disorders • Nephrology • Rare Diseases • Renal Disease

ACTH Secreting Neuroendocrine Tumor Presenting With Pneumocystis Jirovecii Pneumonia (ENDO 2025) - "She had a recent admission at another hospital for hypokalemia and palpitations and underwent workup for hypercortisolism with dexamethasone suppression testing...The patient required high flow supplemental oxygen, a three-week course of Bactrim, and a decreased metyrapone dose to increase the effective steroid dose...Prophylaxis against PJP should be considered in patients with Cushing Syndrome before starting treatment, and awareness for clinical PJP should be elevated in practitioners who are beginning treatment on patients with hypercortisolism.*. .*"

Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Heart Failure • Hepatology • Infectious Disease • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Osteoporosis • Pneumonia • Respiratory Diseases • Rheumatology • Solid Tumor • Type 2 Diabetes Mellitus

Osilodrostat for Ectopic Cushing's Syndrome: A Superior Off-Label Option After Failure of Other Therapies - A Case Report (ENDO 2025) - "We present a case of ectopic CS managed with multiple medications, including metyrapone and pasireotide, with successful control ultimately achieved using osilodrostat.Clinical Case:A 76-year-old male presented with uncontrolled, new-onset diabetes mellitus (A1c: 13.5%)...A 1 mg dexamethasone suppression test (DST) revealed elevated ACTH (85 pg/mL), cortisol (16.4 µg/dL), and DHEA-S (62 µg/dL)...Osilodrostat, though off-label, is an effective and user-friendly option for managing ectopic CS, allowing for straightforward monitoring and improved patient adherence*. .*"

Case report • Clinical • Anorexia • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Lung Cancer • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • SSTR2 • SSTR5

Paradoxical Steroid Use in Ectopic ACTH Syndrome: Navigating Complications of Small Cell Lung Cancer and Chemotherapy-Related Immune Hepatitis (ENDO 2025) - "Initial HbA1c was 11.6% (n <5.7%), reflecting chronic poor glycemic control despite metformin and insulin...Labs demonstrated elevated ACTH (210 pg/mL, n 10-50 pg/mL) and serum cortisol (44 μg/dL, n 6-23 μg/dL), consistent with ectopic ACTH production.Management Treatment began with ketoconazole, later switched to metyrapone and mifepristone due to poor tolerance and drug interactions. His SCLC was treated with cisplatin/etoposide followed by maintenance atezolizumab...Liver biopsy was deferred due to the patient's clinical stability and the high likelihood of drug-induced liver injury (DILI).In a paradoxical therapeutic maneuver, exogenous corticosteroids (prednisone 40 mg daily) were initiated to mitigate the immune-mediated hepatotoxicity...Further investigation is warranted to establish guidelines for the safe and effective use of corticosteroids in patients with hypercortisolism and concurrent immune-mediated complications.*. .*"

Cardiovascular • Cough • Cushing’s Disease • Diabetes • Endocrine Disorders • Hepatology • Hypertension • Inflammation • Liver Failure • Lung Cancer • Metabolic Disorders • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Type 2 Diabetes Mellitus

Ectopic Cushing Syndrome Secondary to Metastatic Neuroendocrine Tumor of Cecal Origin (ENDO 2025) - "The hypokalemia was refractory to potassium supplementation and spironolactone dose titration. A hormonal workup found elevated cortisol, no cortisol suppression on 1mg dexamethasone suppression test, elevated ACTH and increased 24-hour urinary-free cortisol...Liver function tests need to be monitored while on ketoconazole and limited availability is a challenge while utilizing metyrapone as a steroidogenesis inhibitor.*. .*"

Metastases • Cardiovascular • Colon Cancer • Colorectal Cancer • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Gastrointestinal Disorder • Hepatology • Hypertension • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

A Novel Approach to Corticotroph Adenoma Localization: 11C Methionine PET/CT Following Osilodrostat Therapy (ENDO 2025) - "Osilodrostat, a potent 11-β-hydroxylase inhibitor, has demonstrated superior efficacy and tolerability compared to traditional steroidogenesis inhibitors such as ketoconazole and metyrapone.Case: A 28-year-old man with a history of juvenile arthritis, total hip replacement, and post-operative pulmonary embolism presented with uncontrolled hypertension, centripetal obesity, purple striae, and significant weight gain, suggestive of Cushing's syndrome (CS). Laboratory investigations confirmed ACTH-dependent hypercortisolism, with markedly elevated post-1 mg dexamethasone cortisol of 807 nmol/L (<50 nmol/L), ACTH of 56.7 ng/L (10-30 ng/L), and 24-hour urinary free cortisol (UFC) of 774 nmol/24h (0-164 nmol/24h)... This case illustrates a novel preoperative strategy for improving adenoma detection in CD. Cortisol-lowering therapy may enhance functional imaging sensitivity, enabling more accurate tumor localization and optimizing surgical outcomes. If validated in..."

Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genetic Disorders • Hypertension • Idiopathic Arthritis • Immunology • Obesity • Oncology • Orthopedics • Pituitary Gland Carcinoma • Pulmonary Embolism • Respiratory Diseases • Rheumatology

Treatment of MACS with Low Doses of Metyrapone - a Preliminary Report. (ENDO 2025) - "Preliminary observations are encouraging with regard to the anticipated effects of the proposed treatment in MACS patients.As part of this presentation, we have prepared a case report on our first MACS patient who completed the study.*. .*"

Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Metabolic Disorders • Obesity • Osteoporosis • Rheumatology

Overnight Metyrapone Therapy in Patients with Mild Autonomous Cortisol Secretion (MACS): An Open-Label Phase 2 Clinical Trial (ENDO 2025) - "Abstract is embargoed at this time."

Clinical • P2 data

Effects of Switching from Metyrapone to Osilodrostat on Steroid Hormone Profiles and Clinical Outcomes in Patients with persistent Cushing's Disease (ENDO 2025) - "Surgical removal of the tumor is the primary treatment, but medical therapy is required in cases of persistent or recurrent disease or when surgery is infeasible.Drug therapies include agents targeting ACTH secreting tumor (e.g., pasireotide, cabergoline) and those inhibiting adrenal cortisol production (e.g., metyrapone, osilodrostat, ketoconazole)...Steroid hormone concentrations, including cortisol, progesterone, 17-hydroxyprogesterone (17Prog), and 17-hydroxypregnenolone (17Preg), were measured using high-performance liquid chromatography–mass spectrometry...Osilodrostat's superior suppression of CYP17A1, as evidenced by reduced androgen precursors, contributed to improved managementof hypertension and masculinization symptoms.*. .*"

Clinical • Clinical data • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Hypertension • Oncology • Otorhinolaryngology • Pituitary Gland Carcinoma • CYP11B1

In Vitro Study of the Effects of the Novel Aldosterone Synthase Inhibitor Baxdrostat (ENDO 2025) - "Bax, Osilodrostat (Osi), and Metyrapone (Met) were added to the culture medium at concentrations ranging from 0.0001 to 10 μM. In APA cells, the IC50 of Bax for Ald was 0.063 μM, with Osi (0.003 μM) and Met (1.310 μM) showing dose-dependent inhibitory effects. In CPT cells, Bax exhibited a weaker inhibitory effect on F compared to Osi (IC50: 0.438 μM) and Met (0.748 μM). Bax induced a concentration-dependent increase in 11-deoxycorticosterone (DOC) in APA cells, though the increase was lower than that observed with Osi."

Preclinical • Adrenal Cortex Carcinoma • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Hypertension • Oncology • Solid Tumor • CYP11B1

SEP-1: Stress Experience Following Psilocybin (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: University of Calgary | Initiation date: Feb 2025 ➔ Sep 2025

Trial initiation date

Effects of osilodrostat and metyrapone on 2D and 3D models of adrenocortical carcinoma cell lines viability: preliminary results. (ESPE-ESE 2025) - No abstract available

Preclinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Metyrapone treatment lowers hepatic lipid content and improves the cardiovascular risk profile in patients with mild autonomous cortisol secretion (ESPE-ESE 2025) - No abstract available

Clinical • Late-breaking abstract • Cardiovascular

Metyrapone as a bridge therapy after pituitary radiation for aggressive Cushing’s disease: a case report (ESPE-ESE 2025) - No abstract available

Case report • Clinical • Cushing’s Disease • Endocrine Disorders

Treatment of MACS with Low Doses of Metyrapone - a Preliminary Report. (ESPE-ESE 2025) - No abstract available

Cardiovascular

Budget Impact of Metyrapone for the Treatment of Cushing's Syndrome in the US (ISPOR 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 adverse event management and drug acquisition costs."

HEOR • Cushing’s Disease • Endocrine Disorders • Immunology

Ectopic ACTH-secreting pheochromocytoma without typical signs of Cushing syndrome. (PubMed, Oxf Med Case Reports) - "The patient was stabilized preoperatively with alpha-blockers and metyrapone before undergoing a successful laparoscopic adrenalectomy...Surgical resection remains the definitive treatment, with long-term follow-up essential to monitor for recurrence. This case contributes to the limited literature on the coexistence of pheochromocytoma and ectopic ACTH secretion."

Journal • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Hypertension • Metabolic Disorders • Oncology • Pain • Solid Tumor • Type 2 Diabetes Mellitus

Successful Medical Management of Cushing Disease With Metyrapone Throughout Pregnancy: A Report of 2 Cases. (PubMed, JCEM Case Rep) - "After an uncomplicated pregnancy, she developed postpartum preeclampsia requiring temporary antihypertensive therapy. Both cases showed favorable maternal and fetal outcomes, highlighting metyrapone as a therapeutic option for managing CD during pregnancy."

Journal • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Gynecology • Hypertension • Rare Diseases

Ectopic ACTH syndrome secondary to small-cell oropharyngeal cancer. (PubMed, BMJ Case Rep) - "Cortisol and adrenocorticotropic hormone (ACTH) were markedly raised and were not suppressed after overnight and high-dose dexamethasone tests. She was diagnosed with ectopic ACTH syndrome secondary to small-cell oropharyngeal cancer. Metyrapone and spironolactone were commenced; however, the patient deteriorated, and a decision was made to prioritise her comfort over escalating treatment."

Journal • Cardiovascular • CNS Disorders • Cushing’s Disease • Diabetes • Endocrine Disorders • Gastrointestinal Disorder • Head and Neck Cancer • Hypertension • Metabolic Disorders • Nephrology • Oncology • Oropharyngeal Cancer • Solid Tumor

Case Report: Thymic neuroendocrine tumor with metastasis to the breast causing ectopic Cushing's syndrome. (PubMed, Front Oncol) - "After initial treatment with a steroid inhibitor (ketoconazole) and diagnostics including 68Ga DOTA-TATE PET/CT, it was shown to be caused by a small thymic NET...Treatment with a steroid inhibitor (metyrapone) and tumor resection were again curative. The last disease relapse appeared 7 years after the initial treatment, with severe hypercortisolism treated with osilodrostat...Nuclear medicine improves the effectiveness of the tumor search, which is crucial in successful EAS therapy. Our case also underlines the need for lifelong monitoring of patients with thymic NETs and EAS."

Journal • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

Development and characterization of a double-crested cormorant hepatic cell line, DCH22, for chemical screening. (PubMed, Front Toxicol) - "Induction of CYP3A activity and mRNA expression was observed following exposure to hexabromocyclododecane (HBCD), tris(1,3-dichloroisopropyl)phosphate, carbamazepine, and metyrapone. The phase II metabolism gene, UGT1A1, was upregulated following HBCD exposure and DCH22 spheroids expressed vitellogenin protein after exposure to 17α-ethinylestradiol. Based on these data, the novel DCH22 cell line, cultured as 3D spheroids, has potential use as an alternative to DCEH for chemical screening and will permit the evaluation of avian species differences in sensitivity from an in vitro screening perspective."

Journal • Preclinical • UGT1A1

An ACTH-Producing Neuroendocrine Tumor: Clinical Course of Multidisciplinary Therapy Including Peptide Receptor Radionuclide Therapy - A Case Report. (PubMed, Case Rep Oncol) - "Simultaneously, everolimus was continued for about 1 year...As sunitinib and subsequent streptozocin chemotherapy failed to control the disease, PRRT with 177Lu-DOTATATE was performed...The patient was treated with antihypertensive and antidiabetic agents, and required an increased dose of metyrapone and addition of the cortisol biosynthesis inhibitor, osilodrostat...Although PRRT was effective, we should consider the occurrence of hormonal crisis during the therapy. Due to the rarity and complexity of hormone-producing tumors, cooperation between medical oncologists and endocrinologists is important for patient management."

Journal • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Hepatocellular Cancer • Hepatology • Hypertension • Liver Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor