Metopirone (metyrapone) / Perrigo Company - LARVOL DELTA

RARE CASE OF DUAL PARANEOPLASTIC SYNDROMES FROM SMALL CELL LUNG CANCER CAUSING A TRIPHASIC ELECTROLYTE PRESENTATION (ISN-WCN 2026) - "A high-dose dexamethasone suppression test confirmed ectopic Cushing syndrome, so she was started on metyrapone.Within 48 hours, her [sodium] declined from 138 to 130 mmol/L...Tolvaptan was considered, but fluid restriction, salt tablets, and urea normalized her [sodium].Conclusion Hyponatremia resolving to hypokalemia/alkalosis and recurring to hyponatremia again should raise the suspicion for dual paraneoplastic syndrome in SCLC...The high cortisol's mineralocorticoid activity, overwhelming 11beta-hydroxysteroid dehydrogenase, likely masked hyponatremia, and then metyrapone-induced cortisol suppression may have unmasked a 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 • Cushing’s Disease • Endocrine Disorders • Heart Failure • Lung Cancer • Metabolic Disorders • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma

Etomidate, Ketoconazole, and Mitotane for Cushing Disease due to Adrenocortical Carcinoma (SCCM 2026) - "Triple therapy (carboplatin, etoposide, and doxorubicin) was considered but not initiated due to poor functional status...Osilodrostrat, mifepristone, metyrapone, and pasireotide were considered but restricted by primary disease and cost...EI's are safe and effective to reduce cortisol quickly, but many institutions and staff are unfamiliar with its use as a continuous infusion. Many challenges still exist for this difficult and rare disease."

Adrenal Cortex Carcinoma • Cushing’s Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Oncology • Rare Diseases • Solid Tumor

International Real-world study on osilodrostat efficacy and safety in adrenal Cushing syndrome. (PubMed, J Clin Endocrinol Metab) - "Osilodrostat controls hypercortisolism in 66.7% of patients with adrenal CS treated for longer than 4 weeks and in 87.5% of cases treated for longer than 12 weeks, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors have a higher probability of response."

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

APHP211003: CUSHMAH - Benefit of steroidogenesis inhibitors in Mild Cushing syndrome (Mild Autonomous Cortisol Secretion): a randomized trial in patients with Primary Bilateral Macronodular Adrenocortical Hyperplasia (clinicaltrialsregister.eu) - P2/3 | N=70 | Not yet recruiting | Sponsor: Assistance Publique Hopitaux De Paris

New P2/3 trial • Cushing’s Disease • Endocrine Disorders

Gluco-Max: Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake (clinicaltrials.gov) - P=N/A | N=23 | Completed | Sponsor: Eleonora Seelig | Recruiting ➔ Completed | Trial completion date: Jul 2026 ➔ Feb 2026 | Trial primary completion date: Jul 2026 ➔ Feb 2026

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity • CXCL8 • IGF1 • IL1R1 • LEP

Exceptional Response to a Single Dose of Pembrolizumab as Salvage Therapy for Metastatic Adrenocortical Carcinoma. (PubMed, JCEM Case Rep) - "The patient was started on mitotane and metyrapone, followed by 8 cycles of etoposide-doxorubicin-cisplatin plus mitotane. The patient underwent complete surgical resection, achieving full remission. More than 1 year later, she remains disease free."

Journal • Tumor mutational burden • Adrenal Cortex Carcinoma • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Hypertension • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • PD-L1 • TMB • TP53

Does hair cortisol concentration reflect measurable regulatory biology of the HPA axis in healthy humans? (PubMed, Psychoneuroendocrinology) - "Over the course of a month, subjects participated in 5 regulatory tests: ACTH stimulation, dexamethasone/CRH test, metyrapone, dexamethasone suppression (DST), and Trier Social Stress Test. Identifying ways to directly assess them in stress field work may have value. Future studies should also measure hair washing frequency (additional 19 % of variance explained) and recognize that HCC is not a simple way to quantify stress exposure or stress sensitivity."

Journal

Metabolic effects of metyrapone treatment in patients with mild autonomous cortisol secretion: a prospective proof-of-concept trial. (PubMed, EClinicalMedicine) - P4 | "Patients with uni-or bilateral adrenal incidentaloma and MACS defined by cortisol >1·8 μg/dL after 1 mg-dexamethasone-suppression-testing without clinical signs of Cushing's syndrome were included. Treatment of MACS with evening doses of metyrapone lowers hepatic lipid content and improves the metabolic risk profile and might offer a novel therapeutic approach. Esteve (formerly HRA pharma) to the Medical University of Vienna (PI:PW)."

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

A case of immune thrombocytopenia aggravated by therapy for hypercortisolism in adrenocortical carcinoma. (PubMed, Ther Adv Endocrinol Metab) - "Following treatment with metyrapone and surgical resection aimed at reducing cortisol levels, the patient experienced an ITP relapse...This case highlights the immunosuppressive role of endogenous cortisol and underscores the need for careful monitoring in patients with coexisting autoimmune disorders undergoing treatment for CS. Awareness of this interaction may inform individualized steroid tapering strategies and improve outcomes in similar clinical scenarios."

Journal • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Oncology • Solid Tumor • Thrombocytopenia • Thrombocytopenic Purpura

Sleep deprivation disrupts lacrimal gland homeostasis via hypothalamic-pituitary-adrenal axis and gut dysbiosis in mice. (PubMed, Commun Biol) - "Pharmacological inhibition of glucocorticoid synthesis with metyrapone preserves lacrimal gland structure and function while attenuating immune activation...Transcriptomic and immunohistochemical analyses further reveal that all three interventions converge on the downregulation of IL-17 signaling. Collectively, these findings establish an HPA-gut microbiome-lacrimal gland axis that links neuroendocrine stress to microbial dysbiosis and ocular inflammation, and they suggest therapeutic strategies for SD-associated lacrimal gland dysfunction."

Journal • Preclinical • Inflammation • Ocular Inflammation • Transplantation • CD4 • CD8 • IL17A

β-Adrenergic Signaling Contributes to Circadian and Lipid Dysregulation in Meibomian Glands During Chronic Psychological Stress. (PubMed, Invest Ophthalmol Vis Sci) - "Experimental groups included control, stress alone, stress with propranolol (a nonselective β-adrenergic receptor antagonist), and stress with metyrapone (a glucocorticoid synthesis inhibitor). Chronic psychological stress disrupts MG homeostasis through sympathetic overactivation, affecting circadian regulation, immune responses, and lipid metabolism. β-Adrenergic blockade partially reverses these changes, highlighting a potential therapeutic approach for stress-related evaporative dry eye."

Journal • CNS Disorders • Dry Eye Disease • Hypertriglyceridemia • Metabolic Disorders • Ophthalmology • ADRB2

Update and practical recommendations for the use of medical treatment of Cushing´s syndrome. (PubMed, Endocr Rev) - "Currently available medical treatments include adrenal steroidogenesis inhibitors that block cortisol secretion (ketoconazole, levoketoconazole, metyrapone, osilodrostat, mitotane, and etomidate), drugs that modulate pituitary ACTH secretion (pasireotide and cabergoline), and drugs that block peripheral glucocorticoid receptors (mifepristone). In this review, we summarize the main indications for medical treatment in CS, the mechanism of drug action, efficacy, recommended doses, and safety of the currently available drugs, as well as potential future treatments. We also discuss titration and block-and-replace approaches for control of hypercortisolism and provide recommendations for the use and monitoring of medical treatment in CS, including patients with endogenous hypercortisolism in special situations such as pregnancy, cyclic CS and mild autonomous cortisol secretion."

Journal • Cushing’s Disease • Endocrine Disorders

Diabetic Ketoacidosis as the First Manifestation of Ectopic Cushing's Syndrome. (PubMed, Cureus) - "Clinicians should bear in mind this etiology of diabetic ketoacidosis based on clinical signs and younger patients with multiple, age-atypical comorbidities. This would permit the expedited targeted stabilization of Cushing's syndrome and the suitable institution of the diagnostic approach and treatment for this challenging syndrome."

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

Role of 68Ga-DOTATOC Positron Emission Tomography in Locating Pulmonary Neuroendocrine Tumor Presenting with ACTH-Dependent Cushing's Syndrome: A Case Report. (PubMed, J Clin Med) - "Metyrapone was administered to suppress excessive cortisol...After VATS, ACTH and cortisol levels were normalized. Here, we report a case of ACTH-dependent Cushing's syndrome caused by a lung neuroendocrine tumor, in which 68Ga-DOTATOC PET was helpful in detecting the functional tumors."

Journal • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Hematological Disorders • Infectious Disease • Lung Cancer • Neuroendocrine Tumor • Oncology • Pituitary Gland Carcinoma • Pneumonia • Respiratory Diseases • Solid Tumor • Thrombosis

A Rare Case of Adrenocorticotropic Hormone (ACTH)-Secreting Pheochromocytoma Presenting With Severe Cushing Syndrome (CS) and Dual Hormonal Secretion. (PubMed, Cureus) - "She underwent laparoscopic adrenalectomy following medical stabilization with alpha-blockade and metyrapone...It also emphasizes maintaining a high index of suspicion for ectopic ACTH production in rapidly progressing CS. Early diagnosis and appropriate preoperative management are critical to reducing morbidity and mortality."

Journal • Adrenal Cortex Carcinoma • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Movement Disorders • Oncology • Solid Tumor

Executive summary of the consensus document for the management of severe Cushing's syndrome: Consensus document of the Neuroendocrinology Focus Group of the Spanish Society of Endocrinology and Nutrition (SEEN). (PubMed, Endocrinol Diabetes Nutr (Engl Ed)) - "Combination therapy with ketoconazole and metyrapone is a useful option for these patients. Prompt treatment of comorbidities and thrombo- and infection prophylaxis are recommended. In conclusion, a rapid control of hypercortisolism is vital in SCS, and for this purpose combination therapy or potent drugs with a rapid onset of action such as etomidate or osilodrostat are indicated."

Clinical guideline • Journal • Cushing’s Disease • Endocrine Disorders • Infectious Disease

Stress-Induced Disruption of Circadian and Neuroimmune Networks in Lacrimal Glands Drives Dry Eye Pathogenesis. (PubMed, Invest Ophthalmol Vis Sci) - "Tear secretion was assessed by pilocarpine-stimulated phenol red thread test...Propranolol or metyrapone partially restored rhythmic transcription, glandular architecture, and tear secretion. Chronic stress induces circadian output decoupling in the lacrimal gland, driving neuroimmune and metabolic dysfunction and dry eye disease pathogenesis. Partial rescue by β-adrenergic and glucocorticoid pathway inhibition highlights neuroendocrine signaling as a therapeutic target and establishes the LG as a peripheral model of stress-induced circadian disruption."

Journal • Dry Eye Disease • Metabolic Disorders • Ophthalmology • NR3C1

Chronic Restraint Stress Misaligns Corneal Clock via β-Adrenergic and Glucocorticoid Signaling, Altering Epithelial, Neural, Immune, Metabolic States. (PubMed, Invest Ophthalmol Vis Sci) - "Cohorts received either propranolol, metyrapone, or no intervention; non-stressed littermates served as controls. Systemic stress activation was confirmed via plasma levels of adrenocorticotropic hormone, corticosterone, epinephrine, and norepinephrine, along with superior cervical ganglion and adrenal gene expression...RS disrupts corneal circadian output and impairs epithelial, immune, and metabolic homeostasis via β-adrenergic and glucocorticoid mechanisms. Temporal targeting of these neuroendocrine pathways may represent a strategy to mitigate stress-induced ocular-surface dysfunction."

Journal • OCLN • TJP1

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