Recorlev (levoketoconazole) / Xeris Biopharma - LARVOL DELTA

Bilateral macronodular adrenocortical disease with isolated primary aldosteronism and normocortisolemia: a case report. (PubMed, Front Med (Lausanne)) - "This case shows that ARMC5 mutations can cause isolated mineralocorticoid excess without hypercortisolism, expanding the known phenotypic spectrum. Genetic testing for ARMC5 should be considered in patients with bilateral adrenal enlargement regardless of steroid hormone profile."

Journal • Cardiovascular • Endocrine Disorders • Hypertension

Association of antiretroviral therapy regimens with serum cortisol abnormalities in people living with HIV/AIDS: a retrospective study. (PubMed, Front Endocrinol (Lausanne)) - "Subjects were stratified into morning serum hypocortisolemia group (Group A), morning serum normocortisolemia (Group B), and abnormal morning serum hypercortisolemia (Group C)...The NRTIs + PIs regimen was associated with a significantly higher likelihood of reduced cortisol compared with the NRTIs + NNRTIs regimen. This finding was supported by multivariate logistic regression, which indicated that regimen (2) (NRTIs + PIs) was an independent factor associated with decreased cortisol levels."

Journal • Retrospective data • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease

Off-Label Use of Levoketoconazole in the Management of Mild Autonomous Cortisol Secretion (ENDO 2026) - "Biochemical evaluation revealed three abnormal dexamethasone suppression tests (cortisol 2.5-2.8 μg/dL) with normal dexamethasone levels, borderline low ACTH ( 6.8 pg/mL), and low DHEA-S (36.4 μg/dL)...Levoketoconazole was initiated following confirmation of normal baseline liver function tests and ECG... Evidence guiding non-surgical management of MACS remains limited, necessitating the need for further studies. This case supports the potential use of levoketoconazole as a therapeutic option for patients with MACS who cannot undergo surgery. Careful monitoring for hepatotoxicity, QTc prolongation, drug-drug interactions, and the development of adrenal insufficiency, are essential to optimize safety and clinical outcomes."

Cardiovascular • Coronary Artery Disease • Cushing’s Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Obesity • Osteoporosis • Renal Disease • Type 2 Diabetes Mellitus

Evaluation of the Association between Serum Cortisol and Immunological Status in HIV-Positive Patients. (ENDO 2026) - "Materials and A cross-sectional study was conducted between June 2018 and June 2019 at a medium complexity public hospital The primary objectives were to evaluate the association between basal cortisol and CD4+ lymphocyte counts and to analyze immunological differences between normocortisolemic and hypercortisolemic patients... Basal cortisol levels were not significantly associated with CD4+ lymphocyte counts in HIV+ patients. However, the correlations between T3, cortisol, and CD8+ lymphocytes suggest a potential interaction between thyroid function and the immune system. Longitudinal studies, including inflammatory biomarkers and free cortisol fractions, are needed to better understand these interactions and their clinical relevance."

Clinical • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Bilateral Adrenal Nodules with Cosecretion of Cortisol and Aldosterone (ENDO 2026) - "Two separate 1mg dexamethasone suppression tests were consistent with MACS (baseline DHEA-S and ACTH confirmed diagnosis)...Medical management of MACS and PA is being initiated with levoketoconazole and spironolactone...In absence of clear lateralization, medical therapy was favored over surgery. This management reflects a personalized approach and shared decision making."

Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genetic Disorders • Hypertension • Infectious Disease • Obesity • Type 2 Diabetes Mellitus

Brain Evaluation in Cushing Disease: A Longitudinal Pilot Study (ENDO 2026) - "Following surgery, 5 patients became hypocortisolemic and 1 normocortisolemic...Our results require confirmation with larger samples and repeated evaluation during longer follow-up period. Funding: This project was supported by an investigator-initiated grant from Recordati."

Clinical • CNS Disorders • Cognitive Disorders • Cushing’s Disease • Depression

Endogenous Cushing'S Syndrome from Bilateral Adrenal Hyperplasia: A Management Dilemma (ENDO 2026) - "While agents such as mifepristone and ketoconazole have demonstrated efficacy in endogenous Cushing's syndrome, primarily in pituitary-dependent disease, patients with BAH are rarely studied as a distinct subgroup, and guidance for long-term therapy in non-surgical candidates is limited...Her diabetes regimen included metformin, high-dose basal-bolus insulin, and SGLT2 inhibitor, and her hypertension was treated with three antihypertensive agents...Cortisol failed to adequately suppress following a 1-mg overnight dexamethasone suppression test (post-dexamethasone cortisol 2.3 μg/dL), with a therapeutic dexamethasone level (338 ng/dL), and suppressed plasma ACTH ( < 5 pg/mL), confirming ACTH-independent endogenous Cushing's syndrome...When imaging is non-localizing and surgery is not immediately feasible, medical therapy plays a critical role in controlling hypercortisolism while allowing reassessment of disease laterality and surgical candidacy...."

Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

Levoketoconazole: A Potentially Safer Therapeutic Profile for Cushing'S Syndrome via Reduced Toxic Deacetyl Ketoconazole (DAK) Metabolite Formation (ENDO 2026) - "SI may prolong QT and cause hypokalemia, and KTZ, LKTZ, and metyrapone inhibit CYP3A4. Daily exposure of PHH for 72 h resulted in intracellular glutathione loss, decreasing statistically significantly by ~44% with LKTZ and ~53% with KTZ. Both treatments lowered intracellular ATP; KTZ achieved statistical significance (p < 0.046). Median LFT were significantly reduced in the LKTZ group, indicating a shift away from amino acid metabolism toward enhanced detoxification."

Cushing’s Disease • Endocrine Disorders • Hepatology • Liver Failure • Metabolic Disorders • CYP3A4

Bridging the Cortisol Crisis: Use of Etomidate and Steroidogenesis Inhibitors in Metastatic Adrenocortical Carcinoma (ENDO 2026) - "Biochemical evaluation showed two abnormal dexamethasone suppression tests 4.1 and 3.5 μg/dL( normal < 1.8 μg/dL) and suppressed ACTH < 5 pg/mL.(normal 6-50pcg/ml) The patient underwent left adrenalectomy, which revealed a 7.5 cm high-grade adrenocortical carcinoma...Although she initially declined chemotherapy, she later agreed to initiate mitotane; however, treatment was discontinued after several days due to severe hypokalemia and diarrhea...Her course was complicated by refractory hypokalemia (2.2–2.6 mEq/L) and uncontrolled hypertension despite aggressive supplementation, requiring initiation of high-dose spironolactone and amiloride. Continuous etomidate infusion was started for rapid cortisol suppression to stabilize electrolytes and allow initiation of chemotherapy with doxorubicin and etoposide. She was later transitioned to levoketoconazole after four days of etomidate therapy; however, drug interaction with etoposide led to severe bone marrow suppression..."

Late-breaking abstract • Metastases • Adrenal Cortex Carcinoma • Cardiovascular • Endocrine Disorders • Genetic Disorders • Genito-urinary Cancer • Hypertension • Hypotension • Obesity • Oncology • Osteoporosis • Respiratory Diseases • Solid Tumor

The Increased Use of Neoadjuvant Anticorticosteroid Therapy in Adrenal Hypercortisolism Prior to Adrenalectomy (ENDO 2026) - "Background: Cortisol-modulating drugs (e.g., osilodrostat, levoketoconazole, mifepristone) may be used to optimize patients with adrenal hypercortisolism (AHC) prior to adrenalectomy, particularly in those with metabolic derangements or obesity...A total of 816 patients (41.6%) demonstrated biochemically unequivocal AHC, classified (grade 1-3) by low-dose dexamethasone suppression test as mild (1.8–5.0 μg/dL; 79.6%), moderate (5.0–10 μg/dL; 11.7%), or severe (≥10 μg/dL and/or overt Cushing syndrome; 8.7%)... Neoadjuvant anticorticosteroid therapy is increasingly used to manage AHC, particularly in patients with more severe disease. Pre-treated patients demonstrated similar pathology and postoperative adrenal function, without differences in PHC or need for GR. These findings support the perioperative safety of medical therapy as a bridge to adrenalectomy and justify further studies evaluating metabolic and long-term outcomes of neoadjuvant therapy of AHC."

Clinical • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Genetic Disorders • Genito-urinary Cancer • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Solid Tumor

Cyclic Cushing syndrome as a clinical enigma and diagnostic dilemma in advanced endocrinology. (PubMed, J Endocrinol Invest) - "To confirm this disease, it is necessary to record two episodes of hypercortisolism alternating with period of normocortisolism...Thus, the diagnostic algorithm for each individual case will be specific and will depend on the phase of the disease, the patient's condition, and concomitant pathology. Our review summarizes current data on the mechanisms of cyclic hypercortisolism known to date and provides a comparative and critical analysis of modern diagnostic methods that help identify this pathology and indicate its origin."

Journal • Review • Cushing’s Disease • Endocrine Disorders

Atypical Course of ACTH-Dependent Cushing’s Disease With Discordant Biochemical and Clinical Response to Levoketoconazole (AACE 2026) - "Case Description A 57-year-old woman with a history of type 2 diabetes mellitus, pigmentary glaucoma, depression, anxiety, degenerative joint disease, possible polycystic ovary syndrome, infertility, and obesity was referred for evaluation of hypercortisolism after repeatedly elevated 24-hour urinary cortisol and failed dexamethasone suppression tests. Cyclic Cushing’s physiology, variable hepatic metabolism of levoketoconazole, and partial ACTH autonomy are possible explanations of presentation. The increase in salivary cortisol after starting medication may reflect ACTH rebound from reduced negative feedback, episodic cortisol escape during early titration, or cross-reactivity of cortisol precursors in"

Clinical • Discordant • CNS Disorders • Cushing’s Disease • Depression • Diabetes • Endocrine Disorders • Genetic Disorders • Glaucoma • Infertility • Metabolic Disorders • Mood Disorders • Obesity • Ophthalmology • Polycystic Ovary Syndrome • Sexual Disorders • Type 2 Diabetes Mellitus • Women's Health

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

The effect of hypercortisolism treatment on dyslipidemia in Cushing syndrome: systematic review and meta-analysis. (PubMed, J Clin Endocrinol Metab) - "Our study demonstrate a significant improvement in serum lipid levels after treatment of CS. Since the cardiovascular complications of hypercortisolism depend on several factors, further studies are needed to determine whether this directly translates into an adequate reduction in the risk of major cardiovascular events."

Journal • Retrospective data • Cardiovascular • Cushing’s Disease • Dyslipidemia • Endocrine Disorders • Metabolic Disorders

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

Increased Weight Loss With the Combination of Levoketoconazole and Semaglutide in a Patient With Mild Hypercortisolism. (PubMed, AACE Endocrinol Diabetes) - "Medications included sertraline 100 mg daily and metformin 500 mg daily, which was increased; spironolactone was added, and Ozempic 0.25 mg subcutaneously weekly was started and titrated up to 1 mg subcutaneously weekly...A dexamethasone suppression test showed a non-suppressed adrenocorticotropic hormone 10 (reference: 7.2-63.3) and morning cortisol 6.7 ng/dL (reference: <1.8 ng/dL)...Our case shows that combined use of levoketoconazole and semaglutide resulted in significant weight loss and improvement of biochemical and psychological parameters. Hypercortisolism may mimic other diagnoses, and further exploration is needed about possible additive effects of levoketoconazole with semaglutide."

Journal • Acne Vulgaris • Adrenal Cortex Carcinoma • CNS Disorders • Cushing’s Disease • Depression • Endocrine Disorders • Genetic Disorders • Mood Disorders • Obesity • Oncology • Polycystic Ovary Syndrome • Psychiatry • Solid Tumor

Relapse of Cyclic Cushing Syndrome With a 19-Year Remission: Potential Involvement of COVID-19 in the Relapse. (PubMed, JCEM Case Rep) - "Cyclic Cushing syndrome (cyclic CS) is characterized by phases of hypercortisolemia and normocortisolemia or hypocortisolemia...The present case suggests that careful follow-up is essential for patients with uncured cyclic CS even if long-term remission is achieved. Additionally, a relapse of cyclic CS with a glucocorticoid-driven positive feedback mechanism could be induced by infection and treatment with glucocorticoids."

Journal • Carcinoid Tumor • Cushing’s Disease • Endocrine Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Pituitary Gland Carcinoma • Solid Tumor • Thymus Cancer

Levoketoconazole Use Prior to Adrenalectomy (ENDO 2025) - "A one milligram overnight dexamethasone suppression test was abnormal at 2.0 µg/dL...Recorlev®, 150 mg daily was started in December 2023 with Trulicity and metformin discontinued.At a January 2024 follow-up, the Recorlev® dose was increased to 150 twice daily... This is the first documented case of pre-operative use of Recorlev® in a patient undergoing adrenalectomy. The tumor was found to secrete both cortisol and aldosterone. Pre-operative administration of Recorlev® successfully attenuated these hormones, facilitating a smooth surgical procedure and favorable postoperative outcome."

Adrenal Cortex Carcinoma • Asthma • Dyslipidemia • Endocrine Cancer • Genetic Disorders • Immunology • Metabolic Disorders • Obesity • Oncology • Respiratory Diseases • Solid Tumor

Pituitary Macroadenoma With Suprasellar Extension and Optic Chiasm Compression Causing Cushing's Disease: a Case Report (ENDO 2025) - "Ketoconazole was started as Levoketoconazole was not approved by insurance, and she was referred for surgery.Pituitary ACTH-dependent Cushing disease is rare, with high morbidity and mortality, peaking in the 3rd–4th decade (female:male 3:1)...Brain MRI and a high-dose dexamethasone test follow. If an adenoma >6 mm is found, surgery is performed. If <6 mm, bilateral inferior petrosal sinus sampling with CRH or desmopressin stimulation is needed."

Case report • Clinical • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genetic Disorders • Hypertension • Obesity • Ophthalmology • Pain • Pituitary Gland Carcinoma

Serum Inflammation based scores in prediction of liver fibrosis among Cushing syndrome and MACS patients: Data from ERCUSYN Krakow database. (ESPE-ESE 2025) - "There may be an association between FIB4 and SIBS in the following pattern: 1)positive with NLR in CS; 2)positive with NPR and negative with PLR in: CS, MACS and normocortisolemic population; 3)negative with SII in MACS and normocortisolemic population. Further studies are needed to estabilish SIBS role in LF prediction."

Clinical • Cushing’s Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders

Evaluation of the effect of hypercortisolemia treatment on bone metabolism and structure in patients with endogenous Cushing's syndrome- a single center experience (ESPE-ESE 2025) - "Our results confirmed that normocortisolemia improved calcium-phosphate metabolism. Further conclusions regarding changes in calcium-phosphate levels and bone turnover markers over time in normocortisolemic patients can be drawn when a larger study group has been enrolled."

Clinical • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypertension • Metabolic Disorders • Orthopedics • Rare Diseases • DKK1

Xeris Biopharma Delivers Record Fourth Quarter and Full-Year 2024 Results; and Announces 2025 Guidance (Businesswire) - "Gvoke: Net revenue was $82.8 million for the year ended December 31, 2024 – an increase of approximately 24% compared to prior year...Recorlev: Net revenue was $64.3 million for the year ended December 31, 2024 – an increase of approximately 118% compared to prior year...Keveyis: Net revenue was $49.5 million for the year ended December 31, 2024 – a decrease of approximately 13% compared to prior year."

Commercial • CNS Disorders • Cushing’s Disease • Endocrine Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

New Trends in Treating Cushing's Disease. (PubMed, touchREV Endocrinol) - "At the pituitary level, pasireotide is an approved somatostatin receptor ligand, and compounds targeting cell cycle regulation, cell signalling and epigenetics are now under investigation. Levoketoconazole and osilodrostat are novel steroid inhibitors, and relacorilant overcomes the adverse effects of mifepristone. Adrenal ACTH receptor blockage and immunotherapy could also play a role."

Journal • Cushing’s Disease • Endocrine Disorders • Oncology • SSTR

Efficacy and Safety of Levoketoconazole in Managing Cushing's Syndrome: A Systematic Review. (PubMed, Indian J Endocrinol Metab) - "Levoketoconazole has good efficacy and safety in CS. Bigger and longer studies are warranted to establish its superiority over ketoconazole."

Journal • Review • Cushing’s Disease • Endocrine Disorders

Cushings Conundrum: Taming the Hormone Hurricane (ENDO 2024) - "Ketoconazole was initiated but discontinued later due to rising liver enzymes, Metyrapone and spironolactone were initiated and etomidate infusion titrated off...Dexamethasone was initiated given concern for relative adrenal insufficiency during this time and was later switched to hydrocortisone, and eventually discontinued with normalizing cortisol levels...Metyrapone and mitotane are alternatives but supply challenges exist. Osilodrostat, studied for short-term use, has limited data in ectopic ACTH syndromes... Managing ACTH-producing neuroendocrine tumors necessitates a multidisciplinary approach. In severe Cushing's syndrome, etomidate infusion quickly normalizes cortisol but requires intensive care due to sedation risks. Ketoconazole and levoketoconazole carry a hepatotoxicity risk."

Anesthesia • Cardiovascular • Critical care • Cushing’s Disease • Diabetes • Endocrine Cancer • Endocrine Disorders • Hematological Disorders • Hepatology • Hypertension • Metabolic Disorders • Musculoskeletal Diseases • Nephrology • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pulmonary Disease • Rare Diseases • Renal Disease • Solid Tumor