Pituitary, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 14, 2024
Язык: Английский
Nature Reviews Endocrinology, Год журнала: 2024, Номер 20(4), С. 209 - 227
Опубликована: Янв. 25, 2024
Язык: Английский
Процитировано
11
Best Practice & Research Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 37(4), С. 101752 - 101752
Опубликована: Фев. 27, 2023
Язык: Английский
Процитировано
17
AJP Heart and Circulatory Physiology, Год журнала: 2023, Номер 326(3), С. H670 - H688
Опубликована: Дек. 22, 2023
Modulation of the renin-angiotensin-aldosterone system is a foundation therapy for cardiovascular and kidney diseases. Excess aldosterone plays an important role in disease, contributing to inflammation, fibrosis, dysfunction heart, kidneys, vasculature through both genomic mineralocorticoid receptor (MR)-mediated as well nongenomic mechanisms. MR antagonists have been key attenuating pathologic effects but are associated with some side may not always adequately attenuate aldosterone. Aldosterone primarily synthesized by CYP11B2 synthase enzyme, which very similar structure other enzymes involved steroid biosynthesis including CYP11B1, enzyme glucocorticoid production. Lack specificity CYP11B2, off-target on hypothalamic-pituitary-adrenal axis, counterproductive increased levels bioactive intermediates such 11-deoxycorticosterone posed challenges development early inhibitors osilodrostat. In early-phase clinical trials, newer demonstrated promise lowering blood pressure patients treatment-resistant uncontrolled hypertension. It therefore plausible that these agents offer protection disease states heart failure or chronic disease. Further evaluation will be needed clarify inhibitors, promising class represent potentially major therapeutic advance.
Язык: Английский
Процитировано
16
European Journal of Endocrinology, Год журнала: 2023, Номер 188(6), С. K29 - K32
Опубликована: Июнь 1, 2023
Abstract Introduction Osilodrostat is the newest approved steroidogenic inhibitor drug for treatment of hypercortisolism. In this article, we describe 3 patients who experienced a previously undescribed adverse event: prolonged adrenocortical blockade following cessation. Methods Patient records showing history successful hypercortisolism control with followed by at least 4 weeks interruption were reviewed. characteristics and hormonal dosage analyzed. Results Persistence was found in lasted from 6 to 9 months depending on patients. This phenomenon manifested regardless lower or higher daily doses (2-10 mg) total duration did not seem predict severity blockade. Conclusion The finding side effect highlights importance continuing adrenal function monitoring after prevent crisis risk.
Язык: Английский
Процитировано
13
Drug Design Development and Therapy, Год журнала: 2023, Номер Volume 17, С. 1303 - 1312
Опубликована: Апрель 1, 2023
Abstract: Cushing's disease (CD) is caused by endogenous hypercortisolism as a result of adrenocorticotropin (ACTH) secretion from pituitary tumor. The condition associated with multiple comorbidities and increased mortality. First-line therapy for CD surgery, performed an experienced neurosurgeon. Hypercortisolism may often persist or recur after initial surgery. Patients persistent recurrent will generally benefit medical therapy, administered to patients who underwent radiation the sella are awaiting its salutary effects. There three groups medications directed against CD, including pituitary-targeted that inhibit ACTH tumorous corticotroph cells, adrenally-directed adrenal steroidogenesis glucocorticoid receptor (GR) antagonist. focus this review osilodrostat, inhibitor. Osilodrostat (LCI699) was initially developed lower serum aldosterone levels control hypertension. However, it soon realized osilodrostat also inhibits 11-beta hydroxylase (CYP11B1), leading reduction in cortisol levels. drug development then shifted treatment hypertension CD. In series studies (LINC 1 through 4), shown be effective normalizing 24-h urinary free (UFC) majority treated approved have failed surgery not surgical candidates. Further study needed examine role combination well long-term outcomes patients. overall good safety profile. Most common adverse effects include nausea, headache, fatigue, arthralgias, dizziness, prolonged QT c interval, hypokalemia. females, can cause hirsutism acne. twice daily, making choice difficulty adhering more complex regimens. has important, albeit adjunctive, management Keywords: disease, syndrome, LCI699, adenoma, inhibitor,
Язык: Английский
Процитировано
11
Frontiers in Endocrinology, Год журнала: 2022, Номер 13
Опубликована: Дек. 2, 2022
Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It serious endocrine associated with increased mortality and impaired quality of life. The management CD remains challenging. Although transsphenoidal surgery the treatment choice in most cases, approximately half patients, second or third-line options are needed. Currently, new medical therapies available target adrenal steroidogenesis, somatostatin dopamine receptors, glucocorticoid receptors. Selection medication to use should be individualized determined many factors including severity disease, possible side effects, patients preferences local availability. aim this article describe currently therapy help clinicians individualize context recently updated Pituitary Society recommendations.
Язык: Английский
Процитировано
19
Pituitary, Год журнала: 2025, Номер 28(1)
Опубликована: Янв. 25, 2025
Abstract Purpose To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) glycemic in patients with Cushing’s disease. Methods Pooled analysis two Phase III studies (LINC 3 LINC 4), both comprising a 48-week core phase an optional open-label extension. Changes from baseline systolic diastolic BP (SBP DBP), fasting plasma glucose (FPG), glycated hemoglobin (HbA 1c ) were evaluated during treatment with/without hypertension or diabetes at baseline. Results Of 210 patients, 82.9% met criteria for 40.0% In hypertension, reductions mean SBP/DBP observed week (W)12 to W72, 49.1%/58.5% high (> 130/>90 mmHg) had normotensive levels W72. Antihypertensive medication dose was reduced/stopped 26.8% proportion taking antihypertensive decreased 54.3% 47.3% diabetes, FPG HbA W12 33.3%/61.5% FPG/HbA (≥ 100 mg/dL/≥6.5%) normal Antihyperglycemic 35.7% antihyperglycemic 21.9% 17.1% W72; improvements correlated improvement urinary free cortisol but not weight change. BP/glycemic parameters generally remained without hypertension/diabetes Conclusions Patients disease comorbid receiving rapid sustained control, respectively.
Язык: Английский
Процитировано
0
Pituitary, Год журнала: 2025, Номер 28(1)
Опубликована: Янв. 29, 2025
A recent update of consensus guidelines for the management Cushing's disease (CD) included indications medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current therapy approaches by expert pituitary centers through an audit conducted validate criteria Pituitary Tumors Centers Excellence (PTCOEs) and provide initial standard care CD. Based on activities nine international PTCOEs between 2018 2020, we evaluated patients under treatment biochemical control rates. The median number active with CD per center was 117 (35–279), a 10 new managed annually endocrinology units (4–42). percentage receiving 13.3% (4.8–82.9). Ketoconazole most frequently used drug, rate usage 26.5% (5-66.7) those rates metyrapone pasireotide use were 17.2% (0–50) 9.3% (0-51.7), respectively. For cabergoline osilodrostat, therapy, 2.8% (0-33.3), 1.7% (0–25), Combination reported be utilized 13.6% (0-45.5) medically treated patients. Mifepristone single center, representing 1.1% its Overall, 75% (10–100). Adrenal steroidogenesis inhibitors commonly medications amongst centers. Despite combination up 25% did not achieve even PTCOEs, highlighting need either more efficient therapies or novel therapeutic options.
Язык: Английский
Процитировано
0
Frontiers in Oncology, Год журнала: 2025, Номер 15
Опубликована: Фев. 25, 2025
Ectopic adrenocorticotropic hormone secretion (EAS) is responsible for approximately 10%-18% of Cushing's syndrome cases. Thymic neuroendocrine tumors (NETs) comprise 5%-16% EAS; therefore, they are very rare and the data about this particular scarce. We present a case 34-year-old woman with rapid onset severe hypercortisolism in April 2016. After initial treatment steroid inhibitor (ketoconazole) diagnostics including 68Ga DOTA-TATE PET/CT, it was shown to be caused by small thymic NET. successful surgery resolution all symptoms, there recurrence after 5 years observation metastasis breast, PET/CT result confirmed breast biopsy. Treatment (metyrapone) tumor resection were again curative. The last disease relapse appeared 7 treatment, treated osilodrostat. There local mediastinum, thoracoscopic performed good clinical biochemical effect. patient remains under careful follow-up. Our stays accordance recent literature data, showing that patients NETs younger than previously considered severity does not correlate size. symptoms EAS associated NET may develop rapidly as our case. Nuclear medicine improves effectiveness search, which crucial therapy. also underlines need lifelong monitoring EAS.
Язык: Английский
Процитировано
0
Endocrine Journal, Год журнала: 2025, Номер 72(5), С. 463 - 473
Опубликована: Янв. 1, 2025
Cushing's disease is a rare endocrine disorder that presents many systemic complications, and its initial phase management can be difficult in atypical severe cases or at institutes with limited experience. It which several complications may have already progressed the time of diagnosis, become more during phase, potentially becoming life-threatening. In addition, patients are young, depending on this management, their quality life will significantly decline later on. Therefore, review summarizes evidence accumulated to date outlines strategies for focusing stages from detection, referral surgery.
Язык: Английский
Процитировано
0