Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.
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http://dx.doi.org/10.1155/2016/8173182 | DOI Listing |
J Clin Endocrinol Metab
January 2025
Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris, France.
Purpose: Primary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing's syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal and morphological levels. ARMC5 inactivating pathogenic variants are causative of PBMAH and rare variants of PDE11A have been associated with PBMAH.
Methods: Leukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by Next generation sequencing (NGS).
Front Endocrinol (Lausanne)
January 2025
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan.
Metyrapone is commonly used in the initial management of Cushing's syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone.
View Article and Find Full Text PDFCurr Cardiol Rev
January 2025
Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, IMU University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
Cardiovascular Disease [CVD], the leading cause of death globally, poses a significant burden on the healthcare sector. Its association with stress and Cushing's Syndrome has driven cortisol, the 'stress hormone,' to be a potential candidate in determining CVD risk. Cortisol synthesis and release through the hypothalamic-pituitary-adrenal [HPA] axis are regulated by several hormones and receptors involved in the pathological cascade towards CVD.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Cardiology and Internal Medicine, Military Institute of Medicine - National Research Institute, Warsaw, Poland.
The long-term hypercortisolemia of Cushing disease (CD) may lead to hemodynamic disorders by increasing subclinical cardiac and vascular dysfunction. The purpose of this observational cohort study was to assess the relationship between hemodynamic parameters evaluated via impedance cardiography (ICG) and echocardiographic parameters reflecting left ventricular function in 54 patients newly diagnosed with CD. The parameters assessed via ICG included stroke volume index (SI), cardiac index (CI), acceleration index (ACI), velocity index (VI), systemic vascular resistance index (SVRI), total artery compliance index (TACI).
View Article and Find Full Text PDFJ Clin Endocrinol Metab
January 2025
David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California.
Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging.
Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes.
Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023.
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