Exp Clin Endocrinol Diabetes
November 2024
Background: Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS.
Methods: We quantified daily urinary excretion rates of 36 steroid hormone metabolites.
Front Endocrinol (Lausanne)
December 2023
Background: We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets.
Methodology: Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8).
Context: Patients with endogenous Cushing's syndrome (CS) may suffer from a wide range of neuropsychiatric symptoms leading to impaired quality of life (QoL).
Objective: Glucocorticoid receptor (GR) polymorphisms are associated with increased (BclI and N363S) or decreased (A3669G and ER22/23EK) GR sensitivity.
Hypothesis: GR genotypes may modulate and affect QoL and recovery after remission differently via GR sensitivity.
Introduction: Adrenal vein sampling (AVS) is not a routine procedure in patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but has been used to determine lateralization of cortisol secretion in order to guide decision of unilateral adrenalectomy. Our aim was to characterize the steroid fingerprints in AVS samples of patients with PBMAH and hypercortisolism and to identify a reference hormone for AVS interpretation.
Method: Retrospectively, we included 17 patients with PBMAH from the German Cushing's registry who underwent AVS.
Front Endocrinol (Lausanne)
February 2022
Context: Cushing's syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.
Objective: Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers.
Context: Pathogenesis of autonomous steroid secretion and adrenocortical tumorigenesis remains partially obscure.
Objective: To investigate the relationship between transcriptome profile and genetic background in a large series of adrenocortical tumors and identify new potential pathogenetic mechanisms.
Design: Cross-sectional study.
J Clin Endocrinol Metab
March 2020
Context: Signs and symptoms of Cushing's syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications.
Objective: The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis.
J Clin Endocrinol Metab
January 2020
Best Pract Res Clin Endocrinol Metab
April 2019
Cushing's disease (CD) is the most common etiology of Cushing's syndrome (CD) due to corticotroph pituitary adenoma, which are in most cases small (80-90% microadenomas) and in about 40% cannot be visualized on imaging of the sella. First-line treatment for CD is transsphenoidal surgery (TSS) with the aim of complete adenoma removal and preservation of pituitary gland function. As complete adenoma resection is not always possible, surgical failure is a common problem.
View Article and Find Full Text PDF24-h urine free cortisol (UFC) is an indicator of integrated cortisol secretion and established screening tool for Cushing's syndrome (CS). Doubts have been raised regarding specificity of immunoassays, and mass spectrometric techniques have been proposed as an alternative. In the present study we compared diagnostic accuracy of UFC measured with LC-MS/MS vs.
View Article and Find Full Text PDFContext: Unilateral adrenalectomy has been proposed in selected patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but its long-term outcome is unclear.
Objective: The aim of this study was to analyze long-term clinical and biochemical outcomes of unilateral adrenalectomy vs bilateral adrenalectomy in patients with PBMAH in comparison with the outcome of cortisol-producing adenoma (CPA) treated with unilateral adrenalectomy.
Design: Retrospective observational study in three German and one Italian academic tertiary care center.
Objective: Aim of our study was to analyze long-term outcome of patients with the ectopic Cushing's syndrome (ECS) compared to patients with Cushing's disease (CD) regarding cardiovascular, metabolic, musculoskeletal and psychiatric comorbidities.
Design: Cross-sectional study in patients with ECS and CD in two German academic tertiary care centers.
Methods: Standardized clinical follow-up examination was performed including health-related quality of life (QoL) in 21 ECS patients in long-term remission (≥18 months since successful surgery).
Background: Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis.
Methods: In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome.
Purpose: Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known to be associated with obesity and muscle atrophy. We compared Cushing's syndrome with matched obese controls regarding body composition, physical performance, and biochemical markers to test the hypothesis that Cushing's syndrome could be a model for sarcopenic obesity.
View Article and Find Full Text PDFBackground: Cushing's syndrome (CS) is characterized by an excessive secretion of glucocorticoids that results in a characteristic clinical phenotype. One feature of clinical hypercortisolism is breakdown of protein metabolism translating into clinical consequences including glucocorticoid-induced myopathy. While surgery is effective in control of cortisol excess, the effect of biochemical remission on muscular function is yet unclear.
View Article and Find Full Text PDFObjective: To evaluate volumetric and densitometric properties of the adrenal glands in patients with unilateral and bilateral disease in comparison with normal controls.
Design: A total of 77 patients (56 males and 21 females) diagnosed with primary aldosteronism (PA) with a mean age of 53 ± 10 years were prospectively enrolled. Unenhanced and contrast-enhanced computed tomography scans were analysed for adrenal volumes and mean densities.
Objective: Our aim was to review short- and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome.
Methods: We reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution.
Results: BADx is considered if ACTH-dependent Cushing's syndrome is refractory to other treatment modalities.
Objective: The aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome.
Subjects And Methods: We retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses.