Diagnosis of Cushing’s disease

Daniel, Eleni; Newell‐Price, John

doi:10.1007/s11102-015-0649-2

Cited by 13 publications

(10 citation statements)

References 34 publications

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“…Future clinical studies will be necessary to demonstrate such effects. cortisol (24-hours collection), elevated midnight salivary cortisol levels, elevated or inappropriately normal serum ACTH levels, and lack of suppression of serum cortisol following a dexamethasone suppression test (17). All patients also had MRI-evidence of a pituitary adenoma on high-quality sellar MRI with and without gadolinium.…”

Section: Translational Relevancementioning

confidence: 99%

The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes

Salomon

Wang

Marzese

et al. 2018

Clinical Cancer Research

108

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Pituitary adenomas are one of the most common benign neoplasms of the central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, the degree to which these factors contribute to disease remains poorly understood. A multiplatform analysis was performed to identify the genomic and epigenomic underpinnings of disease among the three major subtypes of surgically resected pituitary adenomas in 48 patients: growth hormone (GH)-secreting ( = 17), adrenocorticotropic hormone (ACTH)-secreting ( = 13, including 3 silent-ACTH adenomas), and endocrine-inactive ( = 18). Whole-exome sequencing was used to profile the somatic mutational landscape, whole-transcriptome sequencing was used to identify disease-specific patterns of gene expression, and array-based DNA methylation profiling was used to examine genome-wide patterns of DNA methylation. Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GH-secreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of and genes in GH-secreting adenomas and gene in ACTH-secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes. Taken together, these data stress the contribution of epigenomic alterations to disease-specific etiology among adenoma subtypes and highlight potential targets for future immunotherapy-based treatments. This article reveals novel insights into the epigenomics underlying pituitary adenomas and highlights how differences in epigenomic states are related to important transcriptome alterations that define adenoma subtypes. .

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Section: Translational Relevancementioning

confidence: 99%

The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes

Salomon

Wang

Marzese

et al. 2018

Clinical Cancer Research

108

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“…Cushing's disease (CD), the most common form of endogenous Cushing's syndrome, is one of the most challenging endocrine disorders [ 1 , 2 ]. It is mostly caused by an adrenocorticotropin- (ACTH-) secreting pituitary adenoma, leading to pathological hypercortisolism and, consequently, to increased morbidity and mortality particularly due to metabolic and cardiovascular complications [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

Vilar

Albuquerque

Lyra

et al. 2016

International Journal of Endocrinology

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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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Section: Introductionmentioning

confidence: 99%

“…After confirming a diagnosis of Cushing syndrome, plasma ACTH levels are measured on at least two occasions to demonstrate an ACTHdependent cause of hypercortisolism (3). Differentiating Cushing disease from ectopic secretion of ACTH is first attempted with peripheral ovine or human sequence CRH stimulation, either of which has an overall 85%-90% sensitivity with a specificity of 100% (3). The high-dose dexamethasone suppression test has fallen out of favor, as its sensitivity is lower than the pretest probability of Cushing disease in women with ACTH-dependent Cushing syndrome (3).…”

Section: Introductionmentioning

confidence: 99%

“…Differentiating Cushing disease from ectopic secretion of ACTH is first attempted with peripheral ovine or human sequence CRH stimulation, either of which has an overall 85%-90% sensitivity with a specificity of 100% (3). The high-dose dexamethasone suppression test has fallen out of favor, as its sensitivity is lower than the pretest probability of Cushing disease in women with ACTH-dependent Cushing syndrome (3). Imaging consists of dedicated pituitary protocol magnetic resonance (MR) imaging.…”

Section: Introductionmentioning

confidence: 99%

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An Interventionist’s Guide to Endocrine Consultations

et al. 2017

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Endocrinopathies are a heterogeneous group of disorders often resulting from pathologic sources of hormone production. When the clinical scenario, laboratory testing, and noninvasive imaging fail to aid confident identification of the source of hormone excess, endocrine venous sampling may localize obscure lesions to guide subsequent treatment. Knowledge of basic hormone signaling pathways, common pathophysiologic disruptions of these pathways, and serologic evaluation fosters informed conversations with referring physicians and effective patient selection. Success in the angiography suite requires familiarity with normal and variant anatomy of the multiple organs of the endocrine system, patient preparation, stimulation and sampling techniques, specimen handling, and results interpretation. RSNA, 2017.

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Diagnosis of Cushing’s disease

Cited by 13 publications

References 34 publications

The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes

The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes

The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

An Interventionist’s Guide to Endocrine Consultations

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