Normocortisolemic Cushing's Syndrome Initially Presenting with Increased Glucocorticoid Receptor Numbers

2000 ◽  
Vol 85 (1) ◽  
pp. 14-21 ◽  
Author(s):  
R. S. Newfield
Keyword(s):  
Glucocorticoid Receptor ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome

Effect of Glucocorticoid receptor antagonist administration in a Cushing's syndrome model rat

2019 ◽  
Author(s):  
Toshiro Seki ◽  
Atsushi Yasuda ◽  
Natsumi Kitajima ◽  
Masami Seki ◽  
Masayuki Oki ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome

scholarly journals Decreased ligand affinity rather than glucocorticoid receptor down-regulation in patients with endogenous Cushing's syndrome

2000 ◽  
pp. 472-476 ◽  
Author(s):  
NA Huizenga ◽  
WW De Herder ◽  
JW Koper ◽  
P de Lange ◽  
D AJ v Lely ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
The Body ◽  
The Other ◽  
Down Regulation ◽  
Ligand Affinity ◽  
Other Hand ◽  
Receptor Number ◽  
Cortisol Levels

OBJECTIVE: Glucocorticoids (GCs) serve a variety of important functions throughout the body. The synthesis and secretion of GCs are under the strict influence of the hypothalamo-pituitary-adrenal axis. The mechanisms of action of GCs are mediated by the intracellular glucocorticoid receptor (GR). Over the years, many studies have been performed concerning the regulation of GR expression by GC concentrations. METHODS: In the present study, we determined the characteristics of the GR in peripheral mononuclear blood leukocytes (PBML) from thirteen patients with endogenous Cushing's syndrome and fifteen control subjects, using a whole cell dexamethasone binding assay. Furthermore, cortisol concentrations were determined in order to investigate a possible relationship between serum cortisol levels and receptor characteristics. RESULTS: There were no differences in mean receptor number between patients and controls. On the other hand, a significantly lower ligand affinity was identified in cells from patients with Cushing's syndrome compared with controls. A complete normalisation of the ligand affinity was observed after treatment in the only patient tested in this respect, whereas the receptor number was not affected. In patients, there was a statistically significant negative correlation between cortisol concentrations and ligand affinity, which was not found in controls. CONCLUSION: Receptor down-regulation does not occur in PBML from patients with endogenous Cushing's syndrome. On the other hand, there seems to be a diminished ligand affinity which possibly reflects receptor modification in response to exposure to the continuously high cortisol levels in patients with Cushing's syndrome. This assumption is substantiated by the fact that in one patient a normalisation of the ligand affinity after complete remission of the disease was seen.

scholarly journals Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing’s syndrome

Endocrine ◽  
2016 ◽  
Vol 53 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Sean H. P. P. Roerink ◽  
M. A. E. M. Wagenmakers ◽  
J. W. A. Smit ◽  
E. F. C. van Rossum ◽  
R. T. Netea-Maier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Glucocorticoid Receptor ◽  
Cushing’S Syndrome ◽  
Cardiometabolic Risk ◽  
Cushing's Syndrome ◽  
Cardiometabolic Risk Factors ◽  
Glucocorticoid Receptor Polymorphisms

A New Therapeutic Approach in the Medical Treatment of Cushing's Syndrome: Glucocorticoid Receptor Blockade with Mifepristone

2013 ◽  
Vol 19 (2) ◽  
pp. 313-326 ◽  
Author(s):  
Maria Fleseriu ◽  
Mark Molitch ◽  
Coleman Gross ◽  
David Schteingart ◽  
T. Vaughan ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Medical Treatment ◽  
Cushing’S Syndrome ◽  
Therapeutic Approach ◽  
Cushing's Syndrome ◽  
Receptor Blockade

scholarly journals Medical Treatment of Cushing’s Syndrome: Glucocorticoid Receptor Antagonists and Mifepristone

2010 ◽  
Vol 92 (1) ◽  
pp. 125-130 ◽  
Author(s):  
Frederic Castinetti ◽  
Bernard Conte-Devolx ◽  
Thierry Brue
Keyword(s):  
Glucocorticoid Receptor ◽  
Medical Treatment ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Receptor Antagonists

scholarly journals Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome

2012 ◽  
Vol 97 (6) ◽  
pp. 2039-2049 ◽  
Author(s):  
Maria Fleseriu ◽  
Beverly M. K. Biller ◽  
James W. Findling ◽  
Mark E. Molitch ◽  
David E. Schteingart ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome

scholarly journals Normocortisolemic Cushing’s Syndrome Initially Presenting with Increased Glucocorticoid Receptor Numbers1

2000 ◽  
Vol 85 (1) ◽  
pp. 14-21
Author(s):  
Ron S. Newfield ◽  
George Kalaitzoglou ◽  
Teresa Licholai ◽  
David Chilton ◽  
Javed Ashraf ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Cushing’S Syndrome ◽  
Compression Fracture ◽  
Cushing's Syndrome ◽  
High Dose ◽  
Receptor Sites ◽  
Buffalo Hump ◽  
Cardinal Sign ◽  
Pituitary Adrenal Axis ◽  
Over Time

A girl who developed Cushingoid features in peripuberty, but was eucortisolemic, was previously reported to have markedly elevated lymphocyte glucocorticoid receptor sites per cell with normal binding affinity as a potential cause of her phenotype. Her circadian rhythm of cortisol and pituitary-adrenal axis were initially intact, but later proved to be dysregulated. The patient presented at age 10.8 yr with centripetal obesity, moon facies, buffalo hump, and purple striae, but no statural stunting, which is a cardinal sign of Cushing’s syndrome. At 11.5 yr she suffered a compression fracture of the L1 vertebra. That prompted treatment with the antiprogestin drug mifepristone (RU486), which was administered at high dose to achieve an antiglucocorticoid effect. From ages 13.75 yr through 15.5 yr, RU486 was administered in various intervals to suppress her Cushingoid features. Once RU486 was introduced, however, a consistent correlation over time between the Cushingoid features and glucocorticoid receptor sites per cell was no longer observed. However, the number of glucocorticoid receptor sites per cell tended to decrease in response to administering RU486. Ultimately, her Cushingoid phenotype proved to be transient.

scholarly journals Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome

2012 ◽  
Vol 166 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Laura Trementino ◽  
Gloria Appolloni ◽  
Carolina Concettoni ◽  
Marina Cardinaletti ◽  
Marco Boscaro ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Cushing’S Syndrome ◽  
Low Frequency ◽  
Serum Cortisol ◽  
Protective Role ◽  
Cushing's Syndrome ◽  
Wild Type ◽  
Morning Serum Cortisol ◽  
Midnight Cortisol

ObjectiveGlucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the fourGR(NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile.Patients and methodsSixty-one patients with CS and 71 sex- and age-matched HC were genotyped.ResultsBclI variant was markedly higher in patients with CS compared with HC (62 vs 41%,P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed.In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found.In contrast, A3669GGRcarriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%,P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl,P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl,P=0.01). The negative association between diabetes and A3669GGRpolymorphism remained significant when data were adjusted for potential confounding factors.ConclusionsThe A3669G polymorphism of theGRgene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes.

Sign in / Sign up

Export Citation Format

Share Document