A correlative study between glucocorticoid receptor levels in human mononuclear leukocytes and biochemical data in Cushing's disease

1989 ◽  
Vol 120 (1) ◽  
pp. 55-61 ◽  
Author(s):  
E. M. Pardes ◽  
J. W. de Yampey ◽  
R.J. Soto ◽  
D. F. Moses ◽  
A. F. De Nicola

Abstract. We determined glucocorticoid receptors in human monouclear leukocytes in 9 patients with Cushing's disease, in order to correlate them with laboratory data. Receptors were measured by a whole-cell assay method, after incubation with [3H]-dexamethasone in the presence or absence of excess unlabelled hormone. In Cushing's disease, there were 4425 ± 364 sites/cell (N = 9), similar to in the controls: 4473 ± 476 (N = 10); average Kd was 2.42 ± 0.52 nmol/l (N = 3) similar to in the controls: 2.0 ± 0.20 nmol/l (N = 3). In Cushing's patients we found significant negative correlations between basal glucocorticoid receptors and: 1) morning blood cortisol (r = −0.67, P< 0.05), and 2) 17-ketogenic steroids after 2 mg of dexamethasone (r = −0.85, P< 0.01). No correlations were observed with afternoon blood cortisol, free urinary cortisol, basal and post-8-mg dexamethasone 17-ketogenic steroids, TRH-TSH area, urinary calcium. plasma glucose, or systolic blood pressure. Conclusions: In Cushing's disease, a subtle receptor down-regulation may exist, as suggested by the inverse relationship between glucocorticoid receptors and morning blood cortisol. Secondly, the relationship between basal receptors and 17-ketogenic steroids after 2 mg of dexamethasone suggests that glucocorticoid receptors in human mononuclear leukocytes could reflect the sensitivity of the nervous system-pituitary-adrenal axis to dexamethasone inhibition.

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 359-370 ◽  
Author(s):  
RL Edwards ◽  
FR Rickles ◽  
AM Bobrove

Abstract Human mononuclear leukocytes generate the procoagulant material tissue factor (TF) following stimulation by endotoxin, mitogens, or antigens in vitro. We have examined tissue-factor generation by mononuclear cell subpopulations prepared in a variety of ways in order to determine the cell of origin of mononuclear cell TF and the conditions necessary for maximal in vitro TF generation. We have also examined the relationship between in vitro TF generation and in vivo or in vitro measures of delayed hypersensitivity in response to identical antigen stimulation. Our results demonstrate that the monocyte is responsible for the bulk of mononuclear cell TF generation in vitro and that adhesion alone is not sufficient stimulation for significant.


Endocrine ◽  
2010 ◽  
Vol 37 (2) ◽  
pp. 280-285 ◽  
Author(s):  
Nihal Akar Bayram ◽  
Reyhan Ersoy ◽  
Didem O. Sen ◽  
Serap S. Inancli ◽  
Tahir Durmaz ◽  
...  

1999 ◽  
Vol 45 (11) ◽  
pp. 1467-1471 ◽  
Author(s):  
Cecilia Invitti ◽  
Gabriella Redaelli ◽  
Gabriella Baldi ◽  
Francesco Cavagnini

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katherine N Haseltine ◽  
Hannah Robins ◽  
Vanessa Cohen ◽  
Hannah Baratz ◽  
Anjile An ◽  
...  

Abstract Cushing’s disease (CD) is characterized by chronic exposure to excess glucocorticoids due to an ACTH-producing tumor. Obesity is a prominent feature of CD, although the mechanisms of weight gain have not been completely elucidated. In some patients, obesity persists despite appropriate medical or surgical treatment of CD and normalization of cortisol levels (1). Few studies have followed patients prospectively to understand the effect of CD remission and cortisol normalization on appetite and body weight. Previous studies have not shown a correlation between appetite or food cravings and circulating total peptide YY (PYY), ghrelin, or leptin concentrations, leading to interest in other hormones which may regulate appetite in CD (2). One of these is the neuropeptide Agouti-related protein (AgRP). AgRP is known to promote appetite and decrease energy expenditure by acting as a melanocortin antagonist at the level of the hypothalamus. Plasma AgRP may be elevated in patients with active CD and decreases with normalization of cortisol levels (3). We sought to determine if AgRP may play a role in regulating appetite or food cravings in CD. Plasma AgRP was measured before and prospectively after treatment in 19 patients with CD. Patients completed surveys on appetite and food cravings at these same time points. As expected, AgRP significantly decreased following treatment for CD, with mean AgRP before treatment 128.72 pg/mL (SD 55.41) and mean AgRP after treatment 75.23 pg/mL (SD 23.46). Using a paired t-test, the mean difference of 53.5 pg/mL was significant (p=0.0006). In addition, there were significant decreases in BMI, weight, and waist circumference with CD treatment. We found that plasma AgRP concentrations did not correlate with an 8-question visual analogue scale (VAS) used to assess hunger and satiety. However, treatment of CD significantly reduced Trait Food Craving Questionnaire scores in parallel with circulating AgRP levels using a one-way analysis of variance (p=0.004). Our data suggest that AgRP may play a role in food craving, rather than appetite, in patients with CD. Further research may clarify the relationship between AgRP and food cravings in CD patients before and after treatment. References: 1. Geer et al. Endocrinol Metab Clin North Am. 2014; 43: 75-102. Geer et al. Pituitary. 2016; 19: 117-126.Page-Wilson et al, J Clin Endocrinol Metab. 2019; 104 (3): 961-969.


Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 359-370 ◽  
Author(s):  
RL Edwards ◽  
FR Rickles ◽  
AM Bobrove

Human mononuclear leukocytes generate the procoagulant material tissue factor (TF) following stimulation by endotoxin, mitogens, or antigens in vitro. We have examined tissue-factor generation by mononuclear cell subpopulations prepared in a variety of ways in order to determine the cell of origin of mononuclear cell TF and the conditions necessary for maximal in vitro TF generation. We have also examined the relationship between in vitro TF generation and in vivo or in vitro measures of delayed hypersensitivity in response to identical antigen stimulation. Our results demonstrate that the monocyte is responsible for the bulk of mononuclear cell TF generation in vitro and that adhesion alone is not sufficient stimulation for significant.


2014 ◽  
Vol 60 (6) ◽  
pp. 29-37
Author(s):  
Galina A Melnichenko ◽  
Vera Popovich ◽  
Lyudmila Y Rozhinskaya ◽  
Zhanna E Belaya

Itsenko-Cushing’s disease (ICD) is a severe progressive neuroendocrine pathology characterized by the heterogeneous clinical picture and the high risk of complications. The main goals of ICD therapy include the total removal or the pituitary neoplasm or the reduction of its volume and/or stabilization of its growth, normalization of the cortisol level and secretion rhythm, the achievement of reverse development of clinical manifestations, and the retention of the pituitary hormonal function with a minimal risk of relapses. At present, both the improved methods for diagnostics of ICD and the development of its pharmacotherapy are needed. In the routine clinical practice, ICD is usually treated with the medicines of the following groups: blockers of glucocorticoid receptors and steroidogenesis, dophamine receptor antagonists, and multi-ligand somatostatin analogs. The evidence-based substantiation for the use of the above preparations was provided by the retrospective studies with the description of a series of cases which substantially restricts the reliable interpretation of the data on the effectiveness and safety of various medicines applied to manage the patients presenting with Itsenko-Cushing’s disease. The multi-ligand somatostatin analog pasiretoide is the sole preparation approved for the treatment of adult patients suffering ICD whose surgical treatment is either ineffective or impossible. The evaluation of the effectiveness and safety of pasiretoide therapy is based on the results of the prospective randomized double-blind classical study in which two doses of pasiretoide were used. By month 6 after the onset of the treatment with pasiretoide, the median of the daily decrease of the urinary cortisol level in the patients with ICD was 47.9%. The safety profile of this medication proved to be similar with that of other somatostatin analogs, with the exception of the higher frequency of hyperglycemia. Pasiretoide, like other somatostatin analogs, most frequently caused such adverse reactions as gastrointestinal disorders. At the same time, it ensured the stable reduction of the cortisol level by suppressing the ACTH production, and thereby decreased the main manifestations of hypercortisolism, induced clinical and hormonal remission, and improved the quality of life of the patients suffering Itsenko-Cushing’s disease.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gulzoda Shuhratovna Negmatova ◽  
Rukhangiz Utkurovna Norshodieva ◽  
Umida Akmalovna Mirsaidova

Abstract Cushing’s disease is a severe multimorbid pathology affecting mainly people of young working age. In most cases, the diagnosis of the disease is acute and the patient is observed for a long time by doctors of different specialties with complications of hypercorticism. Purpose: To identify the most frequent clinical manifestations of hypercorticism at the time of diagnosis of Cushing’s disease, to analyze the relationship of clinical manifestations of hypercorticism with the main clinical and laboratory indicators. Material and methods: 25 patients were examined, including 15 women and 10 men with Cushing’s disease, registered in Samarkand Endocrinology Clinic. Results: Majority of patients (68%) were in age 25-40, the average age was 37. The median duration of the disease was 35,5 months. Matronism, the most characteristic manifestation of hypercortisolism was observed in 36% (9 patients). This is most often associated with hypercorticism symptoms were striae and acne, which were found in 56% (14 patients), osteoporosis 40% (10). The most frequent complaints were weight gain, fatigue, headache, menstrual disturbances. A number of symptoms had a positive correlation with cortisol levels. Conclusion: Clinical manifestations of hypercorticolism are mainly nonspecific. Striae and acne were found in high frequency. Therefore these key features, namely a change in facial appearance, weight gain, elevation of BMI and the presence of genital virilisation should alert the clinician to the possibility of Cushing’s disease and initiate laboratory evaluation


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