The effect of naloxone on ATCH and β-endorphin in patients with Cushing's disease

1985 ◽  
Vol 110 (2) ◽  
pp. 170-175 ◽  
Author(s):  
B. Baranowska ◽  
W. Dorobek ◽  
W. Misiorowski ◽  
W. Jeske ◽  
M. H. Abdel-Fattah
Keyword(s):  
Cushing’S Disease ◽  
Healthy Subjects ◽  
Opiate Receptor ◽  
Cushing's Disease ◽  
Receptor Blockade ◽  
Acth Secretion ◽  
Endogenous Opiates ◽  
Paradoxical Response ◽  
Cortisol Release ◽  
Serum Acth

Abstract. Endogenous opiates may be important in the control of ACTH secretion in men. The effect of opiate receptor blockade by naloxone on ACTH, β-endorphin-like substance and cortisol release was studied in healthy women and in 9 patients with Cushing's disease. In the healthy subjects, ACTH, β-endorphin and cortisol levels were increased in response to naloxone. However, in 3 our of the 9 patients with Cushing's disease, a paradoxical decrease in serum ACTH, cortisol and β-endorphin concentrations was observed after naloxone administration. In the patients with a paradoxical response to naloxone, transsphenoidal microadenomectomy was ineffective.

The 24-h cortisol secretory pattern in Cushing's syndrome

1986 ◽  
Vol 112 (2) ◽  
pp. 230-237 ◽  
Author(s):  
J. Tourniaire ◽  
D. Chalendar ◽  
B. Rebattu ◽  
M. Fevre-Montange ◽  
L. Bajard ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Plasma Cortisol ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Cortisol Release

Abstract. The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistance of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.

scholarly journals Diagnostic Accuracy of Chromogranin A and Calcitonin Precursors Measurements for the Discrimination of Ectopic ACTH Secretion from Cushing’s Disease

2009 ◽  
Vol 94 (8) ◽  
pp. 2962-2965 ◽  
Author(s):  
Marina S. Zemskova ◽  
Eric S. Nylen ◽  
Nicholas J. Patronas ◽  
Edward H. Oldfield ◽  
Kenneth L. Becker ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Cushing’S Disease ◽  
Chromogranin A ◽  
Cushing's Disease ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion

Effect of opiate-receptor blockade on normoglycemic and hypoglycemic glucoregulation

1986 ◽  
Vol 250 (3) ◽  
pp. E236-E242 ◽  
Author(s):  
K. M. el-Tayeb ◽  
P. L. Brubaker ◽  
H. L. Lickley ◽  
E. Cook ◽  
M. Vranic
Keyword(s):  
Plasma Glucose ◽  
Glucose Production ◽  
Opiate Receptor ◽  
Receptor Blockade ◽  
Endogenous Opiates ◽  
Counterregulatory Hormones ◽  
Beta Endorphin ◽  
Initial Decrease ◽  
Pituitary Adrenal Axis ◽  
Naloxone Treatment

By use of the opiate antagonist naloxone, we have examined the hormonal and metabolic responses to opiate-receptor blockade under basal conditions and during insulin-induced hypoglycemia in normal dogs. Naloxone treatment had no measurable effect on glucose concentration, turnover, and norepinephrine levels, but stimulated plasma epinephrine, glucagon, and cortisol and inhibited insulin release. Insulin (7 mU X kg-1 X min-1) decreased plasma glucose to 42 +/- 4 mg/dl due to an initial decrease in glucose production and an increase in glucose disappearance. Glucose production then increased, and plasma glucose plateaued. After 50 min of insulin infusion, epinephrine levels increased 26-fold (P less than 0.05), norepinephrine and glucagon 3-fold (P less than 0.02), and cortisol 4-fold (P less than 0.01). Similarly, plasma beta-endorphin and adrenocorticotropin (ACTH) were elevated (6-fold, P less than 0.01, and 16-fold, P less than 0.05, respectively). When naloxone was given during insulin-induced hypoglycemia, there was earlier release of epinephrine, glucagon, beta-endorphin, ACTH, and cortisol as well as a greater release of glucagon (P less than 0.001) and cortisol (P less than 0.0001). This resulted in a greater increase in glucose production (P less than 0.01), thus lessening the insulin-induced hypoglycemic excursion. In conclusion, in the dog, endogenous opiates may play a small role in the regulation of basal insulin and glucagon release and can inhibit the pituitary-adrenal axis under basal conditions and during hypoglycemia. Thus increased glucose production in response to insulin-induced hypoglycemia is consistent with the excessive response of counterregulatory hormones during opiate-receptor blockade.

Octreotide exerts different effects in vivo and in vitro in Cushing's disease

1994 ◽  
Vol 130 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Günter K Stalla ◽  
Steffi J Brockmeier ◽  
Ulrich Renner ◽  
Chris Newton ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Dependent Manner ◽  
Acth Secretion ◽  
Adenoma Cell ◽  
Cortisol Levels ◽  
Corticotropic Adenoma

Stalla GK, Brockmeier SJ, Renner U, Newton C, Buchfelder M, Stalla J, Müller OA. Octreotide exerts different effects in vivo and in vitro in Cushing's disease. Eur J Endocrinol 1994;130:125–31. ISSN 0804–4643 The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 μg of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 μg of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l–1 μmol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14–46% for 1 μmol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated, CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo. Günter K Stalla, Max-Planck-Institute of Psychiatry, Clinical Institute, Kraepelinstr. 10, D-80804 Munich, Germany

Somatomedin A levels in patients with Cushing's disease

1981 ◽  
Vol 97 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Marja Thorén ◽  
Kerstin Hall ◽  
Tiit Rähn
Keyword(s):  
Direct Effect ◽  
Cushing’S Disease ◽  
Healthy Subjects ◽  
Serum Levels ◽  
Significant Rise ◽  
Radioreceptor Assay ◽  
Cushing's Disease ◽  
Stereotactic Radiation ◽  
Retarding Effect ◽  
Selective Impairment

Abstract. The serum levels of immunoreactive somatomedin A (SMA) in 23 patients with Cushing's disease, aged 6–61 years, were within the range of healthy subjects for their ages. No correlation was found between SMA and the excretion of cortisol. After im administration of hGH (8 IU = 4 mg) daily for 3 days there was a significant rise in SMA, both determined by radioimmunoassay and radioreceptor assay. Thus no impairment was found in the GH-dependent SMA levels or the ability of hGH to generate somatomedin, which indicates that the growth retarding effect of cortisol is most likely due to a direct effect on the tissue. After treatment with stereotactic radiation to the hypophysis there was a significant decrease in cortisol excretion without any change in SMA levels, indicating the possibility to achieve a selective impairment of the ACTH-cortisol axis.

Cyproheptadine-Induced Remission of Cushing's Disease Due to Pituitary Basophil Adenoma

1982 ◽  
Vol 16 (12) ◽  
pp. 962-965 ◽  
Author(s):  
J. Jimenez-Alonso ◽  
J. Munoz-Avila ◽  
L. Jaimez ◽  
F. Pérez-Jimenez ◽  
C. Bellido ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumors ◽  
Corticotropin Releasing Factor ◽  
Cushing's Disease ◽  
Patient Support ◽  
Acth Secretion ◽  
Hypothalamic Regulation ◽  
Potent Antagonist ◽  
Factor Secretion ◽  
Acth Release

Serotonin is involved in the control of ACTH secretion, possibly by stimulating corticotropin releasing factor secretion from the hypothalamus. Cushing's disease seems to be due to defective hypothalamic regulation of ACTH release from the pituitary gland. Cyproheptadine is a potent antagonist of serotonin and has been used successfully in some patients with Cushing's disease, although, generally, in women without radiological evidence of pituitary tumors. We report the successful use of cyproheptadine in a 54-year-old man with Cushing's disease due to pituitary basophil adenoma. Significant clinical and biochemical improvement was noted 45 days after treatment began. The results in this patient support our findings that cyproheptadine can be effective in patients with Cushing's disease due to pituitary tumors, as well as in preparing very ill patients for surgery or managing such patients until radiotherapy takes effect.

Cyclic Cushing’s disease with paradoxical response to dexamethasone

2005 ◽  
Vol 28 (10) ◽  
pp. 741-745 ◽  
Author(s):  
S. Checchi ◽  
L. Brilli ◽  
E. Guarino ◽  
C. Ciuoli ◽  
G. Di Cairano ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Paradoxical Response

scholarly journals Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

2013 ◽  
Vol 2013 (jan29 1) ◽  
pp. bcr2012008035-bcr2012008035 ◽  
Author(s):  
A. R. Lila ◽  
V. Sarathi ◽  
T. R. Bandgar ◽  
N. S. Shah
Keyword(s):  
Cushing’S Disease ◽  
Cushing's Disease ◽  
Paradoxical Response

scholarly journals Human Adrenocorticotropin-Secreting Pituitary Adenomas Show Frequent Loss of Heterozygosity at the Glucocorticoid Receptor Gene Locus1

1998 ◽  
Vol 83 (3) ◽  
pp. 917-921
Author(s):  
Nannette A. T. M. Huizenga ◽  
Pieter de Lange ◽  
Jan W. Koper ◽  
Richard N. Clayton ◽  
William E. Farrell ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Loss Of Heterozygosity ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Gene Locus ◽  
Cushing's Disease ◽  
Relative Resistance ◽  
Acth Secretion ◽  
Glucocorticoid Receptor Gene ◽  
Tumor Dna

Corticotropinomas are characterized by a relative resistance to the negative feedback action of cortisol on ACTH secretion. In this respect there is a similarity with the clinical syndrome of cortisol resistance. As cortisol resistance can be caused by genetic abnormalities in the glucocorticoid receptor (GR) gene, we investigated whether the insensitivity of corticotropinomas to cortisol is also caused by de novo mutations in the GR gene. We screened for the GR gene in leukocyte and tumor DNA from 22 patients with Cushing’s disease for mutations using PCR/single strand conformation polymorphism analysis. In a previous study, we identified 5 polymorphisms in the GR gene in a normal population. These polymorphisms were used as markers for the possible occurrence of loss of heterozygosity (LOH) at the GR gene locus. Except for 1 silent point mutation, we did not identify novel mutations in the GR gene in leukocytes or corticotropinomas from these patients. Of the 22 patients, 18 were heterozygous for at least 1 of the polymorphisms. In 6 of these patients, LOH had occurred in the tumor DNA. Of 21 patients examined for LOH on chromosome 11q13, only 1, with a corticotroph carcinoma, showed allelic deletion. As controls we studied 28 pituitary tumors of other subtypes (11 clinically nonfunctioning, 8 prolactinomas, and 9 GH-producing adenomas) and found evidence for LOH in only 1 prolactinoma. In six patients LOH was found at the GR gene locus (chromosome 5) in DNA derived from adenoma cells. Our observations indicate for the first time that LOH at the GR gene locus is a relatively frequent phenomenon in pituitary adenomas of patients with Cushing’s disease. This might explain the relative resistance of the adenoma cells to the inhibitory feedback action of cortisol on ACTH secretion. The specificity of the GR LOH to corticotropinomas supports this concept. Somatic mutations of the GR are not a frequent cause of relative cortisol resistance in these cells.

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