Inhibitory effect of cyproheptadine on ACTH secretion in patients with Addison's disease

Abstract. In 14 patients with Addison's disease plasma levels of ACTH were studied after administration of a single oral dose (16 mg) of cyproheptadine. The drug administration was followed by an inhibition of ACTH release. These results support the view that cyproheptadine may exert an inhibitory effect on ACTH secretion in subjects whose corticosteroid feedback mechanism is normal. We hypothesize that the effect of cyproheptadine might be related to its anti-serotonin or anti-histaminergic action.

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Effects of fludrocortisone withdrawal on plasma angiotensin II, ACTH, vasopressin, and potassium in patients with Addison's disease

Acta Endocrinologica ◽

10.1530/acta.0.1150325 ◽

1987 ◽

Vol 115 (3) ◽

pp. 325-330 ◽

Cited By ~ 5

Author(s):

W. Oelkers ◽

V. Bähr

Keyword(s):

Angiotensin Ii ◽

Salt Intake ◽

Feedback Inhibition ◽

Addison’S Disease ◽

Plasma Potassium ◽

Dietary Sodium ◽

Addison's Disease ◽

Acth Secretion ◽

Plasma Angiotensin ◽

Acth Release

Abstract. We attempted to answer to the question whether excessive rises in endogenous plasma angiotensin II (All) stimulate ACTH secretion by measuring PRA, All, AVP, ACTH, and cortisol in 8 patients with Addison's disease before and after withdrawal of fludrocortisone substitution. Blood was drawn at 14.30 h, exactly 6½ h after the morning dose of hydrocortisone had been taken. PRA and All were initially higher than normal in 4 patients. After withdrawal of fludrocortisone for 1 or 2 weeks, PRA and All rose markedly in 4 patients (up to 260 ng/l) without concomitant changes in plasma ACTH levels (r = −0.081, All vs ACTH). Changes in plasma cortisol could not have obscured a stimulatory effect of All on ACTH by variable feedback inhibition of ACTH release. The increase in plasma All levels in the 4 patients was larger than that observed in a previous study in normal subjects after rigorous dietary sodium restriction. In all patients, hyperkalaemia developed after fludrocortisone withdrawal, independent of changes in PRA and AII. Rises in PRA, All, and plasma potassium were partially reversed by increased sodium intake and further suppressed by resumption of fludrocortisone therapy. Plasma AVP remained in the normal range after fludrocortisone withdrawal, but was slightly elevated after increasing salt intake without fludrocortisone administration. Conclusions: 1) Rises of endogenous plasma All to levels tenfold higher than normal do not stimulate ACTH release. All is probably not a physiological modulator of ACTH secretion. 2) Mineralocorticoid substitution in Addison's disease should be monitored by plasma potassium measurement. Hyperkalaemia may coexist with normal PRA.

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Regulation of CRH-induced secretion of ACTH and corticosterone by SOM230 in rats

Acta Endocrinologica ◽

10.1530/eje.1.01998 ◽

2005 ◽

Vol 153 (3) ◽

pp. R7-R10 ◽

Cited By ~ 36

Author(s):

A P Silva ◽

P Schoeffter ◽

G Weckbecker ◽

C Bruns ◽

H A Schmid

Keyword(s):

Adrenocorticotropic Hormone ◽

Plasma Concentrations ◽

Inhibitory Effect ◽

Corticotropin Releasing Hormone ◽

Acth Secretion ◽

Releasing Hormone ◽

Corticosterone Secretion ◽

Corticosterone Release ◽

Acth Release

Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticosterone in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 μg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 μg/kg), octreotide (10 μg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 μg/kg) inhibited CRH-induced ACTH release by 45±3% and 51±2%, respectively, and corticosterone release by 43±5% and 27±16%, respectively. 10 μg/kg of octreotide tended to be less potent at inhibiting ACTH release (34±6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.

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Parenteral corticosteroids in emergency

Drug and Therapeutics Bulletin ◽

10.1136/dtb.5.2.6 ◽

1967 ◽

Vol 5 (2) ◽

pp. 6-7

Keyword(s):

Oral Dose ◽

Single Oral Dose ◽

Corticosteroid Therapy ◽

Plasma Concentrations ◽

Addison’S Disease ◽

Sudden Increase ◽

Adrenal Failure ◽

Intravenous Therapy ◽

Intramuscular Dose ◽

Acute Adrenal Failure

Corticosteroids are well absorbed from the gut: plasma concentrations of prednisolone or hydrocortisone are at a maximum about 2 hours after a single oral dose.1 An intramuscular dose acts no more quickly. Intravenous corticosteroid acts at once and is required for severe acute adrenal failure, for example in the crises of Addison’s disease, after adrenalectomy, after sudden cessation of corticosteroid therapy and sometimes in severe hypopituitarism. A sudden increase in the requirement of patients who are taking or have taken corticosteroids may also demand intravenous therapy.

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Suppression of ACTH Secretion by Synthetic MSH-Release Inhibiting Factor PRO-LEU-GLY-NH2in Addison's Disease

Hormone and Metabolic Research ◽

10.1055/s-0028-1093565 ◽

1977 ◽

Vol 9 (02) ◽

pp. 150-152 ◽

Cited By ~ 6

Author(s):

K. Voigt ◽

H. Fehm ◽

R. Lang ◽

K. Beinert ◽

E. Pfeiffer

Keyword(s):

Addison’S Disease ◽

Addison's Disease ◽

Acth Secretion ◽

Inhibiting Factor

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No inhibition of corticotrophin (ACTH)-hypersecretion in adrenal insufficiency by somatostatin

Acta Endocrinologica ◽

10.1530/acta.0.0950071 ◽

1980 ◽

Vol 95 (1) ◽

pp. 71-74 ◽

Cited By ~ 2

Author(s):

A. Jara-Albarrán ◽

J. Bayort ◽

A. Caballero ◽

R. Eusebio ◽

P. García-Peris ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Addison’S Disease ◽

Addison's Disease ◽

Plasma Acth ◽

Acth Secretion ◽

Primary Adrenal Insufficiency ◽

No Inhibition ◽

Infusion Period

Abstract. Somatostatin (250 μg as a bolus iv and 250 μg as a I h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease). The fall in plasma ACTH during the infusion period ranged between 0–30% with a mean reduction of 11.2 ± 11.6%. These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.

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BIOLOGICAL HALF-LIFE OF CAFFEINE IN PIGS

Canadian Journal of Animal Science ◽

10.4141/cjas70-006 ◽

1970 ◽

Vol 50 (1) ◽

pp. 49-54 ◽

Cited By ~ 6

Author(s):

H. M. CUNNINGHAM

Keyword(s):

Oral Dose ◽

Water Content ◽

Single Oral Dose ◽

Plasma Levels ◽

Half Life ◽

Intramuscular Injection ◽

Peak Plasma ◽

Growing Pigs ◽

Sufficient Time ◽

Biological Half Life

Five experiments were conducted with growing pigs to determine the biological half-life of caffeine after injection or various periods of ingestion. Peak plasma caffeine levels were reached within 5 hr after a single oral dose and 2 hr after intramuscular injection, and then declined with a biological half-life of about 12 hr. The caffeine content of tissues was approximately proportional to their water content and 6% of orally administered caffeine was excreted in the urine. Upon continuous ingestion of caffeine, peak plasma levels were reached within 2 days, indicating that accumulation was quite limited. When 1.5 g of caffeine per kg of feed was fed from weaning to market weight, the withdrawal of caffeine 2 days prior to slaughter was sufficient time to insure that caffeine levels in the liver, muscle, kidney and backfat were below 1 μg/g.

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Effect of angiotensin II on plasma ACTH in patients with Addison's disease

Acta Endocrinologica ◽

10.1530/acta.0.1100451 ◽

1985 ◽

Vol 110 (4) ◽

pp. 451-455

Author(s):

Hermann Haller ◽

Volker Bähr ◽

Petra Exner ◽

Wolfgang Oelkers

Keyword(s):

Angiotensin Ii ◽

Time Lag ◽

Addison’S Disease ◽

Major Effect ◽

Addison's Disease ◽

Base Line ◽

Plasma Acth ◽

Acth Secretion ◽

Short Term ◽

Sodium Deficiency

Abstract. Short-term angiotensin II (All) infusions (3 ng/kg/min) were performed in 5 patients with Addison's disease in order to assess the effect of AII on ACTH secretion. Base line ACTH levels were elevated due to a 9-h time lag between hydrocortisone administration and onset of the study. In 2 separate infusion periods of 30-min duration, All had no unidirectional effect on plasma ACTH. Mean ACTH increased slightly but insignificantly. Mean blood pressure rose by about 10 mmHg. The degree of angiotensinaemia induced is probably similar to the state of moderate to severe sodium deficiency. Short-term changes of All in this order of magnitude have obviously no major effect on ACTH secretion.

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