Physiological dosing of exogenous ACTH

1985 ◽  
Vol 108 (3) ◽  
pp. 401-406 ◽  
Author(s):  
Michael L. Graybeal ◽  
Victor S. Fang

Abstract. We evaluated the ACTH and cortisol responses to several doses of exogenous ACTH, and compared these values to the physiologic responses obtained in normal subjects undergoing insulin-induced hypoglycaemia. We determined that a cosyntrophin dose of 0.2 μg/kg body weight produced both ACTH and cortisol levels indistinguishable from the 'physiologic' stress-induced values. Since this dose is approximately 4 per cent of the standard 250 μg dose employed in tests of adrenal function, our findings suggest a need for caution in the interpretation of such tests.

1995 ◽  
Vol 145 (3) ◽  
pp. 455-460 ◽  
Author(s):  
A C McFarlane ◽  
S Potocnik ◽  
M Towstoless ◽  
K Moritz ◽  
E M Wintour

Abstract Pituitary-adrenal responses to intravenous infusion of ovine corticotrophin-releasing hormone (oCRH) or arginine vasopressin (AVP) and to haemorrhage were examined in the ovine foetus prior to 90 days of gestation (term 145–150 days). In chronically cannulated foetuses (n=8), between 74 and 84 days of gestation, basal ACTH levels were less than 20 pg/ml while cortisol levels were 6·5 ± 1·5 nmol/l (mean±s.e m.). Intravenous infusion of oCRH (1 μg/h for 60 min) or AVP (1 μg/h for 60 min) significantly increased ACTH (P<0·05 for both treatments) and cortisol (P<0·01 for both treatments) levels, although the response to both hormones was modest. In acutely studied foetuses of a similar age (70–90 days of gestation, mean 82·0 ± 1·4 days, n=7), exteriorization and progressive haemorrhage significantly (P<0·05) elevated ACTH levels from 117·4 ± 32·1 pg/ml to a maximal value of 329·2 ± 112·8 pg/ml, the maximal ACTH response corresponding to the removal of a volume of blood equivalent to 6·6 ±1·2% of the pre-haemorrhage body weight. The present study has demonstrated that the ovine foetal pituitary, in vivo, is responsive to exogenous and endogenous stimuli by mid-gestation and, at this age, although basal cortisol levels are low, the foetal adrenal is capable of responding to elevated ACTH levels in the short term. Journal of Endocrinology (1995) 145, 455–460


1998 ◽  
Vol 139 (6) ◽  
pp. 575-579 ◽  
Author(s):  
B Ambrosi ◽  
L Barbetta ◽  
T Re ◽  
E Passini ◽  
G Faglia

The possibility of assessing hypothalamic-pituitary-adrenal (HPA) function by the standard ACTH test (250 microg) has been widely discussed in the past years and compared with the role of the insulin tolerance test (ITT). Recently, it was shown that low doses of ACTH, such as 1 microg i.v., induce a maximal adrenal response and, by reducing the discrepancies compared with the ITT also allow one to detect mild forms of secondary hypoadrenalism. In the present study the 1 microg ACTH test was performed in patients with hypothalamic-pituitary disease in order to assess adrenal function, and the results have been compared with those obtained after the insulin test. Fifty-seven patients (31 men and 26 women, aged 19-73 years) with hypothalamic-pituitary diseases were studied: 51 patients were affected with pituitary tumor and 6 patients had hypothalamic disorders. All these patients and 18 healthy volunteers (7 men and 11 women, aged 19-46 years) received 1 microg i.v. ACTH injection. In addition, the ITT (0.1-0.15 U/kg body weight) was performed in all patients. In normal subjects mean cortisol levels significantly (P<0.001) increased from a baseline of 393+/-43 nmol/l to a peak of 770+/-41 nmol/l after 1 microg ACTH. In 44 patients with hypothalamic-pituitary disease 1 microg ACTH caused a cortisol rise similar to that of normal subjects (from 332+/-17 to 769+/-24 nmol/l; P<0.001), while an impaired response (from 124+/-23 to 312+/-46 nmol/l) was observed in 13 cases (23%), 7 of them with low morning cortisol levels (10-127 nmol/l) and 6 with basal values at the lower limit of normality. The cortisol response to ITT was compared with that obtained after the 1 microg ACTH test: 10 patients failed both challenges, 4 patients who passed the ACTH test failed the ITT, while 3 patients who failed the ACTH test passed the ITT. The 23 out of 57 patients (40%) who showed a cortisol peak greater than 750 nmol/l after 1 microg ACTH had a normal response to ITT. A positive correlation between cortisol peaks after ACTH and after insulin was also found (r = 0.68, P<0.001). Assuming a 100% accuracy of ITT, the low dose ACTH test yielded a 71% sensitivity and a 93% specificity. In conclusion, the low-dose ACTH test is a useful, safe and inexpensive tool for the initial assessment of HPA function in patients with hypothalamic-pituitary disease. In fact, the ITT is unnecessary when cortisol peaks are greater than 750 nmol/l after 1 microg ACTH and also when very low cortisol basal levels indicate an overt hypoadrenalism. Within these limits the ITT is mandatory and its important role in the recognition of secondary adrenal failure is further confirmed.


1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.


1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.


1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S259-S263 ◽  
Author(s):  
E. de Peretti ◽  
M.G. Forest ◽  
B. Loras ◽  
Y. Morel ◽  
M. David ◽  
...  

SUMMARY In normal subjects, plasma pregnenolone sulfate (PS) levels high at birth, decreased during the first year of life in relation to the pattern of involution of the fetal adrenal zone. Thereafter, PS levels, in contrast with those of DHAS, did not show the abrupt rise characteristic of the adrenarche, but increased very progressively till adulthood. The response of PS to various provocative tests of adrenal and pituitary function (ACTH and Metyrapone stimulation, dexamethasone suppression), has been established in normal subjects. The measurement of plasma PS levels in basal conditions as well as in response to dynamic tests was very useful in the diagnosis of various adrenal and pituitary diseases in children.


Cephalalgia ◽  
1993 ◽  
Vol 13 (6) ◽  
pp. 400-405 ◽  
Author(s):  
Marc L Gordon ◽  
Richard B Lipton ◽  
Serena-Lynn Brown ◽  
Christina Nakraseive ◽  
Marjorie Russell ◽  
...  

The serotonin receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin, and induces migraine-like headaches. We have studied the neuroendocrine and headache responses to m-CPP in 8 subjects with migraine and I0 normal subjects. Each subject underwent two challenge tests, one with 0.25 mg/kg PO of m-CPP and the other with placebo, administered in a double-blind crossover format. Serial measurements of serum cortisol, prolactin, and m-CPP levels were made at 30-min intervals for 210 min following ingestion of the medication. The incidence and severity of headache was assessed by a structured telephone interview after each test. We confirmed that m-CPP stimulates the release of cortisol and prolactin, and may induce headache, in both migraine subjects and normal controls. The cortisol response as well as ratings of headache severity and duration directly correlated with plasma levels of m-CPP. There were highly significant associations between the cortisol response and both headache severity and duration, independent of m-CPP plasma levels. We did not find statistically significant differences between the migraine and normal subjects in terms of their neuroendocrine or headache responses to m-CPP.


1962 ◽  
Vol 203 (5) ◽  
pp. 961-963 ◽  
Author(s):  
Mohinder P. Sambhi ◽  
Max H. Weil ◽  
Vasant N. Udhoji

Pressor responses produced by intravenous injections of graded doses of norepinephrine were recorded in ten normal subjects before and after pharmacologic doses of glucocorticoids. Two subjects had been pretreated with 9α-fluorocortisol. Although a considerable variation was found in the responsiveness to repeated norepinephrine injections, variance analysis demonstrated that administration of adrenal cortical hormones and their analogues did not significantly alter the response. These observations do not support the hypothesis that acute administration of corticosteroids in large doses potentiates the pressor effects of catecholamines in the human subject with normal adrenal function.


1981 ◽  
Vol 96 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Kazumasa Chikamori ◽  
Fumie Suehiro ◽  
Toshiki Ogawa ◽  
Kei Sato ◽  
Hiroyoshi Mori ◽  
...  

Abstract. Synthetic LRH was infused into normal women and women with obesity and anorexia nervosa to determine the distribution volume (DV), metabolic clearance rate (MCR) and half disappearance time (t½) of plasma LRH. In normal women, the DV of LRH was 12.1 ± 0.9 (mean ± se) l, the MCR was 1478.9 ± 39.8 ml/min (28.5 ± 1.2 ml/min/kg body weight) and the initial t½ was 5.6 ± 0.4 min. In obese patients the DV (20.6 ± 1.5 l) was significantly higher than that in normal subjects (P < 0.005), but the MCR and t½ were not significantly different from those in normal subjects. In patients with anorexia nervosa the DV and MCR were 6.5 ± 1.1 l and 621.8 ± 110.5 ml/min (17.9 ± 2.4 ml/ min/kg body weight), respectively, which were both significantly lower than those in normal subjects (P < 0.02), while the t½ (7.3 ± 0.1 min) was longer than in normal subjects (P < 0.02). These data suggest that 1) the abnormal responses of some hormones to provocation tests observed in obese patients and patients with anorexia nervosa should be evaluated in consideration of changes in the DV and metabolic clearance of hormones in these conditions, and 2) in patients with anorexia nervosa changes in MCR and t½ may reflect low metabolism of LRH.


2006 ◽  
Vol 191 (2) ◽  
pp. 491-496 ◽  
Author(s):  
Getu Abraham ◽  
Fioralba Demiraj ◽  
Fritz Rupert Ungemach

The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-α-acetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific time-dependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13–15 and > 120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1.5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (tmax, 0.6–1.5 h) and low maximum plasma concentrations (peak Cmax, 2.99–5.51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13.9 ± 1.3 h) was very much shorter than that of TAA (125.9 ± 15.8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.


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