Threshold Adrenocortical Sensitivity in Man and Its Possible Application to Corticotrophin Bioassay

Landon, J.; James, V. H. T.; Wharton, MargaretJ.; Friedman, M.

doi:10.1016/s0140-6736(67)90976-2

Cited by 76 publications

(47 citation statements)

References 4 publications

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“…The response was greater with larger doses and by extrapolation the minimum dose of 1-24 ACTH which would cause the adrenal cortex to secrete cortisol would be between 3 and 5 ng/kg body weight. These data are consistent with the findings of Landon, James, Wharton & Friedman (1967) …”

Section: Discussionsupporting

confidence: 93%

Studies on Plasma Corticosteroids in the Rhesus Monkey (Macaca Mulatta)

Setchell¹,

Shackleton²,

Himsworth³

1975

Journal of Endocrinology

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The physiological regulation of the plasma corticosteroid concentration, measured by competitive protein-binding, was studied in female rhesus monkeys (M. mulatta) sedated with phencyclidine hydrochloride. Morning basal levels of plasma corticosteroids were found to be in the range 8\ m=. \ 0\ p=n-\ 25\ m=. \ 2 \g=m\g/100ml, which is lower than that previously reported in this species. A circadian rhythm in plasma cortisol concentration was demonstrated. Prolonged sedation with phencyclidine was associated with a gradual increase in the plasma cortisol concentration. Synthetic \ g=a\ 1\ p=n-\ 24 adrenocorticotrophic hormone given intravenously caused a rapid rise in plasma cortisol, the minimum effective dose was between 1 and 10 ng/kg body weight and the response was maximal after 1000 ng/kg. The administration of lysinevasopressin and the induction of hypoglycaemia by insulin were both followed by an increase in the plasma corticosteroid concentration. Metyrapone caused a decline in plasma 11-hydroxycorticosteroids and a concomitant increase in total corticosteroids measured by competitive protein-binding. It is concluded that the hypothalamic-pituitary-adrenal system in the rhesus monkey functions in a manner which is qualitatively and quantitatively similar to that of man.

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Section: Discussionsupporting

confidence: 93%

Studies on Plasma Corticosteroids in the Rhesus Monkey (Macaca Mulatta)

Setchell¹,

Shackleton²,

Himsworth³

1975

Journal of Endocrinology

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“…Several investigators have recently confirmed the early work of Landon et al (8), and reported that much lower doses of ACTH(1-24) -0.5-5 mg -induce maximal cortisol release in vivo (9)(10)(11). These low doses of ACTH may improve the sensitivity of the test and be especially indicated in the screening of latent hypocorticism (12)(13)(14).…”

Section: Introductionmentioning

confidence: 80%

On the meaning of low-dose ACTH(1-24) tests to assess functionality of the hypothalamic-pituitary-adrenal axis

Darmon

Dadoun²,

Frachebois³

et al. 1999

European Journal of Endocrinology

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To analyse further the ACTH(1-24) low-dose test, which is of clinical interest, we have examined the dose-response relationship between plasma ACTH(1-24) and cortisol concentrations after i.v. administration of increasing doses (1, 5 or 250 mg) of ACTH(1-24) as a bolus. In addition, we have measured plasma ACTH(1-39) and cortisol levels after an insulin tolerance test (ITT). Although there was a dose-response relationship between plasma ACTH(1-24) immunoreactivity and the dose injected, cortisol peaks were comparable, but lower than those reached after an ITT. Under these experimental conditions, an increase in plasma ACTH as low as 13 pmol/l (i.e. the increase obtained with the 1 mg dose) induced a near maximal cortisol response. Following injection of 1 mg ACTH(1-24), peak ACTH values were short lasting, similar to physiological daily bursts. After injection of 5 mg ACTH(1-24), plasma ACTH concentrations were higher than those reached during an ITT, but clearly shorter lasting. Injection of 250 mg ACTH(1-24) induced strikingly supraphysiological levels of plasma ACTH. We conclude that neither regular nor low-dose ACTH tests can fully reproduce the ITT. Our observations strongly suggest that the low-dose ACTH(1-24) test (1 mg) can be useful to estimate the adrenal sensitivity under basal, physiological conditions.

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“…These results are consistent with findings on the effects of intravenous Synacthen injection in man, where a dose-response relationship has been demonstrated over the range 0-03-0-25 fig. Synacthen during dexamethasone suppression of endogenous corticotrophin secretion (Landon, James, Wharton & Friedman, 1967).…”

Section: Discussionmentioning

confidence: 99%

Micro-Determination of Corticosteroids in Ovine Peripheral Plasma: Effects of Venipuncture, Corticotrophin, Insulin and Glucose

Bassett¹,

Hinks²

1969

Journal of Endocrinology

177

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A sensitive method for the determination of corticosteroids in 0\m=.\1ml. or less of ovine plasma is described. The method uses the steroid-binding properties of corticosteroid-binding globulin (CBG) and gel filtration on small columns of Sephadex G-25 (fine) at 4\ s=deg\ for separation of CBG-bound and free steroids. Cortisol was found to be the predominant corticosteroid in ovine plasma and accounts for about 90% of the value determined by this method. The corticosteroid concentration in peripheral plasma of unstressed sheep was in the range 0\m=.\1\p=n-\1\m=.\0 \g=m\g./100 ml. In untrained animals, venipuncture increased corticosteroid concentration substantially; training reduced the effect. An infusion of cortisol sodium succinate (100 \g=m\g.cortisol/min.) increased the plasma corticosteroid level to 9\m=.\5 \m=+-\0\m=.\49\g=m\g./100 ml. Intravenous infusion of the synthetic adrenocorticotrophic preparation Synacthen at rates of 10 and 20 \g=m\g./hr. for 2 hr. increased peripheral corticosteroid concentrations to 8 \g=m\g./100 ml. Single i.v. injections of 0\m=.\2\p=n-\0\m=.\8 \g=m\g.Synacthen also significantly increased peripheral corticosteroid concentrations 7\p=n-\15 min. later. The injection of 0\m=.\05 and 0\ m=. \ 1\g=m\g.Synacthen significantly increased the corticosteroid concentration too, but the increase was not significantly greater than that produced by the injection of acidified saline diluent alone. Injection of insulin (0\m=.\25unit/kg. body weight, i.v.) caused a fivefold increase in the corticosteroid concentration 30\p=n-\60 min. later, in both adult sheep and lambs. Glucose (0\m=.\25g./kg. body weight, i.v.) had no effect on corticosteroid concentration.

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Threshold Adrenocortical Sensitivity in Man and Its Possible Application to Corticotrophin Bioassay

Cited by 76 publications

References 4 publications

Studies on Plasma Corticosteroids in the Rhesus Monkey (Macaca Mulatta)

Studies on Plasma Corticosteroids in the Rhesus Monkey (Macaca Mulatta)

On the meaning of low-dose ACTH(1-24) tests to assess functionality of the hypothalamic-pituitary-adrenal axis

Micro-Determination of Corticosteroids in Ovine Peripheral Plasma: Effects of Venipuncture, Corticotrophin, Insulin and Glucose

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