Effect of corticotrophin therapy on pituitary-adrenal function.

Carter, M E; James, V. H. T.

doi:10.1136/ard.29.1.73

Cited by 24 publications

(12 citation statements)

References 15 publications

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“…1 shows that ACTH given in twice daily injections allows the patient to retain for the most part excellent pituitary-adrenal responsiveness to insulin hypoglycaemia. Some tests are slightly subnormal, but the overall results of the group are strictly comparable to those we obtained from patients given their daily requirement of ACTH in one morning injection (Carter and James, 1970a). It is difficult to explain the occasional test which seems to be at variance with the others (E.F. at 4 weeks, H.H.…”

Section: Resultssupporting

confidence: 59%

“…Moreover, it is not at all clear why patients treated with long-term corticotrophin generally retain hypothalamic-pituitary adrenal responsiveness. We have shown (Carter and James 1970a) that patients receiving therapeutic daily doses of ACTH for periods of 2 years or more were able to produce a normal pituitary-adrenal response to the stress of insulin hypoglycaemia, and were also able to produce a normal increase in plasma cortisol levels while undergoing surgical operations without steroid cover (Carter and James, 1970b).…”

mentioning

confidence: 99%

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Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.

Carter¹,

James²

1971

Annals of the Rheumatic Diseases

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It has long been accepted that pituitary-adrenal suppression occurs in the majority of patients treated with corticosteroids in doses of the order of 7 -5 mg. or more daily of prednisolone or equivalent, although it is recognized that there is considerable patient variability. The mechanism of this process is not fully understood, but is attributed to cessation of ACTH release in response to the increased concentration ofcirculating glucocorticoid, and subsequent adrenal atrophy. Moreover, it is not at all clear why patients treated with long-term corticotrophin generally retain hypothalamic-pituitary adrenal responsiveness. We have shown (Carter and James 1970a) that patients receiving therapeutic daily doses of ACTH for periods of 2 years or more were able to produce a normal pituitary-adrenal response to the stress of insulin hypoglycaemia, and were also able to produce a normal increase in plasma cortisol levels while undergoing surgical operations without steroid cover (Carter and James, 1970b).On the other hand, surprisingly, no reasonable therapeutic combination of ACTH with corticosteroids could be found which would preserve the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in terms of stress responsiveness; in fact, the suppressive effect of steroids seems to be enhanced rather than offset, as had previously been supposed, by ACTH in the doses used (Carter and James, 1970c).A series of studies has been made as part of a research programme with two main objectives:(1) An attempt to find an improved therapeutic regime employing long-term corticotrophin and/or corticosteroids for patients suffering from chronically active rheumatic diseases-that is, one combining clinical efficacy as well as simplicity and acceptability of administration, with mitigation of side-effects, especially impairment of HPA function; (2) A parallel aim to acquire from this work a better understanding of the different effects of these substances on the HPA axis.This paper is concerned with the second objective, and deals with studies of the obvious features of corticotrophin therapy which it was thought might explain the different effects resulting from exogenous ACTH and steroid administration. In particular, we have investigated the dose, frequency, and time of administration, and the pattern of the plasma cortisol levels produced. We have also considered the role of two other steroids, androstenedione and dehydroepiandrosterone sulphate (d-sulphate), which are secreted by the adrenal cortex in response to ACTH, and the possibility of increased adrenocortical sensitivity to ACTH has also been studied. Material and methodsOf 29 patients studied, eighteen were women and eleven men; 26 were suffering from classical or definite rheumatoid arthritis according to the American Rheumatism Association criteria (Ropes, Bennett, Cobb, Jacox, and Jessar, 1959) and three from psoriatic arthropathy. Their ages ranged from 28 to 70 years (mean 49). The mean duration from onset of disease was 9 years (range 1 to 27). They were n...

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Section: Resultssupporting

confidence: 59%

mentioning

confidence: 99%

Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.

Carter¹,

James²

1971

Annals of the Rheumatic Diseases

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“…Alternate-day therapy with corticotrophin is presumably even less likely to cause suppression but it appears that full return of hypothalamic-pituitary-adrenal function after changing from long-term corticosteroid to alternate-day corticotrophin does not necessarily occur. We can offer no satisfactory explanation for this when compared with return of normal function in adults who had previously received corticosteroid therapy (Carter and James, 1970), but it is possible that differences in dose and duration of therapy account for the findings in our patients.…”

Section: Discussionmentioning

confidence: 63%

“…Lack of suppression of the hypothalamic-pituitary-adrenal axis by daily corticvtrophin has been reported in adults (Bacon et al, 1968;Carter and James, 1970) and children (Friedman and Greenwood, 1968), but this may not be invariable (Wynn, 1968). Alternate-day therapy with corticotrophin is presumably even less likely to cause suppression but it appears that full return of hypothalamic-pituitary-adrenal function after changing from long-term corticosteroid to alternate-day corticotrophin does not necessarily occur.…”

Section: Discussionmentioning

confidence: 99%

Cortisol and Growth Hormone Secretion in Relation to Linear Growth: Patients with Still's Disease on Different Therapeutic Regimens

Sturge¹,

Beardwell²,

Hartog³

et al. 1970

BMJ

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“…axis than corticosteroid-s themselves. The evidence favouring corticotrophin 'therapy is that the plasma corticosteroid response to insulin-induced hypoglycaemia is virtually normal in most patients treated with corticotrophin (Bacon et al, 1968;Carter and James, 1970) whereas this response is often considerably impaired in those treated with corticosteroids (Daly et al, 1967;Livanou et al, 1967).…”

mentioning

confidence: 99%

Comparison of Effects of Long-term Corticotrophin and Corticosteroid Treatment on Responses of Plasma Growth Hormone, ACTH, and Corticosteroid to Hypoglycaemia

Daly¹,

Fletcher²,

Glass³

et al. 1974

BMJ

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SummaryThe development of the highly sensitive cytochemical bioassay for ACTH has permitted the measurement of plasma ACTH levels during the insulin hypoglycaemia test (I.H.T.) in patients treated with corticosteroids and corticotrophin. The ACTH, corticosteroid, and growth hormone (GH) responses in the I.H.T. were measured in three groups of 12 rheumatoid arthritis patients. One group was receiving long-term corticotrophin treatment, the second was undergoing long-term corticosteroid treatment, and the third had never received systemic hormone therapy. The increments in plasma ACTH, corticosteroids, and GH were diminished in the corticosteroid-treated group, as were increments in plasma GH and ACTH in the corticotrophin-treated group; but in this group the corticosteroid increment was normal. Examination of the area under the curve of the ACTH response showed that the total amount of ACTH secreted was normal though the rate of secretion was reduced. In the corticosteroid-treated group both rate and total secretion were diminished. Introduction A major problem of prolonged corticosteroid therapy is the resulting suppression of hypothalamic-pitui;tary-adrenal

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Effect of corticotrophin therapy on pituitary-adrenal function.

Cited by 24 publications

References 15 publications

Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.

Comparison of effects of corticotrophin and corticosteroids on pituitary-adrenal function.

Cortisol and Growth Hormone Secretion in Relation to Linear Growth: Patients with Still's Disease on Different Therapeutic Regimens

Comparison of Effects of Long-term Corticotrophin and Corticosteroid Treatment on Responses of Plasma Growth Hormone, ACTH, and Corticosteroid to Hypoglycaemia

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