Pituitary adrenal recovery following short-term suppression with corticosteroids

doi:10.1016/0002-9343(79)90444-3

The American Journal of Medicine

Volume 66, Issue 6, June 1979, Pages 910-914

https://doi.org/10.1016/0002-9343(79)90444-3 Get rights and content

Abstract

To provide clinical guidelines for the use of high-dose short-term glucocorticoid therapy, we studied recovery of the hypothalamicpituitary-adrenal axis in 10 normal men following the administration of suppressive doses of prednisone (25 mg twice daily for five days). Cortisol responses to insulin-induced hypoglycemia and synthetic ACTH before treatment were compared with responses two and five days after concluding the prednisone course when adrenal function was not influenced by the presence of exogenous steroid. Two days after prednisone therapy, peak cortisol responses to both hypoglycemia (11.0 ± 0.9 μg/dl mean ± SEM) and synthetic ACTH (13.3 ± 1.4 μg/dl) were significantly reduced compared to pretreatment (20.6 ± 1.6 and 27.3 ± 2.5 μg/dl, respectively, p < 0.001). Five days after concluding the prednisone therapy, peak cortisol response to hypoglycemia had returned to near pretreatment levels although peak cortisol response in the adrenal gland to synthetic ACTH (22.3 ± 1.1 μg/dl) remained reduced (p < 0.05). These data suggest that brief courses of high-dose prednisone therapy may limit the adrenal component of the hypothalamic-pituitary-adrenal response to stress for up to five days.

References (34)

A Naysmith et al.
Pituitary function in patients receiving intermittent cytotoxic and corticosteroid therapy for malignant lymphoma
Lancet
(1976)
A Moses et al.
Assessment of pituitary reserve in subjects pretreated with dexamethasone
Metabolism
(1969)
A Meikle et al.
Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone, and dexamethasone on human pituitary-adrenal function
Am J Med
(1977)
R Silber et al.
Determination of 17,21 dehydroxy-20-keto-steroids in urine and plasma
J Biol Chem
(1954)
J Wood et al.
A rapid test of adrenocortical function
Lancet
(1965)
D Malone et al.
Hypothalamic-pituitary-adrenal function in asthmatic patients receiving long-term corticosteroid therapy
Lancet
(1970)
T Livanou et al.
Recovery of hypothalamo-pituitary-adrenal function after corticosteroid therapy
Lancet
(1967)
J Landon et al.
Threshold adrenocortical sensitivity in man and its possible application to corticotropin bioassay
Lancet
(1967)
K Wilson et al.
Hypothalamic pituitary adrenal function in patients treated with intermittent high dose prednisone and cytotoxic chemotherapy
Lancet
(1976)
J Melby
Systemic corticosteroid therapy: pharmacology and endocrinologic considerations
Ann Intern Med
(1974)

N Christy et al.

Comparative effects of prednisone and of cortisone in suppressing the response of the adrenal cortex to exogenous adrenocorticotropin

J Clin Endocrinol Metab

(1956)

J Plager et al.

Suppression of pituitaryACTH response in man by administration of ACTH or cortisol

J Clin Endocrinol Metab

(1962)

S Grant et al.

Suppression of 17-hydroxycorticosteroids in plasma and urine by single and divided doses of triamcinolone

N Engl J Med

(1965)

T Nichols et al.

Diurnal variation of suppression of adrenal function by glucocorticoids

J Clin Endocrinol Metab

(1965)

A Myles et al.

Single daily dose corticosteroid treatment

Ann Rheum Dis

(1971)

JG Harter

Corticosteroids: their physiologic use in allergic disease

NY State J Med

(1966)

P Osterman et al.

The insulin tolerance test after pretreatment with dexamethasone

Acta Endocrinologica

(1976)

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^☆: This work was supported by grants from the Public Health Service (No. RR00044), Organon, Inc. and Weight Watchers Foundation, Inc. It was presented in part at the annual meeting of the Endocrine Society, June 15, 1978, Miami, Florida.

¹: From the Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry, Rochester, New York.

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Clinical studyPituitary adrenal recovery following short-term suppression with corticosteroids☆

Abstract

Lancet

Metabolism

Am J Med

J Biol Chem

Lancet

Lancet

Lancet

Lancet

Lancet

Systemic corticosteroid therapy: pharmacology and endocrinologic considerations

Ann Intern Med

Comparative effects of prednisone and of cortisone in suppressing the response of the adrenal cortex to exogenous adrenocorticotropin

J Clin Endocrinol Metab

Suppression of pituitaryACTH response in man by administration of ACTH or cortisol

J Clin Endocrinol Metab

Suppression of 17-hydroxycorticosteroids in plasma and urine by single and divided doses of triamcinolone

N Engl J Med

Diurnal variation of suppression of adrenal function by glucocorticoids

J Clin Endocrinol Metab

Single daily dose corticosteroid treatment

Ann Rheum Dis

Corticosteroids: their physiologic use in allergic disease

NY State J Med

The insulin tolerance test after pretreatment with dexamethasone

Acta Endocrinologica

Clinical study
Pituitary adrenal recovery following short-term suppression with corticosteroids☆