Elsevier

The Lancet

Volume 355, Issue 9203, 12 February 2000, Pages 542-545
The Lancet

Early Report
Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment

https://doi.org/10.1016/S0140-6736(99)06290-XGet rights and content

Summary

Background

Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after shortterm, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 μg) corticotropin stimulation test.

Methods

We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 μg corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 μg corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range.

Findings

The adrenal response to 1 μg corticotropin was suppressed in 34 patients and normal in 41. Subsequent lowdose corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment.

Interpretation

Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.

Introduction

Short-term, high-dose treatment with synthetic glucocorticoids is used in a range of inflammatory and immunological disorders. Among the many biochemical and metabolic effects of glucocorticoid treatment, the suppression of the adrenal response is a major and unpredictable complication.1, 2 Neither the dose and duration of glucocorticoid treatment nor a random plasma cortisol measurement are reliable indicators of probable adrenal insufficiency.3, 4, 5 Therefore, stimulation tests are used to assess the adrenal response.6, 7 The low-dose (1 μg) corticotropin test8 is sensitive in revealing partial adrenal insufficiency,9, 10 by providing physiological adrenocortical stimulation.11 The results of the low-dose corticotropin test correlate closely with those of the insulin-induced hypoglycaemia test,12 the generally agreed reference standard,13, 14 and are superior to those of the standard (250 μg) short corticotropin test.10, 15

We aimed to find out the frequency of a suppressed adrenal response by means of the low-dose (1 μg) corticotropin test in patients who had received short-term, high-dose glucocorticoid treatment. We also aimed to ascertain the time to full recovery of the normal adrenal response in patients with a deficiency of the response.

Section snippets

Participants

Between July, 1997, and June, 1998, we undertook a prospective cohort study in a large urban hospital, including patients who were receiving glucocorticoid treatment for the first time in their lives. Reasons for therapy were varied: chronic obstructive lung disease, cancer chemotherapy, neurological disorders, inflammatory bowel disease, collagen vascular disorders, anaphylaxis, and thyrotoxicosis. We excluded patients with a history of previous glucocorticoid treatment, Addison's disease,

Results

41 (55%) of the 75 study patients had stimulated plasma cortisol concentrations above 550 nmol/L and were classified as having a normal adrenal response; the other 34 patients (45%) had stimulated plasma cortisol concentrations below this cut-off (table).

The mean basal plasma cortisol concentration was significantly higher in patients with a normal adrenal response than in patients with a suppressed adrenal response (524 [SD 201] vs 189 [156] nmol/L; p<0·0001, Student's t test; figure 1),

Discussion

Function of the adrenal response in patients treated with glucocorticoids shows little correlation with the dose and duration of glucocorticoid treatment, and a random plasma cortisol concentration does not reliably assess the adequacy of the adrenal response to stress.3, 4, 5, 19 Therefore, stimulation tests are used in the assessment of the adrenal response;7 the insulin-induced hypoglycaemia test, the metyrapone test, and the corticotropin-releasing hormone test are considered accurate.3, 6,

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