Abstract
BackgroundAs supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.MethodsA systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.ResultsAt baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.ConclusionImmediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.
Highlights
As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitaryadrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures
Predicting adrenal insufficiency is challenging, since neither the dose nor the duration of glucocorticoid treatment, nor random plasma cortisol measurements correlate with the function of the HPA axis [4]
On the first day of steroid treatment, 78% of patients had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to 1 μg adrenocorticotropic hormone (ACTH) injection, 2, 5, and 14 days after corticosteroid withdrawal, respectively
Summary
As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitaryadrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures. The administration of a 2 week course of systemic corticosteroids to treat patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has become common practice over the past 30 years [1] This practice, remains debated because corticosteroids are only modestly effective in shortening the duration of exacerbations of COPD and have serious metabolic adverse effects including hyperglycemia, osteoporosis, myopathies, mental disturbances and suppression of the hypothalamic-pituitary-adrenal (HPA) axis, among others [2]. The simpler low-dose corticotropin (ACTH) test is a useful and sensitive substitute as it reveals partial adrenal insufficiency by providing physiological adrenocortical stimulation [6,7]
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