Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease.
BACKGROUND
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-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.


METHODS
A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 mug) 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.


RESULTS
At baseline, all nine patients had normal responses to 1 mug 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.


CONCLUSIONS
Immediate 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.
Schuetz
Philipp
P
Division of Endocrinology, Diabetes and clinical Nutrition, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Schuetzp@uhbs.ch
Christ-Crain
Mirjam
M
Schild
Ursula
U
Süess
Erika
E
Facompre
Michael
M
Baty
Florent
F
Nusbaumer
Charly
C
Brutsche
Martin
M
Müller
Beat
B
D000309:Adrenal Insufficiency / Q000139:chemically induced; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008163:Luminescent Measurements; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011241:Prednisone / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012372:ROC Curve; D020127:Recovery of Function; D012680:Sensitivity and Specificity; D013997:Time Factors
D005938:Glucocorticoids; D008776:Methylprednisolone Hemisuccinate; D000324:Adrenocorticotropic Hormone; D011241:Prednisone; D006854:Hydrocortisone