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

Abstract

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.

Conclusion: 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.

Figure 1

(a) Cortisol values basal (black) and after stimulation with 1 μg corticotropin (grey) and (b) corresponding basal ACTH concentrations for all patients at six clinical visits.

Figure 2

Clinical symptom score in patients with normal (●) and inadequate (▲) response to the 1 μg corticotropin test for each visit. The clinical score asks patients for fatigue, hypoglycemia (hypoglycemic symptoms or fasting glucose < 3,5 mmol), loss of energy, orthostatic disturbance or hypotonia (systolic blood pressure < 100 mmHg, diastolic blood pressure < 60 mmHg), reduced strength, sleep disturbance, muscle pain, mood changes (feeling depressed), nausea, concentration disturbance, weight loss (> 3 kg), stomach pain, hyperpigmentation and eosinophila (> 330 cells/ml) [9].

Figure 3

ROC curve analysis to predict adrenal insufficiency for basal cortisol, ACTH, the cortisol/ACTH ratio and the clinical score.