Altered pituitary-adrenal interaction in nocturnal asthma.
BACKGROUND
Increased airway inflammation at night contributes to the nocturnal worsening of asthma, but the mechanisms regulating circadian variations in airway inflammation are unknown.


OBJECTIVE
We hypothesized that altered hypothalamic-pituitary-adrenal axis function serves as an endogenous controller of inflammation in nocturnal asthma.


METHODS
Patients with nocturnal asthma (n = 7), patients with nonnocturnal asthma (n = 13), and healthy control subjects (n = 11) adhered to a regular sleep-wake cycle for 1 week. Corticotropin and cortisol levels were assayed every 2 hours for 24 hours. Low-dose corticotropin stimulation was performed. Circadian hormonal flux was analyzed by means of cosinor modeling and calculation of the area under the 24-hour curve.


RESULTS
Corticotropin peak levels and areas under the 24-hour curve were significantly increased in patients with nocturnal asthma versus values in patients with nonnocturnal asthma and control subjects. Patients with nonnocturnal asthma demonstrated significantly increased areas under the 24-hour cortisol curve when compared with control subjects, but peak cortisol levels did not differ between groups. Cortisol levels after low-dose corticotropin stimulation did not differ between groups. Corticotropin and cortisol levels were not correlated with the degree of physiologic impairment.


CONCLUSIONS
Nocturnal asthma is marked by increased corticotropin levels that are not accompanied by commensurate increases in cortisol levels. This observation might indicate blunted adrenal responsiveness in the nocturnal asthma phenotype. Conversely, adrenal response to corticotropin might be enhanced in nonnocturnal asthma, attenuating nocturnal worsening of airway inflammation.
Sutherland
E Rand
ER
Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, USA.
Ellison
Misoo C
MC
Kraft
Monica
M
Martin
Richard J
RJ
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013147:Spirometry; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone