Am. J. Respir. Crit. Care Med., Vol 153, No. 2, Feb 1996, 557-560.
Hypothalamic-pituitary-adrenal axis in corticosteroid-resistant bronchial asthma
SJ Lane, BA Atkinson, R Swaminathan and TH Lee
Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
We have examined whether the lack of clinical response to corticosteroids
seen in corticosteroid resistant (CR) bronchial asthma is reflected in
abnormalities of endogenous cortisol secretion and in the sensitivity of
the hypothalamic-pituitary-adrenal (HPA) axis in CR subjects by using a
modification of the standard dexamethasone suppression test (DST) in
response to 0.25 and 1 mg oral dexamethasone. Five corticosteroid-sensitive
(CS) and five CR asthmatic subjects were studied on two occasions 1 mo
apart. In the first limb of the study subjects received 0.25 mg of oral
dexamethasone, and in the second limb they received 1 mg. Urinary cortisol
was measured by fluorimetry after extraction, and plasma cortisol and
adrenocorticotropic hormone (ACTH) concentrations were estimated by
enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assays,
respectively. On Day 1, a 24-h urine sample was collected for estimation of
urinary free cortisol. On Day 2, a fasting blood sample was taken at 9:00
A.M. for estimation of plasma cortisol and ACTH. At 11:00 P.M., 0.25 mg (1
mg) of dexamethasone was taken orally by each subject. On Day 3, blood was
taken at 9:00 A.M. and 3:00 P.M. for similar estimations. The levels of
urinary free cortisol (nmol/24 h) and predose plasma ACTH (ng/L) and
cortisol (nmol/L) were 199 +/- 42, 27.4 +/- 5.7, and 300 +/- 48 (mean +/-
SEM), respectively, in the CS group, and 210 +/- 74, 23.4 +/- 6.7, and 263
+/- 32 (mean +/- SEM), respectively, in the CR group (p > 0.05 for all
comparisons). Plasma ACTH and cortisol concentrations were not
significantly suppressed in either group after 0.25 mg dexamethasone, but
were equally suppressed in both groups to undetectable levels by 1 mg
dexamethasone. We conclude that CR asthma is not reflected in an altered
secretory rate of endogenous cortisol or in an altered sensitivity of the
HPA axis to dexamethasone suppression.
