Hypothalamic-pituitary-adrenal axis in corticosteroid-resistant bronchial asthma.
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.
Lane
S J
SJ
Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
Atkinson
B A
BA
Swaminathan
R
R
Lee
T H
TH
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000652:urine; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003907:Dexamethasone; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D015592:Immunoradiometric Assay; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D011239:Prednisolone / Q000627:therapeutic use*
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D006854:Hydrocortisone