A randomized double-blind study to compare the effects of nasal fluticasone and betamethasone on the hypothalamo-pituitary-adrenal axis and bone turnover in patients with nasal polyposis.

Treatment of nasal polyposis with topical betamethasone is associated with suppression of the hypothalamo-pituitary-adrenal (HPA) axis and, potentially, has adverse effects on bone turnover. Fluticasone propionate is a potent corticosteroid with negligible absorption across the nasal mucosa and extensive first-pass hepatic metabolism. We performed a randomized double-blind study, in patients with nasal polyposis, comparing the effects of 8 weeks' treatment with betamethasone drops or fluticasone nasules on the HPA axis using the 1 micro g tetracosactide test, and on bone turnover using two serum markers. Nine patients were allocated to each treatment. Betamethasone resulted in significant suppression in the tetracosactide test (P = 0.006), but fluticasone did not (P = 0.113). There were no differences in bone turnover or treatment efficacy between treatments. Treatment of nasal polyposis with topical betamethasone drops, but not with fluticasone nasules, suppresses the HPA axis and, given comparable efficacy, fluticasone administered via nasule should be the preferred agent.

Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans.

Altered beta-adrenergic regulation has been reported in individuals with hypertension. The variability in vascular responsiveness to beta-agonists, such as isoproterenol, observed in humans may be explained partially by beta(2)-adrenoceptor polymorphism. Individuals with the Gln27 form of the receptor may show reduced vascular reactivity because of downregulation expression of the receptor in the vasculature. We screened 127 normotensive white subjects, 37 of whom were homozygous for these alleles. Thirty-two subjects (17 Gln27 and 15 Glu27) agreed to receive brachial artery infusions of isoproterenol at doses of 1 to 300 ng. min(-1); forearm blood flow was measured by using venous occlusion plethysmography. Of these subjects, 25 (12 Glu27 and 13 Gln27) received local doses of isoproterenol (0.3 to 30.0 ng. min(-1)) via a dorsal hand vein preconstricted with norepinephrine. Compared with subjects homozygous for the Glu27 allele, subjects with the Gln27 substitution had lower baseline blood flow and, in response to isoproterenol, had a significantly attenuated increase in forearm blood flow. This pattern was more marked in veins. We also studied the relationship between the position 16 polymorphism and vascular reactivity. Homozygotes for Arg16 had significantly lower basal blood flow and attenuated increases in forearm blood flow compared with the Gly16 homozygotes. This was significant in veins but not in arteries. Thus, beta(2)-adrenoceptor genotype determines vascular responses to isoproterenol in forearm resistance vessels and in capacitance vessels. Further studies are necessary to establish whether beta(2)-adrenoceptor polymorphisms are important in the genesis of hypertension.

The effect of six weeks topical nasal betamethasone drops on the hypothalamo-pituitary-adrenal axis and bone turnover in patients with nasal polyposis.

Betamethasone topical nasal drops may have systemic corticosteroid activity and cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis and impairment of bone turnover. The aim of this study was to assess the effect of a standard 6-week regime of betamethasone topical nasal drops on the HPA axis (using a physiological dose (1 microg) ACTH test) and on bone turnover (using markers of bone turnover, urinary deoxypyridinoline and serum bone specific alkaline phosphatase). Eleven patients with nasal polyposis were included in a prospective cohort study. Plasma cortisol was lower after betamethasone treatment at all time intervals (P < 0. 0001). There was no change in urinary deoxypyridinoline corrected for creatinine or bone specific alkaline phosphatase. Six weeks' treatment with recommended doses of betamethasone suppresses the HPA axis, but has no significant effect upon markers of bone turnover. Topical betamethasone in subjects with nasal polyps should be viewed as systemic corticosteroid administration and the long and short-term sequelae should be borne in mind.