Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids.

Objective: Leptin, the obese gene product, is thought to regulate body fat through its action on hypothalamic receptors that influence satiety. The hormonal regulation of leptin is important, since it might affect adiposity. Leptin regulation in man is poorly understood. We studied the relation between endogenous cortisol and leptin levels as well as the acute and chronic effects of a low dose of dexamethasone (DEX) on plasma leptin levels in healthy male volunteers. Subjects and experimental protocol:The correlation between basal plasma levels of leptin and cortisol and the chronic effect of DEX treatment were studied in 12 subjects. Plasma leptin and cortisol levels were determined every other hour for 24 h, before and after 2 weeks of oral administration of 0.1 mg DEX twice daily. The acute effect was studied in 20 subjects, who received 1 mg DEX at 2300 h. Fasting blood samples were taken at 0800 h on the same day (i.e. before DEX) and on the day after. Results: Under basal conditions, we found a correlation between mean plasma levels of leptin and cortisol (r ¼ 0.7, P < 0.02). Mean plasma leptin levels had increased by 50% after 2 weeks of DEX treatment (P < 0.05). The circadian rhythm of leptin was preserved, but the night peak occurred 2.5 h earlier (P < 0.05). Fasting plasma leptin levels were 20% higher 9 h after 1 mg DEX orally than at the same time on the day before (P < 0.002). Conclusion: Physiological variations in cortisol are involved in the regulation of leptin. European Journal of Endocrinology 139 615-620

To provide basic information on the normal functioning of the hypothalamus-pituitary-adrenal axis in relation to pubertal development, growth (weight and height), body composition, and gender and to obtain reference data for serum cortisol concentrations in children, we investigated the basal circadian rhythm of serum cortisol in a group of 235 healthy children (162 boys and 73 girls). The age range was between 2.2-18.5 yr. Serum cortisol was analyzed from venous blood samples taken at 1400, 1800, 2200, 0200, 0400, 0600, and 1000 h. No evidence was found for differences in temporal placement or level of the circadian cortisol rhythm in relation to age, growth, or body composition. However, we found a broad range of cortisol levels in a healthy population, with individual mean diurnal levels ranging from 100-510 nmol/L. Regardless of high or low mean diurnal cortisol levels, repeated measurements within and between pubertal stages indicated that an individual remains in his or her cortisol range throughout pubertal development. In conclusion, the present study shows that 1) serum cortisol levels do not correlate with either age or gender; 2) there is a large and significant interindividual variability in endogenous mean diurnal cortisol levels; and 3) despite this variability between individuals, there is no correlation between cortisol levels and either body composition or growth rate. This suggests that the variability in cortisol levels is an expression of normal homeostasis rather than pathology.

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m²) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

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