Altered peripheral sensitivity to glucocorticoids in primary open-angle glaucoma.

PURPOSE Increased levels of glucocorticoids are associated with raised intraocular pressure (IOP). The activity of glucocorticoids is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11beta-HSD). This study was an investigation of the central and peripheral sensitivity to glucocorticoids in patients with POAG or ocular hypertension (OHT) and the differential metabolism of glucocorticoids by 11beta-HSDs. METHODS Patients with POAG or OHT and normal control subjects were studied. Peripheral sensitivity to glucocorticoids was assessed as dermal blanching and central sensitivity by dexamethasone suppression testing. Daily production rates of glucocorticoids were determined by quantifying metabolites in 24-hour urine. Plasma cortisol levels were determined at baseline (9 AM) and after an overnight low-dose dexamethasone suppression test. In a separate study, plasma and aqueous humor cortisol levels were determined in patients with POAG and normal subjects. RESULTS Patients with POAG exhibited a greater cutaneous vasoconstrictor response to glucocorticoids than patients with OHT and normal subjects (20.7 +/- 3.1 vs. 8.5 +/- 4.4 and 8.6 +/- 4.5 arbitrary units, respectively; P < 0.05 in each case). Total glucocorticoid production rates were not different between groups, nor were total circulating cortisol levels before or after suppression of the hypothalamic-pituitary-adrenal axis by dexamethasone or concentrations in aqueous humor. The ratio of urinary cortisol to cortisone metabolites was elevated in POAG versus normal control and OHT (1.74 +/- 0.13 vs. 1.34 +/- 0.11 and 1.32 +/- 0.14; P < 0.05 in each case), indicating a change in the balance of 11beta-HSDs, without a change in other metabolic pathways. CONCLUSIONS Patients with POAG exhibit increased peripheral vascular sensitivity to glucocorticoids. Increased sensitivity of glucocorticoid receptors, may enhance local glucocorticoid action in the eye and exacerbate the adverse effects of glucocorticoids in this condition.