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Dilemmas of low dosage glucocorticoid treatment in rheumatoid arthritis: considerations of timing
  1. ALFONSE T MASI
  1. Department of Medicine, University of Illinois College of Medicine at Peoria (UICOM-P), One Illini Drive, Peoria, Illinois 61605, USA
  2. Section on Pediatric Endocrinology, Developmental Endocrinology Branch, NICHD, National Institutes of Health, 10 Center Drive MSC 1862, Bethesda, Maryland 10892-1862, USA
    1. GEORGE P CHROUSOS
    1. Department of Medicine, University of Illinois College of Medicine at Peoria (UICOM-P), One Illini Drive, Peoria, Illinois 61605, USA
    2. Section on Pediatric Endocrinology, Developmental Endocrinology Branch, NICHD, National Institutes of Health, 10 Center Drive MSC 1862, Bethesda, Maryland 10892-1862, USA

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      Controversy continues regarding relative benefits versus adverse effects of low dosage glucocorticoid treatment (LDGT) in rheumatoid arthritis.1-5 Opinions differ on the definition of LDGT in patients with rheumatoid arthritis and its variations, depending upon age and gender. We believe that LDGT for rheumatoid arthritis is best considered in terms of ranges of physiological replacement, that is, up to 5 mg of prednisolone (or prednisone) daily for women and up to 7.5 mg for men in their active years, but less in the elderly of either gender.

      Elderly females develop more adverse effects from chronic LDGT than young males, particularly osteoporosis,2 3 5 which may be related to an osteoporosis sparing6 and glucocorticoid protective7 role of androgens. Clinical experience (ATM) suggests that patients with rheumatoid arthritis presenting mainly with polymyalgia-rheumatica-like muscular and systemic manifestations respond relatively better to LDGT than those showing either more aggressive erosive synovitis processes or indications of necrotising vasculitis.

      Another consideration in choosing glucocorticoid dosage levels and in assessing efficacy of LDGT is intrinsic differences between patients in the competence and responsiveness of their hypothalamic-pituitary-adrenal (HPA) glucocorticoid axis.8A subset of patients with rheumatoid arthritis has baseline HPA axis or glucocorticoid action deficiencies.8 9 These patients are expected to benefit relatively more from LDGT than the remainder who have fully normal basal physiology, as may patients with insufficient endogenous HPA axis responsiveness to acute inflammatory mediators.10 11 Additionally, the overall severity of the disease itself and its response to alternative measures dictate the choice between LDGT or higher doses, when glucocorticoid treatment is employed.5

      A single daily morning dose of LDGT is conventional. Evening or night time administration appears to exert greater suppression of morning ACTH and cortisol secretion than dosing in the morning hours.12 Individual patients differ …

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