Review article
Glucocorticoid withdrawal schemes in chronic medical disorders: A systematic review

https://doi.org/10.1016/S0889-8529(02)00008-7Get rights and content

Section snippets

The problem of glucocorticoid withdrawal in chronic medical disorders

Clinicians have used glucocorticoids for more than 40 years. After Kendall and coworkers isolated cortisone in 1935, clinicians administered it to a woman with severe rheumatoid arthritis in 1948. Although the clinical improvement was dramatic, certain adverse effects soon became apparent [1]. Glucocorticoids are used as replacement therapy in Addison's disease, in which therapy is lifelong and withdrawal is not possible. Clinicians use these agents for the treatment of inflammatory and

Types of studies

We included randomized controlled trials including data about the safety and efficacy of glucocorticoid withdrawal schemes.

Types of participants

We studied patients with any chronic medical disorder—a disorder which is permanent, leaves residual disability, is caused by an irreversible pathologic alteration, requires special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care.

Types of interventions

We were interested in comparisons of different forms of

Description of studies

The initial electronic search strategy resulted in 874 (possible randomized controlled or controlled clinical trials) references and 152 review articles.

After scanning these studies we identified 19 potential randomized controlled trials [13], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33] and nine Cochrane reviews [12], [34], [35], [36], [37], [38], [39], [40], [41] that appeared to fulfill the inclusion criteria. Inter-observer

Discussion

We were surprised to find only a few trials addressing the safety and efficacy of glucocorticoid withdrawal schedules in chronic diseases, because these agents are widely used in clinical practice. Theoretically, this could be the consequence of a too-narrow search strategy. We used a sensitive search strategy that had a basic set of key terms we hoped to find in a publication for further scrutiny. In addition, we examined all references of included and excluded studies. Moreover, we used the

Summary

This systematic review highlights the uncertainty about the safety and efficacy of glucocorticoid withdrawal in many chronic diseases, elucidating the need for further research in this area. The problem of glucocorticoid withdrawal seems to be a good example for wide variation in physicians' approaches to weaning patients off glucocorticoids. This practice variation appears justified, given the well known extraordinary array of individual reactions to systemic glucocorticoid therapy [44], the

Acknowledgements

We thank Karla Bergerhoff, Trials Search Coordinator of the Cochrane Metabolic and Endocrine Disorders Group, for establishment and execution of the search strategy.

First page preview

First page preview
Click to open first page preview

References (44)

  • N Ueda et al.

    Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome

    J Pediatr

    (1988)
  • M.B Stanbrook et al.

    Steroids for acute exacerbations of COPD: how long is enough?

    Chest

    (2001)
  • J.H Kehrl et al.

    The clinical use of glucocorticoids

    Ann Allergy

    (1983)
  • J Koch-Weser

    Withdrawal from glucocorticoid therapy

    N Engl J Med

    (1976)
  • N.V Esteban et al.

    Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

    J Clin Endocrinol Metab

    (1991)
  • E.L Helfer et al.

    Corticosteroids and adrenal suppression; characterizing and avoiding the problem

    Drugs

    (1989)
  • K.F Schulz et al.

    Empirical Evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials

    JAMA

    (1995)
  • M Salem et al.

    Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem

    Ann Surg

    (1994)
  • R Schlaghecke et al.

    The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone

    N Engl J Med

    (1992)
  • R.L Byyny

    Withdrawal from glucocorticoid therapy

    N Engl J Med

    (1976)
  • L Axelrod

    Glucocorticoid therapy

    Medicine (Baltimore)

    (1976)
  • G Filippini et al.

    Corticosteroids or ACTH for acute exacerbations in multiple sclerosis

  • Cited by (57)

    • The management of glucocorticoid deficiency: Current and future perspectives

      2020, Clinica Chimica Acta
      Citation Excerpt :

      There are no evidence-based guidelines on how to best taper GC after long-term daily therapy. A systematic review of GC withdrawal in chronic medical disorders found insufficient efficacy and safety evidence to advocate any of the different withdrawal regimens [103]. It is also difficult to which patients receiving long-term GC therapy are likely to develop adrenal atrophy and tertiary AI.

    • Controversy: Pros and cons screening of corticotropic deficiency after exogenous glucocorticoid therapy

      2018, Annales d'Endocrinologie
      Citation Excerpt :

      Although there is currently no rigorous research-based evidence to establish strong recommendations for the management of the risk of GC-induced AI, several observations support the necessity to identify AI through adequate screening procedures. First, slow tapering of GC before withdrawal has no demonstrated efficacy on the risk of secondary AI [9]. On the other hand, screening of AI cannot be easily performed on the basis of clinical findings, the physical signs of secondary AI being often non-specific owing to the lack of mineralocorticoid deficiency in this condition [10].

    View all citing articles on Scopus
    View full text