Glucocorticoid weaning: what is the best strategy?


By Geir O'Rourke

16 Nov 2023

Safe weaning of glucocorticoids is achievable with consideration of three key risks around hormonal withdrawal syndrome, adrenal insufficiency and reactivation of the disease that prompted their initiation, Australian clinicians are advising.

Practically, that means an individualised approach accounting for these risks can guide the rate of glucocorticoid withdrawal, according to the recommendations published by doctors at the Royal Adelaide Hospital.

Lead author endocrinologist Professor David Torpy says the policy has “worked well” with their patients for over a decade, with pacing informed by measures of endogenous cortisol production.

“High disease activity is likely to prohibit glucocorticoid weaning, at least until there is a remission or alternative effective therapies are in place,” they write in a perspective for The MJA (link here).

“Hormone withdrawal syndrome may develop with rapid glucocorticoid withdrawal above the physiological range.”

“Adrenal insufficiency or adrenal crisis may develop with glucocorticoid withdrawal below the physiological range.”

Practical advice

In terms of practical advice, they suggest prevention measures for adrenal crisis events should be in place until 12 months after cessions of glucocorticoids, with patients advised to report renal insufficiency symptoms and temporarily return to higher doses if necessary after each weaning dose reduction.

The use of a morning plasma cortisol or short synacthen testing (SST) is also recommended, with low values predictive of adrenal insufficiency, according to the authors.

They stress the SST is “likely to be more reproducible”, given many patients have indeterminate values on the former test (suggested interpretations below).

In addition, development of symptoms in the supraphysiological dose “requires discernment whether they represent recrudescence of the underlying disease that led to glucocorticoid use or hormone withdrawal syndrome,” according to the authors.

“A slowing of the rate of withdrawal is required if symptoms develop.”

“Excessively slow glucocorticoid withdrawal can prolong adrenal suppression, increasing the risk of adrenal crisis, as seen after treatment for Cushing syndrome.”

Nevertheless, weaning of the drugs remains an inexact science, with no clinical trials yet published on the subject and no algorithms available to clinically predict the risk of adrenal insufficiency in individual patients, the authors say.

That said, adrenal crisis risk may be minimised with advice including prescribing a “stress dose” in case of illness and the use of injectable hydrocortisone when oral medication is not practical.

In addition, patients can be advised to wear a medical alert bracelet or necklace to indicate the need for parenteral hydrocortisone when they may be found unwell and unable to communicate, the authors said.

The authors’ guide to interpretation of morning cortisol and actions suggested to wean glucocorticoid

Morning plasma cortisol (nmol/L) Supraphysiological dose glucocorticoid Physiological dose glucocorticoid
<80 Wean to physiological dose, 5 mg prednisolone per week or equivalent, while observing for disease recrudescence hormone withdrawal syndrome
  • No weaning of glucocorticoid.
  • Repeat morning cortisol at 2-3-month intervals.
  • Consider SST if persistently low morning cortisol
81-400 Can wean to physiological dose over six weeks
  • Consider SST for confirmation of adrenal suppression
  • Glucocorticoid weaning at prednisolone 1 mg per month or equivalent dose for alternative glucocorticoid
>400 Weaning can be rapid to complete withdrawal over 2 weeks if taking a high dose or  more quickly for near physiological doses
  • Stop over one week


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