Canterbury DHB

Prednisone Withdrawal Protocol

In patients with adrenal suppression, please ensure this is recorded in the diagnosis list on letters in Health Connect South.

• Patients receiving any dose of glucocorticoids for <3 weeks are unlikely to have significant hypothalamic-pituitary-adrenal (HPA) axis suppression.
• HPA axis suppression usually only occurs with prolonged steroid given in doses greater than 5 mg prednisone per day (although age, frailty, and duration of therapy may be important).
• Factors determining the degree of HPA axis suppression are not well understood.
• In some individuals, recovery of normal HPA axis function may take 12 months.
• Steroid withdrawal depends not only on clinical and biochemical evidence of HPA axis suppression, but also on underlying disease activity, and in some patients, psychological dependence on steroids.
• An 0800h plasma cortisol 24 hours after the last dose of prednisone gives a guide to suppression of HPA axis function, but not the ability of the HPA axis to respond to a stress.

Step 1: Reduce steroids to physiological replacement dosage (5 mg/day)

The patient is gradually weaned from pharmacological steroid dosage (e.g. >5 mg prednisone/day) over a period of weeks or months. Any symptoms at this stage are unlikely to be caused by steroid insufficiency. If the disease for which the steroids are being given flares, steroids must be increased temporarily and the dose then reduced more gradually. Dose reductions will vary depending on the individual physician but suggested dose reductions, made every one to two weeks, are:

• 10 mg/day for prednisone doses >60 mg/day,
• 5 mg/day for prednisone 20 to 60 mg/day
• 2.5 mg/day for prednisone 10 to 20 mg/day
• 1 mg/day every one to two weeks at prednisone doses 5 to 10 mg/day

When a physiological steroid dose of prednisone 5 mg/day has been reached (equivalent to hydrocortisone 20 mg/day, dexamethasone 0.5 mg/day):

• Check an 0800 plasma cortisol and synacthen test 24 hours after the last dose of prednisone (or hydrocortisone or dexamethasone).
  • If the response is normal (peak cortisol >550 nmol/L), then the steroids can be reduced to zero, e.g. by reductions of 1 mg prednisone (or equivalent) every week, and no further testing is necessary.
  • If the response to synacthen is abnormal (peak cortisol <550 nmol/L), then there are two choices:
    • stay on the physiological prednisone dose (5 mg/day) and repeat the synacthen in 3 months.
    • switch patient to a physiological dose of the shorter acting glucocorticoid, hydrocortisone. This should allow earlier recovery of overnight ACTH secretion. A suitable maintenance dose of hydrocortisone is 20 mg/day, best given as 15 mg mane, 5 mg 1500 hours. Some patients may tolerate a lower dose of hydrocortisone e.g. 10 mg mane, 5 mg 1500 hours. Obviously the lower the dose, the better for recovery of HPA function, but watch out for symptoms of steroid insufficiency - nausea, fatigue, occasional vomiting, light-headedness, which will guide dosage.
    • For both regimes, ensure patient has Medic Alert and instructions to increase steroids for illness or "stress".

  "Stress steroids" - if the person is unwell enough to spend the day in bed, 40 mg oral hydrocortisone/day (20 mg twice a day) should be sufficient, and provided the illness is improving, the dose can be reduced back to the maintenance dose over the next 2 to 3 days. For vomiting, diarrhoea or severe illness, parenteral steroids in the form of hydrocortisone 50 mg IV or IM should be given and repeated if necessary at eight hourly intervals.

Step 2: Monitor for recovery of normal steroid secretion

Repeat synacthen test at 2 to 3 monthly intervals (holding off any hydrocortisone or prednisone for 24 hours before the test).

Once the synacthen test is normal (peak cortisol >550 nmol/L), reduce glucocorticoids to zero over the next 2 to 4 weeks. For hydrocortisone, initially stop the afternoon dose and then withdraw the morning hydrocortisone dose. No further testing is required and the patient no longer needs "stress" steroids or a Medic Alert.

If the synacthen test remains persistently abnormal, then you should lower the maintenance hydrocortisone dose slightly to try and encourage ACTH secretion. For example, from 15/5 to 10/5, and if possible, gradually to only 10 mg mane. During this period the patient may develop symptoms of steroid insufficiency – nausea, fatigue, occasional vomiting, light-headedness, which will guide the tapering of the hydrocortisone. Additional steroids will still be required for "stress".

If you have any queries, don’t hesitate to contact the Endocrinology Department.

Topic Code: 44735