Treatment

This is the same chemical compound as the cortisol that is produced by functioning adrenal glands (‘natural cortisol’).

A suitable dose of hydrocortisone will produce sufficient cortisol levels for 4 – 6 hours in most people, under ‘normal’ circumstances. This is because the body gets rid of it quite quickly (i.e. it does not have a long ‘half-life’).

As the body breaks down hydrocortisone quickly, replacement ‘top-up’ doses are needed throughout the day to prevent cortisol levels from dropping to a level where an adrenal crisis is possible.

This means people typically need to take 2, or more often, 3 doses of hydrocortisone in 24 hours. They are usually taken on waking, at about midday and 5-6 pm.

It takes 20-30 minutes to start to absorb a single hydrocortisone tablet from your stomach.

This means that the cortisol levels in the blood of someone on hydrocortisone will rise with their first dose, then drop, rise with their 2nd dose, then drop and rise with their third dose, then drop.

The result is that cortisol levels in the blood of someone on hydrocortisone are not that similar to the ‘natural’ cortisol curve, in that they rise, drop, rise and drop, rise and drop.

This can lead to fluctuating ‘low cortisol’ symptoms, potentially significantly impacting quality of life.

Taking 3 doses can affect levels of patient compliance and satisfaction.

Hydrocortisone tablets come in 2.5mg, 5mg and 10mg doses.

A ‘common’ dose will be 20mg/day, 10mg in the morning, 5mg at lunch and 5mg in the early evening.

People need quite different doses of these tablets, depending on body size, age and level of activity. Your endocrinologist will start you on what they feel is the best dose and routine to meet your needs, and this can be fine-tuned in line with your feedback.

Hydrocortisone tablets come in 2.5mg, 5mg and 10mg doses. 

At the time of writing (May 2026) the following Drug Tariff prices show:

Hydrocortisone 2.5mg tablets: £35.56/pack
Hydrocortisone 5mg tablets: £38.12/pack
Hydrocortisone 10mg tablets: £1.60 - £3.21/pack

Lower-dose hydrocortisone tablets cost more, so steroid-dependent people often receive 10mg tablets and split them to get the correct dose.

You should receive your hydrocortisone medication in a form that is safe, reliable, and appropriate for your individual needs. 

For those who have no issues splitting their 10mg tablets for different doses, either by hand or using a pill cutter, this is great; however, there are groups of people with steroid-dependency where prescribing 2.5mg and/or 5mg tablets is clinically justified and appropriate.

These include:

• People who cannot reliably split tablets, such as due to poor dexterity, visual impairment, or cognitive difficulties.
• Children and young people who need accurate doses and may feel self-conscious about splitting tablets at school or with their peers, which can make it hard for them to keep to their medication regimen and up-dose.
• Patients who are very dose-sensitive, including those who experience symptoms with small dose changes.
• Patients experiencing crumbling or unreliable splitting, even with scored tablets.
• Patients advised by their endocrinologist to avoid tablet splitting or brand changes.

For these groups, requesting lower-dose tablets is not a preference or convenience issue, but a clinical need and those needs should be met.

Clarifying this helps ensure those with steroid dependency feel confident advocating for themselves and that GPs understand the genuine need, justifying the extra cost to the NHS.

This is a synthetically made cortisol but has a very similar chemical compound to natural cortisol. You can see that the chemical structure is identical, apart from where 2 of the carbon molecules have a double bond between them, rather than a single bond. This difference gives Prednisolone a longer ‘half-life’ than hydrocortisone and also increases its strength (‘potency’), i.e. less of it is needed to achieve the same effect.

Due to the longer half-life, just one dose of prednisolone is required in the morning, and it is degraded gradually during the day, producing a ‘curve’ similar to the natural cortisol curve in someone with fully functioning adrenal glands. Like hydrocortisone, it is rapidly absorbed into the gut.

The fact that prednisolone lasts for longer can be helpful for patients who continue to experience low cortisol symptoms whilst taking hydrocortisone and can also be helpful when patients are experiencing vomiting, as just one dose is required to be absorbed to maintain cortisol levels during a 24-hour period.

As prednisolone is more potent than hydrocortisone, much less is needed. Dosage comparisons suggest that 3 to 4mg is equivalent to 20mg of hydrocortisone. 

Tablets come in 5mg and in some cases 1mg (in the UK, though not always in other countries). Availability of the 1mg tablet is key if the dosage is to be ‘fine-tuned’ to its optimum level for each individual. 

Clinical studies have shown that to be effective in its actions, prednisolone is needed at different strengths/potencies in different tissues of the body.

This is a complicated factor that makes the optimum dosage harder to define. Recent evidence suggests that 5mg is excessive for most people, and explains why prednisolone has been thought of as causing too much osteoporosis. Often it is suggested that 4mg daily is a good starting dose and that many could then reduce to 3mg if they feel well.

Professor Karim Meeran, at Imperial College London has done much research into the use of prednisolone to treat adrenal insufficiency. 

Find out more about his recommendations and research

Historically...

In the UK, hydrocortisone has been used for treating people with Addison's and adrenal insufficiency for over 75 years, so there is plenty of evidence to show a low risk of long-term use complications.

It is therefore significantly more often prescribed as the first course of treatment following diagnosis with adrenal insufficiency.

In 2016, 91.8% of adrenal insufficiency patients were taking hydrocortisone, and 3.7% were taking prednisolone. We don't have up-to-date figures, but it is likely that this will have increased slightly, but not significantly.

In 2003: Pred & bone mineral density

A study by Jodar E, Valdepenas MP, Martinez G, Jara A, & Hawkins F. Long-term follow-up of bone mineral density in Addison’s disease. Clinical Endocrinology 2003 58 617–620. https://doi.org/10.1046/j.1365-2265.2003.01761.x compared 25 patients taking either 30mg hydrocortisone or 7.5mg of prednisolone.  

It concluded that a greater proportion of the patients with prednisolone developed osteoporosis, one of the ‘concerns’ talked about in relation to prednisolone. However, it now looks like the doses used in the past of prednisolone were very excessive, and prednisolone might have advantages if lower doses, such as 3 mg to 5 mg, are used.

In 2016:

In 2016, the British Endocrine Society ran a debate with two eminent endocrinologists arguing for and against using prednisolone as the first treatment choice for adrenal insufficiency.

Following the debate, 60% of the medical audience (over 400 people) voted against using prednisolone as the first treatment choice for adrenal insufficiency, and 37% voted for it.   

As prednisolone is less often prescribed, fewer laboratories in the UK can measure prednisolone levels in a day-curve test than can measure hydrocortisone.

In 2017: Pred & lipid profile

Another historic study, Quinkler M, Ekman B, Marelli C, Uddin S, Zelissen P, Murray RD and EU-AIR Investigators. Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency. Endocrine Connections 2017 6 1–8. https://doi.org/10.1530/EC-16-0081, compared patients taking 21.5mg hydrocortisone with 5mg of prednisolone and found higher total cholesterol levels in the patients taking prednisolone.

More recently

However, further and more recent research suggests that the effects on mortality factors (cardiovascular risk) and morbidity factors (osteoporosis) are related to the dose of prednisolone and the ‘overreplacement’ of cortisol. 

The suggestion is that by better testing using Prednisolone Day Curves, the dosage required can be reduced to a minimum effective dose, suggested to be between 1.8mg and 4.2mg daily (Williams EL, Choudhury S, Tan T, & Meeran K. Prednisolone replacement therapy mimics the circadian rhythm more closely than other glucocorticoids. Journal of Applied Laboratory Medicine 2016 1 152–161. https://doi.org/10.1373/jalm.2016.020206

In 2023: Optimising prednisolone in adrenal insufficiency

A study published in 2023 (Sharma A, Lazarus K, Papadopoulou D, Prabhudev H, Tan T, Meeran K and Choudhury S.  Optimising prednisolone or prednisone replacement in adrenal insufficiency. Endocrine Conditions 2023 Vol 12, Issue 8 https://ec.bioscientifica.com/view/journals/ec/12/8/EC-23-0097.xml concluded that prednisolone doses of 2–4 mg are safe and effective in most patients with adrenal insufficiency.

In Summary:

Some endocrinologists favour prednisolone, and some whom favour hydrocortisone, and there are good reasons for both options. Most would agree that more evidence is required regarding the dosage for both medications. More research is needed to look at the long-term efficacy and side effects of prednisolone.

After initial diagnosis and starting on a medication regimen with hydrocortisone, it is normal and expected that it may take some time to find both the correct dose and the correct timing of when you take your medication. It is important to discuss how you feel on hydrocortisone with your endocrinologist.

How do you feel?

• Do you feel well on your hydrocortisone medication regimen?
• Does your hydrocortisone dose seem to ‘last’ you till your next tablet?
• If not, have you tried, in consultation with your endocrinologist, tweaking the dose and/or the timing of your medication?

If you have and you still do not feel well, then it is worth exploring the option of trialling prednisolone as an alternative.

LIfestyle & Compliance

• Is it difficult for you to take 3 doses of medication a day due to your job, school life or another factor?
• Are you forgetting to take your medication and experiencing low cortisol symptoms as a result?

If it is, then it is worth exploring the option of trialling prednisolone as an alternative.

Hydrocortisone is the first-line replacement glucocorticoid of choice in children, as it has a shorter half-life and less impact on growth compared to Prednisolone.

Prednisolone would only be recommended if growth had stopped.

There is also concern that Prednisolone's longer half-life is more likely to cause side effects in children, such as weight gain and impact on bone mineral density.

This is in line with NICE and BSPED guidance.

Occasionally, Prednisolone is used in adolescence if adherence may be an issue.