Printed on: November 6th, 2025

Please note, once printed or downloaded, articles cannot be updated. By bookmarking the article and continuing to access it online, you can be sure you are reading the most up-to-date information and that you are not in breach of copyright laws.

Adrenal insufficiency and Addison’s disease

Adrenal insufficiency and Addison’s disease

In 2024, NICE published guidance on adrenal insufficiency (including Addison’s disease) (NICE 2024, NG243).

We suspect that, for most of us, a quick reminder of the physiology and common presentations in primary care may be helpful. We’ll address that first, before going into the detail of the NICE guidance.

It is worth noting that we have traditionally been told that the physiological requirement for glucocorticoids was equivalent to 7.5mg/d of prednisolone. NICE tells us it is now thought the requirements are lower: 3 to 5mg/day of prednisolone.

This article was updated in November 2024.

Just a quick reminder of this before we start:

The adrenal cortex produces:

• Glucocorticoids (cortisol): affects the body’s response to stress/illness, blood pressure, glycaemic regulation.
• Mineralocorticoids (aldosterone): regulate salt and water levels.
• Sex hormones: oestrogen/testosterone.

The adrenal medulla produces catecholamines such as adrenaline (usually unaffected by the hypothalamic–pituitary axis).

NICE tells us (NICE press release 28 August 2024):

• There are approximately 1200 hospital admissions/year for adrenal crisis (based on data from 2022–23).
• Around 6–8000 people in England have primary adrenal insufficiency.
• Around 8–16 000 people in England have secondary adrenal insufficiency.  

In primary care, adrenal insufficiency may present because someone is acutely unwell or because other features make us consider the diagnosis. NICE suggests how adrenal insufficiency may present:

Thinking about those presenting who are not acutely unwell:

NICE advises:

• Shift workers on nights: allow a few days for circadian rhythms to normalise or do a different test (e.g. short synacthen test).
• If on ORAL oestrogen: stop for 6w before testing (if for contraception, use alternative contraceptive method; if for HRT, transdermal oestrogen may be used). Why? Cortisol levels are falsely elevated because oestrogen causes a rise in levels of cortisol-binding globulin.
• Those on non-oral glucocorticoids (inhaled, intramuscular, topical) at physiological levels or above may have a low 8–9am serum cortisol.
  • After intramuscular/intra-articular glucocorticoid injection: wait 4w before testing (includes hydrocortisone, triamcinolone, methylprednisolone (depo-medrone) (BNF)).

• Applies to those from age 1y upwards. Seek advice on interpreting cortisol results in those <1y.
• Applies only to modern immunoassays: if alternative assays used, follow local guidance.

In brief, the management of adrenal insufficiency involves:

• Replacement of missing steroids (glucocorticoids for all, mineralocorticoids for some; see below).
• Patient education:
  • Understanding of sick day rules and adjusting doses of glucocorticoids in times of physiological/psychological stress to mimic normal adrenal physiology.
  • Recognising and managing adrenal crises.
• Monitoring for general wellbeing and for features of under- or over-replacement. In children, monitoring growth and progression through puberty is particularly important.

All types of adrenal insufficiency require GLUCOCORTICOIDS.

Some of those with PRIMARY adrenal insufficiency also require mineralocorticoids. Why? In PRIMARY adrenal insufficiency, the problem lies in the adrenal gland itself. This means the glucocorticoids are not produced by the adrenal cortex, but, in addition, the mineralocorticoids (and androgens/oestrogens) may not be produced and may need replacement. Mineralocorticoids are NOT needed in secondary or tertiary adrenal insufficiency.

At Red Whale, we think the decision on who needs which is one for the endocrinologists!

NICE gives doses for babies, children and those aged >16y. Here, we reproduce only the details for adults (≥16y). At Red Whale, we think that primary care will always be following advice from the specialist.

Do note that the doses may need to be increased in those on enzyme inducers (e.g. antiretrovirals).

Congenital adrenal hyperplasia is a form of primary insufficiency, and dosing is similar to that in the table below, but NICE says higher doses may be needed based on specialist advice: follow advice from the specialist.

Subcutaneous pumps, intramuscular or intravenous hydrocortisone should NOT be given for routine daily dosing.

Please follow the link for a PDF version of the GEMS for download/printing: Adrenal crisis: GEMS

In normal circumstances, at times of physiological or psychological stress, the adrenals pump out more cortisol. In adrenal insufficiency, the adrenals can’t do this. This means that the patient has to recognise that that a physiological/psychological stress is occurring, and take additional glucocorticoid to prevent an adrenal crisis. This is called ‘sick day rules’.

Emergency kits (containing injectable glucocorticoids) for prevention and management of an adrenal crisis are described in the next section.

It’s a lot for a patient to take on board!

NICE recommends that for those ≤16y, we follow the sick day rules from British Society of Paediatric Endocrinology and Diabetes (BSPED) Consensus Guidelines on Adrenal Insufficiency. We refer you there because the sites includes calculated doses based on patient weight and surface area.

NICE covers the sick day rules for those ≥16y, and its recommendations are set out in the table below. We have included recommendations for inpatients, surgery and pregnancy, for completeness. The decisions relating to most of these groups of patients will not be taken in primary care.

Note that patients on modified-release hydrocortisone need a supply of immediate-release hydrocortisone to cover sick day situations such as those above.

Emergency kits are for people to use when needed: patients, carers and families should know WHEN and HOW to use them.

Clearly, this is a decision for the specialist, but NICE recommends:

Why are those with tertiary adrenal insufficiency less likely to need an emergency kit? They usually still have some function of the hypothalamic–pituitary–adrenal axis so are less likely to have an adrenal crisis.

There’s a lot for patients to take in!

• Understanding sick day rules/emergency kits is CRITICAL! They need to know WHAT to do and have the confidence to do it! Their relatives also need to be confident in recognising an adrenal crisis and using the emergency kit.
• The Addison’s Disease Self-help Group has lots of useful information (there doesn’t seem to be a support group for other forms of adrenal insufficiency).
• Remind patients to wear a medic alert bracelet.
• They get free prescriptions.
• NICE also says they should:
  • Be on the lookout for features of under- or over-replacement (discussed later in the section on specialist reviews and monitoring).
  • Be aware of how to dose themselves if travelling through time zones, fasting, or doing shift work or other activities that affect sleep patterns.
  • Know not to stop their medication abruptly, except on medical advice.

NICE doesn’t discuss this, but many drugs can interfere with the hypothalamic–pituitary–adrenal axis.

WATCH OUT FOR and PAY ATTENTION TO(!) those automatic warnings that flash up each time you prescribe.

The Society of Endocrinology (exogenous steroids treatment in adults) recommends taking special care with those on adrenal replacement/long-term glucocorticoid therapy and the following potent CYP3A4 inhibitors):

• Potent protease inhibitors: atazanavir, darunavir, fosamprenavir, ritonavir (+/- lopinavir), saquinavir, tipranavir.
• Antifungals: itraconazole, ketoconazole, voriconazole, posaconazole.
• Long-term clarithromycin.

Also remember that in those with undiagnosed thyrotoxicosis, or if thyroid replacement is started in someone with newly diagnosed hypothyroidism, this can also trigger an adrenal crisis in those with adrenal insufficiency (NEJM 2019;381:852).

NICE recommends that those with adrenal insufficiency are followed-up by the relevant specialist team (we presume that, for most, this means endocrinology).

• For adults, this should be based on need, with increased frequency of appointments as appropriate (e.g. for those who are more vulnerable or who have a change in clinical circumstances).
• For children and young people, this should be at least every 6 months (and annually face-to-face to measure height and weight in order to adjust dose of medication, and because abnormal growth rate is a sign of under- or over-replacement).

• Lying and standing BP.
• Bloods: electrolytes, HbA1c and, in adults, lipids.
  • (Cortisol day series levels should not routinely be used to check hydrocortisone dosing.)
• Bone density scan at least every 5 years in adults.

In addition, in children and young people:

• Height and weight.
• Progression through puberty.
• Signs and symptoms of low blood glucose.
• Bone age if still growing (left hand and wrist X-ray), bone density once they have stopped growing.

At specialist review, the following should be covered:

• Understanding of the condition and its management, including sick day rules.
• Adherence to medication.
• How frequently the patient needs to increase doses to cover sick days/using emergency injections.
• Frequency of adrenal crises, hospital admissions and infections.
• Psychological wellbeing and the ability to carry out everyday tasks.

Aim for physiological replacement doses, and monitor for signs and symptoms of glucocorticoid under- or over- replacement.

For those with primary adrenal insufficiency, in addition to the above:

• Monitor for signs/symptoms of mineralocorticoid under- or over-replacement:
  • Under-replacement: light-headedness, salt-craving.
  • Over-replacement: swollen ankles, high BP.
• Consider measuring renin and adjusting fludrocortisone dose if needed.

Women with adrenal insufficiency should be cared for by specialists from before conception to the postnatal period.

Primary care has a role in:

• Ensuring appropriate preconception counselling from secondary care.
• Specialist care during pregnancy/postnatal period.
• Continuing to follow appropriate sick day rules.
• If doses are increased during the pregnancy, reducing back to pre-pregnancy doses after delivery.

For those who want the detail, this is what the NICE guideline recommends:

NICE recommends:

• Continue glucocorticoids, swapping to once-daily formulations and appropriate routes of administration (subcutaneous, intramuscular if unable to take orally) unless a shared decision has been made to withdraw adrenal support.

Inappropriately-rapid withdrawal of glucocorticoids can trigger adrenal insufficiency or an adrenal crisis.

In those who have been on glucocorticoids for more than 4 weeks (3w if <16y), NICE recommends a tapering regimen to prevent adrenal insufficiency. The decision to taper should be made by the team which initiated therapy. In most cases, this will NOT be primary care; polymyalgia rheumatica may be an exception, although we are likely to follow EULAR 2015 guidance because that is written specifically for polymyalgia rheumatica (see our article on Polymyalgia rheumatica).

In brief, this involves:

• Reducing to physiological dose.
• Tapering from physiological dose until off therapy.

Warn people when tapering below physiological dose to:

• Expect temporary symptoms, including fatigue, reduction in appetite, low mood.
• Continue to follow sick day rules, including for surgery and invasive procedures.
• Look out for signs and symptoms of adrenal insufficiency.

• Monitor for signs and symptoms of adrenal insufficiency.
• If these symptoms develop:
  • Prescribe double the physiological dose of glucocorticoid daily until symptoms resolve.
  • Then reduce to physiological dose for 1w.
  • Then taper using the slower regimen outlined above (for those who have been on glucocorticoids for >12w).

NICE recommends:

• In those ≥16y: only test if the person develops signs/symptoms of adrenal insufficiency despite following the slow-dose tapering regimen set out above (for those who have been on glucocorticoids for >12w).
• In those <16y: testing may be considered when reducing from physiological doses, even in the absence of symptoms/signs.

If an 8–9am cortisol is tested in those withdrawing from glucocorticoids:

	Adrenal insufficiency and Addison’s disease Often difficult to spot because symptoms can be common and vague. Think about the 3 key presentations: Babies and children with differences in sex development. Unexplained hyperpigmentation. One or more persisting symptom from NICE’s list outlined above (but remember that adrenal insufficiency is much more likely in patients with these symptoms if they also have a risk factor (such as stopping steroids)). If adrenal crisis suspected: act immediately to replace steroids and admit. For the majority, an 8–9am cortisol is the test of choice. Management is by the specialists and involves: Replacing glucocorticoids (and mineralocorticoids in some with primary adrenal insufficiency). Ensuring patients understand the sick day rules, and know how and when to administer drugs from the emergency kit. Regular specialist review to monitor BP, electrolytes, other relevant bloods and bone density for adults every 5y. In children, particular care is taken to monitor growth rate and progression through puberty. Iatrogenic adrenal insufficiency can be minimised by careful tapering of steroids. This can take many weeks! Prevention is by sick day rules and patients using emergency kits if they suspect they are having a crisis. It is a lot for patients to understand and cope with! All patients should be under specialist follow-up, although the frequency may vary depending on how confident they are with self-management. Extra care is required in pregnancy/postpartum period so refer for advice BEFORE conception.
	Reflect on the challenge of diagnosis: when might you now consider adrenal insufficiency where before you might not have done? Do you have a supply of hydrocortisone sodium phosphate/succinate in the practice emergency kit? Search your practice population for patients with adrenal insufficiency. Are all their notes flagged so that clinicians are alerted to their diagnosis and know to check that sick day rules have been followed/for symptoms of adrenal insufficiency if they present with illness/are being referred for a procedure? Organise reception training on the symptoms of an adrenal crisis and the importance of promptly alerting the duty doctor.
	Useful resources: Websites (all resources are hyperlinked for ease of use in Red Whale Knowledge) For professionals: The Society of Endocrinology – adrenal crisis The Association of Anaesthetists - guidelines for the management of glucocorticoids during the perioperative period for patients with adrenal insufficiency The British Society for Paediatric Endocrinology and Diabetes - adrenal insufficiency For patients: Addison’s Disease Self-help Group (include sections on emergency kits and sick day rules; there doesn’t appear to be a patient group for other forms of adrenal insufficiency) Society for Endocrinology – exogenous steroids leaflet