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Endocrine and metabolic

Addison's disease

Last revised in September 2025

Addison's disease (primary adrenal insufficiency) is caused by destruction of the adrenal cortex.

Addison's disease: Summary

Addison's disease (primary adrenal insufficiency) is caused by destruction of the adrenal cortex. This results in reduced production of glucocorticoids, mineralocorticoids, and adrenal androgens.
In Western countries, Addison's disease is most commonly caused by autoimmunity (around 90% of cases).
- Other causes of primary adrenal insufficiency include congenital adrenal hyperplasia and infections such as tuberculosis.
Addison's disease is rare. There are approximately 9000 people in the UK diagnosed with Addison's disease and around 320 new diagnoses per year.
A person with Addison's disease may present with a sudden crisis precipitated by intercurrent illness or other stress. Adrenal crisis should be suspected in people who are unwell with any of the following:
- Circulatory shock or collapse.
- Condition failing to respond to initial treatments.
- Hyperpigmentation.
- Hypoglycaemia (particularly in children).
- Hyponatraemia.
- Low blood pressure (including postural hypotension).
Addison's disease should also be considered in people with one or more of the following symptoms:
- Diarrhoea.
- Dizziness or light-headedness on standing.
- Early puberty.
- Faltering growth (in children).
- Feeling of muscle weakness.
- Hyperkalaemia.
- Hypoglycaemia (particularly in children).
- Hyponatraemia.
- Hypotensive crisis (particularly in children).
- Lack of appetite or unable to eat a full meal.
- Lethargy.
- Nausea or vomiting.
- Prolonged neonatal jaundice.
- Salt craving.
- Weight loss.
If adrenal crisis is suspected intravenous or intramuscular hydrocortisone should be given immediately, and emergency admission to hospital arranged. The following doses should be given:
- Children aged under 1 year, 25 mg.
- Children aged 1 to 5 years, 50 mg.
- Children aged 6 years and over, and adults 100 mg.
In adults, if adrenal insufficiency is suspected (and urgent admission is not indicated) they should be offered an 8 am to 9 am serum cortisol test. As a general guide, if the serum cortisol level:
- Is less than 100 nanomol/L, the person should be admitted to hospital.
- Is 100–500 nanomol/L, the person should be referred to endocrinology.
In children, investigations should be urgently carried out in secondary care if adrenal insufficiency is suspected — admission to hospital may be required depending on the clinical picture.
Diagnosis of Addison's disease is confirmed in secondary care with an adrenocorticotrophic hormone stimulation (Synacthen^®) test.
Treatment for Addison's disease is initiated and adjusted by a specialist endocrinologist; repeat prescriptions may be provided in primary care under a shared care arrangement.
- Hydrocortisone is usually used for glucocorticoid replacement and fludrocortisone for mineralocorticoid replacement.
- Dehydroepiandrosterone (unlicensed) may be prescribed by some specialists for androgen replacement.
People with Addison's disease should be given information and advice about:
- Increasing their corticosteroid cover during physical stress, such as illness, injury, or surgery to prevent adrenal crisis.
- How to recognize the symptoms of an adrenal crisis and how to give intramuscular hydrocortisone in an emergency.
- The importance of carrying emergency information on their person such as a steroid treatment card and MedicAlert identification.

Have I got the right topic?

From age 1 month onwards.

This CKS topic covers the management of people with primary adrenal insufficiency (Addison's disease).

This CKS topic does not cover the management of people with secondary or tertiary adrenal insufficiency (due to a disorder of the hypothalamus or pituitary glands, or from long-term use of corticosteroids).

There are separate CKS topics on Corticosteroids - oral, Depression, and Tiredness/fatigue in adults.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

September 2025 — reviewed. A literature search was conducted in August 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. Recommendations from the NICE guideline Adrenal insufficiency: identification and management have been incorporated into this topic.

Previous changes

September 2024 — minor update. Information about the interpretation of cortisol levels from the NICE guideline Adrenal insufficiency: identification and management has been incorporated into the diagnosis section of this topic.

December 2020 — reviewed. A literature search was conducted in November 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic.

September 2020 — minor update. Information that people with Addison's disease taking an equivalent dose of 20 mg prednisolone or more per day should receive the pneumococcal vaccination has been added to this topic.

February to March 2016 — reviewed. A literature search was conducted in January 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. There have been minor changes to the recommendations on corticosteroid dosing during intercurrent illness, and it is now recommended that an adrenocorticotrophic hormone stimulation (Synacthen^®) test should be carried out in secondary care.

May 2014 — minor update. Change to the section on choice of hydrocortisone preparation for the treatment of adrenal crisis.

October 2010 — minor update. Text regarding DHEA replacement therapy (unlicensed) reworded to reflect that this may be prescribed by some specialists.

May to September 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2025.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2025.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2025.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 September 2025.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 September 2025.

New policies

No new national policies or guidelines since 1 September 2025.

New safety alerts

No new safety alerts since 1 September 2025.

Changes in product availability

No changes in product availability since 1 September 2025.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

Suspect Addison's disease in people with symptoms suggestive of adrenal insufficiency.
Appropriately manage a person with suspected Addison's disease.
Support the secondary care management plan of a person with confirmed Addison's disease and liaise with specialists when appropriate.
Advise the person and their family on managing long-term replacement medication and ensure they are aware of sick-day rules and the emergency management of an adrenal crisis.
Treat an adrenal crisis and to have the appropriate drugs available.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

What is it?

Addison's disease (primary adrenal insufficiency) is caused by destruction of the adrenal cortex.
- This causes reduced production of glucocorticoids (such as cortisol), mineralocorticoids (such as aldosterone), and adrenal androgens (such as dehydroepiandrosterone).
- The absence of cortisol leads to increased production of adrenocorticotrophic hormone (ACTH) because negative feedback to the pituitary gland is reduced.
Adrenal insufficiency may also be caused by long-term administration of corticosteroids or disorders of the hypothalamus or pituitary gland, but this is not Addison's disease.
- Secondary adrenal insufficiency occurs when pituitary ACTH production is insufficient; this leads to reduced cortisol production and adrenal atrophy. Causes include intracranial disorders, such as pituitary tumours and their treatment, subarachnoid haemorrhage, and traumatic brain injury.
- Tertiary adrenal insufficiency occurs when hypothalamic production of corticotropin-releasing hormone is disrupted and production of ACTH from the anterior pituitary is insufficient. Causes include long-term administration of corticosteroids and less commonly tumours, radiotherapy, or surgery affecting the hypothalamus.

[Bancos, 2015; Bornstein, 2016; Martin-Grace, 2020; Miller, 2020; Simpson, 2020]

What causes it?

In Western countries, Addison's disease is most commonly caused by autoimmunity, accounting for around 90% of cases. Of these:
- In approximately 40% of cases, the adrenal gland is affected in isolation.
- In approximately 60% of cases, Addison's disease occurs as part of a multi-organ autoimmune polyendocrine syndrome.
Other causes of primary adrenal insufficiency include:
- Congenital adrenal hyperplasia (the most common cause of primary adrenal insufficiency in children) and other genetic causes, such as adrenoleukodystrophy.
- Infections, such as tuberculosis, meningococcus, haemophilus influenzae, cryptococcosis, cytomegalovirus, and HIV.
- Adrenal metastases.
- Amyloidosis.
- Haemochromatosis.
- Iatrogenic causes such as bilateral adrenalectomy, adrenal haemorrhage (for example, from anticoagulant treatment), and use of immune checkpoint inhibitor therapies in the treatment of cancer.

[Arlt, 2003; Bornstein, 2016; Barthel, 2019; Betterle, 2019; Miller, 2020; Simpson, 2020]

How common is it?

Addison's disease is rare.
- Reported prevalence varies from 100 to 220 per million people in Western Europe and the US [Husebye, 2014; Bensing, 2016; Bornstein, 2016; Barthel, 2019].
- The estimated annual incidence of Addison's disease in Europe ranges from 4.4 to 6.2 per million [Betterle, 2019].
- In the UK, autoimmune Addison’s disease affects about 1 in 14,000 people, with approximately 9000 people diagnosed and 320 new diagnoses per year [ACAP, 2020].
- In children, the most common cause of primary adrenal insufficiency is congenital adrenal hyperplasia (in 70% of cases) — Addison’s disease accounts for 15% of cases [Bowden, 2018].
Addison's disease can affect all age groups.
- The most common age of onset is between 30–50 years [Betterle, 2019; ACAP, 2020].
More women than men are affected [Betterle, 2019].
Adrenal insufficiency is more common in people who [NICE, 2024]:
- Have recently stopped using glucocorticoids by any route of administration after taking them for more than 4 weeks if aged 16 years and over, or more than 3 weeks if aged under 16 years.
- Are taking glucocorticoids at physiological equivalent doses or above by any route of administration and have had an episode of physiological stress
- Are taking opioids, checkpoint inhibitors, adrenal enzyme inhibitors or medicines that affect the production, metabolism or action of cortisol, such as antifungals or antiretrovirals.
- Have coexisting conditions such as:
  - Primary hypothyroidism.
  - Type 1 diabetes.
  - Premature ovarian insufficiency.
  - Autoimmune polyendocrinopathy syndrome.
  - Hypothalamic or pituitary tumours.
  - Hypothalamo-pituitary disease including infections and infiltrative disorders.
  - Have had cranial, pituitary, hypothalamic, or nasopharyngeal radiotherapy.

What conditions are associated with Addison's disease?

Addison's disease may occur in isolation, but is associated with other autoimmune conditions in 50–80% of cases:
- Conditions associated with Addison’s disease include autoimmune thyroid disease, pernicious anaemia, vitiligo, and type 1 diabetes mellitus.
Of people with autoimmune Addison's disease, about two-thirds present with or go on to develop an autoimmune polyendocrine syndrome (APS):
- APS type 1 (up to 15% of people who develop APS).
  - Autosomal recessive.
  - Typically presents in childhood.
  - Triad of Addison's disease, hypoparathyroidism, and chronic candidiasis.
  - May also be associated with type 1 diabetes mellitus, hypogonadism, premature ovarian insufficiency, pernicious anaemia, autoimmune thyroid disease, autoimmune hepatitis, chronic atopic dermatitis, keratitis, vitiligo, and alopecia.
- APS type 2 (around 68% of people who develop APS).
  - Complex genetic trait with links to human leukocyte antigen (HLA) major histocompatibility complex.
  - Usually involves Addison's disease and autoimmune thyroid disease or type 1 diabetes mellitus.
  - May also include premature ovarian insufficiency, vitiligo, pernicious anaemia, and coeliac disease.

[Husebye, 2014; Bancos, 2015; Bornstein, 2016; Husebye, 2018; Barthel, 2019; Betterle, 2019; Bensing, 2020; Thomsen, 2020]

What is the prognosis?

If untreated, Addison's disease is always fatal — lifelong replacement therapy is essential.
Some studies have shown that even with treatment, people with Addison's disease are at increased risk of premature death; adrenal crisis is a significant cause of mortality (particularly in people under the age of 40 years). Excess glucocorticoid replacement has also been associated with increased mortality.
- A Swedish study prospectively followed up 1675 people with Addison's disease over an average of 6.5 years [Bergthorsdottir, 2006]. The risk ratio for all-cause mortality was 2.19 for men (95% CI 1.91 to 2.51) and 2.86 for women (95% CI 2.54 to 3.20). Cardiovascular disease, cancer, and infectious diseases contributed to excess mortality.
- Another Swedish cohort study assessed data from 3299 people with Addison's disease over 40 years [Bensing, 2008]. This showed an increased standardized mortality ratio of 2.9 in women (95% CI 2.7 to 3.0) and 2.5 in men (95% CI 2.3 to 2.7).

[Bancos, 2015; Murray, 2017; ACAP, 2020]

What are the complications?

The most serious complication of Addison's disease is adrenal crisis, which is a life-threatening emergency [Husebye, 2014; Bornstein, 2016; Barthel, 2019; Betterle, 2019; ACAP, 2020] [Simpson, 2020].
- This occurs when a person with Addison's disease experiences severe physical stress. The adrenal glands cannot supply the extra cortisol needed to cope with the stress, and life-threatening symptoms develop.
- Even if the person is young and otherwise fit, adrenal crisis may result in severe dehydration, hypotension, hypovolaemic shock, altered consciousness, seizures, stroke, or cardiac arrest.
- Children with adrenal crisis are more susceptible to hypoglycaemia, that, if not promptly recognized and treated, can result in permanent brain damage.
- The most common causes of adrenal crisis in people with diagnosed Addison’s disease are:
  - Gastrointestinal illness (23%).
  - Other infections (25%).
  - Peri-operative issues (10%).
  - Physiological stress/pain (9%).
Other complications include:
- Reduced quality of life [Husebye, 2014] [Bancos, 2015] [Bensing, 2016] [Murray, 2017]:
  - Factors affecting quality of life include fatigue, loss of energy, depression, anxiety, reduced ability to cope with daily activities, and loss of libido (particularly in women).
- Adverse maternal and neonatal outcomes [Bancos, 2015] [Bensing, 2016] [Schneiderman, 2017] [Bensing, 2020]:
  - Poorly managed Addison’s disease in pregnancy has been associated with increased risk of maternal mortality, miscarriage, preterm delivery, impaired foetal growth, and congenital abnormalities.
- Premature ovarian insufficiency (POI) [Husebye, 2014] [Bensing, 2020]:
  - Approximately 10–20% of women with autoimmune Addison’s disease develop POI before 40 years of age — the risk of developing POI is particularly high in women with autoimmune polyendocrine syndrome type 1 (up to 50–70% in some studies).

Diagnosis of Addison's disease

When should I suspect Addison's disease?

Diagnosis of Addison's disease is often delayed because symptoms are non-specific, common, and overlap with many other conditions.
A person with Addison's disease may present with a sudden crisis precipitated by intercurrent infection or stress.
- Consider adrenal crisis as a potentially reversible cause in people who are critically unwell with any of the following:
  - Circulatory shock or collapse.
  - Condition failing to respond to initial treatments.
  - Hyperpigmentation.
  - Hypoglycaemia (particularly in children).
  - Hyponatraemia.
  - Low blood pressure (including postural hypotension).
- Consider adrenal crisis in people with, or at high risk of, adrenal insufficiency who are unwell with milder symptoms, including:
  - Clamminess.
  - Confusion or altered mental states.
  - Feeling cold or feverish.
  - Lethargy.
  - Pallor.
  - Weakness.
Consider adrenal insufficiency in people with unexplained hyperpigmentation, or when there is no other clinical explanation for the presence of one or more of the following persistent symptoms, signs or features:
- Diarrhoea.
- Dizziness or light-headedness on standing.
- Early puberty.
- Faltering growth (in children).
- Feeling of muscle weakness.
- Hyperkalaemia.
- Hypoglycaemia (particularly in children).
- Hyponatraemia.
- Hypotensive crisis (particularly in children).
- Lack of appetite or unable to eat a full meal.
- Lethargy.
- Nausea or vomiting.
- Prolonged neonatal jaundice.
- Salt craving.
- Weight loss.
Be aware that hyperpigmentation may not be seen on black or brown skin. Ask the person if they have noticed a change in their skin colour and assess the buccal mucosa or any surgical scars.
Also consider Addison's disease in a person with:
- Other symptoms including headache, fever, increased thirst or urination, loss of axillary or pubic hair in women, and anxiety or depression.
- Hypothyroidism, where symptoms worsen when levothyroxine is started — elevated thyroid-stimulating hormone in isolation may indicate hypoadrenalism.
- Other autoimmune diseases, such as vitiligo, pernicious anaemia, hepatitis, alopecia, and coeliac disease.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Adrenal insufficiency: identification and management [NICE, 2024], the Addison's Disease Self Help Group (ADSHG) Addison’s Clinical Advisory Panel (ACAP) guides Diagnosing Addison's: a guide for GPs [ACAP, 2020] and Caring for the patient with Addison’s: information for GPs [ACAP, 2024], Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline [Bornstein, 2016], the consensus statement The diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [Husebye, 2014], the Society for Endocrinology guideline Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients [Arlt, 2016], and expert opinion in narrative reviews Diagnosis and management of adrenal insufficiency [Bancos, 2015], Pediatric adrenal insufficiency: diagnosis, management, and new therapies [Bowden, 2018], and Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings [Miller, 2020].

What else might it be?

Symptoms of Addison's disease may mimic:
- Acute abdomen
  - Severe dehydration, circulatory shock, nausea, vomiting, and abdominal pain associated with adrenal crisis can be mistaken for an acute abdominal emergency.
- Gastroenteritis
  - Nausea and vomiting are key features of adrenal insufficiency and crisis.
  - For more information, see the CKS topic on Gastroenteritis.
- Depression
  - Chronic fatigue, malaise, and anorexia may mimic depression.
  - Adrenal crisis can be precipitated in unrecognized Addison's disease by antidepressant drug treatment, as some antidepressants are sodium-depleting.
  - For more information, see the CKS topic on Depression.
- Eating disorders
  - Weight loss, nausea, vomiting, and vague abdominal pain may be confused with symptoms of an eating disorder.
  - For more information, see the CKS topic on Eating disorders.
- Type 1 diabetes mellitus
  - Fatigue, unexplained weight loss, and thirst may occur in either condition, however, blood glucose is usually normal or low in adrenal failure.
  - For more information, see the CKS topic on Diabetes - type 1.
- Chronic fatigue syndrome
  - Fatigue is a predominant feature in many people with Addison's disease.
  - For more information, see the CKS topic on Tiredness/fatigue in adults.
- Hyperemesis and chloasma of pregnancy
  - Symptoms of Addison's disease may be attributed to vomiting and pigment changes associated with pregnancy.
  - For more information see the CKS topic on Nausea/vomiting in pregnancy.

Basis for recommendation

This information is based on the Addison's Disease Self-Help Group (ADSHG) Addison’s Clinical Advisory Panel (ACAP) guide Diagnosing Addison's: a guide for GPs [ACAP, 2020], and expert opinion in narrative reviews Addison's disease [Vaidya, 2009], and Addison disease in adults: diagnosis and management [Chakera, 2010].

How should I investigate suspected adrenal insufficiency?

If there is clinical suspicion of impending adrenal crisis emergency treatment should never be delayed to carry out investigations.
- Untreated adrenal crisis can be rapidly fatal.
In adults, if adrenal insufficiency is suspected on the basis of clinical features, and urgent treatment is not indicated:
- Offer an 8 am to 9 am serum cortisol test to people aged 1 year and over, and use Table 1 to interpret results and aid decision-making.
- For babies aged under 1 year, measure serum cortisol levels at any time of day and seek paediatric or paediatric endocrinology advice for interpretation of results.
Do not test for adrenal insufficiency in people taking oral glucocorticoids at physiological equivalent doses or above.
- Be aware that people taking exogenous glucocorticoids by routes other than oral such as inhaled, intramuscular or topical, at physiological equivalent doses or above, may have a low 8 am to 9 am cortisol level.
After an intramuscular or intra-articular glucocorticoid injection, wait 4 weeks before doing an 8 am to 9 am serum cortisol test.
Advise people taking oral oestrogen to stop taking it for 6 weeks before serum cortisol is measured because cortisol levels will be falsely elevated and:
- Advise them to use other contraception methods to avoid unplanned pregnancy if oestrogen is used for contraception.
- Consider a switch to a transdermal preparation if oestrogen is used for hormone replacement therapy.

Table 1: Interpretation of serum cortisol levels 8 am to 9 am test

Serum cortisol level	People aged 16 years and over	Children and young people (aged 1 year and over to under 16 years)
Below 150 nmol//L	Recognise that the person may have adrenal insufficiency. Refer the person to endocrinology. Consider starting management for adrenal insufficiency. If the person is acutely unwell, follow recommendations for managing adrenal crisis.	Recognise that the person may have adrenal insufficiency. Refer the person urgently to paediatrics or paediatric endocrinology. If the person is acutely unwell, follow recommendations for managing adrenal crisis.
150–300 nmol/L	Recognise that the probability of adrenal insufficiency is uncertain. Consider repeating the serum cortisol test. If it remains at this level, seek endocrinology advice or referral.	Recognise that the probability of adrenal insufficiency is uncertain. Consider repeating the serum cortisol test. If it remains at this level, seek paediatric or paediatric endocrinology advice or referral.
Above 300 nmol/L	Recognise that adrenal insufficiency is very unlikely.	Recognise that adrenal insufficiency is very unlikely.
Source: [NICE, 2024]

Seek specialist advice from an endocrinologist before obtaining a serum cortisol level in:
- People who work shifts — it is uncertain when the best time to obtain a serum cortisol level is, and interpretation of the results can be difficult.
  - An adrenocorticotrophic hormone stimulation (Synacthen^®) test may be required.
- People receiving long-term corticosteroid treatment — interpretation of results can be difficult.
  - An adrenocorticotrophic hormone stimulation (Synacthen^®) test may be required.
- People receiving oestrogen treatment (such as oral contraception or hormone replacement therapy) — interpretation of the results can be difficult as oestrogens increase hepatic production of cortisol-binding globulin, and therefore increase cortisol levels.
- Pregnancy — if adrenal insufficiency is suspected in pregnancy, seek urgent specialist advice.
  - Interpretation of investigations is difficult, and untreated adrenal insufficiency in pregnant women is associated with serious complications, including increased mortality.
When interpreting cortisol results, be aware that laboratories use many different assays — check local reference ranges. As a general guide, if the serum cortisol level is:
- Less than 100 nanomol/L — admit the person to hospital, adrenal insufficiency is highly likely.
- Between 100 and 500 nanomol/L — refer the person to endocrinology for further investigations. The urgency of referral depends on the severity of symptoms and the serum cortisol level.
In children, if adrenal insufficiency is suspected:
- Urgently arrange for investigations to be carried out in secondary care — emergency admission to hospital may be required depending on clinical judgement.
- Untreated adrenal crisis can be rapidly fatal; children with adrenal insufficiency are particularly at risk of hypoglycaemia that requires prompt treatment to avoid long-term neurological deficits.
Other tests that may be appropriate include:
- Urea and electrolytes.
  - Sodium levels may be low and potassium levels high in Addison's disease, but normal serum sodium and potassium levels do not exclude the diagnosis.
  - Seek specialist advice if unsure.
- Blood glucose.
- Other blood tests, including calcium, full blood count, liver and thyroid function tests.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Adrenal insufficiency: identification and management [NICE, 2024], the Addison's Disease Self Help Group (ADSHG) Addison’s Clinical Advisory Panel (ACAP) guides Diagnosing Addison's: a guide for GPs [ACAP, 2020], Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline [Bornstein, 2016], the consensus statement The diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [Husebye, 2014], the Society for Endocrinology Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients [Arlt, 2016], Guidance for the prevention and emergency management of adult patients with adrenal insufficiency [Simpson, 2020], and expert opinion in narrative reviews Diagnosis and management of adrenal insufficiency [Bancos, 2015], Pediatric adrenal insufficiency: diagnosis, management, and new therapies [Bowden, 2018], Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults [Betterle, 2019], and what CKS considers good medical practice.

Seeking specialist advice

Shift workers — CKS found no guidelines or published expert opinion on when to test shift workers and how to interpret the results. This recommendation is based on expert opinion from previous reviewers of this CKS topic.
People receiving long-term corticosteroid treatment — this recommendation is based on expert opinion from previous reviewers of this CKS topic and a consensus statement [Husebye, 2014].
People who are receiving oestrogen treatment or are pregnant — this advice is based on the Endocrine Society guideline [Bornstein, 2016], the ACAP guide [ACAP, 2020], and expert opinion in a narrative review [Bancos, 2015].

Arranging admission to hospital

The recommendation to admit people to hospital if the cortisol level is less than 100 nanomol/L is based on the ACAP guide [ACAP, 2020], which recommends immediate and urgent referral if the person is hypotensive and vomiting, or where the 9 am cortisol is less than 100 nanomol/L.
- NICE recommends referral for people aged over 16 years with a cortisol level below 150 nanomol/L, and urgent referral to paediatrics or paediatric endocrinology in children aged under 16 years [NICE, 2024].

Endocrinology referral

Expert opinion varies regarding the serum cortisol level at which adrenal insufficiency can be excluded:

The Endocrine Society guideline [Bornstein, 2016] recognises that the choice of what morning cortisol concentration to utilize to rule out adrenal insufficiency (100% sensitivity) is controversial, with studies arguing levels from over 285 nmol/L to over 480 nmol/L.
ACAP suggests that adrenal insufficiency is unlikely if the 8–9 am serum cortisol level is more than 400 nanomol/L (unless the person is acutely unwell) and that further testing should be undertaken for people with a serum cortisol level of 100–400 nanomol/L [ACAP, 2020].
Other experts [Wallace, 2009; Bowden, 2018] suggest a cut-off value of around 500 nanomol/L.
NICE advises that if the cortisol level is [NICE, 2024]:
- Below 150 nanomol/L the person may have adrenal insufficiency and should be referred to endocrinology (children should be referred urgently).
- 150-300 nanomol/L the probability is uncertain, a repeat cortisol test should be considered, and the person referred to endocrinology if it remains at this level.
- Above 300 nanomol/L adrenal insufficiency is very unlikely.
Taking this information and the expert opinion of previous reviewers of this topic into account, CKS recommends referral for further investigation if the serum cortisol level is 100–500 nanomol/L.

How is the diagnosis of Addison's disease confirmed?

The diagnosis of Addison's disease is confirmed in secondary care. If emergency admission is not indicated:
- Refer adults to a specialist endocrinology unit.
- Urgently refer children to a paediatrician (preferably one with an interest in endocrinology).
Investigations in secondary care include:
- An adrenocorticotrophic hormone stimulation (Synacthen®) test — to confirm the diagnosis.
- Adrenocorticotrophic hormone (ACTH) levels — serum ACTH levels are high in Addison's disease (primary adrenal insufficiency) but are low in secondary adrenal insufficiency.
- Plasma renin and aldosterone levels — renin levels are typically high, and aldosterone levels are low in Addison's disease. In secondary adrenal insufficiency, the renin-angiotensin system can function normally.
- Serum DHEA-S — typically low in Addison’s disease.
- Thyroid function tests.
- Autoantibody levels — adrenal cortex autoantibodies or antibodies against 21-hydroxylase are present in more than 80% of people with recent-onset autoimmune adrenalitis.
- Computed tomography (CT) or magnetic resonance imaging (MRI) is not usually required if autoimmune adrenalitis is likely, but may be requested if infection, haemorrhage, infiltration, or neoplastic disease is suspected.

Adrenocorticotrophic hormone stimulation (Synacthen®) test

For the adrenocorticotrophic hormone (ACTH) stimulation (Synacthen^®) test (in secondary care):
- Blood samples are obtained to check serum cortisol levels before and 30 or 60 minutes after administering 250 micrograms of tetracosactide (a synthetic analogue of ACTH) intravenously or intramuscularly.
- This test can be performed at any time of day, as the post-stimulation value is used for diagnostic purposes.
A normal response to the ACTH stimulation test is an increase in the serum cortisol level.
- In people with normal adrenal reserve, cortisol levels increase to more than 500–550 nanomol/L after 30 or 60 minutes.
- In people with adrenal insufficiency, serum cortisol levels do not increase adequately in response to tetracosactide because the adrenal cortex is already receiving maximum stimulation from endogenous ACTH. A peak serum cortisol of less than 500 nanomol/L is diagnostic of primary adrenal insufficiency.
  - The exact diagnostic cut-offs depend on assay-specific local reference ranges.

[Bornstein, 2009; Husebye, 2014; Bancos, 2015; Bowden, 2018]

Basis for recommendation

Management

Scenario: Management

From age 1 month onwards.

How is Addison's disease treated?

Treatment regimens for Addison's disease are initiated and adjusted by a specialist endocrinologist.
- Repeat prescriptions may be provided in primary care under a shared care arrangement.
- Glucocorticoids and mineralocorticoids (if needed) are offered to people with primary adrenal insufficiency — androgen replacement is not routinely prescribed in the UK. See Table 2 for details of corticosteroid treatment and doses in adults, and Table 3 for children and young people.

Table 2: Corticosteroid replacement for primary adrenal insufficiency in people aged 16 years and over.

Treatment	Primary adrenal insufficiency
First-choice glucocorticoid	Hydrocortisone total daily dose 15–25 mg orally in 2 to 4 divided doses.
Alternative glucocorticoid (for example, if multiple daily doses are not appropriate)	Prednisolone (if they have stopped growing) total daily dose 3–5 mg orally.
	Modified-release hydrocortisone tablets (if they have stopped growing) orally.*
Mineralocorticoid if needed (to normalise serum electrolytes and plasma renin, and reduce postural symptoms and salt craving)	Fludrocortisone total daily dose initially 50 micrograms and adjusted according to response up to 300 micrograms orally. Consider a higher daily dose orally for young and physically active people.
Source: [NICE, 2024]. ^*Note: this is an off-label indication for people aged under 18 years

Table 3: Corticosteroid replacement for primary adrenal insufficiency in children and young people aged 1 year and over to under 16 years.

Treatment	Primary adrenal insufficiency
First-choice glucocorticoid	Hydrocortisone total daily dose 8–10 mg/m² orally in 3 to 4 divided doses.
Alternative glucocorticoid (for example, if multiple daily doses are not appropriate)	Prednisolone (if they have stopped growing) total daily dose 3–5 mg orally in 1 to 2 divided doses.
Alternative glucocorticoid (for example, if multiple daily doses are not appropriate)	For young people over 12 years, consider modified-release hydrocortisone tablets (if they have stopped growing) orally.^*
Mineralocorticoid if needed (to normalise serum electrolytes and plasma renin, and reduce postural symptoms and salt craving)	Fludrocortisone total daily dose initially 50 micrograms to 300 micrograms orally, adjusted according to response
Source: [NICE, 2024]. ^*Note: this is an off-label indication for people aged under 18 years

Glucocorticoid replacement
- Ideally, glucocorticoid replacement should mimic the natural cycle of corticosteroid release. Three divided doses are usually given (the highest dose should be given in the morning on waking, the next either in the early afternoon or at lunch, and afternoon (for example, 15 mg on waking, 5 mg at noon, and 5 mg in the afternoon), as this aims to provide even levels of glucocorticoid throughout the day and avoid high doses in the evening. Two divided doses are also an option (for example, 15 mg in the morning, and 10 mg in the afternoon or early evening).
- For people doing shift work, doses of glucocorticoid should follow the person's daily routine, not the time on the clock. For example, the first dose should be given on getting up after sleep, even if this is not in the morning.
Mineralocorticoid replacement
- The amount of fludrocortisone required is related to individual fluid and electrolyte intake/losses. A daily dose of 50–200 micrograms is usually sufficient, but a higher dose is sometimes needed in children or in pregnancy.
- People are advised not to restrict salt intake, and infants may need salt supplements.
- In hot climates, the fludrocortisone dose may need to be increased to compensate for the increased salt loss from sweating.
Androgen replacement — dehydroepiandrosterone (DHEA) is an androgen made in the adrenal cortex; therefore, levels are decreased in Addison's disease.
- DHEA replacement (unlicensed) may be prescribed in certain circumstances (such as persistent fatigue) by endocrinology.
- It is normally taken as a single morning dose.
Ensure people with Addison's disease have 2 or 3 emergency management kits. They should contain:
- An intramuscular hydrocortisone injection.
  - Premixed hydrocortisone sodium phosphate 100 mg/1 ml (1 vial), or
  - Hydrocortisone sodium succinate 100 mg powder and 5 ml or 10 ml water for injection (1 vial).
- Two blue needles.
- Two 2 ml syringes.
- Written instructions in an easy-to-understand format on how to prepare and give emergency intramuscular hydrocortisone and how to safely dispose of needles and syringes.
- Steroid emergency cards.
- Glucose gel (only for babies, children and young people aged under 16 years).
- One orange needle and a 1 ml syringe (only for babies aged under 1 year).
- Provide training on how to use emergency management kits. Advise people with Addison's disease and their families and carers to check the expiry date on hydrocortisone, needles and syringes and replace as necessary.
Offer additional supplies of oral glucocorticoids to cover increased dosing during periods of physiological stress (sick-day dosing).
- For people on modified-release hydrocortisone, provide supplies of immediate-release hydrocortisone.

Basis for recommendation

Mineralocorticoid dose

NICE recommends an initial fludrocortisone dose of 50 micrograms which should be adjusted according to response up to 300 micrograms orally, and advises that higher daily doses may be needed for young and physically active people [NICE, 2024].
ACAP advises that the normal adult dose for fludrocortisone is 50–200 micrograms daily, which is usually taken as either a single morning dose or in two divided doses, and that the dose is dependent on metabolism and exercise levels and will alter during a person's lifespan [ACAP, 2024]. This is supported by expert opinion in a narrative review and the Endocrine Society guideline [Husebye, 2014; Bornstein, 2016].
Higher doses may be necessary in children and younger adults as well as during pregnancy [Husebye, 2014; Bancos, 2015; Bornstein, 2016].

What self-care advice should I give a person with Addison's disease?

Ensure that the person with Addison's disease and their family or carers (if appropriate) are aware of:

The need for lifelong glucocorticoid replacement treatment and the potentially life-threatening complications that may arise with inadequate replacement, especially at times of illness, surgery, and physical stress.
Give information to people with Addison's disease and their families and carers on:
- How to obtain an NHS Steroid Emergency Card for adults, or a British Society of Paediatric Endocrinology and Diabetes (BSPED) Adrenal Insufficiency Paediatric Steroid Treatment Card, and medical alert jewellery, and the importance of carrying this information.
  - The Addison's Disease Self Help Group website provides a letter for people with Addison's disease to carry with them when travelling abroad to give healthcare professionals in case of medical emergency. This is available in a variety of languages.
- Daily dosing, sick-day rules and crisis management during periods of physiological stress.
- How to set up medical alerts, medical IDs, and apps on mobile phones.
- Relevant support groups and charities.
  - For example, the Addison's Disease Self-Help Group (www.addisonsdisease.org.uk).
- How to access free NHS prescriptions.
- How to discuss their diagnosis and treatment with employers, in educational settings, and with friends and family.
- Pneumococcal and influenza vaccination — people taking systemic steroids equivalent to 20 mg of prednisolone or more per day (any age) and children under 20 kg taking a dose of 1 mg or more per kg per day, should be offered seasonal influenza and pneumococcal vaccination.
  - For more information, see the CKS topics on Immunizations – pneumococcal and Immunizations - seasonal influenza.
Reassure people that having Addison's disease does not prevent living a full and active life, and give information on the following topics to help them, and their families and carers, make informed decisions to support self-management:
- The importance of glucocorticoid as a life-essential hormone replacement and life-saving treatment for adrenal crisis.
- Why they have been prescribed glucocorticoids and mineralocorticoids, and the planned duration of treatment.
- Long- and short-term adverse effects because of under- or over-hormone replacement and symptoms to look out for signs and symptoms of glucocorticoid under- or over-replacement.
- When to take additional glucocorticoids, for example at times of physiological or significant psychological stress.
- How to recognize the symptoms of an adrenal crisis and how to seek clinical advice when unwell, including when to access or call emergency services (for example, using the 999 service).
  - Give advice about registering with their local ambulance trust to ensure any 999 callout is allocated high priority and the ambulance is equipped with injectable hydrocortisone.
- How to administer glucocorticoids in an emergency and seek medical advice after using emergency medicine (a family member/carer should also know how to do this).
  - Patient information with clear instructions and videos of how to self-inject are available on the Addison's Disease Self Help Group website.
- The need to maintain a good supply of oral medicines at all times, including when travelling or moving between places of residence and how to obtain additional supplies if needed for sick-day dosing.
- How to adjust the timing of medicine dosing when travelling through time zones, fasting, or doing shift work or activities that affect sleep patterns.
  - Advise that when travelling, they should take an extra supply of medication with them (for example, double what they normally need) plus an emergency hydrocortisone injection kit.
  - It may be necessary to supply a doctor's note for airport security explaining the need for medication, needles, and syringes in hand luggage.
- The importance of not stopping medicines abruptly, except on clinical advice.
The need to make the team responsible for their care aware that they may need extra glucocorticoid replacement if they are undergoing a procedure such as surgery, dental treatment, or endoscopy.
The emergency telephone numbers for their specialist endocrine team.

Basis for recommendation

How should I follow up a person with Addison's disease?

Follow-up will usually be shared between primary and secondary care.

Offer ongoing reviews with an appropriate specialist team.
- Offer children and young people under 16 years an appointment at least every 6 months and a face-to-face review at least annually to measure their height and weight and adjust glucocorticoid and mineralocorticoid doses accordingly.
- Adjust the frequency of ongoing reviews according to clinical and individual needs using a shared decision-making model.
Offer more frequent reviews:
- Around the time of diagnosis.
- During periods of rapidly changing clinical needs.
- During periods of rapid growth (including for babies and children, and for young people during puberty).
- During periods of rapidly changing family or personal circumstances (such as changes in parental responsibility or moving schools).
- During transition of care to adult services.
- If there are concerns about medicines adherence.
- If there are concerns about the person, their carers or family being able to safely manage the condition.
- For vulnerable people.
Offer less frequent reviews to the following groups:
- Adults on exogenous glucocorticoids.
- Adults who are confident with self-management.
- Adults with stable clinical needs.
Review information and support needs regularly as children grow up, during times of transition (for example, starting school or university) and when significant life events occur (for example, when having children).
- Continue to offer information and support to people with Addison's disease even if this has been declined previously.
During a review, ask about:
- The person's psychological wellbeing and ability to carry out everyday activities.
- How well they feel they understand their condition and how confident they are about managing it.
- Medication adherence.
- How frequently they are using additional glucocorticoids (for sick-day dosing and emergency injections).
- Their understanding of sick-day rules and any education or information needed.
- The frequency of adrenal crisis, hospital admissions and infections.
Monitor for signs and symptoms of glucocorticoid:
- Under-replacement — weight loss, early satiety, decreased appetite, nausea, fatigue that is significantly affecting the person's ability to carry out activities of daily living, worsening hyperpigmentation, or muscle weakness. In children and young people also monitor for abnormal growth rate and timing of puberty.
- Over-replacement — weight gain, increased appetite, disturbed sleep, skin thinning, new or worsening diabetes, new or worsening hypertension, Cushingoid appearance, skin infections, acne, thrush, frequent, low-impact or fragility fractures, or height loss.
  - Around 10% of people treated for Addison’s disease have essential hypertension. The person should be assessed by endocrinology to ensure that glucocorticoid and mineralocorticoid replacement is not excessive. If essential hypertension is confirmed, treatment with ACE inhibitors or calcium blockers is preferred (diuretics should be avoided)
- If over- or under-replacement is suspected, seek specialist advice from an endocrinologist, with urgency depending on clinical judgement.
Monitor for signs and symptoms of mineralocorticoid:
- Under-replacement — light-headedness or salt craving.
- Over-replacement — swollen ankles or high blood pressure.
Consider measuring plasma renin and adjust fludrocortisone dose if needed.
Offer the following measurements and tests to people and use the results to aid decision-making:
- Blood pressure (lying and standing).
- Electrolytes.
- HbA1c.
- Bone density (for adults at least once in the 5 years after diagnosis).
- Lipid profile (for adults).
For babies, children and young people under 16 years, check:
- Any changes regarding personal or family circumstances (including education and training).
- Signs and symptoms of low blood glucose.
- Height and weight.
- Progression to and through puberty and frequency of menstrual periods, if relevant.
- Bone age in children and young people who are still growing, with an X-ray of the left hand and wrist.
- Bone density (once they have stopped growing or if they have had frequent, low-impact or unexpected fractures).
Advise the person to adjust glucocorticoid dose depending on lifestyle factors and any temporary increased demands on activities of daily living (for example, an unusually long day, endurance exercise, shift working and travel).
Ensure that the following areas have been covered:
- Provision of hydrocortisone for injection with needles and syringes to treat adrenal crisis.
  - Check that the person and their family/carers are competent to administer an intramuscular injection of hydrocortisone in an emergency.
- Screening for other endocrine or autoimmune disorders (such as pernicious anaemia, type 1 diabetes mellitus, and thyroid dysfunction).
- Reproductive health:
  - Ask about the menstrual cycle in women of childbearing age to check for premature ovarian insufficiency.
  - Pregnancies occur in about 20% of women diagnosed with Addison’s disease — close monitoring from endocrinology and obstetric teams is required throughout pregnancy.
Explain to carers of people with Addison's disease (including young carers) about their right to a carer's assessment and tell them about other sources of information and support.

Basis for recommendation

Screening for other autoimmune disorders and premature ovarian failure

These recommendations are based on a clinical guideline, a consensus statement [Husebye, 2014; Bornstein, 2016], and expert opinion in a narrative review [Betterle, 2019].
Most people with Addison’s disease will already have or will develop another associated endocrine or autoimmune condition in the future — primary care clinicians must remain alert to the development of new symptoms and be ready to refer back to the endocrinologist or other specialists [ACAP, 2024].

How should I manage a suspected adrenal crisis?

If adrenal crisis is suspected in people aged 16 years and over, give 100 mg intravenous or intramuscular hydrocortisone immediately, and arrange emergency admission to hospital. Do not delay admission by doing diagnostic tests.
- Give 1 litre of 0.9% sodium chloride intravenous infusion over 30 minutes to the person having an adrenal crisis (if available) before transfer to hospital.
- Transfer in a sedan or a carry chair should be avoided as this increases the risk of circulatory complications.
In babies, children, and young people aged 16 years and under, give intravenous or intramuscular hydrocortisone and additional fluids immediately, and arrange emergency transfer to hospital. For children aged:
- Under 1 year, give 25 mg.
- Aged 1 to 5 years, give 50 mg.
- Aged 6 years and over, give 100 mg.
The preferred formulations of hydrocortisone are:
- Hydrocortisone sodium phosphate. This is licensed for the treatment of adrenal crisis and may be more suitable for self-injection kits because it is a solution and does not require reconstitution.
- Hydrocortisone sodium succinate. This is licensed for treating adrenal crisis, but it is in powder form requiring reconstitution and so may be less suitable.
Do not use hydrocortisone acetate injection to treat an adrenal crisis as it is a slow-acting preparation.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Adrenal insufficiency: identification and management [NICE, 2024], the Addison's Disease Self Help Group (ADSHG) Addison’s Clinical Advisory Panel (ACAP) guides Diagnosing Addison's: a guide for GPs [ACAP, 2020] and Caring for the patient with Addison’s: information for GPs [ACAP, 2024], Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline [Bornstein, 2016], the consensus statement The diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [Husebye, 2014],the Society for Endocrinology guidance Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients [Arlt, 2016], the British Society of Paediatric Endocrinology and Diabetes (BSPED) Emergency and peri-operative management of adrenal insufficiency in children and young people: BSPED consensus guidance [BSPED, 2023], Guidance for the prevention and emergency management of adult patients with adrenal insufficiency [Simpson, 2020], expert opinion in narrative reviews Diagnosis and management of adrenal insufficiency [Bancos, 2015], Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings [Miller, 2020], and the manufacturers' summaries of product characteristics for hydrocortisone sodium phosphate [EMC, 2024] and hydrocortisone sodium succinate [EMC, 2025].

Arranging emergency admission to hospital

Adrenal crisis is a life-threatening emergency, and there is consensus amongst guidelines and experts that emergency admission is necessary [Husebye, 2014; Bornstein, 2016; ACAP, 2020; Simpson, 2020] [Bancos, 2015; Arlt, 2016].

Hydrocortisone injections

Expert opinion in clinical guidance [Husebye, 2014; Bornstein, 2016; ACAP, 2024; Simpson, 2020] and narrative reviews [Bancos, 2015; Arlt, 2016] is that initiation of life-saving hydrocortisone treatment is essential in suspected adrenal crisis — this should never be delayed to carry out diagnostic investigations.
- The Endocrine Society [Simpson, 2020] states that all patients, in particular pregnant patients, considered at risk of or with suspected incipient adrenal crisis should be treated immediately; a single high dose hydrocortisone administration has no adverse effects on the developing foetus (and is mostly inactivated in the placenta), but not treating rapidly could result in the loss of life of the mother and the unborn child.
The recommendation on the choice of intravenous or intramuscular hydrocortisone is based on the NICE guideline [NICE, 2024].
- ACAP advises that hydrocortisone acetate should not be used as this is a speciﬁc slow-acting preparation for joint injections [ACAP, 2024].
Recommendations on emergency hydrocortisone doses for children align with the NICE guideline which recommends following the BSPED consensus guidelines on adrenal insufficiency [BSPED, 2023]. These doses are also recommended in the BNF for children [BNFC, 2025].
- The manufacturer's summary of product characteristics notes that while hydrocortisone injection can be given intravenously or intramuscularly the preferred method in an emergency is intravenous injection [EMC, 2024; EMC, 2025].
- Recommendations on emergency treatment doses for children vary in the literature:
  - The Endocrine Society [Bornstein, 2016] recommends immediate parenteral injection of 50 mg/m² hydrocortisone for children with suspected adrenal crisis.
  - Expert opinion from the working group of the Pediatric Endocrine Society Drug and Therapeutics Committee [Miller, 2020] is that children 3 years or younger should be given 25 mg; school-age children between 3 and 12 years 50 mg; and older children and adolescents (12 years or older) 100 mg as an initial stress dose.

How should glucocorticoid treatment be managed if the person is to undergo a medical or dental procedure?

Ensure that if the person is undergoing surgery, endoscopy, or dental treatment, the team responsible for their care are aware that the person has Addison's disease and extra glucocorticoid replacement may be required.
Glucocorticoid cover for major surgery will be managed by the hospital.
For primary care procedures in adults, the Addison's Clinical Advisory Panel advises that for:
- Minor surgical procedures (for example, skin lesion excision with local anaesthetic) — an extra oral dose 60 minutes ahead of the procedure and an extra dose 60 minutes after the procedure, then return to the normal dose.
- Dental surgery without general anaesthetic (for example, root canal work with local anaesthetic) — double oral glucocorticoid dose (up to 20 mg hydrocortisone) 1 hour before surgery; after the procedure, double the dose of oral medication for 24 hours, then return to the normal dose.
- Minor dental procedures (for example, replacement filling, scale and polish) — an extra oral dose, 60 minutes ahead of the procedure and an extra dose where hypoadrenal symptoms occur afterwards. Then return to normal dose.
Seek specialist advice for children undergoing dental procedures.

Basis for recommendation

These recommendations are based on the Addison's Disease Self Help Group (ADSHG) Addison's Clinical Advisory Panel (ACAP) Surgical guidelines for Addison’s disease [ACAP, 2025], and the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency [Woodcock, 2020].

NICE [NICE, 2024] does not make any recommendations on glucocorticoid requirements for people having planned or emergency surgery or invasive medical procedures, but advises that this should be in accordance with the recommendations in the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK Guideline [Woodcock, 2020].
The recommendation to seek specialist advice for children undergoing dental procedures is based on the ADSHG guidance on dental procedures [ADSHG, 2024].

How should I manage people who are experiencing physiological or psychological stress?

It is important for people with Addison's disease to be aware of circumstances when they should increase their corticosteroid (such as during a period of illness or strenuous exercise) to reduce the risk of adrenal crisis.

For people aged over 16 years experiencing physiological stress:
- Offer at least 40 mg oral hydrocortisone daily in 2 to 4 divided doses or at least 10 mg oral prednisolone daily in 1 to 2 divided doses until the acute illness or physical trauma has resolved.
  - Do not increase glucocorticoid dosing for a long duration.
  - Advise people taking a daily oral prednisolone dose of 10 mg or more that they do not need additional sick-day dosing, but they can split their total daily dose into two equal doses.
- If the person vomits within 30 minutes of taking an oral dose, advise them to take a further dose once vomiting subsides, at double the original dose.
- If vomiting recurs within 30 minutes, give intramuscular hydrocortisone, and advise the person to attend the emergency department.
- Admit the person to hospital during periods of physiological stress if they are unable to absorb oral glucocorticoids (for example, during prolonged diarrhoea and vomiting). Give 100 mg intramuscular or intravenous hydrocortisone.
For babies, children, and young people experiencing physiological stress:
- Offer a total daily dose of oral hydrocortisone of around 30 mg/m² daily in four evenly spaced doses for as long as the illness lasts.
For people aged 16 years and over experiencing psychological stress:
- Consider sick-day dosing for 1 or 2 days (the same daily dose as for those experiencing physiological stress).
- Consider sick-day dosing at times of severe mental health crisis (for example, a psychotic episode). Consider giving 100 mg of intramuscular hydrocortisone for a person in severe mental health crisis who is unable to take oral glucocorticoids.
For babies, children and young people aged up to 16 years experiencing psychological stress:
- Consider 1 or 2 sick-day doses (the same daily dose as for those experiencing physiological stress).
Advise people to reduce or manage psychological stress by:
- Using condition-specific patient support groups that offer peer support or other organisations offering information and support.
- Exploring with their employer or education provider reasonable adjustments to be made in the workplace or educational setting.
- Exploring the role of self-management (including activities they could take part in to reduce their stress).
Consider referring the person, or ask the person to self-refer, to NHS talking therapies or mental health services.
For adults who are fasting:
- Ensure a thorough risk assessment (ideally several months before Ramadan) has been done by the endocrinology team. Depending on level of risk, religiously compatible alternatives to fasting or medication changes may be discussed.
- Prior to fasting, ensure the person understands the sick day rules (including when to terminate or abstain from fasting) and ensure the person has a valid intramuscular hydrocortisone pack and knows how to administer this.
For adults who are exercising:
- Strenuous exercise (such as a marathon) — advise the person to increase their medication (up to double the normal dose of glucocorticoid and mineralocorticoid) and drink sufficient fluids.
- Sports or activities with a risk of injury (such as skiing) — advise the person to ensure that a teammate is trained in administration of emergency hydrocortisone if needed.
Seek specialist advice for people who are taking alternative glucocorticoids.

Basis for recommendation

The NICE guideline development committee discussed that there is variation in practice regarding doubling a dose of hydrocortisone versus increasing the frequency of dosing [NICE, 2024].
- They recommended an increase to at least 40 mg daily, because on balance this is easier for people to manage.
- The committee agreed a dose of oral hydrocortisone 2-4 times daily is the preferred option because it’s a shorter-acting glucocorticoid. However, they noted that significant intercurrent illness (such as a fever over 39°C, diarrhoea and vomiting) four times daily would be preferential, because diarrhoea and vomiting means that hydrocortisone will not be absorbed adequately leading to a significant risk of adrenal crisis.
ACAP advises that for intercurrent illness or injury, if the person has [ACAP, 2024]:
- A moderate intercurrent illness (such as illness with fever [more than 37.5°C], or for infection requiring antibiotics) they should double their usual dose of hydrocortisone until recovered.
- Severe nausea they should take 20 mg hydrocortisone orally and sip oral rehydration solution.
- Had a major injury they should take 20 mg hydrocortisone orally immediately to avoid shock.

Supporting evidence

This CKS topic is largely based on the National Institute for Health and Care Excellence (NICE) guideline Adrenal insufficiency: identification and management [NICE, 2024], the Addison's Disease Self Help Group (ADSHG) Addison’s Clinical Advisory Panel (ACAP) guides Diagnosing Addison's: a guide for GPs [ACAP, 2020] and Caring for the patient with Addison’s: information for GPs [ACAP, 2024], Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline [Bornstein, 2016], the consensus statement on The diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [Husebye, 2014], the Society for Endocrinology guidance Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients [Arlt, 2016], and expert opinion in a narrative review Diagnosis and management of adrenal insufficiency [Bancos, 2015]. The rationale for individual recommendations is discussed in the relevant basis for recommendation sections of this topic.

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This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

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Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Addison's disease.

Search dates

January 2016 - October 2020.

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

Addisons disease/
addison$.ti,ab.
Primary adrenal insufficiency.mp.
Hypoadrenalism.mp.

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Sources of systematic reviews and meta-analyses

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Medline (with systematic review filter)
EMBASE (with systematic review filter)

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Sources of randomized controlled trials

The Cochrane Library:
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Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)

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Competing interests declared for this topic:

None.

References

Addison’s Clinical Advisory Panel (2020) Diagnosing Addison's: a guide for GPs. Addison's Disease Self-Help Group. https://www.addisonsdisease.org.uk [Free Full-text]
Addison's Clinical Advisory Panel (2024) Caring for the patient with Addison’s: information for GPs. Addison's Disease Self-Help Group. https://www.addisonsdisease.org.uk [Free Full-text]
Addison's Clinical Advisory Panel (2025) Surgical Guidelines for Addison’s disease and other forms of adrenal insufficiency. Addison's Disease Self Help Group. https://www.addisonsdisease.org.uk [Free Full-text]
ADSHG (2024) Addison's and adrenal insufficiency: advice for dentists. Addison's Disease Self Help Group. https://www.addisonsdisease.org.uk [Free Full-text]
Arlt, W. and Allolio, B. (2003) Adrenal insufficiency. Lancet 361(9372), 1881-1893. [Abstract]
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Bancos, I., Hahner, S., Tomlinson, J. and Arlt, W. (2015) Diagnosis and management of adrenal insufficiency. Lancet Diabetes and Endocrinology 3(3), 216-226. [Abstract]
Barthel, A., Benker, G., Berens, K., et al. (2019) An update on Addison's disease. Experimental and Clinical Endocrinology and Diabetes 127(2-03), 165-175. [Abstract]
Bensing, S., Brandt, L., Tabaroj, F., et al. (2008) Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clinical Endocrinology 69(5), 697-704. [Abstract]
Bensing, S., Hulting, A. L., Husebye, E. S., et al. (2016) Epidemiology, quality of life and complications of primary adrenal insufficiency: a review. European Journal of Endocrinology of the European Federation of Endocrine Societies 175(3), R107-R116. [Abstract]
Bensing, S., Giordano, R. and Falorni, A. (2020) Fertility and pregnancy in women with primary adrenal insufficiency. Endocrine 70(2), 211-217. [Abstract]
Bergthorsdottir, R., Leonsson-Zachrisson, M., Oden, A. and Johannsson, G. (2006) Premature mortality in patients with Addison's Disease: a population-based study. Journal of Clinical Endocrinology & Metabolism 91(112), 4879-4853. [Abstract]
Betterle, C., Presotto, F. and Furmaniak, J. (2019) Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults. Journal of Endocrinological Investigation 42(12), 1407-1433. [Abstract]
BNF (2025) British National Formulary. National Institute for Health and Care Excellence. https://bnf.nice.org.uk
BNFC (2025) British National Formulary for Children. National Institute for Health and Care Excellence. https://bnfc.nice.org.uk
Bornstein, S.R. (2009) Predisposing factors for adrenal insufficiency. New England Journal of Medicine 360(22), 2328-2339. [Abstract]
Bornstein, S.R., Allolio, B., Arlt, W., et al. (2016) Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 101(2), 364-389. [Abstract]
Bowden, S.A. and Henry, R. (2018) Pediatric adrenal insufficiency: diagnosis, management, and new therapies. International Journal of Pediatrics 2018. [Abstract]
BSPED (2023) Emergency and peri-operative management of adrenal insufficiency in children and young people: BSPED consensus guidance. British Society of Paediatric Endocrinology and Diabetes. https://www.bsped.org.uk [Free Full-text]
Chakera, A.J. and Vaidya, B. (2010) Addison disease in adults: diagnosis and management. American Journal of Medicine 123(5), 409-413. [Abstract]
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Husebye, E.S., Anderson, M.S. and Kämpe, O. (2018) Autoimmune polyendocrine syndromes. New England Journal of Medicine 378(12), 1132-1141. [Abstract]
Hussain, S., Hussain, S., Mohammed, R., et al. (2020) Fasting with adrenal insufficiency: practical guidance for healthcare professionals managing patients on steroids during Ramadan. Clinical Endocrinology (Oxford) 93(2), 87-96. [Abstract]
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Addison's disease: Summary

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Changes

Previous changes

Update

New evidence

Evidence-based guidelines

HTAs (Health Technology Assessments)

Economic appraisals

Systematic reviews and meta-analyses

Primary evidence

New policies

New safety alerts

Changes in product availability

Goals and outcome measures

Goals

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

NICE quality standards

Background information

What is it?

What causes it?

How common is it?

What conditions are associated with Addison's disease?

What is the prognosis?

What are the complications?

Diagnosis of Addison's disease

When should I suspect Addison's disease?

Basis for recommendation

What else might it be?

Basis for recommendation

How should I investigate suspected adrenal insufficiency?

Basis for recommendation

Seeking specialist advice

Arranging admission to hospital

Endocrinology referral

How is the diagnosis of Addison's disease confirmed?

Adrenocorticotrophic hormone stimulation (Synacthen®) test

Basis for recommendation

Management

Scenario: Management

How is Addison's disease treated?

Basis for recommendation

Mineralocorticoid dose

What self-care advice should I give a person with Addison's disease?

Basis for recommendation

How should I follow up a person with Addison's disease?

Basis for recommendation

Screening for other autoimmune disorders and premature ovarian failure