Addison's disease and adrenal crisis
(Note: Primary adrenal insufficiency = Addison’s disease, mineralocorticoid and glucocorticoid deficiency, adrenal insufficiency can occur secondary to long-term steroids, hypothalamus or pituitary disorder etc. but these are not Addison’s disease)
Questionnaire/history:
Fatigue (most people with Addison's disease)?
Hyperpigmentation (due to increased pituitary adrenocorticotrophic hormone) (92% of people with Addison's disease, particularly in sun-exposed areas, recent scars, pressure points, areas of friction, palmar creases, and mucous membranes)?
Gastrointestinal symptoms?
Weight loss?
Loss of appetite?
Premature satiety?
Nausea?
Vomiting?
Abdominal pain?
Cravings for salt, soy sauce or liquorice?
Musculoskeletal symptoms?
Muscle weakness?
Muscle cramps?
Joint pains?
Cardiovascular symptoms?
Postural dizziness due to hypotension (blood pressure decrease of 20 mmHg between sitting and standing measurements)?
Other symptoms?
Headache?
Low-grade fever?
Increased thirst or urination?
Loss of axillary or pubic hair in women?
Delayed puberty in children?
Investigations:
Hyponatraemia and hyperkalaemia on blood biochemistry?
(Note: Hyponatraemia is present in 90% and hyperkalaemia in 65% of people with established Addison's disease, but not diagnostic of
Diagnosis:
Consider if:
Hypothyroidism with worsening symptoms when levothyroxine is started?
Type 1 diabetes mellitus with recurrent unexplained hypoglycaemic episodes?
Other autoimmune diseases, such as vitiligo, pernicious anaemia, chronic active hepatitis, alopecia, and coeliac disease?
Crisis?
- Hypotension?
- Hpovolaemic shock?
- Acute abdominal pain?
- Low-grade fever?
- Vomiting?
Differential diagnosis:
(Acute abdomen, gastroenteritis, depression, eating disorders, type 1 diabetes mellitus, chronic fatigue syndrome, hyperemesis and chloasma of pregnancy)
Management:
Treatment regimens for Addison's disease will be initiated and adjusted by a specialist endocrinologist
Sick day rules and when to increase steroids:
(Notes:
It is important for people with Addison's disease to increase their corticosteroid cover if they are under physical stress (period of illness or strenuous exercise), to reduce the risk of adrenal crisis
It is difficult to accurately predict the needs of each person, but as a guide for adults (for children, seek advice from their specialist):
- Double the normal dose of hydrocortisone (or alternative glucocorticoid) if they have a fever or are prescribed antibiotics for an infection until they are recovered
- 20 mg hydrocortisone orally and sip oral rehydration solution (such as Dioralyte®) if they experience severe nausea (often with headache)
- If the person has vomited, they should use their emergency hydrocortisone injection and seek immediate medical advice - this is an Addison's disease emergency and early self-administration of hydrocortisone intramuscularly will often stabilise an episode of vomiting or diarrhoea
After a major injury, the person should take 20 mg hydrocortisone orally
If the person has diarrhoea, seek specialist advice from their endocrinologist as to whether the glucocorticoid dose needs to be adjusted
Exercise
- Strenuous exercise (eg marathon), up to double the normal dose of glucocorticoid and mineralocorticoid and increasing fluid intake is suggested
- If a less strenuous activity (eg hiking) add 5 mg to 10 mg hydrocortisone to the normal regimen shortly before the activity
Adrenal crisis (Addison’s complication or if suddenly stopped corticosteroids):
100 mg hydrocortisone (for an adult) IM or intravenously (if not already self-administered) and urgently admit to hospital
- Do not delay admission by doing diagnostic tests
- Rehydrate with IV saline (if available) whilst awaiting hospital transfer
Preferred formulations of hydrocortisone are:
- Hydrocortisone sodium phosphate (Efcortesol®). This is licensed for the treatment of adrenal crisis but it is not recommended for use in children
- Hydrocortisone sodium succinate (Solu-Cortef®). This is licensed for treating adrenal crisis, but it is in powder form requiring reconstitution and so may be less suitable
- Dose of hydrocortisone depends on the person's age:
--- Adults: 100 mg
--- Children 6 years of age or older: 50 mg to 100 mg
--- Children 1–5 years of age: 50 mg
--- Infants up to 1 year of age: 25 mg
Emergency administration of fludrocortisone is not required because high-dose hydrocortisone has a mineralocorticoid effect
Managing adrenal crisis during COVID-19: see Society for Endocrinology
Patients who suffer from a suspected or confirmed infection with coronavirus usually have high fever for many hours of the day, which results in the need for larger than usual steroid doses, so the Society for Endocrinology advise slightly different sick day rules, which are listed below.
In patients with a suspected (or confirmed) coronavirus infection:
On hydrocortisone:
- Increase hydrocortisone to 20 mg four times daily every 6 hours.
- On Plenadren: switch to the regular, immediate release hydrocortisone preparation and take 20 mg orally every 6 hours.
On prednisolone:
- On 5-15 mg prednisolone daily should take 10 mg prednisolone every 12 hours.
- On oral prednisolone > 15 mg should continue their usual dose but take it split into two equal doses of at least 10 mg every 12 hours
On fludrocortisone, continue taking usual daily dose
Advised:
To have sufficient supplies to cover increased doses if becoming unwell and an emergency injection of hydrocortisone 100 mg
To drink plenty of fluid (even at night if fever is high) and to make sure to pass urine regularly
If urine is very dark, to try to drink more fluids
Paracetamol 1000 mg every six hours
If short of breath, breathing fast, unable to talk in sentences or breathing is getting worse call 111 or 999 and take 100 mg IM emergency hydrocortisone injection
Coronavirus infections can come with 1-2 weeks of almost continuous fever
Signs indicating a deterioration: dizziness, intense thirst despite drinking, shaking uncontrollably, drowsiness, confusion, and increasing shortness of breath (struggling to speak, struggling to breathe), which indicated that the coronavirus starts to attack the lung or other organs
In this situation and also if any vomiting or severe diarrhoea immediately self-inject 100 mg hydrocortisone intramuscularly using the emergency injection
To immediately call 999 to arrange for further treatment and transfer to the hospital
To take hydrocortisone at a dose of 50 mg every six hours until in hospital, can be started on intravenous hydrocortisone 200 mg per 24 hours
If admitted to hospital very unwell Society for Endocrinology recommendation:
Hydrocortisone 100 mg per IV injection followed by continuous IV infusion of 200 mg hydrocortisone/24h (alternatively 50 mg every 6 h per intravenous or IM bolus injection)
Pause fludrocortisone
Intravenous fluids
Resource(s):
Society for Endocrinology: Adrenal Crisis during COVID-19 pandemic
Information for patient/carer(s):