Addison's disease

Adrenal failure causing glucocorticoid and mineralocorticoid insufficiency. The diagnosis typically refers to auto-immune destruction of the gland, and is confirmed using a Synacthen test.

Investigations normal, and no alarm symptoms for malignancy

If all screening investigations are negative, including a synacthen test, the patient should be reassured and discharged to their primary physician.

Diagnoses such as depression or chronic fatigue syndrome may be considered.

Clinical suspicion is high and the patient is unwell

Take blood for a random cortisol and start emergency treatment.

Emergency treatment

Hydrocortisone 100mg should be given by intramuscular injection and continued every six hours until the patient has responded.

Intravenous fluid resuscitation, typically with 0.9% sodium chloride, should be initiated until the patient has responded.

If clinical suspicion is modest and the patient is not acutely unwell await results of 9am cortisol or synacthen test before starting treatment. A 9am or random cortisol above 500nmol/l is sufficient to exclude the diagnosis.

Borderline results should be interpreted in the light of clinical findings and usually require a formal synacthen test prior to treating or reassuring the patient. Ensure thyroid function, blood count and electrolytes have all been assessed at this stage.

Addison's disease is confirmed on synacthen test

Start replacement therapy. Emergency intramuscular treatment is not usually required at diagnosis.

Patients with severe symptoms should be treated with higher starting doses, for example 20mg on waking, and again five and ten hours later. Once clinical improvement occurs, revert to standard replacement therapy.

Standard glucocorticoid replacement therapy

Typical maintenance doses are hydrocortisone 10mg on waking, 5mg at lunchtime, 5mg with the evening meal, or at 0, five and ten hours after waking.

Replacement doses of hydrocortisone do not need to be taken with food, and so should be taken as soon as possible after waking to prevent symptoms of insufficiency, for example dizziness on rising.

The final dose should be taken at least four hours before retiring, or it may interfere with sleep.

Some patients prefer to take just two doses a day which are typically taken on waking and after approximately eight hours. Such a regime frequently requires larger doses to control symptoms throughout the day, which may have adverse long term consequences.

Standard mineralocorticoid replacement therapy

Typical maintenance dose of fludrocortisone is 100mcg in one or two divided doses.

Fludrocortisone is required in all patients on modern low dose glucocorticoid replacement therapy. It is not necessary to start in the acute phase since very high serum cortisol levels will access renal mineralocorticoid receptors.

Adrenal suppression due to medication use

Adrenal suppression due to long term steroid use may be difficult to manage. Where possible, the causative agents should be slowly withdrawn under supervision. However, as the dose is reduced it is important to assess for axis recovery, usually with a 9am cortisol. If this is below 100nmol/l the axis clearly remains suppressed. Patients with levels between 100-500nmol/l  should undergo a synacthen test to confirm whether they are safe to continue weaning off treatment.

Where there is evidence of on going adrenal suppression, low dose hydrocortisone (10mg, 5mg and 5mg) may be started, to protect the patient from hypoadrenalism while the causative drug is reduced and stopped. Pre dose cortisol and ACTH levels may then be assessed periodically to assess for axis recovery before considering reducing the dose of hydrocortisone. Once the axis appears normal, hydrocortisone or the causative drug can both be stopped safely.

Complications of Cushing's syndrome for example osteoporosis, hypertension, skin damage and glucose intolerance may all occur with long term exogenous steroid use. These patients therefore require aggressive screening and treatment.

Education on long term steroid use

All patients on glucocorticoid replacement therapy need to understand the importance of absolute compliance with their regime and be educated as to what to do in emergencies and during intercurrent illnesses. A formal education session with an endocrine nurse is ideal as soon as possible after diagnosis. Written information should be provided, and patients and their families should be taught how to administer intramuscular hydrocortisone, and how to recognise when this is necessary. All patients should be offered a steroid identification card, and other forms of emergency identification should be discussed.

The Addison's disease self help group has produced excellent advice sheets on long term steroid use, emergency identification, and instructions on what to do in emergency situations.

Patients should be offered a further education session six to 12 weeks after diagnosis to ensure good understanding. Future education updates should then be offered regularly and life long, for example at alternate year visits.

Arrange clinical review within six weeks

All patients newly diagnosed with Addison’s will need early clinical review which may be appropriately performed by an endocrine specialist nurse, or general practitioner. They should then be reviewed by an endocrinologist at around six weeks.

Check symptoms, postural blood pressure and serum electrolytes.

Consider performing a hydrocortisone day curve with renin assessments pre and 120 minutes post dose. This is useful if there is any doubt about dose titration, for example if the patient is taking a relatively large dose on waking but still feels symptomatic prior to the next dose.

It is useful to document a hydrocortisone day curve on at least one occasion in most patients, once they are taking what appears to be an appropriate dose, in order to confirm this as their life long regime.

Annual life long follow up

Check symptoms, weight and postural blood pressure annually. Serum electrolytes should also be checked at least annually prior to clinic. TSH and thyroxine should be checked at least every other year, or annually in patients with positive thyroid autoantibodies.

Ensure that the patient's steroid card, emergency instructions, and emergency medical identification are all up to date.

Routine repetition of hydrocortisone day curves and plasma renin activity are not usually required.

It may be appropriate to alternate annual visits between endocrinologist and endocrine specialist nurse where available.

Pregnancy, delivery and breast feeding

Pregnant patients with Addison's disease require particular care. Patients need to be reminded to take an additional oral dose of hydrocortisone if they have vomited. They also need ready access to emergency im hydrocortisone to be taken in the event of severe vomiting. Close monitoring of symptoms, blood pressure (including postural BP) and electrolyte estimation is useful to help determine whether an increase in the dose of mineralocorticoid or glucocorticoid is necessary. This is commonly required later in pregnancy, with dose requirements returning to normal post partum.

100mg hydrocortisone should be given im at the start of labour, and repeated every 6 hours until the baby has delivered. Patients can usually revert to their pre pregnancy dose following delivery, but may require double dose for 24 to 48 hours depending on their clinical status. 

During breast feeding and the early post partum weeks, patients may require advice on changing the timing of their glucocorticoid therapy in view of frequent night waking. However, total daily dose does not typcially need to be increased during this period. 

Practical advice for patients undergoing procedures or surgery

As a rule, very minor procedures eg skin biopsy under local anaesthetic will not require any special precautions.

Other procedures performed under local anaesthetic, but which will not affect the patient's ability to eat and drink, e.g. minor dental work, do require an increase in steroid dose. Generally, patients should double their usual dose of glucocorticoid therapy on the morning of hte procedure and for 24hours, but if they then feel back to normal, they can resume their usual replacement therapy. 

More invasive procudures, though not requiring a prolonged recover time e.g. major dental work under general anaesthetic, cataract surgery, hernia repair or endoscopy, will usually require a single dose of 100mg intra-muscular hydrocortisone at the start of the procedure, followed by double the patient's usual dose of oral steroids for 24 hours.

Colonoscopy and barium enema requiring extended bowel preparation can be difficult to plan for due to unpredictable absorption of oral doses. Ideally, patients should be admitted for intravenous fluids and 6 hourly intra-muscular hydrocortisone throughout the purgative phase until the start of the procedure. Patients should then take double their usual dose for 24 hours, and then can usually revert to their usual dose. 

Labour and delivery requires 100mg intra-muscular hydrocortisone to be given at the start of labour, then every 6 hours until the baby is delivered. Most people then need double their usual dose for 24-48 hours and then if they are well, revert to their usual pre-pregnancy doses.

Major procedures e.g. caesarian section, joint replacement or other operations requiring a general anaesthetic always require parental steroids. As a rule, patients should take their usual doses the day before surgery, and on the morning of surgery for later procedures. 100mg intra-muscular hydrocortisone should then be administered on induction of the anaesthetic, and the dose repeated 6 hourly thereafter for 24-48 hours or until the patient is able to eat and drink normally. Patients should then typically take double their usual dose for 48hours, or until they are feeling back to normal, at which they should resume their usual dose.

Very major surgery e.g. open heart surgery, or anything requiring an admission to intensive care will require 100mg intra-muscular hydrocortisone on induction of anaesthetic/admission to ITU, to be repeated until the patient is discharged and can eat and drink normally. Patients should then usually stay on double their usual dose for at least 48 hours depending on their clinical conditino.

Please note, this guidance is general, and if in doubt, patients and their practicioners should contact their endocrine specialist nurse, consultant or the Addison's diease self help group.