In the disease, lack of cortisol will lead to feedback induced high levels of CRH and ACTH – and thus induce hyperpigmentation in some cases.
- Addison’s disease is rare – it has an incidence of 3-4 per 1,000,000 per year, and a prevelance of 40-60 per 1,000,000.
- It is far more common in females
- >90% of cases are a result of autoimmune disease
- The remainder are mostly a result of TB.
It often presents as unexplained; fatigue, hyponatremia and hypotension. Other symptoms may include weight loss, anorexia
, myalgia, dizziness, fainting. There may also be low self-esteem and depression
In some cases an addisonian crisis occurs, whereby there is severe hypotension and dehydration, often with a precipitating event such as illness or trauma. In this case, the administration of a glucocorticoid is necessary, but the administration of sodium is more important than giving an aldosterone replacement.
Pigmentation (dull, slaty brown) is present in over 90% of cases.
Hypotension as a result of hypovolaemia is present in 80-90% of cases, however, in may cases the hypotension is only postural and systolic.
This hypotension is a result of mineralocorticoid deficiency.
Sodium levels will be low (hyponatremia) and potassium levels will be high (hyperkalemia)
due to low mineralocorticoids. Glucose will be low
due to low cortisol levels.
Therefore, the test you should do are:
- Random serum cortisol will often be low, but it can be normal, and so again, you can not use this test diagnostically. However, if random cortisol is very high, it is unlikely to be hypoadrenalism (e.g. 460nmol/L).
- ACTH stimulation test – the patient is given a dose of synthetic ACTH in an attempt to stimulate cortisol production. Ideally you would then take cortisol blood levels at 0 and 30 minutes. The cortisol should rise sharply. Addison’s should be ruled out if the cortisol rises to above 550nmol/L.
- Note that during pregnancy or whist on the oral contraceptive, levels may be falsely high due to raised cortisol binding globulin.
- 0900 levels of ACTH will usually be high in Addison’s disease, but they will be low in secondary hypoadrenalism.
- Adrenal antibodies
- CXR/AXR – may show evidence of TB and calcified adrenal glands
- Hypercalcaemia and anaemia
- Serum aldosterone may be low.
If hypoadrenalism is suspected, and the patient is hypotensive you should give 100mg hydrocortisone and saline immediately without confirmation of diagnosis. Ideally, you should do this as soon as a measurement of cortisol has been taken. Give further 0.9% saline and 6 hourly infusion of 100mg hydrocortisone until patient is stable. Also consider glucose if patient is hypoglycaemic.
Once the patient is stable, oral doses of hydrocortisone can e given. Initially every 8 hours, 2-3 times a day. You should avoid giving it at night as it can induce insomnia.
Long term – this involves replacement glucocorticoids and mineralocorticoids. Also if TB is suspected then this should also be treated. Glucocorticoids should be monitored by restoration of suitable, but not excessive weight, and also by checking cortisol levels during the day. Mineralocorticoid (fludrocortisone) levels should be monitored by checking serum electrolytes, blood pressure (and response to posture), and suppression of plasma renin to normal levels.
Note that in severe hyponatremia you should not normalise the levels of sodium too quickly or you may cause demyelination.
Patients need to be educated on the use of long-term steroids. They should carry a steroid card, or wear a bracelet. Patients should know to increase steroid therapy during times of illness (dose should be doubled). Patients also need to know they should increase their dose of hydrocortisone by 5-10mg a day before strenuous exercise. They should also keep an injectable form of hydrocortisone at home incase they are unable for any reason to take an oral dose, in case of emergencies.
A very poor response to treatment suggests an associated autoimmune disease.
This has two major causes:
- Hypothalamic-pituitary disease leading to inadequate ACTH production
- Long-term steroid therapy, leading to hypothalamic pituitary suppression
The second cause is by far the most common, but the disease only tends to become apparent on withdrawal of glucocorticoid therapy.
The first causes is often a result of pan hypopituitarism
, and as a result patients may need T4 as well as replacement steroids.
Perform the ACTH stimulation test. The likely result is similar to that of Addison’s disease – i.e. there is not a large enough rise in cortisol. To distinguish between primary and secondary hypoadrenalism you should also take an ACTH level. In Addison’s, the level is likely to be very high, whilst in secondary disease the level is likely to be low.
Treatment will be similar to that for Addison’s, or may involve modification of steroid therapies
Management of glucocorticoid therapies
Often, glucocorticoids are used to manage many non-endocrine diseases. In the short term (3 weeks or less) or in small doses (less than 10mg/day prednisolone) then this is usually not an issue. However, problems arise when patients are subjected to long-term therapy. Often patients are on long-term therapy ‘mistakenly’ because the doctor has ‘forgotten’ or they keep taking their pills when they don’t have to.
Essentially, long-term steroid use will mimic endogenous Cushing’s syndrome.
The use of any type of glucocorticoid (inhaled, systemic etc) can affect the HPA (hypothalamic-pituitary-adrenal axis). Generally, the longer the treatment, and the more systemic its affects, the more likely the HPA is to be affected, and the longer it will take to recover when treatment is stopped
You should never withdraw treatment suddenly.
recovery is aided if glucocorticoid treatments are only used in the morning. Using synthetic ACTH has no effect, because it keeps the pituitary suppressed.
You can test endogenous glucocorticoid levels at about 0900h, as long as the patient has not had a dose of glucocorticoid for over 12 hours. This is generally the case anyway as glucocorticoids are not given in the evening because they cause insomnia, and are more likely to suppress the HPA axis if given then. You should keep testing endogenous glucocorticoids as you wean somebody off steroids. Once they become detectable in the blood, perform an ACTH stimulation test.
You should constantly asses whether or not a patient needs to be on steroids due to their serious side effects. Wherever possible consider alternative drugs. Perhaps the most widely acceptable replacement is azathioprine
an immunosuppressant which can be used in rheumatoid arthritis
, as well as Crohn’s and UC. Patients should also be put on some sort of osteoporosis preventative.