ADDISONS DISEASE DEFINATION
Addison’s disease is a rare disorder that affects men and women of all ages. Addison’s disease is also referred to as primary adrenal insufficiency. Adrenal insufficiency develops when your adrenal glands do not produce enough of the hormone cortisol. This can be due to a problem within the adrenals (called Addison’s disease or primary adrenal insufficiency) or due to a problem with the signal the brain sends to the adrenals instructing them to make cortisol (called secondary adrenal insufficiency).
An important distinction for patients is that people with primary adrenal insufficiency (Addison’s disease) usually don’t make enough of the hormone aldosterone; so in addition to taking cortisol replacement, they also need aldosterone replacement. People with secondary adrenal insufficiency are only low on cortisol. Cortisol and aldosterone are just two of the more than 50 hormones the adrenal glands generate. One adrenal gland sits directly above each kidney.
ADDISONS DISEASE CAUSES
Addison’s disease results when your adrenal glands are damaged, producing insufficient amounts of the hormone cortisol and often aldosterone as well. These glands are located just above your kidneys. As part of your endocrine system, they produce hormones that give instructions to virtually every organ and tissue in your body.
Your adrenal glands are composed of two sections. The interior (medulla) produces adrenaline-like hormones. The outer layer (cortex) produces a group of hormones called corticosteroids, which include glucocorticoids, mineralocorticoids and male sex hormones (androgens).
Some of the hormones the cortex produces are essential for life — the glucocorticoids and the mineralocorticoids.
- Glucocorticoids. These hormones, which include cortisol, influence your body’s ability to convert food fuels into energy, play a role in your immune system’s inflammatory response and help your body respond to stress.
- Mineralocorticoids. These hormones, which include aldosterone, maintain your body’s balance of sodium and potassium to keep your blood pressure normal.
- Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, libido and a sense of well-being in both men and women.
ADDISONS DISEASE PATHOPHYSIOLOGY
Addison disease (or Addison’s disease) is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed.
ADDISONS DISEASE SIGNS AND SYMPTOMS
Addison’s disease can be difficult to detect at first, because early symptoms are similar to symptoms of many other health conditions.
Initial symptoms of Addison’s disease can include:
- fatigue (lack of energy or motivation)
- lethargy (abnormal drowsiness or tiredness)
- muscle weakness
- low mood (mild depression) or irritability
- loss of appetite and unintentional weight loss
- the need to urinate frequently
- increased thirst
- craving for salty foods
Dehydration can also be an early sign of Addison’s disease. It’s caused by lack of the hormone aldosterone in your body, which is used to regulate the balance of salt and water.
Further symptoms of Addison’s disease tend to develop gradually over months or years. However, additional stress, caused by another illness or an accident, for example, may cause your symptoms to suddenly get worse.
You may go on to develop:
- low blood pressure when you stand up, which can cause dizziness and fainting
- feeling sick (nausea)
- abdominal, joint or back pain
- muscle cramps
- chronic exhaustion, which may cause depression
- brownish discolouration of the skin, lips and gums (hyperpigmentation), particularly in the creases on your palms, on scars or on pressure points, such as your knuckles or knees
- a reduced libido (lack of interest in sex), particularly in women
Some women may also have irregular periods or miss some periods completely. Children with Addison’s disease may experience pubertylater than usual.
Some people with Addison’s disease also develop low blood sugar (hypoglycaemia). This can cause symptoms such as difficulty concentrating, confusion, anxiety and even unconsciousness (particularly in children).
If you’re experiencing symptoms of Addison’s disease, see your GP so they can diagnose or rule out the condition. These symptoms will usually improve with appropriate treatment.
Read more about diagnosing Addison’s disease and treating Addison’s disease.
If Addison’s disease is left untreated, the levels of hormones produced by the adrenal gland gradually decrease in the body. This causes your symptoms to get progressively worse and eventually lead to a life-threatening situation called an adrenal or Addisonian crisis.
During an adrenal crisis, the symptoms of Addison’s disease appear quickly and severely. This could happen when you’re already experiencing initial symptoms or without any symptoms at all.
Signs of an adrenal crisis include:
- severe dehydration
- pale, cold, clammy skin
- rapid, shallow breathing
- severe vomiting and diarrhoea
- severe muscle weakness
- severe drowsiness or loss of consciousness
An adrenal crisis is a medical emergency. If left untreated, it can be fatal. If you think you or someone you know with Addison’s disease is having an adrenal crisis, dial 999 for an ambulance.
If an adrenal crisis isn’t treated, it can lead to a coma and death. There’s also a risk your brain won’t get enough oxygen if treatment is delayed, which can cause permanent disability.
ADDISONS DISEASE DIAGNOSIS
If your doctor thinks that you may have Addison’s disease, you may undergo some of the following tests:
- Blood test. Measuring your blood levels of sodium, potassium, cortisol and ACTH gives your doctor an initial indication of whether adrenal insufficiency may be causing your signs and symptoms. A blood test can also measure antibodies associated with autoimmune Addison’s disease.
- ACTH stimulation test. This test involves measuring the level of cortisol in your blood before and after an injection of synthetic ACTH. ACTH signals your adrenal glands to produce cortisol. If your adrenal glands are damaged, the ACTH stimulation test shows that your output of cortisol in response to synthetic ACTH is limited or nonexistent.
- Insulin-induced hypoglycemia test. Occasionally, doctors suggest this test if pituitary disease is a possible cause of adrenal insufficiency (secondary adrenal insufficiency). The test involves checking your blood sugar (blood glucose) and cortisol levels at various intervals after an injection of insulin. In healthy people, glucose levels fall and cortisol levels increase.
- Imaging tests. Your doctor may have you undergo a computerized tomography (CT) scan of your abdomen to check the size of your adrenal glands and look for other abnormalities that may give insight to the cause of the adrenal insufficiency. Your doctor may also suggest an MRI scan of your pituitary gland if testing indicates you might have secondary adrenal insufficiency.
ADDISONS DISEASE TREATMENT
In patients in acute adrenal crisis, IV access should be established urgently, and an infusion of isotonic sodium chloride solution should be begun to restore volume deficit and correct hypotension. Some patients may require glucose supplementation. The precipitating cause should be sought and corrected where possible.
- In stress situations, the normal adrenal gland output of cortisol is approximately 250-300 mg in 24 hours. This amount of hydrocortisone in soluble form (hydrocortisone sodium succinate or phosphate) should be given, preferably by continuous infusion.
o Administer 100 mg of hydrocortisone in 100 cc of isotonic sodium chloride solution by continuous IV infusion at a rate of 10-12 cc/h. Infusion may be initiated with 100 mg of hydrocortisone as an IV bolus. Some hospitals mix 300-400 mg in 1 liter saline and infuse over 24 h to avoid needing to renew the infusion every 8-10 hours.
o An alternative method of hydrocortisone administration is 100 mg as an IV bolus every 6-8 hours.
o The infusion method maintains plasma cortisol levels more adequately at steady stress levels, especially in the small percentage of patients who are rapid metabolizers and who may have low plasma cortisol levels between the IV boluses.
- Clinical improvement, especially blood pressure response, should be evident within 4-6 hours of hydrocortisone infusion. Otherwise, the diagnosis of adrenal insufficiency would be questionable.
- After 2-3 days, the stress hydrocortisone dose should be reduced to 100-150 mg, infused over a 24-hour period, irrespective of the patient’s clinical status. This is to avoid stress gastrointestinal bleeding.
- As the patient improves and as the clinical situation allows, the hydrocortisone infusion can be gradually tapered over the next 4-5 days to daily replacement doses of approximately 3 mg/h (72-75 mg over 24 h) and eventually to daily oral replacement doses, when oral intake is possible.
- As long as the patient is receiving 100 mg or more of hydrocortisone in 24 hours, no mineralocorticoid replacement is necessary. The mineralocorticoid activity of hydrocortisone in this dosage is sufficient.
- Thereafter, as the hydrocortisone dose is weaned further, mineralocorticoid replacement should be instituted in doses equivalent to the daily adrenal gland aldosterone output of 0.05-0.20 mg every 24 hours. The usual mineralocorticoid used for this purpose is 9-alpha-fludrocortisone, usually in doses of 0.05-0.10 mg per day or every other day.
- Patients may need to be advised to increase salt intake in hot weather.