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We are pleased to include articles by two sufferers of Addison's Disease.
Click here for details of tests performed for Diagnosis of Addison's Disease.
#1: So Tell Me Please, Just What Is Addison's Disease?.........
The History of Addison's Disease From 1849 to now.
In 1849, Dr. Thomas Addison, published an article entitled:-
Now known universally as Addison's Disease, the condition has also been at various times known as Addison’s melanoderma, Addison’s syndrome, adrenocortical hypofunction, adrenal cortical insufficiency, adrenocortical insufficiency, bronzed disease, bronze skin disease, chronic hypoadrenocorticism, melasma suprarenale, and suprarenal melasma.
Addison's disease is a rare disorder of the hormone, or endocrine, system and is caused by a lack of cortisol and aldosterone production and/or release inthe body. It can affect most if not all mammals, including man and dogs in which it is most commonly observed.
The disease is seen in all age groups and in both sexes. In man the incidence of Addison's disease, which can sometimes be seen to affect females a little more often than males, has been quoted variously from 1 in 24,000 in the UK, to 1 in 100,000 in the USA and Australia.
For the United Kingdom with a population of approximately 60 million, the number of diagnosed cases of Addison's disease is likely to be in the region of 2500.
Outline of Symptoms. In the human body the disease is most often characterised by a group of symptoms which may include inappropriate tanning of the skin, excessive sweating, a need for extra salt which may be as severe as a craving, fatigue, hypotension (low blood pressure), headaches, muscular weakness, aches and/or pain in various parts of the body, and usually weight loss, accompanied by loss of appetite.
Addisonian crisis is regarded as a potentially fatal acute medical emergency and should always be treated as such.
Symptoms may include nausea and/or vomiting, dizziness and confusion often accompanied by low blood pressure, drowsiness eventually progressing to coma, and severe headache akin to migraine. The patient may also complain of extreme weakness, bodily pain and/or tenderness, and of feeling feverish, & may be found to have tachycardia (fast heart rate), bradycardia (slow heart rate), or an irregular heart rate (palpitations). (See also 'Addison's Crisis' page.)
The Effects of Addison's and Steroids on the Human Body.
The disease, which is progressive and destructive, is almost always insidious in onset and although incurable and potentially fatal, is thankfully controllable by replacement therapy. Patients who are well controlled with the appropriate replacement steroid therapy may usually have a normal life expectancy.
Cortisol belongs to a group of steroid hormones called glucocorticoids.
The second vital hormone produced by the adrenal glands, aldosterone, plays a vital role in maintaining the correct sodium and thus potassium levels in the blood. Sodium and potassium have a seesaw relationship with each other in the bloodstream. When the level of aldosterone, which belongs to a group of steroid hormones called mineralcorticoids, drops, the kidneys are unable to retain sodium which is excreted in the urine in excess. The same happens via the sweat glands and in the excretion of most other bodily fluids. This loss of sodium which can be dramatic at times, results in a corresponding increase in blood plasma potassium levels. This produces a diuretic affect resulting in excessive fluid loss, taking even more sodium with it which can result in an even more precipitous increase in potassium. This can be dramatic and can quickly precipitate an Addisonian crisis which is one of the most acute medical emergencies and may be fatal if not treated promptly.
What Causes Addison's Disease?
Whilst both describe the disease and its effects, the two writers approach the condition from different angles. We hope that by including both, the reader will gain an even better insite and understanding than by either article on its own.
By Mike Welch.
"Disease: Chronic Suprarenal Insufficiency, Usually due to Tuberculosis of Suprarenal Capsule." (London Medical Gazette, 1849, 43: 517-518.)
It is likely that both of these figures understate the true incidence of Addison's due to the insidious nature of the disease.
Symptoms of Addison's disease often do not manifest until 90 percent of the adrenal glands, which are located immediately above each kidney and are responsible for the production and release of cortisol and aldosterone, have been destroyed.
Perhaps the most important function of cortisol is to assist the body to respond to stress. However it has a number of other vital functions which include helping to maintain blood pressure, helps the body maintain the rate at which proteins, carbohydrates, and fats, are metabolised, and assists the body in balancing the effects of insulin obtaining energy from sugar.
The normal range for plasma potassium is 3.5 to 5.5 mmol per litre, (the equivalent levels for sodium are 135 to 155 mmol per litre) and levels for potassium in excess of 6.5 mmol per litre are increasingly liable to be fatal even with prompt medical intervention.
The causes of Addison's disease are many and are classified as either primary or secondary. Until the middle of the 20th century, the most common cause of primary Addison's was renal tuberculosis which spread to the adrenal glands. In the 1950s and '60s the incidence of tuberculosis waned with the introduction of specific
antibiotics and chemotherapeutics such as Streptomycin, INAH, and PAS to which Mycobacterium tuberculosis was sensitive. These drugs were prescribed two at a time to reduce the strong chances that the tubercle bacilli would develop immunity or resistance against a single drug.
Since that time the cause of some 70% of the total cases of primary Addison's disease has been autoimmune in nature.
A suggested reason for this is a genetic predisposition, with the relevant gene being 'switched on' by a viral agent. Herpes zoster, the causative virus of Chicken Pox and Shingles (the latter known as Zona in some countries) is the most likely candidate. The Epstein Barr virus (aka EBV), causative agent of Glandular Fever (Infectious Mononucleosis) has also been suggested as being capable of switching on latent genes. Several articles have been published recently by research clinicians providing evidence that certain HLA groupings (Human Leucocyte Antigens, the white blood cell equivalents of the well known red cell blood groups)
However, other causes of Addison's Disease can be seen in the remaining 30%. These may include adrenal haemorrhage, surgical removal of the adrenals, tumours of the adrenal glands, and with a reduced uptake of BCG immunisation from the late '70's onwards, even occasional cases caused by tuberculosis again.
Secondary disease is attributed to hypopituitarism, where disease of the pituitary gland prevents release of ACTH (AdrenoCorticoTropic Hormone), the "messenger protein" which instructs the adrenal glands what quantity of cortisol to release.
Control of the level of cortisol in the bloodstream is maintained by a feedback mechanism operated through the pituitary gland and hypothalamus in the brain. In the normal patient a satisfactory level of cortisol in the blood is registered by the pituitary gland which lowers its secretion of ACTH in response to a lower secretion of cortisol releasing hormone (CRH) from the hypothalamus in response to its detection of a normal level of cortisol in the blood plasma, thus preserving a balance.
Diagnosing Addison's Disease.
The diagnosis of Addison's disease is dependent on a thorough examination of the patient's case history and clinical state, together with a series of biochemical tests and and may be accompanied by MRI scans (Magnetic Resonance Imaging) of the pituitary gland and the adrenal glands. The range of laboratory tests commonly used for the diagnosis of Addison's disease may include a random cortisol level, a SynActhEn (Synthetic ACTH Enhancement test), an Insulin tolerance stress test (or a Glucagon test as an alternative test if the insulin test is contra-indicated)
Often a blood urea & electrolyes (U's&E's) will be requested at the same time to check on the balance between sodium and potassium levels. Because of the high incidence of co-existing Hashimoto's autoimmune thyroiditis in patients with Addison's, a thyroid function test (TFT), and possibly a full autoimmune screen, will often be performed simultaneously. Other tests which the examining physician may ask for include the sex hormones (FSH, LH, testosterone, and prolactin) as the adrenal glands are also involved in the control of these levels.
Click here for details of tests performed for Diagnosis of Addison's Disease.
Treatment.
The treatment of Addison's disease, primary or secondary, is almost invariably by replacement therapy. Glucocorticoids in the form of the steroids Hydrocortisone, Prednisilone, or Dexamethasone, are the drugs of choice usually prescribed by physicians to replace the missing cortisol, whilst the mineralcorticoid Fludrocortisone (Cortef) can be used to replace the missing steroid aldosterone.
If the patient has coincidental hypertension (high blood pressure) then instead of taking Fludrocortisone the patient may be instructed by the physician to maintain a normal level of their plasma sodium, which a low aldosterone level may cause, with additional common salt, together with adequate water to alleviate the ever present risk of dehydration in the Addison's patient.
If not offered, the patient should request from their medical practitioner or endocrinologist a prescription for an emergency injection kit, which will usually be one or two vials of 100mg of freeze dried hydrocortisone (e.g. Solu Cortef) together with accompanying vial(s) of sterile water to reconstitute the hydrocortisone, plus sufficient sterile needles, syringes, and Mediswabs, and instructions how to prepare and give him- or herself the emergency injection, (and then seek emergency medical assistance as a matter of urgency). (See also 'Addison's Crisis' page.)
If two vials of hydrocortisone have been supplied, the prescribing physician will often have instructed the patient to repeat the injection with the second dose after 10-15 minutes if there has not been any significant improvement.
All patients on long term steroid therapy should carry a 'Steroid card' with them which details their disease and treatment regime. A Medicalert (or similar) bracelet or necklace with full details of their medical conditions and treatment, etc. is also strongly recommended to be worn at all times.
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#2: WHAT IS ADDISON’S DISEASE?
(With grateful thanks to Alison Hirst) As we go through life enjoying a good functioning body, we quite often forget that each little part of the human system is built for a specific reason. Of course, we know that we would be in severe trouble if our heart, lungs, kidneys or other commonly known organs were not doing their jobs efficiently. These organs are quite well known about by everyone, but there are also numerous other 'little workers' that people are not so familiar with, and yet they are very essential.
The adrenal glands are representative of these. They are small, but essential for life.
In contrast, the outer portion of the adrenal gland, the cortex, is more critical and this is the part that is affected by Addison’s Disease.
This group is so named because of their sugar regulating properties. They are also important during growth and development, suppress the immune response and provide the response to stress.
This group are so named because of their salt regulating properties.
The sex hormones produced by the adrenal cortex are collectively known as:
The amount of cortisol produced by the adrenal glands is very precisely balanced, and is regulated by the brain’s hypothalamus and the pituitary gland.
PRIMARY ADRENAL INSUFFICIENCY.
The most common cause of Addison’s Disease is something called auto-immune adrenal destruction. This accounts for about 70% of cases in the UK. It results from the body’s immune system attacking its own tissue, in this case the tissue forming the cortex of the adrenal glands. This causes the adrenal tissue to shrink and fail to produce the essential hormones as described previously.
Adrenal insufficiency occurs when at least 90% of the adrenal cortex has been destroyed. As a result, often both glucocorticosteroid and mineralocorticosteroid hormones are lacking. Sometimes only the adrenal gland is affected, as in idiopathic adrenal insufficiency; sometimes other glands also are affected, as in the polyendocrine deficiency syndrome.
The polyendocrine deficiency syndrome is classified into two separate forms, referred to as type I and type II.
SECONDARY ADRENAL INSUFFICIENCY.
Secondary adrenal insufficiency is caused by a lack of ACTH, which causes a drop in the adrenal glands’ production of cortisol, but not aldosterone.
Another cause of secondary adrenal insufficiency is the surgical removal of benign or non-cancerous, ACTH-producing tumours of the pituitary gland (Cushing’s Disease).
THE NATURAL DAILY CYCLE OF ADRENAL HORMONE PRODUCTION.
In a person with healthy adrenal glands, levels of the hormone cortisol start to rise at about 4am and by the time you wake up, they are at their maximum.
FUNCTIONS OF MEDICATION.
The goal of treatment is to replace the missing function of the adrenal glands by producing “normal” levels of corticosteroid hormones. However, it should be noted that synthetic replacement will never match the functions that occur naturally in the body. At best, we can only hope to restore function to as near 'normal' as possible. Specific treatment for Addison’s Disease will be determined by your GP or Endocrinologist, usually based on your laboratory test results; overall health and medical history; the extent of the disease and your tolerance for specific medications, procedures and/or therapies.
Since Addison’s Disease is potentially life threatening, treatment begins with the administration of corticosteroids, normally Hydrocortisone, either orally or intra-venously, depending on the individual’s condition. Treatment may also include Fludrocortisone (Florinef), which is a drug that helps restore the body’s levels of sodium and potassium.
Addison’s Disease is a chronic condition, therefore daily replacement medication can never be stopped. It is important for Addisonians to always carry a medical identification or steroid card that states the type of medication and the proper dose needed in case of an emergency. It is also important that you request an 'emergency injection kit' from either your GP or Endocrinologist.
IS YOUR MEDICATION RIGHT FOR YOU?.
The treatment for Addison’s Disease is to replace the hormones that the adrenal glands are not making. Previously, many Endocrinologists advocated a single daily dose of Hydrocortisone (or whatever the preferred replacement steroid may be) for both men and women, no matter what their size or weight was. Nowadays, the majority of Endocrinologists and Addisonians believe this to be inappropriate.
Normally, women do not need as high a dose as men, but obviously size and weight are contributing factors in this. As a guideline, a good 'starting' dose of Hydrocortisone is 20mg daily. From this starting dose, you can then gauge how you feel. If you are still showing signs and symptoms of Addison’s Disease, then you can increase your daily dose in increments of 2.5mg until an improvement in your general well-being is felt. Once you have reached your 'maintenance' dose, your Endocrinologist will normally arrange a 'Day Curve Analysis' or '24 hour Cortisol Profile' to check if your dose is right for you (see Monitoring Hormone Levels Through Blood Tests).
Generally, you should be looking to take the smallest dose possible, without showing any signs and symptoms. It is not considered harmful to take more steroid than you actually need for a short period of time. Therefore, if you feel that you are developing an illness, then you can quite safely increase your normal daily dose for the period of that illness. You should then gradually taper your dose until you return to your normal 'maintenance' dose.
Taking too high a dose of Hydrocortisone over a long period of time can cause serious side effects. These can include osteoporosis, weight gain, insomnia, mood swings, depression, fluid retention, thinning skin and 'moon' face.
OTHER ADRENAL HORMONES THAT CAN BE REPLACED.
As previously discussed, the adrenal glands produce three groups of hormones- glucocorticosteroids, mineralocorticosteroids, and sex hormones collectively known as androgens. While it is essential to replace glucocorticosteroids and any deficient mineralocorticosteroids, not all doctors believe it is important to replace androgens. The most common replacement androgen, world-wide, is Dehydroxyepiandosterone (DHEA).
DHEA is thought to improve energy levels, give protection against osteoporosis, improve libido, give relief from dry skin and encourage lean muscle.
ALTERNATIVE THERAPIES.
Liquorice root has a similar stimulating effect to aldosterone. Some Addisonians experience cravings for liquorice, but by eating real liquorice root in addition to Fludrocortisone, you risk over-medicating yourself. It is not recommended to use liquorice root instead of Fludrocortisone because it is not possible to accurately gauge the potency of it. You should check the ingredients on items such as liquorice sweets and cough bottles for their content before consuming, as some do contain liquorice root. However, most liquorice-based sweets only contain a liquorice flavouring and are, therefore, quite safe to eat.
There are no known herbal supplements that mimic the effects of either human or synthetic cortisol. Up until the 1950’s, there was no steroid medication available and Addison’s Disease was, therefore, fatal. Any Addisonian who tries to use herbal replacements or supplements in place of their prescribed medication risks a similar fate. However, benefits can be found in some “complementary” therapies (used in addition to your prescribed medication), such as physiotherapy, massage, yoga and relaxation techniques. Joint and muscle pain can be eased with physiotherapy and massage, and stress and fatigue can be alleviated through yoga and relaxation techniques.
MONITORING HORMONE LEVELS THROUGH BLOOD TESTS.
Once you have been diagnosed and your medication regime commenced, you should be followed up regularly and lifelong by your Endocrinologist and GP.
There is no single blood or urine test that is perfect by itself. The routine bloods usually checked are as follows:
The most comprehensive of the blood tests is the Day Curve Analysis or 24 hour Cortisol Profile. This requires to be carried out as an in-patient of the Endocrinology Department of your hospital. If you have not had this test done, then you should request that your GP refer you to a suitable hospital to have it carried out.
If you are unable to travel to hospital to have this test carried out, then it is possible for your GP to carry out a 'shortened' version, which combines a 24 hour urine collection and mid-morning and mid-afternoon blood samples to record cortisol and ACTH levels.
Click here for details of tests performed for Diagnosis of Addison's Disease.
Copyright © 2004-2008 Mike Welch
There are normally two adrenal glands, which are about the size of a walnut and are positioned just above the kidneys, at the top of the abdomen, near the back. These adrenal glands are really two endocrine (ductless or hormone producing) glands in one. The inner or middle of each gland (called the medulla) produces the hormone 'epinephrine' (commonly known as 'adrenaline') which is produced at times of stress and helps the body respond to 'fight or flight' situations by raising the pulse rate, adjusting blood flow and raising blood sugar. However, the adrenal medulla is not essential for survival, its absence does not cause disease and the lack of epinephrine can be adequately compensated for by the rest of the nervous system.
In Addison’s Disease, the cortex atrophies (shrivels up), often to almost nothing, thus reducing the amount of hormones produced. The hormones produced are called adrenocorticosteroids (commonly known as steroids). There are over fifty different steroids, but these can be divided into three groups:
The most important member of this group is:
This is a type of steroid essential for the general running of the body’s metabolism, especially at times of stress or during illness. It mobilises nutrients, modifies the body’s response to inflammation, stimulates the liver to raise the blood sugar and also helps to control the amount of water in the body.
The most important of this group is:
These hormones are produced in small quantities and are present in both sexes. In the female, this is essentially the only source for such hormones and these have a role in sexual libido and also in the distribution of the female body hair. In females, oestrogens are also produced by the adrenal cortex.
In pre-menopausal women, adrenal oestrogens account for only 4% of the oestrogen supply, but in post-menopausal women, the adrenal cortex is the major source of oestrogens. Oestrogens may also play a part in the distribution of female body hair since they can be converted to steroids with androgen activity in hair follicles.
The hypothalamus sends a “message” to the pituitary gland. The pituitary gland responds by secreting other hormones that regulate growth, thyroid and adrenal function, and sex hormones, such as oestrogen and testosterone. One of the pituitary’s main functions is to secrete Adrenocorticotrophic Hormone (ACTH), a hormone that stimulates the adrenal glands. When the adrenals receive the pituitary’s signal in the form of ACTH, they respond by producing cortisol. Completing the cycle, cortisol then signals the pituitary to lower the secretion of ACTH.
In the past, tuberculosis was the main cause of Addison’s Disease. Less common causes of primary adrenal insufficiency are chronic infections (usually fungal); cancer cells spreading from other parts of the body to the adrenal glands; amyloidosis; surgical removal of the adrenal glands; haemorrhage (bleeding) into the adrenal glands as a result of septicaemia, such as that associated with meningitis, and rare inherited disorders.
Polyendocrine deficiency syndrome could be inherited because frequently more than one family member has one or more endocrine deficiency.
A temporary form of secondary adrenal insufficiency may occur when a person who has been receiving a glucocorticoid hormone, such as prednisolone, for a long time, abruptly stops or interrupts taking the medication.
Glucocorticoid hormones, which are often used to treat inflammatory illnesses, like rheumatoid arthritis, asthma or ulcerative colitis, block the release of both corticotrophin-releasing hormone (CRH) and ACTH. Normally, CRH instructs the pituitary gland to release ACTH. If CRH levels drop, the pituitary is not stimulated to release ACTH, and the adrenals then fail to secrete sufficient levels of cortisol.
Throughout the day, these levels gradually taper off, until shortly after you go to sleep, when hormone levels will be at their lowest. The body’s natural production of aldosterone follows a similar pattern to that of cortisol, with highest levels occurring at around the time you wake up. Therefore, it is advisable that you take your Fludrocortisone at the same time as your morning medication.
Cortisol is normally replaced orally with Hydrocortisone tablets, a synthetic glucocorticoid, taken twice or three times a day. If aldosterone is also deficient, then it is replaced with oral doses of a mineralocorticoid, called Fludrocortisone (Florinef), which is taken once a day, usually first thing in the morning. The doses of each of these medications are adjusted for the individual’s size, weight and any co-existing medical conditions.
Sometimes, merely changing the divided amounts and timings of medication is all that is required to feel the benefit (see Timing your Medication).
Although this drug is not licensed in the UK, there have been clinical trials carried out and the results have shown that there are some benefits for most Addisonians. However, side effects were apparent, with some testers developing acne, greasy hair and skin and experiencing some weight gain. DHEA is available to buy over the internet, but quantity and quality cannot be assured when obtained this way. It is, therefore, advisable to discuss it with your GP or Endocrinologist should you be considering DHEA. They can then check your blood levels and give advice on where to get it. Some GP’s and Endocrinologists will seek permission from their Local Prescribing Authority to enable them to prescribe DHEA for Addisonians. The prescription can be taken to your local Pharmacist, who can order it through any company that imports drugs and medications. This is possibly the safest way to try DHEA as it will be under medical supervision.
Addison’s Disease causes the blood potassium to be high and blood sodium to be low due to the lack of aldosterone, therefore proper maintenance treatment requires these regular visits for examinations, laboratory tests and discussions about your symptoms. Certain blood tests, including sodium, potassium, blood counts and plasma renin are very useful in monitoring the response to adjustments in dosage.
This test starts early in the morning, before you take your first dose of medication and involves having blood tests taken every hour, on the hour for 24 hours to monitor the levels of cortisol in the blood. The blood results throughout the day can then be compared to the 'ideal' for that of healthy adrenal glands. It is the most accurate way of establishing if you are on the correct dose of Hydrocortisone and allows dose and timings to be adjusted accordingly.
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The Genealogist - UK census, BMDs and more online
family tree research since November 2006. Excellent source of family tree data. Has taken me many years ahead/generations back in time. I can personally recommend it as the best value website for all genealogists! MLW. (PS: You may even find a branch where members died early from Addison's)." |