- Nausea, vomiting and acute abdominal pain.
- Weight loss, usually rapid.
- Dizziness and fainting especially on standing up,
(due to a fall in blood pressure).
- Generalised weakness and fatigue.
- Symptoms of low blood sugar (Hypoglycaemia) may also occur,
which include sweating and palpitations.
The most important thing to remember is to try to prevent acute adrenal insufficiency by not forgetting to take the corticosteroids and to have injectable corticosteroids in case of vomiting.
Once acute adrenal insufficiency occurs, it is essential that the patient receive injectable corticosteroids which can be administered by relatives in the first instance but the doctor should also be consulted as soon as possible. If the patient is vomiting or dehydrated, admission to hospital and administration of intravenous fluids is essential.
I must say, to a doctor the treatment of Addison’s disease is rarely simple. You open up the big medical text books and there are 2000 pages of medical. There will be a page or so on Addison’s disease and half a page on the treatment. You take Cortisone Acetate 25mgs morning and 12.5mgs in the afternoon or evening. You take a bit of Florinef twice a day. If you get sick you take a bit more, and that’s it! That is basically what medical students are taught. Now you only have to treat one person (with Addison’s) to find that very simple description of treatment is hopeless and does not work very well!The things you need to be aware of are when you wake up in the morning a normal person without Addison’s disease, has a high level of Cortisol in their blood and that stays up in the morning and trickles down to a lower level in the afternoon and evening. The first thing we should try and do with treatment is to mimic that higher level in the morning and lower levels in the afternoon and evening that the body normally produces provided you are sleeping well at night. My recommendation to patients is they take their morning dose, whether it be cortisone, hydrocortisone, cortisone acetate, whatever, three and a half seconds after they open their eyes in the morning! They should have their tablets on the bedside table with a glass of water and when they open their eyes the first thing they should do is swallow their medication, because a person without Addison’s disease would already have a high level of cortisone at that time. It is going to take half to three-quarters of an hour for even the quick acting ones (tablets) to get up and work, and during that time you will feel tired and washed out. So the timing of the morning tablet is very important if you want to have any energy.The next thing you should know is if you take your steroids with or after food, the mixing of the steroids with food is going to slow down it’s absorption and it is going to take longer to work.
Someone with normal kidneys and normal adrenal glands adjusts blood volume / blood pressure, very quickly and very easily. You can’t. You have to rely on certain medication so you are not changing it (blood volume) as quickly. Sure you have all the other systems but you are lacking some of the control systems. One of the things alcohol does is dehydrate you. It dehydrates you because you end up passing a lot more water because of the alcohol. So one of the problems you would have which would exacerbate, make things worse, is that your blood volume would be way down. So that one of the more important things to do is to drink a lot of fluid. Replace your water and salt as well as the cortisone.
I have not really seen any research or any investigation on alcohol and the problem you mentioned but on first principles, I would argue very strongly, one of the first things to do in Addison’s disease is keep your blood volume up. You should alway be hydrating in anticipation. I think you are probably talking about dehydration the next morning being a major problem.
Yes. The treatment of Addison’s disease should result in achieving the same blood cortisone levels from tablet therapy as would have been achieved with normal adrenal gland secretion. The small amount of cortisone in the breast milk should therefore be little different from the normal situation.
Are there any special things I should be aware of concerning Addison’s disease and pregnancy?
Yes. Cortisone circulates in the blood in two forms, the largest amount being stuck on to a carrier protein with a small amount being free in the blood, this latter part being the active component of cortisone. The cortisone stuck on the carrier protein is inactive.In early pregnancy, as a result of the stimulatory effects of the very high levels of oestrogen or female hormone in the liver, the liver produces larger quantities of the cortisone carrier protein which then "mops up" quite a bit of the free or active cortisone.
For the first two or three months of pregnancy you may need to take some additional cortisone to saturate the newly formed cortisone binding protein so that the levels of cortisones in the blood do not fall.A similar thing happens to thyroid hormones in pregnancy in women who are on thyroxine, the dose of thyroxine usually needing to be increased the first two or three months of pregnancy because of the increase in levels of thyroxine-carrier protein.
I have been diagnosed with Addison's disease for 9 months and have started to loose hair from my head by the handful! Is it going to grow back? Other members have said they have lost body hair. What would cause this hair loss?
The correct treatment for Addison's disease should not result in any hair loss from the head. As Addison's disease is an autoimmune disease, it may be associated with other autoimmune diseases including thyroid disfunction which can cause hair loss and autoimmune alopecia both of which may occur more commonly in people with Addison's Disease. In well treated Addison's disease there should be no decrease in body hair in male or females. However if excessive glucocorticoids are taken by males, testosterone levels may reduce with resultant reduction in body hair.
Some tests I have had require me to fast for 12 hours, after which I feel unwell. Is it OK to fast if you have Addison's disease? Should I take my tablets when I am meant to be fasting?
Patients with Addison's disease who are unable to take their medication must have injectable steroids instead of the oral medication at the time the oral medication is normally given. The patient should check with their doctor as to whether they are able to take oral medication with a sip of water before the procedure or will require injectable hydrocortisone.
I have had Addison's disease for a few years now and I seem to have problems with healing. Why would this occur?
Patients with adrenal insufficiency should not have any problem with wound healing however if the steroid replacement dose is excessive then this may be a factor in interfering with wound healing.
My work involves working at times in very hot conditions. I have had 2 Addison’s Crisis’s in the last month both brought on by dehydration. Why can’t I stop a crisis when it starts even if I take some extra Prednisone (1mgs tablets), fluid and salt?
An Addisonian crisis occurs because of a deficiency of both hydrocortisone and aldosterone, leading to a combination of salt and water loss form the body and low blood pressure.Prednisone tablets have two disadvantages in an Addisonian crisis. Firstly, Prednisone needs to be converted by the liver to Prednisolone. This takes some time and it is thought that the conversion of Prednisone to Prednisolone may take longer if the body is dehydrated and hence, if blood flow through the liver is reduced. Most endocrinologists advise the use of Prednisolone tablets rather than Prednisone which must be converted to Prednisolone before it becomes active.Most endocrinologists advise a doubling of the steroid at the time of crisis. Taking additional supplements of 1mg could probably be too little, working too slowly.
It may also be helpful during hot weather to increase the dose of Florinef because the normal adrenal would secrete more Aldosterone in hot weather when dehydration is likely to occur.
Finally, during an Addisonian crisis, the best approach is to have an injection of at least 100mgs but, preferably 250mgs of hydrocortisone.
Is it necessary to increase my Cortisone during psychological and emotional stress the same as I should with physical stress?
Psychological or emotional stress can precipitate an Addison’s crisis with the same effectiveness as physical stress or illness, and most endocrinologists recommend the same increase in cortisone or steroid dose during psychological stress and emotional upsets as they do during physical stress or physical illness.
I have had a lot of problems with my teeth and mouth. I always seem to get infections that take along time to heal after any dental work and constantly have problems with mouth ulcers. Other members have mentioned they also have problems clearing up mouth infections and ulcers. To what extent does Addison’s disease effect dental problems?
Addison’s disease does not appear to predispose to dental problems or mouth ulcers, fairly common amongst the general population in any case.
Are Addisonians who still have dark pigmentation less likely to suffer from skin cancer?
Dark skin is a result of the number of pigment containing cells. called melanocytes, that occur per unit area of skin. When these cells are stimulated by ACTH, the pigment granules within the melanocytes disperse throughout the cells and the skin appears darker. Ultraviolet light (eg. sunlight) also causes this same pigment granule dispersal (a 'tan' occurs). These pigment granules absorb ultraviolet light. Ultraviolet light can cause disruption of DNA molecules which make up our genes. Any DNA disruption can cause mutations in genes and some mutations can result in cancer. Melanocyte pigment granules protect our DNA Rom ultraviolet light and, hence, make it less likely that sun exposure will lead to damage to our genes and resultant skin cancer. Addisonians who have dark pigmentation are therefore less likely to suffer skin cancer from sunlight exposure.
Why is my ACTH still elevated although my doctor says I am taking adequate steroid replacement? I am taking 25mgs Cortisone Acetate in the morning and 12.5mgs at night, 0.lmgs of Florinef per day and 150mgs of Thyroxine per day.
ACTH secretion is normally regulated by a complex feedback of cortisol on the pituitary ACTH-secreting cells and, more importantly, on cells in the hypothalamic area of the brain which stimulate ACTH release. There are about 15 episodes of cortisol release per day in a person with an unimpaired pituitary-adrenal system. It is impractical to administer this number of doses of cortisol per day to an Addisonian patient. Therefore, ACTH cannot be as precisely controlled in Addisonians, and should not be expected to fall into the reference range for non-Addisonians. Your dose of 37.5mg per day of cortisone is certainly at the upper end of the dosage range for basal glucocorticoid (cortisone) replacement. Other clinical criteria, such as blood pressure level, are used by doctors to gauge adequacy of steroid replacements, rather that the ACTH level.
When experiencing difficulty during hot weather, should Addisonians be increasing the Florinef Cortisone?
Hot weather results in water and salt loss due to sweating. Florinef is a long-acting medication that simulates the salt-, or sodium-, retaining activity of the hormone aldosterone normally produced in the adrenal gland. Florinef and aldosterone act to cause reabsorption of salt in the kidneys before the salt escapes into the urine. When we lose salt by sweating, the kidneys can reabsorb salt more efficiently as long as there is enough aldosterone (or Florinef) around to stimulate the salt retention. If an Addisonian is losing too much salt by sweating and/or by salt loss in the urine, then eating more salt or taking more Florinef should help to achieve balance again. Your doctor should be consulted if you are experiencing difficulty in the hot weather. The doctor will examine you for signs of dehydration and other possible reasons why you might be experiencing difficulty (eg. thyrotoxicosis or heart trouble) and advise you about appropriate measures to alleviate your distress, which may not be due to salt and water imbalance.
What are the effects of taking Prednisone or other cortisones on the bone marrow and bone density? I have been told there is no effect as dosage is replacement only. Do I have a valid concern?
Prednisolone/Prednisone, Hydrocortisone and other "glucocorticoids" lead to loss of bone density, if given in doses greater than replacement. The problem is there is no simple way of precisely adjusting dose, to be sure if it is not slightly excessive for certain individuals. A risk of osteoporosis has been reported in patients with treated Addison’s disease, and bone densitometry is being suggested as a part of the follow-up of Addison’s patients by some physicians. Loss of adrenal androgen production, particularly in women, as well as other factors, may play a role in lowering bone density in some Addison’s patients.
Through three generations of my family we have: diabetes, Cushings disease, secondary & primary Addison’s disease. Although I am told they are not hereditary, I find it hard to believe that it is just coincidence that these illnesses can happen in one family without them being connected in some way. Do we carry some type of gene that is causing these problems?
Addison’s disease (adrenal failure), is often caused by an auto-immune process. In other words, the cause often appears to be an immune attack on adrenal tissue, particularly the adrenal cortex – where cortisol, aldosterone and androgens are made. Evidence for this includes the microscopy of the adrenal glands and the presence of antibodies in patients’ blood, to adrenal tissue. Although the Addison’s disease may be an isolated phenomenon, damage to other organs, through an auto-immune process may occur. This leads to associated diseases such as Auto-Immune Thyroid disease, Type 1 Diabetes Mellitus and Pernicious Anaemia. The coexistence of these and other disorders is known as Auto-Immune Polyglandular Syndrome Type II. Addison’s disease may also rarely occur as part of Auto-Immune Polyglandular Syndrome Type I, where it is associated with mucocutaneous candidiasis ("thrush"), and loss of Parathyroid function, leading to low calcium levels. Addison’s disease, whether it occurs alone, or in association with other auto-immune related diseases may run in families. Familial diseases are likely to have a genetic cause. In the more common forms of familial Addison’s however, families vary in inheritance patterns, suggesting different genes may be responsible in different families. A particular gene mutation has been pinpointed in some families as Type I Auto-Immune Polyglandular Syndrome.Click here to read an article on this topic
What blood tests would you advise an Addison’s sufferer to have as a regular routine?
No simple blood test can assess the adequacy of glucocorticoid replacement.
Glucocorticoid doses are adjusted, based on knowledge of suitable doses and clinical follow up. Plasma Renin activity provides a measure of adequacy of the dose of fludrocortisone replacement. Plasma electrolytes eg: sodium/potassium, may be abnormal, but generally, only if replacement hormone doses are well outside of the acceptable range. Blood pressure and body weight should be performed routinely, as well as an assessment of symptoms and signs, relating to under-or over-dosage of hormones.
Most doctors recommend taking the first steroid dose as soon as possible after waking in the morning. When should it be taken if you wake up and stay awake during the night (eg due to illness, etc)?
Cortisol levels in blood normally peak at time of waking, each day. Recent detailed investigations have shown that cortisol levels arc, close to their highest level for the day, shortly before waking. They will rise further in the following first 20 - 30 mins, possibly as a response to walking.Ideally, we would like steroid preparations to produce peak blood levels, that are similar to the body's circadian rhythm. This is not possible with current steroid preparations, particularly when one takes in to account that cortisol production is pulsatile, (i.e. it has peaks and troughs throughout the day. These are superimposed on a general trend for cortisol production to be higher in the early morning, and lower in the evening.).In general, satisfactory responses are obtained by delivering short - acting cortisol preparations, with the largest dose given in the morning. Some people require a lower dose in the early afternoon, (e.g. from 2.00 p.m. onwards.). Short-acting preparations include: Hydrocortisone, and Cortisone Acetate. Longer-acting preparations can be readily given on a once a day basis.
Practices vary, such that most people give longer-acting drugs (e.g. Prednisilone, and Dexamethasone), first thing in the morning. Some authorities advocate these drugs for evening doses, so that they more closely mimic circadian steroid levels. Late night steroid dosing can interfere with sleep.
In answer to the question, I would suggest taking the majority, or all of a short-acting steroid, at the " usual" time of waking. If using a longer-acting preparation, try taking all of the dose at the "usual" time of waking.
I take 8mg Prednisone in the AM and 3mg in the PM. Often if I’m unwell or extra tired, when I take the first dose, I get very sleepy, for 2-3 hours before I can get up and going. Any ‘kick-in’ feeling is very mild. Is there are reason for this?
11 mg Prednisone daily, is well above the recognised replacement dose, for glucocorticoids. Prednisone is quite long acting, and it is possible to take the whole dose in the a.m. There may, however, be an unusual reason for taking 11mg Prednisone, in your case. So, be guided by your doctor.It must be noted, that excessive doses of Prednisone may cause weight gain, (particularly in the abdominal area), relative muscle weakness, thin skin, bruising, and bone density loss, (with a concurrent predisposition to fracture).In specific response to your question, the drowsiness, experienced for several hours after taking the Prednisone dose, could be a result of: individual differences in response to glucocorticoids, (with respect to mood, behaviour and sleep patterns); and glucorticoids have affects on many brain functions, (one of which is to sharpen cognition, as part of a generalised stress response.). Synthetic glucocorticoids responses vary individually, with regard to mood, behaviour and sleep. Drowsiness, in relation to steroid dosing, is not uncommon.
You may wish to explore with your doctor, the taking of Prednisone, at night, before bed. In addition, you may wish to discuss your current Prednisone dose, as approx. 5 mg daily is sufficient for many individuals. An alternative steroid, e.g. Hydrocortisone, or Cortisone Acetate, may suit you better.
Does no medication for one week cause permanent injury?
If you have adrenal insufficiency and take no replacement medications for one week, I would expect you to feel quite tired and perhaps light headed, but once replacement is restored, there should be no lasting consequences.
by Dr Paul Margulies M.D., FACE, FACP Medical Advisor to the National Adrenal Diseases Foundation (USA)
Can I take Florinef on an as-needed basis? I'd like to take it on extremely hot and dry days, but not on others. Can I do this? I have a strong family history of hypertension, should I worry about Florinef affecting this?
Most addisonian patients need at least a small dose of Florinef daily in order to retain sodium and water adequately for blood pressure maintenance. It is a slow-moving drug, so it usually should not be used for acute situations. I would recommend using added salt in addition to the usual Florinef dose on hot or especially active days when you may sweat more.
by Dr Paul Margulies M.D., FACE, FACP Medical Advisor to the National Adrenal Diseases Foundation (USA)
Many Addisonians cope with other health problems. Is it reasonable that some might require alterations to their steroid dose, to cope with the draining effects of ongoing symptoms like: chronic pain, asthma, severe arthritis, Lupus, Sjogren's, heart conditions, etc.) ?
You mentioned a number of conditions, some of which are inflammatory but may co-exist with Addison's. Some of the conditions, such as asthma and arthritis, are often treated with glucocorticoid. In these situations the dose is much higher than the replacement doses used for Addition's Disease. It is necessary to distinguish between replacement doses of steroid, e.g., hydrocortisone 20-30mg and anti-inflammatory doses which may be many times higher. Otherwise, illnesses which may impair glucocorticoid absorption may necessitate a higher dose, for example, gastrointestinal disorders. For chronic illnesses of other types increased glucocorticoid doses are generally not needed, except during intervening acute illness such as infection.
Does Florinef have adverse effects on eye pressure? Is there a way to detect this, if it is so?
I am unaware of any affect of flurin F (fludrocortisone) on intraoccular (inside the eye) pressure. Elevated intraoccular pressure, or glaucoma, is readily detected with a device known as a tonometer, or automated devices available at optometrists or opthalmologists.
Some of our Addisonians report often having sharp pains over their lower back ( near the kidneys). What are likely reasons for such pain, apart from spinal problems?
Lower back pain in a person with Addison's Disease is likely to have a similar basis to that in people without Addison's, such as disc degeneration and arthritis, perhaps exaccerbated by posture and lack of exercise. One must bear in mind that there is an increased prevalence of osteoporosis in Addison's Disease which may require specific treatment. In this case, specific treatment may be needed and the cause of pain may be a fracture. I am not aware of any other unusual predisposition to low back pain in Addison's Disease, although it would be difficult to be sure of this as most people experience back pain from time to time the general community.
Is there any research being done which looks into charting individual requirements for cortisol for "normal " people, as well as Addisonians, to create a data bank of information, to aid future treatment regimes?
Recent research has estimated that the usual production rates of cortisol is somewhat lower than previously estimated. This knowledge, in conjunction with evidence of an increased prevalence of osteoporosis in Addison's Disease patients has led many physicians to recommend lower glucocorticoid doses. This move to lower glucocorticoid doses mirrors similar, earlier trends towards lower doses of hormone replacement in the thyroid field. I am not aware of any research focussing on estimating individualised hydrocortisone dose to specific individuals.
Do you advise An Addison's patient to have blood test on a regular basis - say every 6 months? What is the significance of these tests, which ones should be done regularly and how important is the monitoring of lipid levels?
Patients with Addison's Disease should have medical follow-up 6 to 12 monthly. There are a number of issues that need to be assessed at each visit. These issues can be discussion generally but often need to be individualised. There is no blood test that can tell us whether a particular glucocorticoid dose is a little too high or a little too low for a particular patient. Glucocorticoid dose is based on clinical assessment, for example, low blood pressure or blood pressure that drops excessively with standing or the presence of excessive fatigue suggests inadequate glucocorticoid dose. Excessuve glucocorticoid dose on the other hand, may be manifest by weight gain and/or a redistribution of fat away from the arms and legs and towards the abdomen as well as facial rounding. In addition, there may be evidence of muscle weakness or osteoporosis on bone density scanning or fracture, if glucocrticoid dose is excessive. The adequacy of a mineralocorticoid dose can be assessed quite readily with a blood test, namely the plasma renin activity. A high plasma renin activity suggests inadequate fludrocortisone dose whereas a low plasma renin activity would suggest excessive fludrocortisone dose. More severe excursions of fludrocortisone dosage could result in a change in plasma potassium levels or blood pressure. Once the plasma renin activity is stable, it should perhaps be checked every 12 months, although there is no definite consensus on this matter. An additional important issue in Addison's Disease is to review the patient's general health looking for evidence of associated immune-endocrine disease in the larger group of patients who have Addison's Disease on an autoimmune basis. The monitoring of plasma lipid levels should be performed on the same basis as that in the non-Addison's population.
Many Addisonians report that ‘several years down the track’, their Bone Mineral Density is considerably lowered. They report having “80 year old bones in a 40 year old body”. Some report this, after some 5 to 15 years of taking steroid replacement at a replacement dose, and not a high dose for that time. Did they just have low BMDs anyway? Is there some concern to have “Pre-steroid Treatment” BMDs for all patients contemplating long term steroid courses, e.g. Addisonians, chronic severe asthmatics, rheumatoid patients, etc? As well as having follow-up BMDs, especially if there is some indication for concern.
The Bone Mineral Density measurement is normally performed by dual X-ray absorptiometry. Measurements of bone density are performed in the lumbar spine (lower back) and upper femur (hip) regions. The measurement correlates with risk of fracture although many other factors, such as exposure to trauma or falls, influence this risk. Glucocorticoids, such as hydrocortisone, prednisone or dexamethasone, are among the most potent causes known for rapid bone loss, when administered in doses beyond that required for replacement of adrenal gland glucocorticoid production. Theoretically, a perfect replacement dose of glucocorticoid should leave the Addisonian patient feeling well, and should not accelerate the usual bone loss seen with ageing. In Addison’s disease, the situation is made a little more complex by the possibility that other Addison’s-related factors may have a negative effect on bone, such as the loss of adrenal androgens including DHEA, which provide a significant amount of androgen activity, particularly in women. There may be other factors relating to auto-immune disease, such as coeliac disease, which may co-exist with Addison’s, that may influence bone density and premature menopause in women, or loss of testosterone production in men These factors occur in some patients with auto-immune endocrine diseases and can accelerate bone loss.With regard to your questions, it is important to realise that the bone density measurement provides only a cross-sectional assessment of the individual. It is not possible to say whether a person with a low bone density at one point in time, has arrived at this bone density due to the effects of steroids, or whether that person had a relatively low peak bone mass in their early twenties, due to other factors such as genetic background. I personally feel that there is an argument for performing a pre-treatment, or at least early treatment bone density in patients with Addison’s disease. Bone density can then be followed. A fall in bone density is possible evidence of excessive glucocorticoid replacement. This would help with later interpretations of bone density values. It is also important in patients with severe asthma and rheumatoid arthritis, who require glucocorticoid treatment at anti-inflammatory doses, that can be quite high and long-term. Many physicians are now using treatments to avoid bone loss in this patient group, as there is now evidence of the effectiveness of other drugs for relief of inflammatory symptoms.
Many Addisonians report having difficulty coping with some psychological stresses. Is there a recognised list of psychological stresses that might indicate adjustments to steroid replacement dose(s)? Recognised high psychological stressors like: death of a spouse, moving house, loss of employment might indicate dosage alterations. Do the lower, more chronic stresses like job stress require attention?
In general, most physicians do not recommend increased doses of glucocorticoid or mineralocorticoid in patients with Addison’s, who encounter either short-term or long-term psychological stress. There are no good studies in relation to the use of increased glucocortocoid dosing during psychological stress in Addison’s patients to my knowledge. However, there are numerous studies of the effects of psychological stress in normal individuals, and generally increased cortisol levels are brief, and 24-hour cortisol secretion is generally not elevated in subjects with psychological stressors. Many patients who have chronic stress of various forms, including chronic pain-related conditions, and some psychiatric disorders actually have low cortisol secretion. The administration of excess glucocorticoid for prolonged periods during stress could actually exacerbate the situation, by worsening sleep patterns and anxiety levels. In addition, long-term effects of excessive glucocorticoid exposure needs to be considered, especially with reference to weight gain and bone loss.
What happens to mosquitoes, fleas and other blood-drinking nasties, that fill themselves with steroid-laden human blood? Are we potentially responsible for a “super race of mozzies”? Or is the dose of steroids lethal to them?
Surprisingly, there is some evidence that cortisol can increase the growth and development of some insects! So Watch Out!! The limitation of this fearful scenario is that cortisol levels in the blood of patients with Addison’s disease should not be consistently higher than people without Addison’s. This, in combination with the limited life-span of these organisms suggest that there be no real effect.
Would using Dexamethasone, as the replacement steroid for Addison's, increase the possibility of diabetes developing?
In doses above those used for physiologic replacement, i.e. anti-inflammatory doses, (rather than the doses required to treat Addison's disease), Dexamethasone may certainly provoke diabetes in pre-disposed individuals. However, in the doses used for Addison's Disease, provided excessive doses are not given, and weight gain does not ensue, then diabetes should not be a complication of steroid replacement.
Some people from overseas, report using a combination of steroid types, over the course of the day, to, in effect 'smooth out' the peaks and troughs of steroid provision vs. body requirements. Is this a useful proposition? (e.g. Using Hydrocortisone in the am, then Prednisone in the afternoon, and then either Prednisone or Dexamethasone in the pm). And are there any clinical trials looking at such combinations and their effectiveness?
Combinations of different glucocorticoids are generally not used as first-line therapy for replacement in Addison's disease. The different glucocorticoids differ mainly in duration of action, from a clinical point of view. They do vary in mineralocorticoid activity. Doses used for Addison's disease, make this not a practical consideration. The shorter-acting glucocorticoids, such as the natural steroid Hydrocortisone, may have advantages, in that subtle over-dosage is less likely. The longer-acting glucocorticoids (like Prednisone and Dexamethasone), have the advantage that it may be possible to use them once a day, whereas Hydrocortisone is generally needed twice daily. Some individuals do notice fatigue before the next dose of Hydrocortisone, and they may need to manage different timing for their dose, or, use an even longer-acting glucocorticoid.
I do not use combinations of glucocorticoids in my practice, and tend to settle on a regime that is acceptable with a single glucocorticoid. I am not aware of any clinical trials, using combinations of different glucocorticoids. In general, the type of glucocorticoid, and its dosage, needs to be highly individualised. There may be many factors that can influence dose amounts, and timing. In the long term the major concern, is the avoidance of excessive overall glucocorticoid dosages which can lead to obesity and osteoporosis. The use of doses which are too low, can lead to chronic tiredness. However, it is important to remember that tiredness in Addisonian patients may well be attributed to other causes.
The combination of Florinef and Prednisone together, can lower blood electrolyte potassium levels in some people. Would the combination of Florinef and Dexamethasone, possibly produce a similar result?
Certainly Prednisolone, which in itself has some Florinef-type activity, plus taking Florinef itself, could lead to low potassium levels. Dexamethasone has little mineralocorticoid, (or Florinef-like activity), so this steroid would be less likely to cause low potassium blood levels. However, Florinef is a far more potent cause of lowering potassium levels. If Prednisolone or Dexamethasone were in fact being given in quite low doses, (i.e. required for Addison's replacement), then it is likely that Florinef would be the major cause of low potassium, rather than Prednisolone. The dose of Florinef required for Primary Addisonians, needs to be between 0.05 and 0.3mg daily, and must be individualised to suit the patient. That is equivalent to between half of a 100mcg tablet, and 3 x 100mcg tablets of Florinef/day.
Are there any contra-indications for pre-menopausal women, who might use a hormone replacement/supplement for contraception? What about for post-menopause women?
The use of Oestrogen and/or Progesterone, for contraception in pre-menopausal women, who have Addison's disease is not contra-indicated. Likewise, hormone replacement is not contra-indicated for post-menopausal women, unless there are other possible issues to do with HRT and breast cancer complications.
A recent edition of New Scientist had an article on the psychological effect of low testosterone. Is there a link for Addisonians, who may experience low hormone levels as a result of their adrenal insufficiency (-symptoms which might cause low confidence levels, and a tendency to feel less able to cope with life)?
This is a good question, and has been the subject of some research. Testosterone is an androgen. The adrenal glands produce a weak androgen called dehydroepiandrosterone (DHEA). DHEA can be converted to testosterone. The adrenals also produce other hormones and precursors to hormones, which may be converted to testosterone, such as androstenedione.
In males, the contribution of the adrenal gland to total androgens, or testosterone-like substances in the blood stream, is fairly small, (about 10% of all androgens). This is because the testes in men produce relatively large amounts of testosterone. In women, the ovaries produce less androgens than the testes do in men.
The adrenal glands are a relatively important source of androgens in women, accounting for perhaps 50% of total androgens.
If the adrenal glands stop producing androgens because of Addison's disease, this has little effect on androgen levels in men, but will have a greater effect in women. With aging, the testes decline, in terms of testosterone production late in life, in men. However, in contrast, the ovaries stop producing androgens in women at around the time of menopause, so the adrenal glands become the principle source of androgens in post-menopause women.Overall, the adrenal glands are an important source of androgens in women, but a less important source in men. The importance of the adrenals glands as a source of androgen is potentially greater, later in the life of women.
In terms of androgen production, the adrenal glands undergo their own demise in association with aging. Specifically, DHEA production falls by about 1/3, for each decade after the twenties. This has been called the "andropause". For this reason, as well as some non-human evidence that DHEA may be of value in preventing arteriosclerosis, DHEA has been touted as a "youth hormone". DHEA has become widely available without prescription in the USA. It is regarded there, as a food additive, rather than a drug, by the regulatory authority, the FDA. In Australia, DHEA is not regarded in the same way. It was not intended that this hormone would become widely available. Even so, the use of DHEA in Australia appears to be increasing.
Although DHEA is a major product, in terms of quantity from the adrenal glands, it has historically been considered as a precursor for the production of other hormones, both within the adrenal glands and outside the adrenal glands. Here, there has been little clinical work with DHEA, and its overall role in health, disease and aging is controversial.In Addison's disease, DHEA levels are low. There has been one study suggesting that the administration of DHEA, in combination with the usual hormone replacement ( glucocorticoid and mineralocorticoid), produces subtle effects on well-being. This requires further confirmation and study. Some endocrinologists would agree with the notion of treating women who have the combination of Addison's disease and ovarian failure, plus testosterone levels below normal female range, with DHEA supplements. Low levels of testosterone in women can affect sense of well-being and libido.
However, the use of androgens in women is an area where there has been very little research done, and the long term effects and safety issues have not been fully addressed. The case of a woman with both ovarian and adrenal failure, (especially if a relatively young woman), would probably represent the most extreme case for suitability for supplementation. Many specialists would agree with low- dose androgen replacement if the female was experiencing certain symptoms. There would need to be careful monitoring and medical supervision, as well as careful consideration of the patient's individual circumstances.
With regard to androgens and their psychological effects, it is very difficult to predict and quantify for an individual patient. Some men have low androgen levels, and yet experience little benefit if androgen levels are raised with supplementation. Others notice dramatic effects on their confidence and sense of well-being. The effects of testosterone, with regard to libido are a little more clear- cut, but still vary greatly between individuals.
Could you briefly outline the role of the adrenal glands and the production of sex and supplementary hormones?
This was addressed in Question 1, with regard to dehydroepiandrosterone (DHEA) and testosterone. It should also be noted that dehydroepiandrosterone can also be converted to oestrogen, which may have some beneficial effects. In addition, DHEA may have unique effects of its own, independent of other hormones, although this area is very controversial.
Lastly, there are several adrenal biosynthetic intermediates which are really early steps in adrenal hormone production, and some of these have weak effects on the cardiovascular and other systems in the body. It is not generally thought that these intermediates have a key role in health and well-being. Their main involvement in disease, occurs when there is a block in one of the adrenal synthetic pathways, which lead to vastly increased amounts of these hormones, that can then interfere with normal function. Some examples would include: excess production of 11-deoxycortisol, which is associated with high blood pressure and low potassium; and excess androgens before birth can lead to virilisation, or the alteration of a girl's sexual organs to those that begin to, or do resemble those of a male child.
Can you explain the term "adrenal fatigue" as opposed to "adrenal insufficiency"?
"Adrenal fatigue" has no widely accepted medical meaning. Although 'fatigue' itself, is a common feature of people who lack adrenal function.
"Adrenal insufficiency" implies that the adrenal glands are incapable of producing sufficient hormones, either in the basal (unstressed) state, representing severe adrenal insufficiency; or under conditions of stress such as infection or trauma, indicative of milder degrees of adrenal insufficiency. So, there are differing degrees of effect. The term does not imply a cause for the adrenal insufficiency, which may be Addison's disease, or derive from a regulatory dysfunction like a pituitary problem, where the adrenal glands are no longer properly regulated by the pituitary ACTH.
Many Addisonians appear to have been prescribed anti-depressants at some stage pre- and post-diagnosis. Does this have to do with the nature of problems with low hormone levels affecting coping ability, or lowered coping ability as part of having a chronic illness?
I would agree that many Addisonians seem to be prescribed antidepressants. Nevertheless, I am not sure if people with Addison's disease are prescribed more antidepressants, than in the general population. I am unaware of any study specifically addressing this issue. I think it is an important question, as cortisol, and perhaps other adrenal gland hormones may well affect mood. It is well known, for example, that excessive glucocorticoids can produce depression, or less commonly elation. In addition, low corticosteroid levels may also produce depression. Spontaneous melancholic depression, without primary adrenal disease is associated with increased cortisol levels, in about 50% cases. Conversely, some individuals with what is termed "atypical depression", have relatively low cortisol levels. This effect, is probably not mediated by the adrenal gland, but rather, by the brain's control over the adrenal gland function. Interestingly, another psychiatric disorder which can develop after suffering an extreme stressful event(s), post-traumatic stress disorder (PTSD) syndrome, is associated with low cortisol levels. This has been shown for patients with post-traumatic stress in comparison with patients without PTSD syndrome.
It should be noted, that the cortisol levels are certainly not as low in PTSD, or atypical forms of depression, as they are in Addison's disease. There is no evidence that cortisol supplementation for these patients, is useful. In fact, their low cortisol levels may be a marker of something else going on, particularly in the brain regulation of cortisol levels.
Does cortisone replacement depend on a person’s size, e.g. does a 100kg man need more than a 50 kg woman?
Yes, cortisone replacement does depend on body size. It has been recommended that body surface area, calculated using height and weight, be used to determine initial cortisone replacement doses.
When ill with the flu or other infections, is it necessary to increase our Florinef dosage for a few days as we are told to do with our Cortisone medication?
When ill with significant infections causing fever and general malaise, it is advisable to increase the glucocorticoid medication, such as cortisone acetate, for approximately 2 days usually doubling the dose. In normal physiology aldosterone production does not increase under these circumstances and hence it is not necessary to increase the Florinef dosage during illness.
How can a patient help themselves when presenting at a hospital with an illness or crisis?
In general, for all chronic illnesses, it is a good idea to have some written information including your diagnoses and a list of the medications that you are currently taking. This saves time and helps to eliminate errors, particularly when you may be well and unable to recall certain details. In Addison’s disease because a crisis can lead to confusion or reduced consciousness, it is a good idea to wear a Medic Alert bracelet or necklace with the Addison’s disease diagnosis mentioned so that hydrocortisone stress doses can be given promptly when people are acutely unwell.
Is the timing of taking our daily medication important for an Addisonian?
There remains controversy surrounding this issue and in general medication doses and timing often need to be individualised. It is possible with short acting glucocorticoids such as hydrocortisone to give a higher dose in the morning than in the afternoon in an attempt to more closely mimic the circadian rhythm of cortisol levels. However, with hydrocortisone alone it is not possible to exactly mimic normal cortisol release. Longer acting preparations of glucocorticoids such as prednisolone produce a profile much further from the normal circadian rhythm of cortisol, but they do seem to suit some people quite well. Taking of glucocorticoids such as hydrocortisone or prednisolone late in the evening sometimes leads to disturbed sleep. Fludrocortisone is used to replace the aldosterone missing in patients with Addison's and is very long acting so that the timing of fludrocortisone should not affect health or well being.
Should the skin colouration (tanned look) continue once on steroids?
The skin tanning associated with Addison’s is due to elevated levels of ACTH from the pituitary gland. When hydrocortisone is replaced, the tanned look does fade to a variable degree, although some patients notice slightly increased tan compared to their condition prior to developing Addison’s. In part, this may be due to the ACTH levels generally not falling all the way to normal on routine hydrocortisone replacement therapy.
Why does Addison’s sometimes take so long to diagnose?
The symptoms of Addison’s are insidious, often developing over many months or years and are often quite non specific given that fatigue, the commonest symptom, is a very frequent symptom in the community. Unfortunately, cases are often not diagnosed until an Addisonian crisis, where investigations reveal abnormalities of blood chemistry, or until patients develop pigmentation which is relatively specific. Occasionally, Addison’s is diagnosed because of its association with other autoimmune hormonal disorders or on observing a relatively low blood pressure. The relative rarity of Addison’s and the quite non specific symptoms in the early stages often conspire to delay diagnosis.
I am taking ½ a tablet of Florinef morning and evening. Is it possible to take 1 tablet of Florinef a day and will it still have the same effect? Some Addisonians take ½ a tablet of Florinef a day. Is it possible to take 1 tablet of Florinef every 2 days? What effect would this have? These questions are raised because Florinef has now changed to the white colour that is difficult to cut in half?
Florinef (Fludrocortisone) has a biological half-life of 18-36 hours so it is not necessary for most people to take the drug more often than once daily. It is also possible to have adequate effects with less frequent dosing in some people but this requires individual assessment. Overall, once daily Florinef is suitable for most people, unless there are special circumstances such as drugs that may accelerate Florinef's metabolism. Less frequent or more frequent than once daily Florinef is unusual and usually relates to a special individual circumstance.