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Steroids - Friend and Foe

Recently on the forum we've had several discussions about steroids.  It is clear that there are a lot of misconceptions and fears about them, so this is a very basic discussion about taking steroids, their actions, side effects, long term effects and potential dangers.  First, we need to be clear that we are talking about the body's natural steroids and not about the anabolic steroids misused to gain abnormal strength and muscle mass.  The category of steroids we use in the treatment of MS, of inflammation, and of autoimmune and allergic diseases is called "corticosteroids."  The main one in the body is called "cortisol."  This is the one we are discussing here.  Cortisol is produced by the adrenal glands, which are hormone glands that sit on top of the kidneys - one on each side.   Specifically cortisol is made made the outer layer of the adrenal glands, the adrenal "cortex."  Cortisol is made constantly by the body but, has a pattern that produces it highest in the mid-morning and in the lowest amounts at about 1am to 2am, a couple hours after going to sleep.  The adrenal gland is regulated mainly by the pituitary gland in the brain, but is also affected by many other factors.


What does Cortisol Do?

 

Cortisol has many, many functions in the body.  It's most important purposes are to support the vascular system, helping to regulate the blood pressure and the salt balance, or "electrolytes" in the body.  Another critical function of cortisol is to help regulate the glucose in the blood.   In fact, another name for the category of hormones that cortisol belongs to is "glucocorticoid."    This name comes from "glucose" and (adrenal) "cortex."   Cortisol plays a role in proper bone metablosm.  It also plays a part in fat and protein metabolism and storage and in supporting the the immune system.  We cannot live without the constant production of cortisol.  Without enough of it many organ systems' functions break down.  A complete deficiency which goes untreated can be fatal.  The name of the disease in which cortisol is not made in sufficient quantities is "Addison's Disease" or "Adrenal Insufficiency."

While too little cortisol can be fatal, too much is a problem, too.  Too much cortisol and we put on weight around the trunk.  Glucose metabolism goes wonky and we may develop Insulin Resistance or Type II Diabetes.  Prolonged overproduction of cortisol can cause osteoporosis, imbalance in other hormone systems, weakness, cataracts  and disruption of the immune system.  This is only a partial list. The major disease  of prolonged over-productuion of cortisol is called Cushing's Syndrome.

 

There is very little difference between many of the corticosteroids we use in medicine and the action of cortisol in the body.  The simplest, hydrocortisone, is virtually identical in the body.  However, many types of corticosteroids have been developed to minimize one of more of cortisol's undesirable effects.  For our purposes, when we talk about using steroids, we are essentially talking about giving the body larger doses of what it already makes - Cortisol.


Main Immediate SIDE EFFECTS:

 

Potassium loss - this can lead to muscle cramps, heart palpitations,

 

Sodium retention - this leads to fluid retention and edema

 

Appetite increase - The longer you take it the more weight you tend to gain.  This weight tends to deposit in the belly, at the base of the neck and in the face

 

Mood changes - this can be anything from a euphoria to grumpiness to overt severe dpression

 

Energy changes - the usual is increased energy, but some people feel listless

 

Insomnia - This is related to increased energy and stimulated mood.

 

Why are Cortisosteroids so Helpful?

First off, cortisol does more than just keep everything functioning smoothly.  In times of severe stress the adrenal glands are immediately directed to make huge amounts of cortisol to support life.  For instance, in the case of a person severely injured in an accident, the cortisol works almost immediately to maintain blood glucose to prevent tissue starvation.  It supports the blood pressure by feeding extra electrolytes like sodium into the blood to expand its volume.  We depend on a properly working adrenal gland to help us survive  physical stressors like injury, infection or disease.

 

In the mid-20th Century scientists discovered that Cortisone (the medicine equivalent of the body's cortisol) was very useful for calming down many diseases which caused severe inflammation in the body.  For a long time it was the only medicine we had for diseases such as Rheumatoid Arthritis, Lupus, Eczema, and dozens of others.  They discovered that high doses would help break the most severe asthma attacks and that it could help save the lives of people with shock from certain, severe, bacterial infections.   It could be used along with cancer chemotherapy to increase cancer survival.  It helped allow organ transplant by suppressing the rejection response of the recipient. 

 

Over time, though, it became clear that steroid use was a double-edged sword.   People on high doses for a long time suffered from suppressed immune systems which allowed serious infections to take hold that a normal immune system would fight off.  Latent tuberculosis might become active.  The bones became thin and people had fractures from minor trauma.  They put on weight around their girths and face.  The skin thinned and became shiny and loose.  People developed Type II Diabetes.  Cataracts were common.  Very high doses could cause beeding ulcers in the stomach.  Sudden gastric bleeds could happen within just a few days of using very high doses of steroids.


The Hidden Problem with Prolonged Steroid Use

But, there was a side effect that was a little less obvious.  With "prolonged" use the adrenal glands would slow or stop their normal production of cortisol.  In the body the adrenal gland is able to "monitor" how much cortisol is circulating in the bloodstream.  When we give someone a corticosteroid like cortisone, prenisone, or methylprednisolone (Solu-Medrol) the adrenal glands "see" this as extra cortisol floating by.  Since there is more than enough (because we are taking higher doses than the adrenal gland would normally produce), the gland sits back and decreases how much cortisol it makes.  So far, so good.  A nice feedback system.

 

Ideally, in a feedback system like this, the adrenal gland would just immediately resume making the needed amount of cortisol when the person stopped taking the oral steroid.  And, this IS what happens if the extra steroid is taken for a "short" period of time (days).  However, if the gland sees extra steroids in the blood for too long (more than a week and a half or so), then it gets lazy.   It might not kick back into action for a few days or more.   If the medication is taken for long enough, the adrenal gland may actually shut down and go on vacation.   (It has been reported as far away as the south of France).  The medical term for this is "adrenal suppression."  The problem is that we don't have a perfect definition of "short" and "too long."  Many doctors that use steroids routinely feel that a course of about 10 days does not usually cause a problem.   A normal person can take a full dose for that long and stop it abruptly without suffering adrenal insufficiency.  Other doctors disagree and feel that anything over 6 days in a row can have significant effects on the adrenal glands.  They recommend a taper after a shorter time on steroids.  I was taught and very frequently used the 10 day course.  I never had a problem with it.

 

What about the person that needs another 10 days a few weeks or months later?  This is where it is hard to predict how a single person's adrenal gland will react.   What we do know is that the longer a person takes steroids and the more often a person takes steroids, the more likely they are to suffer adrenal suppression and have adrenal insufficiency if they stop the steroids abruptly.  This is where the "steroid-taper" comes in.  If you slowly lower the dose of steroids over a time that corresponds with the length of time they were used at high dose, the adrenal glands will usually wake up and get the production of cortisol started back up.

 

Over the years, though, we learned that each time the adrenal glands get suppressed within a year or so, the more sluggish they can be about returning to active duty.  So, as we give steroids to people in repeated, longer courses, the more careful we have to be about tapering them off.  Again, as we said earlier, it is more related to the "length of time" on steroids than to the dose.

 

Any person that has been on significant steroids for long periods or repeated periods should be presumed to be at least somewhat adrenal suppressed.  The medical term for this is "steroid dependent."   While their adrenal glands may get them through normal times just fine, it might be that they will not be able to respond with enough cortisol in an emergency.  These people should wear alert pendants or bracelets to inform medical personel that in an emergency they might require extra steroids.  This is so critical that paramedics know to immediately give hydrocortisone while still in the field. 

 

Once a person is felt to be steroid-dependent, it should be assumed that their adrenal gland may not respond sufficiently in a crisis for the next year, presuming that no more steroids are given in that time.  The year continues to extend after each course.


Stopping Steroids Abruptly and "ADRENAL CRISIS"

If a person has been taking medical steroids for long enough to really suppress the adrenal gland, and if they stop the steroids abruptly, the consequences can be disastrous.   The symptoms that result are termed "Adrenal Crisis" or the older term "Addisonian Crisis."   Within a day or so of stopping the meds they may begin to feel weak, nauseated and begin vomiting.  Without cortisol the body cannot adequately keep the electrolytes balanced, and the person's sodium may drop dangerously.  This can cause brain swelling, confusion and can lead to coma and death.  The person becomes progressively dehydrated, glucose levels may drop to a degree in which the brain cannot function, and the heart and vascular system become unstable.  If this goes untreated the result can be cardiovascular collapse, coma and death.

 

The treatment is first to recognize that this isn't just the flu and to seek emergency treatment.  The treatment is simple.  Lots of IV fluids that contain sufficient electrolytes and fairly high doses of IV steroids.  Once the person is stable, a proper tapering program of the medical steroids must begin.  The taper must be quite slow and with every drop in dose the patient should be evaluated for the early signs of adrenal insufficiency.  A large part of this is patient education.  A good discussion of the symptoms of Adrenal Crisis can be found at:

http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/000357.htm

 

So, Are Repeated Courses of Steroids Ever Safe?

Actually, yes, maybe.  Over the next 40 years, there has been a lot of research into what doses of steroids were safe and how we could minimize them.  In my teaching, reinforced with discussion by my current neurologist, a couple of of 3 to 5 day pulses of steroids are safe and don't require a taper.  He prefers not to use these more often than a month apart, but feels that needing them very often (except for the occasional severe relapse) means the basic therapy or DMD, needs to be changed.  A very common pattern of steroid use in MS is to augment the DMD with a monthly, 1-day, high-dose infusion.  This would give a total of 12 days of steroid use a year.  The duration is only one day, barely enough for the adrenal gland to notice.  The recovery interval is a full month.  He has not seen adrenal suppression using this.  This is also likely true with the use of 3 to 5-day infusions at longer intervals.  Again, though, it's the "total time" on steroids, plus the length of time they have to recover, that is important.  There is no hard and fast rule that every person's body will follow.  Again, if you add in a couple 3 to 5 day courses  given for relapses or Optic Neuritis during that year, then it is not as clear what the adrenal gland's status would be.

 

What About Other Long -Term Side Effects?

 

One other side effect that is concerning MS doctors currently is whether or not repeated, short bursts of steroids will cause osteoporosis.  There  is not much in the medical literature looking at osteoporosis and steroids the way they are used in MS.  There is one small study that looks at short bursts done "repeatedly" and it found no evidence that this causes osteoporosis.  My neurologist has a colleague who has collected, but not published this data, who also found that very short bursts of steroids (he uses 1 day every month), done over a long period of time also does not cause measurable loss of calcium from the bones.   Note that this would only be 12 days of steroids widely spaced over a year.  But, this issue is not settled.

 

The person should have a baseline DEXA scan and take supplemental Vit D and Calcium.  The DEXA should be followed regularly.  I don't have a specific schedule.  that would be determined by the patient's treating physician, taking into account the patient's age, scores on the DEXA scans and the amount of steroid being used.

 

Cataracts are a known complication of long term steroid use.  I was always taught that cataracts are an effect of cummulative dose.  Thus, a person receiving regular, prolonged or repeated steroids should have full eye exams yearly.

 

Type II Diabetes - Regular, prolonged or repeated steroids can push a susceptible person over into Type II Diabetes.  So, a regular check on the fasting glucose is mandatory.  Known diabetics may need increased medication during times of steroid use. 

 

Hypertension - Steroids act to raise the blood pressure during the time they are given.  In people with hypertension the BP should be monitored the entire time on steroids and afterward to ensure that the blood pressure has returned to its previous levels.

Other topics like Immune suppression and how steroids are used specifically in MS will be discussed in other essays.

 

Stay tuned,

 

Quix

 

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