Thursday, 30 January 2014

Steroids (glucocorticoids): the third most important, but least understood, major category of therapeutic drug


The most important drugs, the one you'd least like to be without, are the opiates - especially morphine; because they are the only effective treatment for extreme pain, and extreme pain is the worst thing.

The second most important drugs are the antibiotics.


But the third most important drugs are probably the 'steroids' - which mimic the action of the hormone cortisol (secreted by the outer part of the adrenal gland) specifically the type of steroids called glucocorticoids: prednisone, prednisilone, hydrocortisone, betamethasone, beclomethasone and many others.

The discovery of both antibiotics and steroids in the middle of the twentieth century represents the greatest breakthrough era in the history of medicine.

But, unlike antibiotics, steroids are not well known, and very poorly understood; in fact, (like opiates) they tend to be regarded as more of a problem than a benefit - we take for granted their wonderful life-saving and life-enhancing power, and focus almost exclusively on the problems of side effects. 


(There are also other kinds of therapeutically-useful steroid drugs which mimic different natural hormones; for example mineralocorticoid steroids which mimic a hormone from the kidney, female sex steroids which mimic oestrogen or progesterone from the ovaries, and anabolic steroids which mimic testosterone from the testis.)   


What do glucocorticoid steroids do?

In a sense, steroids do the opposite of antibiotics. Antibiotics enhance or assist the immune system by killing invading bacteria (or allowing the immune to kill invading bacteria); but steroids modify and suppress the immune system when it is attacking the body - instead of attacking invading micro-organisms.

And it turns out that a lot of symptoms and diseases are essentially, or mostly, a matter of the immune system attacking the body 


Steroids mimic the effect of cortisol, which is secreted from the outer part of the adrenal gland. Cortisol is essential to life - if your adrenal glands were removed, you would certainly die, probably within a few weeks (unless you took replacement therapy); but what cortisol does is (unlike most of the other hormones) hard to describe - because conrtisol sustains pretty-much every cell in the body.

On the other hand, excess amounts of glucocorticoids causes 'Cushing's Syndrome' - moon face, muscle wasting and weakness, osteoporosis, thinning and damage to skin, psychiatric symptoms...

And sometimes these serious side effects are unavoidable in order to have a large enough and sustained enough level of steroid to treat severe diseases.

Steroids work slowly, compared with most drugs - usually building up over a few days, perhaps because they need to get into the cell nucleus and alter DNA transcription. 


So what are steroids used for?

Well, they have saved many lives. Among people I know personally, two would have died of the auto-immune disease sarcoidosis, if it wasn't for steroids. Other automimmune dieases include rheumatoid arthritis, SLE (systemic lupus erythematosus), systemic sclerosis and many with no names.

Steroids get used in all kinds of medical emergencies such a premature babies, or head injuries (with swelling of the brain), or as a palliation in terminal cancers. 

Almost all of the effective and lifesaving types of chemotherapy - e.g. for leukaemia, includes steroids.Steroids are also used to prevent rejection in organ transplants.

Steroids are the mainstay of treatment of many skin diseases, including the commonest - eczema/ dermatitis; but also psoriasis.

Steroids (either inhaled or - in emergencies - by mouth) are the mainstay of treatment of asthma, and also severe hay fever type allergies.

Many many uses.


Let me close by my own recent personal experience of what steroids can do.

I have 'osteoarthritis' in my knees - which means that on X-ray there are bone deformities in the joints.

It turns-out I cannot tolerate the usual symptomatic treatment - which is Non-Steroidal Anti-Inflammatory drugs such is diclofenac or ibuprofen - and anyway they were not terribly effective.

But a steroid injection into the joint produced a very substantial improvement - reduced swelling and redness, and a much more solid and stable joint - which lasted about three months.


What this tells us, indirectly, is that many medical problems are side effects of our own bodies responses to infection and injury - or due to errors in the immune system itself.

It turns out that the arthritis was not really the main problem with my knee - it was the body's inflammatory response to that arthritis which was causing pain, swelling, instability and at one point collapse of the joint. Dampen the inflammation, and 66 percent of the problem disappeared - although the arthritis was itself unchanged.

And, quite often it seems, the underlying pathology causing an disease is relatively trivial - it seems that most of the medical problem was the body's response to a trivial, maybe temporary, underlying cause.


One of the mysteries of steroids is that they are apparently temporary-acting drugs, yet so often have a permanent and curative effect.

Somebody has sarcoidosis, or temporal arteritis, or acute rheumatoid arthritis - and they would certainly die - but that high dose steroids stop them from dying (at the cost of severe Cushing's syndrome side effects).

Yet once the crisis is over and the situation is under control, the side effects of the steroids become the most pressing problem. So, as soon as maybe, after a while, the steroids are reduced and tapered-off - often to nothing.

Yet the disease does not come back.


At medical school we were told that steroids suppressed disease, but did not really cure it.

True enough in one sense - but in another sense, the temporary suppression is apparently enough to allow the body to cure the disease. 

So indirectly, steroids are indeed potentially curative.

At any rate, overall, I believe that the cortisol-mimicking, glucocorticoid steroids are worthy of the third place in a pantheon of all-time most-useful drugs.


NOTE: My doctoral thesis (Neuroendocrine correlates of depression - awarded in 1988) was substantially about cortisol and its hormonal control. I then studied the microanatomy of the adrenal cortex, specifically the neural control of cortisol secretion, for a further three years.)


Ingemar said...

Those non-medical people who are most interested in steroids actually consider cortisol as the bogeyman of hormones due to its "catabolic" effects.

Bruce Charlton said...

@I - Yes, glucocorticoids are catabolic - that is, they cause break down and loss of muscle and connective tissue.

Karl said...

I am grateful for posts like this one in which you share your perspective on modern medicine.

One of the few times I think a doctor may be said to have worked a cure on me was when a dose of these corticosteroids cleared up a case of contact dermatitis that I got from unwittingly digging among the roots of poison ivy. (If you don't have poison ivy in England, I advise you not to import it!) Perhaps given time it would have cleared up on its own, but two weeks had seen no improvement whatever, and my betrothed wished to make sure that the ring would fit on my finger at my forthcoming wedding.

Luqman said...

The utility and efficacy of these drugs can sometimes border on the miraculous. They are indeed overprescribed around the world, but this is not the practice in the UK as far as I have observed, where the side-effects are so powerfully driven into the heads of trainees that they almost seem to fear them - as you mentioned.

I once saw a patient who had been complaining of a niggling pain in their forearm for some time. Non-steroidal anti-inflammatory drugs did not help at all, nothing had, and the condition (intersection syndrome to be specific) was affecting their work and mood severely despite how minor it seemed. Strongly needle-phobic, so I prescribed a short course of oral steroids; for which there is no evidence as far as I am aware (locally injected, definitely). Nevertheless in three days the pain was gone and did not recur. I had to take some negative criticism from a senior for what was perceived as poor practice but the patient was so happy about being rid of the problem that it more than made up for it. Corticosteroids definitely deserve the rank you have given them.

Not to denigrate the opiates, about which I entirely agree with you Dr. Charlton, but I would ask why you would not place antibiotics at the very top? Considering their impact on life in the modern world that is.

Bruce Charlton said...

@L - Yes, that kind of thing happens - IF doctors care enough to try and help the patient rather than practice according to 'guidelines' based on faked mega randomized trials.

I was talking to a knee surgeon who said that some men with X ray confirmed arthritis in a single joint (and severe functional disability) get apparently permanent benefit from a single steroid injection.

Mechanism of benefit unknown - presumably the breaking of a self-perpetuating, positive feedback cycle of inflammation-induced response.