Sunday, March 12, 2006

Steroids 1

Corticosteroids are so called because they are made by the cortex of the adrenal gland. The gland makes a number of steroid hormones. Rarely the gland stops working - in the past it was usually secondary to TB; nowadays it is usually caused by an autoimmune process. People without functioning adrenal glands have Addisn's disease, named after Thomas Addison, a physician at Guy's Hospital in London from 1824 to 1860. Addison was a contemporary at Guy's of Thomas Hodgkin who decribed Hodgkin's disease. As well as hypoadrenalism Addison also described pernicious anemia.

If you lack adrenals you become weak and watery, you lose weight, your blood pressure falls, your muscles waste and you get a low blood sugar. The clue to diagnosis is to look for brown pigmentation of the skin creases of the palm. I remember in the days when doctors did house calls being asked to see a middle aged woman in bed with lassitude because her doctor thought she was anemic. A glance at her skin creases made the diagnosis for me and made me some sort of genius in the eyes of her doctor. I have to confess to missing the diagnosis in my next door neighbor. She became increasingly suntanned and all I could think of was how they could afford so many foreign holidays.

What is lacking in Addison's disease are the adrenal hormones, cortisone and aldosterone. Cortisone is called a glucocorticoid, because it particularly affects blood sugar, and aldosterone a mineralocorticoid because it controls the balance between sodium and potassium in the body, causing sodium retention and potassium loss by the kidneys, and thus affecting the blood pressure - if you don't have enough of it your blood pressure falls and if you have too much of it your blood pressure rises. Although cortisone is mainly a glucocorticoid it does have some mineralocorticoid effects.

Too much cortisone production is known as Cushing's syndrome, though strictly speaking this should refer only the the form that is caused by the production of too much adrenocorticotrophic hormone (ACTH) by a pituitary tumor. Harvey Cushing, perhaps the greatest of neurosurgeons, was an American pioneer first at Johns Hopkins and later at Harvard with an interlude at Oxford with Sir William Osler. He died of a heart attack in 1939 at the age of 70.

In Cushing's syndrome there is typically a moon face and a change in body shape. A 'buffalo hump' is part of a round body, but the arms and legs are spindly. The shape has been describes as a 'lemon on matchsticks'. The muscles are wasted and weak, the skin is thin with stretch marks, there is often blleding into the skin. The bones become weakened with crush fractures of the spine. Often the patient becomes diabetic as the blood sugar gets out of control and the blood pressure may also be high. Sometimes there are masculizing effects becuse the adrenals also make a certain amount of testosterone, and this is probably the reason for the rise in hemoglobin. Finally the brain is also affected with inability to sleep, enormous energy, emotional lability, and even psychosis.

This disease is important because although Cushing's syndrome is rare, when steroids are used in treatment the side effects are the same.

The adrenal gland makes cortisone, but it is converted in the liver to hydrocortisone. The relationship between prednisone and prednisolone is the same. Today neither cortisone nor prednisone is much used, we use hydrocortisone and prednisolone almost exclusively. In Addison's disease replacement of the missing steroids requires 20 to 30 mg of hydrocortisone a day given in a divided dose morning and evening with the larger portion in the morning because that is how the body manages it. We need a big dose of steroids to get us out of bed in the morning. To replace the missing aldosterone a small dose, 50-300 micrograms, of the mineralocorticoid, fludrocortisone, is given.

Hydrocortisone is also used intravenously in acute situations like shock or asthma, but generally most people requiring treatment have prednisolone for small to moderate doses and either methylprednisolone or dexamethasone when larger doses are needed. This is because prednisolone has less mineralocorticoid activity (and therefore less fluid retention) than hydrocortisone and dexamethasone less still. Betamethasone and Beclametasone have very high topical effects without being absorbed systemically and are therefore often used on the skin or in the lungs (as an inhaler).

It is important to recognise the dose equivalants for the various types of steroids.

20 mg of hydrocortisone is equivalent to 5 mg of prednisolone is equivalent to 4 mg of methylprednisolone is equivalent to 750 micrograms of dexamethasone.


Anonymous said...

A wonderful thing to look forward to if one takes these drugs as part of a cancer treatment plan. I have heard of some horror stories. Then there are some who miss the expected burst of energy, though it seems insomnia is fairly common.

Anonymous said...

Doc: Are patients who have diabetes able to take steroids? and do patients who develop diabetes while on steroids usually return to normal after they are taken off steroids?

Anonymous said...

I have just had one of our dogs diagnosed with Cushings. Over the weekend we were administering Vetoryl tablets (only 2 tablets), now we find he has Addisons due to being overloaded with the Vetorly. Steriods are now being administered to try and obtain an equilibrium.