Corticosteroids can be dangerous but also life-saving

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Corticosteroids can be dangerous but also life-saving Lecture on 19 September 1998 for the CIB-league department West-Vlaanderen by Dr E. Dhondt, rheumatologist, AZ Sint-Jan Brugge.
In a part of our brainstem lies the hypothalamus, which stimulates the underlying hypophysis. This gland consists of a frontal and a posterior lobe and regulates the functioning of the adrenal glands. These are situated like a cap upon each kidney and are made up of marrow, surrounded by a cortex.
History of corticosteroids
As early as in 1855, Addison wrote that the destruction of the cortex of the adrenal glands has serious consequences for our organism and in 1949 Ph. Hench proves that cortisol and ACTH (a hormone of the frontal lobe of the hypophysis) have a spectacular effect on rheumatoid arthritis.
Production and functioning of cortisol, the most important natural corticosteroid; hydrocortisone
Our adrenal cortex (cortex =the outside) produces 2 types of steroid hormones, i.e. androgens and corticosteroids. The latter produce cortisol (gluco-corticoids) and aldosterone (mineralocorticoid). Cortisol influences the metabolism, is anti-inflammatory and controls immunity. Our natural production of cortisol, about 20 mg daily, is determined by the hypothalamus and our circadian rhythm (biological 24-hours rhythm) with high peaks in the morning and four times a lower peak in the late afternoon. Shorter periods of fluctuation e.g. when getting up or going to work may influence the production.
Effects of corticosteroids
Our production of cortisol influences: A. our metabolism by: 1) An increased production of glucose or sugar in the liver from amino acids and a reduced decomposition of blood sugar. As a consequence, the saccharine level in the blood increases, which causes the production of insulin in the pancreas to go up. There is a danger for the pancreas to become exhausted and for diabetes to develop. It is clear that this only happens if there is an overproduction of corticosteroids. 2) A reduced production and an increased decomposition of proteins 3) An increased retention of fat, a stimulated appetite, redistribution of fat towards the trunk and the retention of salt or fluid (minerals) cause the typical corticoid figure with the swollen face and high back. B. inflammation 1) The reaction to an immunological stimulus decreases because of the reduced amount of monocytes or macrophages. The response of the T-helpercells and B-lymphocytes also decreases and the amount of eosinophiles decreases e.g. at the level of the mucous membranes. The result is leukocytosis or a strongly increased amount of white blood cells. 2) Mediators - interleukins: substances that decrease inflammation and fever by reducing the production of macrophages and T-lymphocytes. - interferon gamma: activates the macrophages and stimulates the production of antibodies and inflammatory mediators. - reducing the amount of lipids or fats, which slows down the production of prostaglandins
The use of corticosteroids in rheumatology
1) local usage: intra-articular injection (in a joint), a local infiltration 2) general usage: - peroral (through the mouth), especially in case of long-term therapy - intramuscular (in a muscle), for a single administration - intravenous (in a vein), if a very high dose is necessary, e.g. in an acute situation
Which type of corticosteroids?
There is a difference in relative strength of the various types of corticosteroids. The anti-inflammatory effect varies according to the type, and their relative potencies are: Hydrocortisone 1, prednisolone 4, methylprednisolone 5. There is a difference in equivalent doses, so to obtain the same effect, the patient has to take 20 mg hydrocortison, 5 mg prednisone, 5 mg prednisolone or 4 mg methylprednisolone (Medrol). There is also a difference in half-life (the time needed to lose half of its effect). One type has longer effects than the other. .
When is treatment with corticosteroids necessary?
1. local treatment of rheumatoid arthritis and tendinitis 2. general treatment if a) insufficient results have been achieved with the basic treatment and the use of NSAIDs (nonsteroidal anti-inflammatory drugs) b) NSAIDs are contra-indicated in case of stomach conditions or if NSAIDs cannot be combined with other medications the patient takes c) In case of very aggressive systemic involvement which needs to be treated urgently. 3. in vasculitis, which occurs by itself or as a part of another systemic disease; in most cases corticosteroids are used in combination with cyclophosphamide or azathioprine.
What are the side effects of corticosteroids?
The side effects are related to the length of the treatment, the dose and the way of administering. There is a difference between short-term usage like infiltrations and continuous usage. * In short-term usage general side effects like heart palpitations, hot flashes, sweating, insomnia and deregulation in patients with diabetes may occur. Injections have local side effects, with possible infections or pain afterwards. Atrophy of the skin and subcutaneous tissue or cartilage may occur and even atrophy of the tendon tissue with ruptures (tears) have been described. * In continued usage: 1) side effects are determined by the total dose of corticosteroids =length of treatment and daily dose. 2) two kinds of side effects: - due to exaggerated physiological functioning of the corticosteroids on the metabolism, the immunity system and the salt retention. - due to the discontinuation of corticosteroids. * Side effects may also be inherent to the corticosteroids, like an increased appetite, retention of salt, altered fat deposition and muscle atrophy. This will result in weight gain and a cushingoid appearance (swollen effect), with moon face, buffalo neck, hirsutism (excessive hair growth of the sexual type), acne, bruises, purple stretch marks (stripy scars on the abdominal skin). * Characteristic is the increased susceptibility, the reduced immunity and a greater risk for infections. The symptoms of an infection are suppressed so that certain disorders are misinterpreted. * Glucose intolerance or diabetes can be induced or worsened when the patient takes high doses. * Mental changes can cause irritability and difficulty in sleeping, euphoria and concentration difficulties. Depressions, paranoia (persecution complex) and manical reactions are possible. * Elevated blood pressure, oedema. * Myopathy with weakness of the proximal muscles (close to the trunk) and atrophy. * Bone deformities like osteoporosis and bone necrosis, e.g. in the hip, knee or shoulder. * Corticosteroids can cause eye complaints like increased ocular pressure or glaucoma and cataract (loss of transparency). Other additional problems may be irregular periods, night sweating, atrophy of the gastric mucosa with an increased risk for ulcers, retardation of growth in children.
What are the side effects when the corticosteroid treatment is discontinued?
Stopping the therapy suddenly increases the need for corticosteroids, due to the long-term suppressing of the adrenal gland, which is no longer used to produce cortisol on its own. The symptoms of the disease appear again and weakness, extreme fatigue, low blood pressure, diarrhoea and even a major flare may occur. An operation may require increasing the intake of corticosteroids up to e.g. 75-150 mg. If adrenal insufficiency is very obvious cortisol can be injected intravenously until 300 mg a day. In life-threatening situations corticosteroids may be the last resort.
How do you have to lower the dosage of corticosteroids to avoid side effects?
Serious problems can occur when the intake of corticosteroids is discontinued. The adrenal gland, which has been suppressed for a long time, has to start functioning again. That is why a gradual dose reduction is necessary and after a long-term treatment with corticosteroids the patient has to stay under medical supervision for a year. Other side effects can be limited by using the lowest dose, for the shortest time and as local as possible. Your doctor may also prescribe an alternate-day schedule.
Advice for a systemic corticosteroid therapy
Preferably intake in one dosage, in the morning around 8 o'clock In children, intake in alternate days to reduce the impact on growth evolution Pay attention to the equivalence between the different types of corticotherapies To prevent osteoporosis, increase the intake of calcium and vitamin D If there is an anamnesis of tuberculosis, start specific prevention Monitor weight, blood pressure, psychological condition, kalemia (presence of kalium in the blood), glycemia (presence of glucose in the blood) A bolus of corticosteroids (extremely high dosage) is the last (final, sometimes life-saving) resort, e.g. 1 gram methylprednisolone A corticosteroid therapy of less than 10 days can be terminated at once Long-term corticotherapy has to be tapered with 10% every ten days
Brand names of corticosteroids
The following prescription drugs may have other brand names Hydrocortisone: solucortef (only for intravenous or intramuscular injections) Betamethasone: diprophos, celestone,... Dexamethasone: a(a)cidexam, decadron, Methylprednisolone: medrol, solumedrol, depomedrol Prednisolone: deltacortril, prednicort, soluydacortine Triamcinolonekenacort: ledercort, albicort, lederspan Back to Articles