Steroids are hormonal substances produced from cholesterol and released into the blood under the control of adrenocorticotropic hormone (ACTH) in the adrenal glands.
The zona glomerulosa is the outermost layer in the adrenals and secretes mineralocorticoids (salt-retaining cortisones). These hormones generally regulate the body’s water-salt balance.
In the zona fasciculata, which is the middle part of the adrenal, glucocorticoids, which are vital for the human body, are synthesized.
The zona reticularis is located in the innermost part and androgens such as DHEA (male hormone-like hormones) are produced from here. This hormone is the largest source of androgen produced in women.
Steroid hormones bind to the cytoplasmic (intracellular) receptor (receptors) in the target cell. The receptor-hormone junction initiates transcription, the process necessary for protein production in the nucleus. Steroids perform different functions in different cells and tissues.
EFFECTS OF GLUCOCORTICOIDS:
1) Liver and renal (kidney) amino acid uptake, gluconeogenesis (production of glucose from other structural elements such as fat and the like); In other words, it increases blood sugar by producing glucose from amino acids and fats. Because of these properties, steroids are known as Contrainsuliner (working opposite to insulin) hormones.
2) By increasing blood glucose in acute stress situations, it provides to meet the increasing energy need in the body. The amount of cortisol released in acute stress situations can increase up to 10 times the normal level, which increases the endurance of the human body against stress. At the same time, they cause an increase in blood pressure because they have some vasoconstrictor (vascular contraction) effect on arterioles (small vessels) that can contract and determine vascular tone.
3)Steroids are substances that have important effects on the blood picture and today, treatment with external steroids is used quite frequently for this reason. While steroids increase the number of neutrophils, erythrocytes and platelets in the blood and the amount of hemoglobin %, they decrease the number of eosinophils, basophils and monocytes, especially lymphocytes. These effects on the blood picture are used in autoimmune and allergic diseases, malignancies (cancer patients). While steroids enable both T and B lymphocytes to return to the lymphoid system from the peripheral blood, initiation of inflammation as a result of antigenic stimuli; IL-1, IL-2, PAF, Gamma IFN, TNF-alpha, etc., which are synthesized from antigen-activated monocytes and lymphocytes and released into the environment, enabling the stimulation of defense system cells. By blocking cytokines, it prevents T lymphocytes from turning into cytotoxic T cells and monocytes into macrophages. In addition, steroids increase the synthesis of Lipocortin, which is a strong enzyme inhibitor; In this way, by suppressing the activation of Phospholipase A2, they prevent the synthesis of Prostaglandin, Thromboxan A2 and Leukotriene, which have important functions in the inflammatory process, and cause a decrease in phagocytic functions due to the increase in lysosomal membrane stabilization in phagocytic cells. Due to these effects, they have the capacity to suppress the immune system at almost every stage.
3) In terms of their effects on the endocrine system, exogenous steroids block the hypothalamo-pituitary axis with negative feedback, decrease CRH and ACTH secretion, GH (growth hormone) secretion increases, TSH (thyroid gland) stimulating hormone) production decreases.
4) High steroid doses increase gastric acid – pepsin secretion, active ulcers occur. There are mental-emotional (brain and emotional) changes on the central nervous system. Again, at high doses, protein catabolism (breakdown) increases; muscle weakness occurs. As the absorption of calcium decreases, its excretion increases, and because it also increases osteoclastic activity, osteoporosis (bone resorption) occurs. They cause a delay in wound healing by increasing the destruction of collagen (connective tissues).
Types of Steroids
In general, their properties are changed according to the places of use; In its forms used for immunosuppression (in cases where the immune system should be suppressed) and anti-inflammatory (anti-inflammatory) activity, steroid types are used with reduced mineralocorticoid activity, increased immunosuppression and anti-inflammatory activity in order to prevent sodium – water retention and fluid increase in the body.
STEROID METABOLISM
Cortisol is 95% bound in the plasma to corticosteroid binding globulin (a special alpha-2 globulin also called Transcortin). The remaining small amount of cortisol is transported by binding to albumin. It becomes water-soluble by conjugation in the liver and is excreted through the kidneys. The half-life of steroids is increased in hepatic dysfunction.
WHERE STEROIDS ARE USED
* In diagnosing endocrine diseases:
Steroids’ inhibition (suppression) of ACTH secretion by suppressing the hypothalamus and pituitary allows these drugs to be used for diagnostic purposes. For this purpose, dexamethasone is the most commonly used steroid.
* It is used as a replacement therapy in Addison’s disease, primary, secondary and tertiary adrenal insufficiency.
In these patients, there is no response to acute stress because there is no cortisol in the blood, and this is a dangerous event where patients can die due to hypotension (low blood pressure), hypoglycemia (low blood sugar) and shock. With replacement therapy, the deficient cortisol in the body is given externally in accordance with the biorhythm of the hypothalamo-pituitary axis. In cases of acute stress, the doses used are increased. Hydrocortisone, which has almost equal mineralocorticoid and anti-inflammatory activities in the treatment, in order to adapt to the rhythm of normal cortisol secretion; It is used by giving 2/3 of the total dose in the morning and 1/3 in the evening. If hypotension is significant, Fludrocortisone with high mineralocorticoid activity is added to the treatment.
In Congenital Adrenogenital Hyperplasia, which is caused by the congenital absence of various enzymes in the steroid hormone synthesis pathways, hyperplasia (growth) occurs in the adrenal gland cells as a result of the increase in the amount of the Pituitary ACTH hormone, which cannot be suppressed due to cortisol deficiency. What should be done in this disease, just as in adrenal insufficiency, is to give ready-made end products that cannot be produced from outside.
* Inflammation (against inflammation) use:
Steroids are used effectively today because of their previously mentioned anti-inflammatory effects. It is used in the treatment of chronic inflammatory events, especially rheumatoid arthritis, and their acute exacerbations, which cannot be controlled despite the use of drugs known as Non-Steroid Anti-Inflammatory Drugs, effectively reducing the complaints and findings; but in such chronic – progressive (progressive) diseases, the symptoms become more severe as soon as the steroids are stopped.
* They are used in the treatment of allergic reactions, which is one of the undesirable effects of the defense system in our body. It is used topically (cream, spray, etc.) in the treatment of superficial signs of allergy, while it is used intravenously in the treatment of severe allergic manifestations such as anaphylactic shock. Here, of course, it is necessary to remind that; The main drug in anaphylaxis treatment is adrenaline…
In severe bronchial asthma attacks, inhaled beta-mimetics (bronchial openers) are used, as well as inhaled steroid forms, especially to reduce late-phase damage. In cases where inhaled forms are ineffective, such as status asthmaticus, steroids are given as an intravenous injection or infusion.
* Autoimmune diseases:
In connective tissue diseases other than systemic sclerosis (Systemic Lupus Erythematosus, Polyarteritis Nodosa, dermatomyositis , vasculitis etc.). good results are obtained. Initially, it is used at a high dose (1mg/kg or more) until symptoms resolve, then the dose is gradually reduced.
* Skin and eye diseases:
Allergic dermatitis, contact dermatitis, intertrigo, cheloid, alopecia areata (regional hair loss), seborrheic dermatitis, lichen sclerosis etc. topically in diseases; They are applied systemically in serious diseases such as pemphigus and exfoliative dermatitis. Atrophy (thinning of the skin) may occur in long-term applications on the skin. Its local forms are applied in allergic conjunctivitis (conjunctivitis) and blepharitis. Local application may increase intraocular pressure, it should not be applied in viral diseases and on scar tissue.
* Use as an immunosuppressant:
Steroids, the immune system; They are drugs that are used almost as the first drug and in high doses in some cases where it works against the organism (preventing allograft rejection after organ transplantation, aplastic anemia, minimal lesion disease, membranous glomerulonephritis, serum sickness, autoimmune hemolytic anemia, ITP..). The most commonly used for this purpose is Prednisone.
* They are included in chemotherapy protocols as antineoplastic. It is used especially in leukemias where the lymphocyte precursors increase too much in the peripheral blood because of the effect of steroids on reducing the number of lymphocytes in the periphery.
* Other usage areas:
In cases where vital functions are endangered; It is used in high doses (300 mg Hydrocortisone intravenous infusion, repeated if necessary) in septic shock, Addisonian crisis. It is used in post-traumatic situations, increased intracranial pressure syndrome, brain edema, and neuron stabilization and increased endurance.
In the treatment of pulmonary edema (lung edema) caused by aspiration pneumonia, toxic and irritant gas inhalation or other reasons, in the treatment of hypercalcemia caused by various reasons (malignancy, Granulomatous diseases, hyperparathyroidism …), when heart involvement in acute rheumatic fever, They are used to reduce organ damage in Good-Pasture syndrome, auto immune hepatitis, sclerosing cholangitis, Miasthenia gravis, inflammatory bowel diseases, severe bacterial infections.
SIDE EFFECTS of Steroids:
Long-term and high-dose use of corticosteroids causes numerous and serious side effects. The most important of these is Iatrogenic Cushing’s Syndrome. Classically, moon face, buffalo hump, centripetal adiposity (thin extremities, wide body) are due to high-dose corticosteroids disrupting the fat distribution in the body. Increased mineralocorticoid activity causes Na – water retention , increase in intra – extravascular volume , hypertension and edema . Due to the fact that steroids disrupt collagen production and increase its destruction, skin atrophy, striae (cracks), delayed wound healing, telangiectasias (vein clarification), ecchymoses (bruises) even with minor traumas occur. Due to changes in the amount of androgen hormone, gynecomastia (breast growth in men), hirsutism (increased hair growth in women), acne (pimples) occur. Due to the side effects of steroids on bone metabolism, osteoporosis (bone loss) occurs, calcium excretion increases, and absorption decreases. Excessive amounts of cortisol cause myopathy, muscle weakness and atrophy by increasing protein catabolism (destruction). Gastric acid secretion increases, peptic ulcers occur, gluconeogenesis and glycogenolysis increase, blood sugar rises, secondary Diabetes Mellitus develops.
Since corticosteroids suppress immunity, susceptibility to infections increases; In particular, suppression of cellular immunity facilitates the development of viral and fungal infections. There may be exacerbation of tuberculosis. Apart from this, the risk of developing sepsis increases in infections with other bacterial pathogens.
Prolonged use of steroids can produce psychic disturbances; It can be addictive due to personality changes, psychoses, and even the psychological excitatory effect of steroids.
Long-term and high-dose use in children stops growth. This problem can be minimized to some extent by applying it every other day.
Exogenous steroids show aldosterone-like activity; In addition to causing hypertension and edema with Na – water retention, it can cause congestive heart failure in prone patients. Since aldosterone also has the effect of increasing potassium excretion, severe hypokalemia may result in decreased motor power, paralytic ileus (intestinal paralysis), arrhythmias (rhythm disturbances), and cardiac diastolic asystole (cardiac arrest).
Other side effects; They can exacerbate corneal ulcers, glaucoma, cataracts and viral infections in the eye where they are applied locally. They cause increased intracranial pressure, hypercoagulability, tendency to thrombosis, convulsions, and accelerate atherosclerosis.
Wishing you a healthy day…
Prof. Dr. Cengiz KIRMAZ
