Healthcare in India


The adrenal cortex secretes steroidal hormones which have glucocorticoid, mineralocorticoid and weakly androgenic activities. Conventionally, the term ‘corticosteroid’ or ‘corticoid’ includes natural gluco and mineralo-corticoids and their synthetic analogues.
By the middle of 19th century it was demonstrated that adrenal glands were essential for life. Later it was appreciated that the cortex was more important than the medulla. A number of steroidal active principles were isolated and their structures were elucidated by Kendall and his coworkers in the 1930s. However, the gate to their great therapeutic potential was opened by Hench (1949) who obtained striking improvement in rheumatoid arthritis by using cortisone. The Nobel Prize was awarded the very next year to Kendall, Reichstein and Hench.
The corticoids (both gluco and mineralo) are 21 carbon compounds having a cyclopentanoper hydro-phenanthrene (steroid) nucleus. They are synthesized in the adrenal cortical cells from cholesterol. A simplified version of the biosynthetic pathways is presented in Figure. Adrenal steroidogenesis takes place under the influence of ACTH which makes more cholesterol available for conversion to pregnenolone and induces steroidogenic enzymes. Since adrenal cortical cells store only minute quantities of the hormones, rate of release is governed by the rate of biosynthesis.
The normal rate of secretion of the two principal corticoids the main is-
Hydrocortisone – 10-20 mg daily (nearly half of this in the few  morning hours).
Aldosterone – 0.125 mg daily.
The  corticoids have widespread actions. They maintain fluid-electrolyte, cardiovascular and  energy substrate homeostasis and functional status of skeletal muscles and nervous system. They prepare the body to withstand effects of all kinds of noxious stimuli and stress. The involvement of hypothalamo-pituitary-adrenal axis in stress response is depicted in Figure.
Corticoids have some direct and some  premissive actions. By premissive action is meant that while they do not themselves produce and effect, their presence facilitates other hormones to exert that action, e.g. they do not have  any effect on BP but the pressor action of Adr is markely blunted in their absence. Actions of corticoids are divided into:
Glucocorticoid : Effects on carbohydrate, protein and fat metabolism, and other activities that are inseparably linked to thse.
Mineralocorticoid : Effects on carbohydrate, protein and fat metabolism, and other activities that are inseparably linked to these.
Mineralocorticoid : Effects on Na+, K+ and fluid balance.
Marked dissociation between these two types of actions is seen among natural as well as synthetic corticoids. Accordingly, compounds are labelled as ‘glucocorticoid’ or ‘mineralocorticoid’.
Mineralocorticoid actions
The principal mineralocorticoid action is enhancement of Na+ rebsorption in the distal convoluted tubule in kidney. There is an associated increase in K+ and H+ excretion. Its deficiency results in decreased maximal tubular reabsorptive capacity for Na+ kidney is not able to retain Na+ even in the deficient state ® Na+ is progressively lost: kidneys absorb water without attendant  Na+ (to maintain e.c.f. volume which nevertheless decreases) ® dilutional hyponatraemia ® excess water enters cells ® cellular hydration: decreased blood volume and raised haematocrit. Hyperkalaemia and acidosis accompany. These distortions of fluid and electrolyte balance progress and contribute to circulatory collapse. Thus, these actions make adrenal cortex essential for survival.
Similar action on cation transport is exerted in other tissues also. The action of aldosterone is expressed by gene mediated increased transcription of m-RNA in renal tubular cells which directs synthesis of proteins (aldosterone-induced proteins-AIP). The Na+ K+ ATPase of tubular basolateral membrane responsible for generating gradients for movement of cations in these cells is the major AIP. Synthesis of b subunit of amiloride sensitive Na+ channel is also induced. Because of the time taken to induce protein synthesis, aldosterone has a latency of action of 1-2 hours. In addition, aldosterone rapidly induces phosphorylation and activation of amiloride sensitive Na+ channel.
The main adverse effect of excessive mineralocorticoid action is fluid retention and hypertension. The natural and some of the synthetic glucocorticoids have significant mineralocorticoid activity responsible for side effects like edema, progressive rise in BP, hypokalemia and alkalosis. The diuretic induced hypokalemia is aggravated.
Aldosterone has been shown to promote CHF associated myocardial fibrosis and progression of the disease.
Glucocorticoid actions

  • Carbohydrate and protein metabolism : Glucocorticoids promote glycogen deposition in liver (they are assayed on the basis of this action) by inducing hepatic glycogen synthase and promoting gluconeogenesis. The inhibit glucose utilization by peripheral tissues. This along with increased glucose release from liver results in hyperglycaemia, resistance to insulin and a diabetes-like state. They also cause protein breakdown and amino acid mobilization from peripheral tissues – responsible for side effects like muscle asting, lympholysis, loss of osteoid from bone and thinning of skin. The amino acids so mobilized funnel into liver ® used up in gluconeogenesis, excess urea is produced ® negative nitrogen balance. Glucocorticoids are thus catabolic. Their function appears to be aimed at maintaining blood glucose levels during starvation – so that brain continues to get its nutrient. When food is withheld from and adrenalectromized animal – liver glycogen is rapidly depleted and hypoglycaemia occurs.

They also increase in uric acid excretion.

  • Fat metabolism : The action is primarily permissive in nature: promote lipolysis due to glucagon, growth hormone, Adr and thyroxine. cAMP induced breakdown of triglycerides is enhanced. Fat depots in different areas respond differently – redistribution of body fat occurs. Subcutaneous tissue over extremities loses fat which is deposited over face, neck and shoulder – ‘moon face’, ‘fish mouth’, buffalo hump’. Explanation offered is – because peripheral adipocytes are less sensitive to insulin, corticosteroid enhanced lipolytic action of GH and Adr predominates, whereas truncal adipocytes respond mainly to enhanced insulin levels under the influence of glucocorticoids.
  • Calcium metabolism: They inhibit intestinal absorption and enhance renal excretion of Ca2+. There is also loss of calcium from bone indirectly due to loss of osteoid (decreased formation and increased resporption), negative calcium balance. Spongy bones (vertebrae, ribs, etc.) are more sensitive.
  • Water  excretion : Effect on water excretion is independent of action on Na+ transport; hydrocortisone and other glucocorticoids, but not aldosterone, maintain normal g.f.r. In adrenal insufficiency, the capacity to excrete a water load is markedly reduced-such patients are prone to water intoxication from i.v. infusions.

Glucocorticoids also enhance secretory activity of renal tubules.

  • CVS : Glucocorticoids restrict capillary permeability, maintain tone of arterioles and myocardial contractility. Applied topically, they cause cutaneous vasoconstriction. They have a permisive effect on pressor action of Adr and angiotensin. They also play a permissive role in development of hypertension – should be cautiously used in hypertensives.

Adrenal insufficiency is attended by low cardiac output, arteriolar dilatation, poor response to Adr (repeated doses of Adr cause destructive changes in blood vessels) and increased permeability of capillaries. These changes along with hypovolemia (due to lack of mineralocorticoid) are responsible for cardiovascular collapse.

  • Skeletal muscles : Optimum level of corticosteroids is needed for normal muscular activity. Weakness occurs in both hypo- and hypercorticism, but the causes are different.

Hypocorticism: diminished work capacity and weakness are primarily due to hypodynamic circulation.
Hypercorticism: excess mineralocorticoid action ® hypokalaemia ® weakness;
Excess glucocorticoid action ® muscle wasting and myopathy ® weakness.

  • CNS : Mild euphoria is quite common with pharmacological doses of glucocorticoids. This is a direct effect on brain, independent of relief of disease symptoms; sometimes progresses to causes increased motor activity, insomnia, and hypomania or depression. On the other hand, patients of Addison’s disease suffer from apathy, depression and occasionally psychosis.

Glucocorticoids also maintain the level of sensory perception and normal level of excitability of neurones. High doses lower seizure threshold-cautious use in epileptics. This action is independent of electrolyte changes in the brain and is not shared by aldosterone.

  • Stomach : Secretion of gastric acid and pepsin is increased – may aggravate peptic ulcer.
  • Lymphoid tissue and blood cells: Glucocorticoids enhance the rate of destruction of lymphoid cells (T cells are more sensitive than B cells); but in man  the effect on ormal lymphoid tissue is modest. However, a marked lytic response is shown by malignant lymphatic cells; basis of their use in lymphomas.

Glucocorticoids increase the number of RBCs, platelets and neutrophils in circulation. They decrease lymphocytes, eosinophils and basophils. this is not due to destruction of these cells but due to their sequestration in tissues. Blood counts come back to normal after 24 hours.

  • Inflammatory responses : Irrespective of the type of injury or insult, the attending inflammatorry response is suppressed by glucocorticoids. This is the basis of most of their clinical uses. The action is nonspecific and covers all components and stages of inflammation. This includes reduction of increased capillary permeability, local exudation, cellular infiltration, phagocytic activity and late responses like capillary proliferation, collagen deposition, fibroblastic activity and ultimately scar formation. The action is direct and local-topical  use is possible. The cardinal signs of inflammation – redness, heat, swelling and pain are suppressed.

Glucocorticoids interfere at several steps in the inflammatory response (see cellular mechanism below), but the most important overall mechanism appears to be limitation of recruitment of inflammatory cells at the local site and production of proinflammatory mediators like PGs, LTs, PAF through inhibition of phospholipase A2.
Corticoids are only palliative, do not remove the cause of inflammation; the underlying disease continues to progress while manifestations are dampened. They favour spread of infections because capacity of defensive cells to kill micro organisms is impaired. They also interfere with healing and scar formation: peptic ulcer may perforate asymptomatically. Indiscriminate use of corticoids is hazardous.

  • Immunological and allelrgic responses : Glucocorticoids impair immunological competence. They suppress all types of hypersensitization and allergic phenomena. At high concentrations and in vitro they have been shown to interfere with practically every step of the immunological response, but at therapeutic doses in vivo there is no impairment of antibody production or complement function. The clinical effect appears to be due to suppression of recruitment of leukocytes at the site of contact with antigen and of inflammatory response to immunological injury.

They cause greater suppression of CMI in which T cells are primarily involve, e.g. delayed hypersensitivity and graft rejection – basis of use in autoimmune diseases and organ transplantation. Factors involved may be inhibition of IL-2 formation and action ® T cell proliferation is not stimulated; suppression of natural killer cells, etc.
The broad action seems to be interruption of communication between cells involved in the immune process by interfering with production of or action of lymphokines.

Gene mediated cellular actions of glucocorticoids

Translocation of glucose transporters from plasma membrane to deeper sites.

? glucose uptake and utilization in peripheral tissues.

Induction of hepatic gluconeogenetic enzymes.

­ production of glucose from amino acids.

Induction of hepatic glycogen synthase.

Deposition of glycogen in hepatocyts.

Site specific changes in sensitivity of adipocytes to GH, Adr, insulin.

Altered distribution of body fat.

­ expression of vascular adrenergic and AT1 receptor.

Enhanced reactivity to vasopressor substances.

? expression of POMC gene in pituitary corticotropes

? production of ACTH

Adtiinflammatory and Immunosuppresant action


Induction of lipocortins in macrophages, endothelium and fibroblasts.

Lipocortins inhibit phospholipase A2 ® decreased production of PGs, LTs & PAF.

Negative regulation of COX-2

? inducible PG production

Negative regulation of genes for cytokines in macrophages, endothelial cells and lymphocytes.

? production of IL-1, IL-2, IL-3, IL-6, TNFa, GM-CSF, g interferon ® fibroblast proliferation and T-lymphocyte function are suprressed, chemotaxis interfered.

? production of acute phase reactants from macrophages and endothelial cells

Complement function is interfered.

? production of ELAM-1 and ICAM-1 in endothelial cells.

Adhesion and localization of leukocytes is interfered.

? production of collagenase and stromolysin

Prevention of tissue destruction

POMC – Proopiomelanocortin; II-Interleukin, TNFa - Tumour necrosis factors a; GM-CSF-Granulocyte macrophage colony stimulating factor; ELAM-1 – Endothelial leukocyte adhesion molecule-1: ICAM-1-Intracellular adhesion molecute-1

Mechanism of action at cellular level

Corticosteroids penetrate cells and bind to a high affinity cytoplasmic receptor protein ® a structural change occurs in the steroid receptor complex that allows its migration into the nucleus and binding to glucocorticoid response elements (GRE) on the chromatin ® transcription of specific m-RNA ® regulation of protein synthesis. This process takes at least 30-60 min: effects of corticosteroid are not immediate, and once the appropriate proteins are synthesized – effects persist much longer than the steroid itself. In many tissues, the overall effect is catabolic, i.e. inhibition of protein synthesis. This may be a consequence of steroid directed synthesis of an inhibitory protein.
The glucocorticoid receptor (GR) is very widely distributed (in practically all cells). It has been cloned and its structure determined; made up of ~ 800 amino acids.
Several coactivators and corepressors modulate the interaction of liganded GR with the GREs, altering the intensity of response.
Because the GR largely maintains uniformity throughout the body, tissue specificity is not exhibited by different glucocorticoids, and all members produce the same constellation of effects.
The functional scheme of glucocorticoid receptor is presented in Figure. Direct evidence of gene  expression mediated action has been obtained for actions listed in the box.
Some actions of corticoids are exerted more rapidly (like inhibition of ACTH release from pituitary). These may be mediated by a cell membrane receptor or a different mechanism not involving protein synthesis.
All natural and synthetic corticoids, except DOCA are absorbed and are effective by the oral route. Water soluble esters, e.g. hydrocortisone hemisuccinate, dexamethasone sod, phosphate can be given i.v. or i.m., act rapidly and achieve high concentration in tissue fluids. Insoluble esters, e.g. hydrocortisone acetate, triamcinolone acetonide cannot be injected i.v., but are slowly absorbed from i.m. site and produce  more prolonged effects.
Hydrocortisone undergoes high first pass metabolism, has low oral: parenteral activity ration. Oral bioavailability of synthetic corticoids is high.
Hydrocortisone is 90 % bound to plasma protein, mostly to a specific cortisol-binding globulin (CGB; transcortin) as well as to albumin. Transcortin concentration is increased during pregnancy and by oral contraceptives – corticoid levels in blood are increased but hypercorticism does not occur, because free cortisol levels are normal.
The corticosteroids are metabolized primarily by hepatic microsomal enzymes. Pathways are –

  • Reduction of 4, 5 double bond and hydroxylation of 3-keto group.
  • Reduction of 20-keto to 20-hyroxy from.
  • Oxidative cleavage of 20C side chain (only in case of compounds having a 17-hydroxyl group) to yield 17-ketosteroids.

These metabolites are further conjugated with glucuronic acid or sulfate and are excreted in urine.
The plasma t ? of hydrocortisone is 1.5 hours. However, the biological t ? is longer because of action through intracellular receptors and regulation of protein synthesis – effects that persist long after the steroid is removed from plasma.
The synthetic derivatives are more resistant to metabolism and are longer acting.
Phenobarbitone and phenytoin induce metabolism of hydrocortisone, prednisolone and dexamethasone, etc. to decrease their therapeutic effect.


Fig. 20.3 depicts the chemical structure of desoxycorticosterone in blue line. It is a selective meineralocorticoid. Chemical modifications that result in clinically useful compounds are also indicated. Fluorination at position 9 or 6 has resulted in highly potent compounds. Synthetic steroids have largely replaced the natural compounds in therapeutic use, because they are potent, longer acting, more selective for glucocorticoid / mineralocorticoid action and have high oral activity.

The relative potency and activity of different natural and synthetic corticosteroids employed systemically is compared in Table 20.1
1.         Hydrocortisone (cortisol) Acts rapidly but has short duration of action. In addition to primary glucocorticoid, it has significant mineralocorticoid activity as well. Used for :
Replacement therapy – 20 mg morning + 10 mg afternoon orally.
Shock, status asthmaticus, acute adrenal insufficiency – 100 mg i.v. bolus + 100 mg 8 hourly i.v. infusion.
Topically and as suspension for enema in ulcerative colitis
LYCORTIN-S, EFCORLIN SOLUBLE 100 mg/2 ml inj. (as hemisuccinate for i.v. inj.) WYCORT, EFCORLIN 25 mg/ml inj (as acetate for i.m / intraarticular inj.) PRIMACORT 100, 200, 400 mg/vial inj.
2.         Prednisolone : It is 4 times more potent than hydrocortisone, also more selective glucocorticoid, but fluid retention does occur with high doses. Has intermediate duration of action; causes less pituitary-adrenal suppression when a single morning dose or alternate day treatment is given. Used for allergic, inflammatory, autoimmune disease and in malignancies: 5-60 mg/day oral, 10-40 mg i.m., intraarticular; also topically.
DELTACORTRIL, HOSTACORTIN-H, 5, 10 mg tab, 20 mg/ml (as acetate) for i.m., intraarticular inj., WYSOLONE NUCORT 5, 10, 20, 30, 40 mg tabs.
3.         Methylprednisolone : Slightly more potent and more selective than prednisolone: 4-32 mg/day oral. Methylprednisolone acetate has been used as a retention enema in ulcerative colitis.
Pulse therapy with high dose methylprednisolone (1 g infused i.v. every 6-8 weeks) has been tried in nonresponsive active rheumatoid arthritis, renal transplant, pemphigus, etc. with good results minimal suppression of pituitary-adrenal axis.
SOLU-MEDROL Methylprednisolone (as sod. succinate) 40 mg, 125 mg, 0.5 g (8 ml) and 1.0 g (16 ml) inj, for i.m. or slow i.v. inj.
The initial effect of methylprednisolone pulse therapy (MPPT) is probably due to its antiinflammatory action, while long term benefit may be due to temporary switching off of the immunodamaging processes as a consequence of lymphopenia and decreased Ig synthesis.
4.         Triamcinolone : Slightly more potent than prednisolone but highly selective glucocorticoid: 4-32 mg/day oral, 5-40 mg i.m., intraarticular injection. Also used topically.
KENACORT, TRICORT 1, 4, 8 mg tab., 10 mg/ml, 40 mg/ml (as acetonide) for i.m., intraarticular inj., LEDERCORT 4 mg tab.
5.         Dexamethasone : Very potent and highly selective glucocorticoid. Long acting, causes marked pituitary-adrenal suppression, but fluid retention and hypertension are not a problem.
It is used for inflammatory and allergic conditions 0.5-5 mg/day oral. Shock, cerebral edema, etc. 4-20 mg/day i.v. infusion or i.m. injection. Also used topically.
DECADRON, DEXONA 0.5 mg tab, 4 mg/ml (as sod. phosphate) for i.v., i.m. inj., 0.5 mg/ml oral drops; WYMESONE, DECDAN 0.5 mg tab, 4 mg/ml inj.
6.         Betamethasone : Similar to dexamethasone, 0.5-5 mg/day oral, 4-20 mg i.m., i.v. injection or infusion, also topical.
BETNESOL, BETACORTRIL, CELESTONE 0.5 mg, 1 mg tab, 4mg/ml (as sod. phosphate) for i.v., i.m. inj., 0.5 mg/ml oral drps. BETNELAN 0.5 mg, 1 mg tabs.
Dexamethasone or betamethasone are preferred in cerebral edema and other states in which fluid retention must be avoided.
7.         Desoxycorticosterone acetate (DOCA) It has only mineralocorticoid activity. Used occasionally for replacement therapy in Addison’s disease: 2-5 mg sublingual, 10-20 mg i.m. once or twice weekly
In DOCABOLIN 10 mg/ml inj (along with nandrolone).
8.         Fludrocortisone : A potent mineralocorticoid having some glucocorticoid activity as well, orally active, used for:
Replacement therapy in Addison’s disease 50-200 mg/day.
FLORICORT 100 mg tab.
9.         Aldosterone : The most potent mineralocorticoid. Not used clinically because of low oral bioavailability and difficulties in regulating doses.
In addition a number of topically active glucocorticoids have been developed.
Beclomethasone dipropionate budesonide, etc. are used by inhalation in asthma, as spray in nasal allergy, as well as for skin and mucous membrane lesions.
Fluocinolone acetonide, fluocortolone, clobetasol propionate and esters of betamethasone, dexamethasone, triamcinolone are described in Ch. 64.


A.        Replacement therapy

  • Acute adernal insufficiency : It is an emergency. Hydrocortisone or dexamethasone are given i.v., first as a bolus injection and then as infusion, along with isotonic saline and glucose solution. Amount of fluid infused i.v. is guided by monitoring central venous pressure, because these patients have reduced capacity to excrete water load. Short-term i.v. infusion of a vasopressor (dopamine) may be needed.
  • Chronic adrenal insufficiency (Addison’s disease) Hydrocortisone given orally is the most commonly used drug along with adequate salt and water allowance. Some patients in addition need a mineralocorticoid: fludrocortisone is added.
  • Congential adrenal hyperplasia (Adrenogenital syndrome) It is a familial disorder due to genetic deficiency of steroidogenic enzymes, mostly 21-hyroxylase. As a result the synthesis of hydrocortisone and aldosterone suffers. There is compensatory increase in ACTH secretion – adrenals hypertrophy: enzyme deficiency being only partial in most cases, normal amounts of gluco and mineralocorticoids are produced along with excessive amounts of weak androgens ® virilization / precocious sexual development.  If deficiency is severe, salt wasting also occurs.

Treatment is to give hydrocortisone 0.6 mg/kg daily in divided doses round the clock to maintain feed back suppression of pituitary. If salt wasting persists – fludrocortisone 10-20 mg/kg daily may be added.

B.        Pharmacotherapy (for nonendocrine diseases)
Systemic as well as topical corticosteroids have one of the widest spectrum of medicinal uses for their antiinflammatory and immunosuppressive properties. Steroids are powerful drugs. They have the potential to causes dramatic improvement in many severe disease as well as produce equally dramatic adverse effects if not properly used. The use in nonendocrine disease is empirical and palliative, but may be life saving. The following general principles must be life saving.
The following general principles must be observed.

  • A single dose (even excessive) is not harmful: can be used to tide over mortal crisis, even when benefit is not certain.
  • Short courses (even high dose) are not likely to be harmful in the absence of contraindications; starting doses  can be high in severe illness.
  • Long-term use is potentially hazardous: keep the duration of treatment and dose to minimum, which is found by trial and error; even partial relief may have to be tolerated.
  • Initial dose depends on severity of the disease; start with a high dose in severe illness-reduce gradually as symptoms subside, while in mild cases start with the lowest dose and titrate upwards to find the correct dose.
  • No abrupt withdrawal after a corticoid has been given for > 2 to 3 weeks: may precipitate adrenal insufficiency.
  • Injection, severe trauma or any stress during corticoid therapy – increase the dose.
  • Use local therapy (cutaneous, inhaled, intranasal, etc.) wherever possible.

1.         Arthritides
(i)        Rheumatoid arthritis: Corticosteroids are indicated only in severe cases as adjuvants to NSAIDs when distress and disability persists despite other measures, or when there are systemic manifestations
(ii)       Osteoarthritis: It is generally treated with analgesics and NSAIDs: systemic use of corticoids is rare. Intraarticular injection of a steroid may be used to control an acute exacerbation. Injections may be repeated 2-3 times a year, but have the potential to cause joint destruction.
(iii)     Rheumatic fever : Corticoids are used only in severe cases with carditis and CHF, because they afford faster relief than aspirin, or in patients not responding to aspirin. Aspirin is given in addition and is continued after corticoids have been withdrawn.
(iv)      Gout: Corticoids (short course) should only be used in acute gouty arthritis when NSAIDs have failed to afford relief and colchicine is not tolerated. Intraarticular injection of a soluble glucocorticoid is preferable to systemic therapy.
Though they are uricosuric-use in chronic gout is not recommended.
2.         Collagen disease : Most cass of systemic lupus erythmatosus, polyarteritis nodosa, dermatomyositis, nephrotic syndrome, glomerulonephritis and related diseases need corticoids. They may be life saving. Therapy is generally started with high doses which are tapered to maintenance dose when remission occurs.
3.         Severe allergic reactions : Corticoids may be used for short periods in anaphylaxis, angioneurotics edema, urticaria and serum sickness. However, even i.v. injection of steroid takes 1-2 hours to act and is not a substitute for Adr (which acts immediately) in anaphylactic shock and angioedema lf larynx. Topical use is made in allergic conjunctivitis and rhinitis.
4.         Autoimmune diseases : Autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, active chronic hepatitis respond to corticoids. Prednisolone 1-2 mg / kg / day is given till remission, followed by gradual withdrawal of low-dose maintenance depending on the response. Remission may also be induced in severe cases of myasthenia gravis, in which their use is adjunctive to neostigmine.
5.         Bronchial asthma : Early institution of inhaled glucocorticoid therapy is now recommended in most cases needing inhaled b2 agonists almost daily. Systemic corticosteroids are used only for:

  • Status asthmaticus: give i.v. glucocorticoid: withdraw when emergency is over.
  • Acute asthma exacerbation: short course of high dose oral corticoid, followed gradual withdrawal.
  • Severe chronic asthma not controlled by inhaled steroids and bronchodilators: add low dose prednisolone daily or on alternate days.

6.         Other lung disease : Corticosteroids benefit aspiration pneumonia and pulmonary edema from drowning. Given during late pregnancy, corticoids accelerate lung maturation and surfactant production in the foetus and prevent respiratory distress syndrome at birth. Two doses of betamethasone 12 mg i.m. at 24 hour interval may be administered to the mother if premature delivery is contemplated.
7.         Infective diseases : Administered under effective chemotherapeutic cover, corticosteroids are indicated only in serious infective diseases to tideover crisis or to prevent complications. They are indicated in conditions like severe forms of tuberculosis, sever lepra reaction, certain forms of bacterial meningitis and Pneumocystis carinii pneumonia with hypoxia in AIDS patients.
8.         Eye diseases : Corticoids are used in a large number of inflammatory ocular diseases – may prevent blindness. topical instillation as eye drops or ointment is effective in diseases of the anterior chamber – allergic conjunctivitis, iritis, iridocyclitis, keratitis, etc. Ordinarily, steroids should not be used in infective conditions. But if inflammatio is severe, they may be applied in conjunction with an effective antibiotic. Steroids are contraindicated in herpes simplex keratitis and in ocular injuries. Posterior segment afflictions like retinitis, optic neuritis, uveitis require systemic steroid therapy. Retrobulbar injection is occasionally given to avoid systemic side effects.
9.         Skin diseases : Topical corticosteroids are widely employed and are highly effective in many eczematous skin disease. Systemic therapy is needed (may be life-saving) in pemphigus vulgaris, exfoliative dermatitis, Stevens Johnson syndrome and other severe afflications.
10.       Intestinal diseases : Ulcerative colitis, Crohn’s disease, coeliac disease are chronic inflammatory intestinal diseases with remissions and exacerbations. Corticoids are indicated during acute phases-may be used orally or as retention enema, if not responding to 5-amion salicylic acid compounds and other measures. Some advocate small maintenance doses to prevent relapses.
11.       Cerebral edema : Due to tumours, tubercular meningitis, etc. responds to corticoids. Dexa-or betamethasone are preferred because they donot have Na+ retaining activity. Their value in traumatic and poststroke cerebral edema is questionable. Large doses given soon after spinal injury may reduce the resulting neurological sequelae.
A short course of 2-4 week oral prednisolone can hasten recovery from Bell’s palsy and acute exacerbation of multiple sclerosis. In the latter, methyl prednisolone 1 g i.v. daily for 2-3 days may be given in the beginning.
Neurocysticercosis: when albendazole/praziquantel is used to kill cysticerci, prednisolone 40 mg/day or equivalent is given for 2-4 weeks to suppress the reaction to the dying larve.
12.       Malignancies : Corticoids are an essential component of combined chemotherapy of acute lymphatic leukaemia, Hodgkin’s and other lymphatic, because of their marked lympholytic action in these conditions. They have a secondary place in hormone responsive breast carcinomaact probably by causing pituitary-adrenal suppression-decreasing production of adrenal androgens which are converted to estrogens in the body.
Corticoids also afford symptomatic relief in other advanced malignancies by improving appetite and controlling secondary hypercalcaemia. For the latter, however, bisphosphonates are more effective and have superseded corticosteroids.
13.       Organ transplantation and skin allograft : High dose corticoids are given along with other immunosuppressants to prevent rejection reaction followed by low maintenance doses.
14.       Septic shock : High dose corticosteroid therapy for septic shock has been abandoned, because it worsens outcome. However, many such patients have relative adrenal insufficiency. Recent studies have documented beneficial effects of low-dose (hydrocortisone 100 mg TDS i.v. infusion for 5-7 das) therapy in patients who are adrenal deficient and require vasopressor drug despite adequate fluid replacement.
15.       Thyroid storm : Many patients in thyroid storm have concomitant adrenal insufficiency. Moreover, corticosteroids reduce peripheral T4 to T3 conversion. Hydrocortisone 100 mg TDS may improve outcome.
16.       To test adrenal-pituitary axis function : Dexamethasone suppresses adrenal pituitary axis at doses which do not contribute to steroid metabolities in urine responsiveness of the axis can be tested by measuring daily urinary steroid metabolite excretion.


These are extension of the pharmacological action occuring with prolonged therapy, and are a great limitation to the use of corticoids in chronic diseases.
A.        Mineralocorticoid : Sodium and water retention, edema, hypokalaemic alkalosis and a progressive rise in BP. These are now rare due to availability of highly selective glucocorticoids.
Gradual rise in BP occurs due to excess glucocorticoid action as well.
B.        Glucocorticoid

  • Cushing’s habitus: characteristic appearance with rounded face, narrow mouth, supraclavicular hump, obesity of trunk with relatively thin limbs.
  • Fragile skin, purple striae-typically on thighs and lower abdomen, easy bruising, telangiectasis, hirsutism. Cutaneous atrophy occurs with topical use also.
  • Hyperglycaemia, may be glycosuria, precipitation of diabetes.
  • Muscular weakness: proximal (shoulder, arm, pelvis, thigh) myopathy occurs occasionally-withdraw corticoids.
  • Susceptibility to infection: this is nonspecific; latent tuberculosis may flare; opportunistic infections with low grade pathogens.
  • Delayed healing: of wounds and surgical incisions.
  • Peptic ulceration: risk is doubled; bleeding and silent perforation of ulcers may occur. Dyspeptic symptoms are frequent with high dose therapy.
  • Osteoporosis: Specially involving vertebrae and other flat spongy bones. Compression fractures of vertebrae and spontaneous fracture of long   bones can occur, especially in the elderly. Radiological evidence of osteoporosis is an indication for withdrawal of corticoid therapy. Corticosteroid induced osteoporosis can be prevented / arrested by calcium supplements + vit D, bisphosphonates and by estrogen / androgen replacement therapy in females / males respectively.

A vascular necrosis of head of femur, humerous, or knee joint is an occasional abrupt onset complication of high dose corticosteroid therapy.

  • Posterior subcapsular cataract may develop after several years of use, especially in children.
  • Glaucoma: may develop in susceptible individuals after prolonged topical therapy.
  • Growth retardation: in children occurs even with small doses if given for long periods. Large doses do inhibit GH secretion, but this may in addition be a direct cellular effect of corticoids.
  • Foetal abnormalities: Cleft palate and other defects are produced inanimals, but have not been encountered on clinical use in pregnant women. The risk of abortion, still birth or neonatal death is not increased, but intrauterine growth retardation can occur after prolonged therapy, and neurological / behavioral disturbances in the offspring are feared. Prednisolone appears safter than dexa/beta methasone, because it is metabolized by placenta, reducing foetal exposure.

Prolonged corticosteroid therapy during pregnancy increases the risk of gestational diabetes, pregnancy induced hypertension and preeclampsia.

  • Psychiatric disturbances: mild euphoria frequently accompanies high dose steroid treatment. This may rarely progress to manic psychosis. Nervousness, decreased sleep and mood changes are noted by few. Rarely a depressive illness occurs after long term use.
  • Suppression of hypothalamo-pituitary-adrenal (HPA) axis: occurs depending both on dose and duration of therapy. In time, adrenal cortex atrophies and stoppage of exogenous steroid precipitates a withdrawal syndrome – malaise, fever, anorexia, nausea, postural hypotension, weakness, pain in muscles and joints and reactivation of the disease. Subjected to stress, these patients may go into acute adrenal insufficiency.

Any patient who has received > 20-25 mg/day hydrocortisone or equivalent for longer than 2-3 weeks should be put on a scheme of gradual withdrawal: 20 mg hydrocortisone / day reduction every wek and then still smaller fractions once this level has been achieved. Such patients may need protection with steroids if a stressful situation develops up to one year after withdrawal. Administration of ACTH during withdrawal does not hasten recovery because it has been found that adrenals recover earlier than pituitary and hypothalamus.
If a patient on steroid therapy develops and  infection – the steroid should not be discontinued despite its propensity to weaken host  defence. Rather, the dose may have to be increased to meet the stress of infection.
Measures that minimise HPA axis suppression are:

  • Use shorter acting steroids (hydrocortisone, prednisolone) at the lowest possible dose.
  • Use steroids for the shortest period of time possible.
  • Give the entire daily dose at one time in the morning.
  • Switch to alternate-day therapy if possible.

It has been found that moderate dose of a short acting steroid (e.g. preddnisolone) given at 48 hr interval did not cause HPA suppression, whereas the same total amount given in 4 divided 12 hourly doses produced marked HPA suppression. Alternate-day therapy also resulted in less immunological suppression-lower risk of infection. The longer acting steroids (dexamethasone, etc.) are not suitable for alternate-day therapy. Only problem with alternate day therapy is that many steroid dependent patients are incapacitated on the ‘off day’.

  • If appropriate, use local (dermal, inhaled, ocular, nasal, rectal, intrasynovial) preparations of a steroid with poor systemic availability (beclomethasone, triamcinolone acetonide, fluticasone, etc.)

The following disease are aggravated by corticosteroids. Since steroids may have to be used as a life-saving measures, all of these are relative contraindications:

  • Peptic ulcer
  • Diabetes mellitus
  • Hypertension
  • Viral and fungal infections
  • Tuberculosis and other infections
  • Osteoporosis
  • Herpes simplex keratitis
  • Psychosis
  • Epilepsy
  • CHF
  • Renal failure

Combination of any drug with corticosteroids in fixed dose formulation for internal use is banned.
Metyrapone : Inhibits 11-b hydroxylase in adrenal cortex and prevents synthesis of hydrocortisone ® increased ACTH release ® increased excretion of 11-desoxycortisol in urine. Thus, it is used to test the responsiveness of pituitary and its ACTH producing capacity.
Aminoglutethimide, trilostane and high doses of the antifungal drug Ketoconazole also inhibit steroidogenic enzymes-occasionally used to treat Cashing’s disease. Ketoconazole reduces gonadal steroid synthesis as well.
Glucocorticoid antagonist : The antiprogestin mifepristone acts as a glucocorticoid receptor antagonist as well. In cushing’s syndrome, it can suppress the manifestations of corticosteroid excess, but blockade of feedback ACTH inhibition leads to ovoersecretion of ACTH ® more hydrocortisone is produced, which tends to annual the GR blocking action of mifepristone. It is indicated only for inoperable cases of adrenal carcinoma and in patients with extopic ACTH secretion.