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									Adrenal Gland
 Cortex: Secretes steroidal hormones.
 Medulla: Secretes adrenaline and
Deficiency of adrenal cortical hormones

        Addison’s disease
 NaturallyOccurring Glucocorticoids –
  Hydrocortisone .
 Synthesized from cholesterol.

 Rate of secretion - circadian rhythm
 Pulses of ACTH that peak in the early
  morning hours and after meals.
 Plasma  - bound to circulating

 Corticosteroid-bindingglobulin -
  binds about 90% of the circulating

 5–10%    - free form.
T   ½ - 60–90 minutes.
 T ½ - stress, hypothyroidism, or
  liver disease .

 Metabolized   in the liver .
 One third of the cortisol - excreted in
  the urine as dihydroxy ketone

 Mechanism    of Action
 Enter target cells by simple diffusion.
 Bind to cytosolic receptors.
 The steroid receptor complex is translocated
  into the nucleus.
 Where it regulates the synthesis of specific
Synthetic Corticosteroids
Short acting:
 Hydrocortisone-- short and rapid acting with
  equal guco and mineralocorticoid activity
 Prednisolone—more potent, more
  glucocorticoid activity
Intermediate acting:
 Triamcinolone –no mineralocorticoid activity
Long acting:
 Betamethasone
 Dexamethasone
Most potent, widely used ,
no mineralocorticoid activity
 Aldosterone
 Fludrocortisone
 Desoxycorticosterone
Inhalation steroid preparations:
 Beclomethasone
 Budesonide
 Fluticasone
 Triamcinolone
        Physiologic Effects

 Widespread effects - influence the function of
  most cells in the body
 Permissive effects.
Metabolic Effects

   Dose-related effects - carbohydrate, protein,
    and fat metabolism

Carbohydrate metabolism :
   stimulate and are required for
    gluconeogenesis and glycogen synthesis in
    the fasting state .
   increase serum glucose levels
   inhibit the uptake of glucose by muscle cells
Lipid metabolism
   + Lipogenesis
-  Lipolysis
 Net increase in fat deposition.
 Prolonged use - cause redistribution of
  body fat ; deposited over the neck, face,
  shoulder etc.
Protein metabolism

 Catabolic
 Increased  breakdown
 Mobilization of amino acids for glucose
Anti-Inflammatory and
Immunosuppressive Effects

   Reduce the manifestations of inflammation.

   Suppressive effects on the inflammatory
    cytokines and chemokines and on other
    mediators of inflammation
   inhibit the functions of tissue macrophages and
    other antigen-presenting cells

   reducing the prostaglandin, leukotriene, and
    platelet-activating factor
Other Effects

 Chronically suppress the pituitary
  release of ACTH, GH, TSH, and LH.
 Development of the fetal lungs
 Peptic ulcer.
 Bone: Osteoporosis with pathologic
 Cortisol deficiency - impaired renal
Therapeutic uses
   Endocrinal uses
Acute adrenal insufficiency
 Parenteral hydrocortisone
 Correction of fluid and electrolyte
 Treatment of precipitating factors.
 Chronic     adrenal insufficiency:
   Addison's Disease
   Hydrocortisone has some mineralocorticoid
Congenital Adrenal Hyperplasia
    Defect is- lack of 21 -hydroxylase
       Decrease in cortisol synthesis
          Increase in ACTH release
      Gland hyperplastic, produces 17-
   Divert to androgen pathway- virilization

        Treated by hydrocortisone
Cushing's Syndrome

 Bilateral adrenal hyperplasia secondary to an
  ACTH-secreting pituitary adenoma
 Hypersecretion - rounded, plethoric face and
  trunk obesity .
 Muscle wasting; thinning, purple striae, and
  easy bruising of the skin; poor wound healing;
  and osteoporosis.
 Mental disorders, hypertension, and diabetes.
 Treatment –
 surgical removal of the tumor producing
  ACTH or cortisol,
 irradiation of the pituitary tumor, or resection of
  one or both adrenals

 Soluble hydrocortisone -continuous I.V.
  infusion on the day of surgery
 Dose must be reduced slowly to normal
  replacement levels, since rapid reduction in
  dose may produce withdrawal symptoms

 Excessive production of aldosterone by an
  adrenal adenoma
 Primary aldosteronism - hypertension,
  weakness, and tetany are related to the
  continued renal loss of potassium,

which leads to hypokalemia, and elevation of
serum sodium concentrations
      Diagnostic Purposes
   Dexamethasone suppression test
   Diagnosis of Cushing's syndrome
Stimulation of Lung Maturation in
the Fetus
 I.M. betamethasone
 Less Maternal protein binding
 Placental metabolism – reduced.
Nonendocrinal uses

 Beneficial effects - due to their
  antiinflammatory and immunosuppressant
 Rheumatoid arthritis
 Osteoarthritis - Intra-articular injection
 Gout
 Rheumatic fever
 Allergic diseases
   Bronchial asthma

   Skin diseases

   Ocular diseases

   Hematological disorders -Autoimmune
    haemolytic anemias, leukaemia, lymphomas,
    Hodgkin’s disease, multiple myeloma etc.
   Intestinal diseases - ulcerative colitis -
    Methyl prednisolone - as retention enema

   Organ transplantation

   Hypercalcemia

 A single dose - practically harmless
 Undesirable effects - supraphysiological
  doses for more than 2-3 weeks
        Metabolic Effects

 >= 100 mg of hydrocortisone or more
 2 weeks - iatrogenic Cushing's syndrome.

 Cushing’s habitus: Abnormal fat distribution
  causes peculiar features with moon face,
  buffalo hump and thin limbs.
 Hyperglycemia, precipitation of diabetes
  mellitus or aggravation of pre-existing
 GIT: Peptic ulceration sometimes with
  hemorrhage or perforation.
 Bone: Osteoporosis with pathologic
 Bacterial and mycotic infections, may be
  masked by the corticosteroids
 Severe myopathy
 Hypomania or acute psychosis may
   Cortisone and hydrocortisone -
   cause some sodium and fluid retention
    and loss of potassium
   Patients with heart disease, even small
    degrees of sodium retention may lead to
    heart failure
   Minimized - synthetic non–salt-retaining
    steroids .
Adrenal Suppression

 More than 2 weeks .
 2–12 months for the hypothalamic-pituitary-
  adrenal axis to function acceptably .
 Long term treatment- HPA suppression
 Aprupt withdrawal - malaise, fever,
  weakness, joint pain, reactivation of
 Avoided by gradually tapering the dose
Special Precautions

 Hyperglycemia, glycosuria, sodium retention
  with edema or hypertension, hypokalemia,
  peptic ulcer, osteoporosis, and hidden
 Dosage – low , intermittent administration .
 Short acting drug.
 Administer large dose in the morning.
 Topical use – recommended.

   Glucocorticoids must be used with
    great caution in patients with peptic
    ulcer, heart disease or hypertension with
    heart failure, certain infectious illnesses
    such as varicella and tuberculosis,
    psychoses, diabetes, osteoporosis, or
 Aldosterone
 Fludrocortisone,a synthetic corticosteroid,
  is the most commonly prescribed salt-
  retaining hormone.
 zona glomerulosa of the adrenal cortex
Physiologic & Pharmacologic
 Promote   the reabsorption of sodium from
  the distal part of the distal convoluted
  tubule and from the cortical collecting
  renal tubules.

 Secreted at the rate of 100–200 mcg/d in
  normal individuals with a moderate dietary
  salt intake .
 Excreted free or as the 3-oxo glucuronide

 Synthetic steroid analog.
 Strong mineralocorticoid and relatively mild
  glucocorticoid effect.
 Available for oral or parenteral
 Used in conjunction with cortisol in the
  treatment of adrenal insufficiency.
Antagonists of glucocorticoids
 Metyrapone
 Aminoglutethimide
 Ketoconazole
 Mifepristone (RU 486)
 Mitotane
 Trilostane
 Abiraterone

 Blocks the conversion of cholesterol to
 Reduce steroid secretion in patients with
  Cushing's syndrome due to
  adrenocortical cancer

 Inhibits 11-hydroxylation and thus the
  synthesis of cortisol
 Used in Cushing's syndrome, specially in
  pregnant women, since this is the only
  safe antagonist.
 Also used in tests of adrenal function
 Hirsutism ,oedema are the adverse effects
 An antifungal imdazole
 Inhibit the enzymes required for steroids
 Hepatotoxicity

Mifepristone (RU486)
 Has strong antiprogestin activity
 High doses block glucocorticoid receptors
 Mainly used as contraceptive,
 Reverse the cushingoid phenotype
Antagonists of mineralocorticoids
 Used in treatment of Primary
 Androgen antagonist - Used in Hirsutism
 Adverse effects - hyperkalemia, cardiac
  arrhythmia, menstrual abnormalities,
Eplerenone- approved for hypertension
Drospirenone (progestin) - antagonizes the
  effects of aldosterone

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