Adrenocorticoids

• Aldosterone is the primary mineralocorticoid hormone that regulates sodium, potassium, and water balance.
• Cortisol is the major glucocorticoid hormone produced by the adrenal cortex.
• Glucocorticoids are involved in metabolism regulation and have anti-inflammatory effects.
• Cortisol (hydrocortisone) is the major glucocorticoid produced by the adrenal cortex.
• The hypothalamic-pituitary-adrenal axis plays a role in regulating stress responses through the release of CRH from the hypothalamus, ACTH from the pituitary gland, and cortisol from the adrenal cortex.
• The hypothalamus secretes CRH (corticotropin-releasing hormone) to stimulate ACTH release from the anterior pituitary gland.
• ACTH binds to receptors on the zona fasciculata cells of the adrenal cortex, leading to increased production and secretion of steroid hormones such as cortisol.
• Zona fasciculata produces cortisol, which helps maintain homeostasis during stressful situations.
• Cholesterol is converted into pregnenolone, which can be further processed into other steroid hormones.
• Adrenal Gland


  • Adrenal cortex – mineralocorticoids, glucocorticoids, adrenal androgens (androstenedione & dehydroepiadrosterone)
  • Adrenal medulla – catecholamines (Epinephrine and Norepinephrine)
• Adrenocorticosteroids


  • Bind to specific intracellular cytoplasmic receptors in target tissue
  • Production is diurnal with a peak early in the morning and a smaller peak in the late afternoon
• Natural glucocorticoids


  • Cortisone
  • Hydrocortisone
• Semi-synthetic and synthetic glucocorticoids

  • Prednisolone
  • Fludrocortisone
  • Triamcinolone
  • Dexamethasone
  • Fluocinonide
• Glucocorticoids


  • Preparations available: systemic, topical, inhalation, ophthalmic, otic, nasal
  • Discontinuation/withdrawal of therapy should be gradual after long-term use
• Classification of Adrenocorticosteroids


  • Short to medium-acting glucocorticoids
  • Intermediate-acting glucocorticoids
  • Long-acting glucocorticoids
  • Mineralocorticoids
• Short to medium-acting glucocorticoids

  • Hydrocortisone (cortisol)
  • Cortisone
  • Prednisone
  • Prednisolone
  • Methylprednisolone
  • Meprednisone
• Intermediate-acting glucocorticoids


  • Triamcinolone
  • Paramethasone
  • Fluprednisolone
• Long-acting glucocorticoids


  • Betamethasone
  • Dexamethasone
• Mineralocorticoids


  • Fludrocortisone
  • Desoxycorticosterone acetate
• Physiologic effects of adrenocorticosteroids

  1. Carbohydrate and protein metabolism

  2. Lipid metabolism

  3. Electrolyte and water balance

  4. Cardiovascular system

  5. Skeletal muscle

  6. CNS

  7. Formed elements of blood

  8. Anti-inflammatory and Immunosuppressive action

  9. Other effects
• Aldosterone


  Promotes reabsorption of Na+ from the distal convoluted tubules and proximal collecting tubules; loosely coupled with K+ and H+ ions, t1/2 15-20mins, excreted in the urine as tetrahydroaldosterone and 3-oxo-glucoronide
• Deoxycortisone


  As precursor of aldosterone
• Fludrocortisone


  Most widely used; both mineralocorticoid and glucocorticoid activity
• Disease in which patients lack cortisol from zona fasiculata, and thus lacks negative feedback that suppresses ACTH production
• Result: overproduction of ACTH, skin color will darken
• Diagnosis of Cushing's syndrome

  1. Hypersecretion of glucocorticoids that results either from excessive release of ACTH or adrenal tumor

  2. Dexamethasone suppression test is used to diagnose the cause

  3. Suppresses cortisol release in pituitary dependent Cushings, but not when it is released from adrenal tumors
• Replacement therapy for congenital adrenal hyperplasia

  1. Group of diseases resulting from an enzyme defect in the synthesis of one or more of the adrenal steroid hormones

  2. Leads to virilization in females due to overproduction of adrenal androgens

  3. Treatment: give enough steroids to normalize the patient's hormone levels of CRH and ACTH
• Therapeutic uses of adrenal corticosteroids

  • Relief of inflammatory symptoms
  • Infectious Disease – P. carinii pneumonia, H. influenzae type b meningitis
  • Ocular disease
  • Skin diseases
  • GIT diseases
  • Hepatic diseases
  • Malignancies
  • Cerebral edema
  • Miscellaneous diseases
• Side effects of long term usage

  • Hyperglycemia
  • Fluid and electrolyte disturbances
  • Increased susceptibility to infection
  • Myopathy
  • Osteoporosis
  • Osteonecrosis
  • Cataracts
  • Behavioral disturbances
  • Iatrogenic adrenal insufficiency
• Glucocorticoids are involved in metabolism, immune function, and inflammation.
• Pregnenolone is synthesized from cholesterol via side chain cleavage enzymes.