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• Adrenal cortex


  Secretes two types of corticosteroids (glucocorticoids and mineralocorticoids) and the adrenal androgens

  
• Zones of the adrenal cortex


  • Zona glomerulosa (produces mineralocorticoids)
  • Zona fasciculata (synthesizes glucocorticoids)
  • Zona reticularis (secretes adrenal androgens)

  
• Mineralocorticoids


  Regulate salt and water metabolism
• Glucocorticoids


  Involved with metabolism and response to stress

  
• Adrenal androgens


  Secreted by the inner zones of the adrenal cortex

  
• Secretion of steroids by the adrenal cortex


  1. Controlled by pituitary adrenocorticotropic hormone (ACTH) in response to hypothalamic corticotropin-releasing hormone (CRH)

  2. Glucocorticoids serve as feedback inhibitors of ACTH and CRH secretion

  
• Exogenously administered glucocorticoids can suppress the hypothalamic-pituitary-adrenal axis and inhibit endogenous cortisol production, leading to adrenal insufficiency when the exogenous glucocorticoid is withdrawn
• Glucocorticoids and mineralocorticoids differ in their metabolic (glucocorticoid) and electrolyte-regulating (mineralocorticoid) activity
• Glucocorticoid receptors


  Widely distributed throughout the body
• Mineralocorticoid receptors


  Confined mainly to excretory organs, such as the kidney, colon, salivary glands, and sweat glands
• Mechanism of action of corticosteroids


  1. Corticosteroids bind to specific intracellular cytoplasmic receptors in target tissues

  2. The receptor-hormone complex dimerizes, recruits coactivator (or corepressor) proteins, and translocates into the nucleus

  3. In the nucleus, it acts as a transcription factor to turn genes on (when complexed with coactivators) or off (when complexed with corepressors)

  
• Glucocorticoids


  Promote normal intermediary metabolism, increase resistance to stress, alter blood cell levels in plasma, possess anti-inflammatory action, and affect other systems

  
• Mineralocorticoids


  Help to control fluid status and concentration of electrolytes, especially sodium and potassium
• Aldosterone


  Acts on mineralocorticoid receptors in the distal tubules and collecting ducts in the kidney, causing reabsorption of sodium, bicarbonate, and water, and decreasing reabsorption of potassium
• Elevated aldosterone levels may cause alkalosis and hypokalemia, retention of sodium and water, and increased blood volume and blood pressure
• Spironolactone


  A mineralocorticoid receptor antagonist used to treat hyperaldosteronism
• Therapeutic uses of corticosteroids


  • Replacement therapy for primary adrenocortical insufficiency (Addison disease)
  • Replacement therapy for secondary or tertiary adrenocortical insufficiency
  • Diagnosis of Cushing syndrome
  • Replacement therapy for congenital adrenal hyperplasia (CAH)
  • Relief of inflammatory symptoms

  
• Addison disease is caused by adrenal cortex dysfunction and requires replacement therapy with hydrocortisone and fludrocortisone

  
• Secondary or tertiary adrenocortical insufficiency is caused by a defect in CRH production by the hypothalamus or in ACTH production by the pituitary, and is treated with hydrocortisone

  
• Cushing syndrome is caused by hypersecretion of glucocorticoids and is diagnosed using cortisol levels and the dexamethasone suppression test

  
• Congenital adrenal hyperplasia (CAH) is a group of diseases resulting from an enzyme defect in the synthesis of one or more of the adrenal steroid hormones, leading to virilization in females, and is treated with corticosteroids to suppress ACTH and normalize hormone levels

  
• Corticosteroids significantly reduce inflammation associated with rheumatoid arthritis and inflammatory skin conditions
• Congenital adrenal hyperplasia (CAH)


  Condition caused by overproduction of adrenal steroid hormones, leading to virilization in females due to overproduction of adrenal androgens

  
• Treatment of CAH


  1. Administration of sufficient corticosteroids to suppress release of CRH and ACTH and normalize hormone levels, decreasing production of adrenal androgens

  2. Choice of replacement hormone depends on the specific enzyme defect

  
• CAH


  • Chronic disease
  • Treatment based on glucocorticoids or mineralocorticoid to reduce androgen, as well as regulate sodium and potassium levels
  • Surgery of the vagina and clitoris is an option
• Decreased steroid production


  Leads to increased ACTH, which causes adrenal hyperplasia
• Decreased aldosterone


  Leads to hypoglycemia, hypokalemia, and hypoglycemia/hypovolemia
• Increased androgen


  Leads to virilization
• Corticosteroids


  Significantly reduce inflammation associated with various conditions, including rheumatoid arthritis, inflammatory skin conditions, asthma, and inflammatory bowel disease
• Corticosteroids


  Not curative in these disorders, but important for symptom control
• Conditions treated with corticosteroids


  • Corneal inflammation, atopic (contact) and seborrheic dermatitis, pruritus, psoriasis, sunburn
• Corticosteroids in allergies


  Beneficial in the treatment of allergic rhinitis, as well as drug, serum, and transfusion allergic reactions
• Corticosteroids used for nasal insufflation or oral inhalation


  • Beclomethasone, fluticasone, mometasone
• Inhaled glucocorticoids


  Often first-line therapy for allergic rhinitis and asthma, minimizing systemic effects

  
• Acceleration of lung maturation


  1. Fetal cortisol is a regulator of lung maturation

  2. Betamethasone or dexamethasone administered to the mother within 48 hours preceding premature delivery can accelerate lung maturation in the fetus and prevent respiratory distress syndrome
• Corticosteroids


  • Immunosuppressive and anti-inflammatory activities are highly helpful in severe immune-related diseases such as rheumatoid arthritis, allergic reactions, hemolytic anemia, idiopathic thrombocytopenic purpura, active chronic hepatitis, Stevens–Johnson's syndrome, and to avoid allograft rejection
• Other conditions treated with corticosteroids


  • Cerebral edema, malignancies (lymphocytic leukemias and lymphomas), septic shock, thyroid storm, various ocular inflammatory conditions, collagen diseases

  
• Corticosteroids


  Suppress immunity, which can be beneficial in some conditions but detrimental in viral infections
• Pharmacokinetics of corticosteroids


  • Readily absorbed after oral administration, can also be administered intravenously, intramuscularly, intraarticularly, topically, or via inhalation or intranasal delivery
  • All topical and inhaled glucocorticoids are absorbed to some extent and can suppress the hypothalamic–pituitary–adrenal (HPA) axis
  • Metabolized by the liver and excreted by the kidney
  • Half-life may increase in hepatic dysfunction

  
• Prednisone in pregnancy


  Preferred because it minimizes steroid effects on the fetus, as it is converted to the active compound prednisolone in the maternal liver but not the fetal liver