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• Congenital adrenal hyperplasia (CAH)

  A group of autosomal recessive disorders involving a deficiency in an enzyme crucial for cortisol and/or aldosterone synthesis
• Congenital adrenal hyperplasia (CAH)

  A group of autosomal recessive disorders involving a deficiency in an enzyme crucial for cortisol and/or aldosterone synthesis
• Clinical manifestations of CAH

  • Degree of cortisol deficiency
  • Degree of aldosterone deficiency
  • Accumulation of precursor adrenocortical hormones
• Clinical manifestations of CAH

  • Degree of cortisol deficiency
  • Degree of aldosterone deficiency
  • Accumulation of precursor adrenocortical hormones
• Supraphysiologic precursor concentrations


  • Lead to excess androgen production causing virilization
  • Lead to mineralocorticoid properties causing sodium retention and hypertension
• Supraphysiologic precursor concentrations


  • Lead to excess androgen production causing virilization
  • Lead to mineralocorticoid properties causing sodium retention and hypertension
• Phenotype


  Determined by the degree or type of gene deletion or mutation
• Phenotype


  Determined by the degree or type of gene deletion or mutation
• Resultant deficiency of the steroidogenic enzyme

  Influences the phenotype
• Resultant deficiency of the steroidogenic enzyme

  Influences the phenotype
• Enzymes and corresponding genes

  • CYP21A codes for 21-hydroxylase enzyme
  • CYP11B1 codes for 11-beta-hydroxylase enzyme
  • CYP17A1 codes for 17-alpha-hydroxylase/17,20-lyase enzyme
• Enzymes and corresponding genes

  • CYP21A codes for 21-hydroxylase enzyme
  • CYP11B1 codes for 11-beta-hydroxylase enzyme
  • CYP17A1 codes for 17-alpha-hydroxylase/17,20-lyase enzyme
• Many enzymes involved in cortisol and aldosterone synthesis are cytochrome P450 (CYP) proteins
• Many enzymes involved in cortisol and aldosterone synthesis are cytochrome P450 (CYP) proteins
• Two copies of an abnormal gene are needed for disease manifestation
• Two copies of an abnormal gene are needed for disease manifestation
• Phenotype spectrum


  • Clinically inapparent disease (occult or cryptic adrenal hyperplasia)
  • Mild disease expressed in adolescence or adulthood (nonclassic adrenal hyperplasia)
  • Severe disease that results in adrenal insufficiency in infancy with or without virilization and salt wasting (classic adrenal hyperplasia)
• Phenotype spectrum


  • Clinically inapparent disease (occult or cryptic adrenal hyperplasia)
  • Mild disease expressed in adolescence or adulthood (nonclassic adrenal hyperplasia)
  • Severe disease that results in adrenal insufficiency in infancy with or without virilization and salt wasting (classic adrenal hyperplasia)
• Most common form (due to 21-hydroxylase deficiency)

  • Salt-wasting phenotype
  • Simple virilizing phenotype
  • Nonclassic phenotype
• Most common form (due to 21-hydroxylase deficiency)

  • Salt-wasting phenotype
  • Simple virilizing phenotype
  • Nonclassic phenotype
• Patient education


  • Educate caretakers and patients about the disease nature for understanding adrenal cortical hormone replacement importance
  • Emphasize the need for extra glucocorticoids during illness/stress to prevent adrenal crises
  • Teach patients the significance of intramuscular (IM) glucocorticoid injections and proper administration techniques
• Patient education


  • Educate caretakers and patients about the disease nature for understanding adrenal cortical hormone replacement importance
  • Emphasize the need for extra glucocorticoids during illness/stress to prevent adrenal crises
  • Teach patients the significance of intramuscular (IM) glucocorticoid injections and proper administration techniques
• Clinical phenotype of CAH

  • Varies with enzyme deficiency nature and severity
• Clinical phenotype of CAH

  • Varies with enzyme deficiency nature and severity
• Most common form is 21-hydroxylase deficiency (CYP21)
• Most common form is 21-hydroxylase deficiency (CYP21)
• About 50% of classic CAH cases from CYP21A mutations have salt wasting due to low aldosterone
• About 50% of classic CAH cases from CYP21A mutations have salt wasting due to low aldosterone
• Initial neonatal sex determination can be unclear due to genital ambiguity in CAH cases
• Initial neonatal sex determination can be unclear due to genital ambiguity in CAH cases
• Clinical presentation in females

  • Classic Virilizing Adrenal Hyperplasia
  • Simple Virilizing Adrenal Hyperplasia
  • Nonclassic Adrenal Hyperplasia
  • 17-hydroxylase Deficiency
• Clinical presentation in females

  • Classic Virilizing Adrenal Hyperplasia
  • Simple Virilizing Adrenal Hyperplasia
  • Nonclassic Adrenal Hyperplasia
  • 17-hydroxylase Deficiency
• Clinical presentation in males

  • Classic Salt-Wasting Adrenal Hyperplasia
  • Simple Virilizing Adrenal Hyperplasia in Males
• Clinical presentation in males

  • Classic Salt-Wasting Adrenal Hyperplasia
  • Simple Virilizing Adrenal Hyperplasia in Males
• 21-hydroxylase deficiency in males may be mistaken for gastroenteritis or pyloric stenosis, delaying crucial glucocorticoid treatment
• 21-hydroxylase deficiency in males may be mistaken for gastroenteritis or pyloric stenosis, delaying crucial glucocorticoid treatment
• Steroidogenic acute regulatory (StAR) deficiency, classic 3-beta-hydroxysteroid dehydrogenase deficiency, or 17-hydroxylase deficiency can lead to ambiguous or female genitalia in males due to insufficient testosterone in early fetal stages
• Steroidogenic acute regulatory (StAR) deficiency, classic 3-beta-hydroxysteroid dehydrogenase deficiency, or 17-hydroxylase deficiency can lead to ambiguous or female genitalia in males due to insufficient testosterone in early fetal stages
• Other findings


  • Signs of Adrenal Insufficiency
  • Epinephrine Synthesis Impact
  • Simple Virilizing Adrenal Hyperplasia
  • Forms of Adrenal Hyperplasia and Hypertension
  • Diagnostic Factors in CAH due to CYP17A1 Defects
  • Adrenal Hyperplasia and Genital Development
  • Aldosterone Deficiency Presentation
  • 11-hydroxylase Deficiency Presentation
  • StAR Deficiency (Lipoid Adrenal Hyperplasia) Presentation
• Other findings


  • Signs of Adrenal Insufficiency
  • Epinephrine Synthesis Impact
  • Simple Virilizing Adrenal Hyperplasia
  • Forms of Adrenal Hyperplasia and Hypertension
  • Diagnostic Factors in CAH due to CYP17A1 Defects
  • Adrenal Hyperplasia and Genital Development
  • Aldosterone Deficiency Presentation
  • 11-hydroxylase Deficiency Presentation
  • StAR Deficiency (Lipoid Adrenal Hyperplasia) Presentation