What are the symptoms of Congenital Adrenal Hyperplasia (CAH)?

Symptoms of Congenital Adrenal Hyperplasia (CAH)

Congenital adrenal hyperplasia presents with distinct symptoms depending on the severity of enzymatic defect, ranging from severe salt-wasting forms to milder nonclassical variants, with manifestations affecting multiple body systems.

Clinical Presentation by CAH Type

Classic CAH (Severe Form)

• Female infants: Genital virilization and ambiguity present at birth due to prenatal androgen exposure 1
• Male infants: Normal external genitalia at birth but may have hyperpigmentation 2, 3
• Salt-wasting crisis (in 75% of classic cases):
  • Vomiting, dehydration, and hypotension 4
  • Hyponatremia and hyperkalemia 4, 2
  • Potentially fatal if untreated 3
• Cortisol deficiency symptoms:
  • Fatigue, weakness, weight loss 4
  • Hypotension 4
• Growth abnormalities:
  • Advanced bone age 5
  • Accelerated linear growth velocity in childhood 5, 2
  • Ultimately diminished final height 5, 2

Nonclassical CAH (Milder Form)

• Children:
  • Premature development of pubic hair 2
  • Early growth spurt 2
  • Advanced bone age 2
• Adolescent/Adult females:
  • Hirsutism and acne 2, 6
  • Menstrual irregularities (primary amenorrhea or secondary amenorrhea) 2
  • Polycystic ovary-like syndrome 5, 2
  • Temporal baldness 2
  • Infertility 5, 2
• Adolescent/Adult males:
  • Early beard growth 2
  • Severe cystic acne 2
  • Oligozoospermia or diminished fertility 5, 2

Behavioral and Psychological Manifestations

• Females with CAH may display:
  • "Tomboyish" personality 1
  • Preference for toys typically favored by boys 1
  • More rough play than unaffected girls 1
  • Possible gender dysphoria in adolescence or adulthood (in a small subset) 1
  • Higher likelihood of bisexual or homosexual interests compared to unaffected women 1

Fertility Issues

• Females: Pregnancy rates correlate with severity of enzyme deficiency (lower rates in salt-wasting forms) 5
• Males: Testicular adrenal rest tumors are a common cause of subfertility 5
• Subfertility is frequently found in both sexes 5, 7

Long-term Complications

• Metabolic: Insulin resistance may develop 1
• Reproductive: Ongoing hormonal imbalances affecting fertility 5, 7
• Growth: Reduced adult height due to advanced bone age and premature growth plate closure 5

Warning Signs Requiring Immediate Medical Attention

• In newborns: Ambiguous genitalia in phenotypic males requires immediate specialist consultation to rule out disorders of sex development, including CAH 1
• Salt-wasting crisis: Vomiting, dehydration, and shock in the first weeks of life 4, 7

Early diagnosis and appropriate treatment with hormone replacement therapy can prevent life-threatening complications and improve long-term outcomes for patients with CAH 4, 7.