Adrenogenital Syndrome: Symptoms, Complaints, Signs

The following symptoms and complaints may indicate adrenogenital syndrome (AGS):

The expression and severity of symptoms depend on which of the enzymes is defective and the extent to which there is residual activity of the affected enzyme, as well as on the sex of the affected person.

Main symptoms of 21-hydroxylase deficiency

• Consequences of hyperandrogenemia (increased production of androgens (male sex hormones)).
  • Girls:
    • Pseudohermaphroditism femininus – the genotype (XX) is female, but the girls look male
      • Intersexual genitalia already conspicuous at birth (clitoral hypertrophy (enlargement of the clitoris) in the presence of normal female internal genitalia (uterus/uterine and ovaries/ovaries))
      • Increasing virilization (masculinization).
      • Male hair pattern (upper lip beard, hair on the chest).
      • Premature pubic hair
      • Lack of breast development
      • Primary amenorrhea (no menstrual bleeding for more than three months with an already established cycle).
  • Boys:
    • Pseudopubertas praecox (form of premature sexual maturity in the juvenile (adolescent) type).
      • Hypogonadism (gonadal hypofunction, i.e., small testes) contrasts with increased development of secondary sexual characteristics (pubic hair and penis growth)
  • Both sexes:
    • If untreated, infantile tall stature (due to accelerated bone maturation) and short stature in adulthood occur (due to premature closure of the epiphyseal joints)
    • In adulthood, affected individuals often suffer from obesity, metabolic changes and fertility (fertility) disorders.
• Hypocortisolism (deficiency of cortisol).
  • Anorexia (loss of appetite)
  • Exhaustion, fatigue
  • Irritability
  • Weight loss
  • Hypercalcemia (excess calcium)
  • Hypoglycemia (hypoglycemia)
  • Vertigo (dizziness)

The residual activity of 21-hydroxylase determines the course:

• Classic adrenogenital syndrome with salt-wasting syndrome (“salt-wasting”-AGS; 75% of cases) – the enzyme is completely defunct
  • Occurs as early as infancy
  • Lack of mineralcorticoid action of insufficiently formed aldosterone; aldosterone is a mineralocorticoid that is also produced in the adrenal cortex. It represents an important link in the renin-angiotensin-aldosterone system (RAAS), which helps regulate blood pressure and salt balance. Hypoaldosteronism (deficiency of aldosterone) causes disturbances in salt balance with fluid loss (“salt wasting syndrome”).
    • Electrolyte disturbance (sodium ↓ , potassium ↑).
    • Emesis (vomiting), diarrhea (diarrhea), desiccosis (dehydration), weakness in drinking, apathy (apathy), hypotension (low blood pressure), hyponatremia (sodium deficiency), hyperkalemia (potassium excess), metabolic acidosis/metabolic acidosis).
    • Cortisol deficiency and hyperandrogenemia
• Classic adrenogenital syndrome without salt wasting syndrome (“simple virilizer”-AGS; 25% of cases) – residual 21-hydroxylase activity of 1-2%.
  • Occurs as early as infancy
  • Cortisol deficiency and hyperandrogenemia
• Nonclassical adrenogenital syndrome (“late-onset” AGS) – residual 21-hydroxylase activity of 20-60%; mild symptomatology.
  • No prenatal masculinization; usually does not manifest until puberty or adulthood
  • No salt loss
  • No adrenal insufficiency (adrenal weakness)
  • In girls: Hirsutism (increased terminal hair (long hair) in women, according to the male distribution pattern (androgen-dependent)), oily skin, acne, deep voice, menstrual disorders.
  • Premature pubic hair
  • Disruption of fertility (fertility)

Main symptoms of 11β-hydroxylase deficiency

• There is increased production of mineralcorticoid-acting deoxycorticosterone (DOC) with mineralcorticoid excess:
  • Hypertension (high blood pressure)
  • Hyperkalemia (excess potassium)
• In the female sex: virilization (masculinization).

Main symptoms of 17α-hydroxylase deficiency

• There is increased production of mineralcorticoid-acting deoxycorticosterone (DOC) with mineralcorticoid excess:
  • Hypertension
  • Hyperkalemia
  • Hyponatremia (sodium deficiency)
  • Metabolic alkalosis (metabolic disorder characterized by an increase in bicarbonate or loss of hydrogen ions).
• In the female sex: primary amenorrhea (absence of the first menstrual period).
• In the male sex: feminization (formation of male sexual characteristics is absent).
• Lack of pubertal development in both sexes.