Chapter 34. Endocrinology

Virilization of Females

(Female Pseudohermaphroditism)

• Most commonly: enzymatic deficiencies in cortisol pathway → excessive ACTH, leading to congenital adrenal hyperplasia and excess androgen production
• Most common is 21-hydroxylase deficiency
• Other causes include virilizing tumors and maternal use of androgens (systemic or topical)

Inadequate Male Virilization

(Male Pseudohermaphroditism)

Three possible etiologies:

• Decreased androgen production (nonvirilizing adrenal hyperplasia, inadequate Müllerian inhibiting substance)
• Decreased end-organ response to androgen (testicular feminization—due to abnormal receptor)
• 5α-reductase deficiency

Abnormal Gonadal Differentiation

• True hermaphroditism (both testicular and ovarian tissue present in one individual)
• Gonadal dysgenesis: partial (with one functional gonad, one streak) or total (two streak gonads; chance of neoplastic transformation high in Y-chromosome form)

Chromosomal Abnormalities or Associations

• Trisomies 13 and 18
• Triploidies
• Smith–Lemli–Opitz syndrome
• Rieger's syndrome
• CHARGE association
• VACTERL association

• Caused by mutations in DAX1 and SF1 genes
• These genes encode a nuclear transcription factor expressed in both gonads and the adrenal cortex
• Results in deficiency of all adrenal steroids

Pseudohypoaldosteronism:

• Mutation of aldosterone receptor gene or of epithelial sodium channel genes
• Clinical presentation with salt wasting, hyperkalemia, shock, dehydration

Familial unresponsiveness to ACTH:

• Results in normal mineralocorticoid activity, with diminished glucocorticoid activity
• Clinical presentation with profound hypoglycemia and hypotension

StAR (acute steroid regulatory protein) deficiency:

• Mediates transfer of cholesterol across mitochondrial membrane
• Adrenals are large and lipid laden
• Decreased levels of all adrenal steroids
• 46 XY males appear female or only minimally virilized

3-β-Hydroxysteroid dehydrogenase deficiency:

• Catalyzes the conversion of pregnenolone, 17-OH-pregnenolone, DHEA, and androstenedione
• Clinical manifestations:
  • Salt-wasting adrenal crisis
  • 46, XX female may be mildly virilized
  • 46, XY male is undervirilized
  • Elevated substrates: DHEA and 17-OH-pregnenolone
  • Elevated 17-OH-progesterone

21-Hydroxylase deficiency:

• Most common cause of CAH
• Classic salt-wasting CAH:
  • Adrenal crisis with shock, hyperkalemia, and hyponatremia
  • Polyuria
  • Presentation at 1–4 wk of life
  • 46, XX infants are virilized

Exogenous glucocorticoid administration:

• Infants receiving high-dose glucocorticoids for >10–14 d are at high risk
• May require hydrocortisone for unexplained hypotension or hypoglycemia or in preparation for surgery

Bilateral adrenal hemorrhage:

• Can be seen in LGA infants with difficult delivery/coagulopathy
• Asymptomatic infants can have suprarenal calcifications on plain film of abdomen

• 46, ...