Endocrine · Year 2 · from Endocrine
Case 1: Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)
Patient Demographics
- Age: 5 days
- Sex: Female (46,XX)
- Occupation: N/A (neonate)
Chief Complaint
"The baby has ambiguous genitalia."
History of Present Illness
A 5-day-old infant, born at term via uncomplicated vaginal delivery, is referred for evaluation of ambiguous genitalia noted at birth. The parents are non-consanguineous with no family history of adrenal disorders or infant deaths. The pregnancy was uncomplicated with no exposure to androgens. The newborn screening test is pending. The infant has been breastfeeding well but the mother notes the baby seems more sleepy over the past day and has not been feeding as vigorously.
Physical Examination
- Vital Signs: HR 160 bpm, BP 58/35 mmHg (low), Temp 36.2°C
- General: Sleepy, mildly dehydrated appearing
- Genitalia:
- Clitoromegaly (phallus-like structure ~2 cm)
- Single urogenital opening
- Fused, rugated labioscrotal folds with hyperpigmentation
- No palpable gonads
- Prader stage IV virilization
- Skin: Hyperpigmentation of areolae and genitalia
- Abdomen: No palpable masses
Workup
- Laboratory Studies:
- Sodium: 126 mEq/L (low)
- Potassium: 6.8 mEq/L (high)
- Glucose: 52 mg/dL (low)
- 17-hydroxyprogesterone: 15,000 ng/dL (markedly elevated, normal <100)
- Cortisol: 2.1 μg/dL (low)
- ACTH: 520 pg/mL (markedly elevated)
- Aldosterone: Low
- Plasma renin activity: Markedly elevated
- Testosterone: Elevated for female infant
- Androstenedione: Elevated
- Karyotype: 46,XX
- Pelvic ultrasound: Normal uterus and ovaries present
- Genetic testing: Homozygous mutation in CYP21A2 gene
Diagnosis
Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency - salt-wasting form
Treatment
ACUTE (adrenal crisis):
- IV normal saline bolus for volume resuscitation
- IV dextrose for hypoglycemia
- IV hydrocortisone 25 mg/m² bolus, then 50-100 mg/m²/day divided every 6 hours
- Calcium gluconate and insulin/glucose for hyperkalemia if severe
- Fludrocortisone 0.05-0.2 mg daily once oral intake established
LONG-TERM:
- Glucocorticoid replacement: Hydrocortisone 10-15 mg/m²/day divided TID
- Mineralocorticoid replacement: Fludrocortisone 0.05-0.2 mg daily
- Sodium chloride supplementation in infancy
- Stress dosing education (2-3x maintenance during illness)
- Surgical: Feminizing genitoplasty (timing and extent controversial)
- Psychology/endocrinology multidisciplinary follow-up
- Monitor: Growth, bone age, 17-OHP levels, androstenedione
Clinical Pearl
21-hydroxylase deficiency accounts for ~95% of CAH cases. The enzyme block prevents cortisol and aldosterone synthesis while accumulating precursors that are shunted to androgen production. In classic salt-wasting CAH, both glucocorticoid and mineralocorticoid deficiency occur, leading to adrenal crisis (hyponatremia, hyperkalemia, hypotension, hypoglycemia) typically in the first 2 weeks of life. Excess adrenal androgens cause virilization of 46,XX females in utero. ACTH elevation (due to lack of cortisol negative feedback) causes hyperpigmentation via melanocyte-stimulating hormone effects. Newborn screening for 17-hydroxyprogesterone can detect CAH before adrenal crisis occurs.
Clinical Image
Adrenal steroidogenesis pathway showing the block at 21-hydroxylase and resulting accumulation of 17-hydroxyprogesterone with shunting to androgen synthesis.
Image Source: Wikimedia Commons - "Steroidogenesis pathway" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Steroidogenesis.svg