Congenital Adrenal Hyperplasia (CAH) Case Discussion & Key Points
Model Case Presentation
Patient Demographics
Name: Baby Priya, Age: 18 days, Karyotype: 46,XX (Genetic Female), Informant: Mother (Reliable)
Chief Complaints
- Ambiguous genitalia noticed at birth
- Repeated vomiting for 5 days
- Poor feeding and excessive crying – 5 days
- Failure to regain birth weight
History Summary
Baby was born at term via NVD with birth weight 2.9 kg. Immediately after birth, the midwife noticed ambiguous genitalia and the sex could not be assigned. The baby fed well for the first 10 days. Since day 12, the mother noticed increasing vomiting (non-bilious, non-projectile), refusal to feed, excessive crying, and noticeable weight loss. No antenatal steroids were given to the mother. No family history of similar illness or ambiguous genitalia. Parents are non-consanguineous.
No history of maternal virilization, use of androgens, or anti-epileptic drugs during pregnancy. No sibling deaths in neonatal period (important clue for undiagnosed salt-wasting in prior affected males).
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Weight | 2.6 kg (birth wt 2.9 kg) | Weight loss >10% — adrenal crisis |
| HR | 180/min | Tachycardia — dehydration/shock |
| BP | Low; poor pulses | Hypovolemic shock |
| Skin | Hyperpigmentation of genitalia and areolae | ↑ACTH stimulating melanocortin receptors |
| External Genitalia | Clitoromegaly, labioscrotal fusion, single perineal orifice (urogenital sinus) — Prader Stage III | Virilized female (46,XX DSD) |
| Uterus/ovaries | Present on pelvic ultrasound | Confirms genetic female with Müllerian structures |
General: Sunken eyes, dry mucous membranes, decreased skin turgor, lethargic infant — signs of severe dehydration and impending adrenal crisis.
No palpable gonads in the labioscrotal folds (gonads not descended = ovaries, i.e., genetic female until proven otherwise).
✅ Complete Diagnosis
Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) — Classic Salt-Wasting Form — with Virilized Female (46,XX DSD, Prader Stage III) in Adrenal Crisis with Hypovolemic Shock.
📝 History — Exam Q&A
CAH is a group of autosomal recessive disorders caused by enzyme deficiencies in the cortisol biosynthesis pathway, leading to reduced cortisol, raised ACTH, and compensatory adrenal hyperplasia with accumulation of precursors shunted toward androgen production.
Most common cause: 21-Hydroxylase deficiency (21-OHD) — accounts for ~90–95% of all CAH. Gene: CYP21A2 on chromosome 6p21.3.
Second most common: 11β-Hydroxylase deficiency (~5–8%) — CYP11B1 gene.
| Form | Frequency | Cortisol | Aldosterone | Androgens | Clinical Features |
|---|---|---|---|---|---|
| Classic — Salt-Wasting | ~75% of classic | ↓↓ | ↓↓ | ↑↑ | Ambiguous genitalia (46,XX); salt-wasting crisis 1–4 weeks |
| Classic — Simple Virilizing | ~25% of classic | ↓ | Near normal | ↑↑ | Virilization in females; precocious puberty in males; no crisis |
| Non-Classic (Late onset) | Most common overall (1:60) | Normal | Normal | Mildly ↑ | Premature adrenarche, PCOS-like, acne, hirsutism, infertility in adulthood |
💡 Remember
The more severe the enzyme block, the less aldosterone and cortisol, and the more androgens are produced. Salt-wasting = most severe block.
At birth, the infant still has some maternal cortisol and mineralocorticoid transferred transplacentally, which provides a brief protective effect. As maternal hormones are cleared, the infant's own deficient adrenal glands cannot maintain sodium balance. Aldosterone deficiency leads to renal sodium wasting, volume depletion, hyperkalemia, and crisis — typically by day 7–14, most commonly around 2–3 weeks.
In a 46,XX female: Excess androgens (mainly DHEA → androstenedione → testosterone) produced from 8–12 weeks in utero virilize the external genitalia — causing clitoromegaly, labioscrotal fusion, and urogenital sinus formation. Internal genitalia (uterus, fallopian tubes, ovaries) are normal as they are Müllerian-derived and unaffected.
In a 46,XY male: The excess androgens do not cause abnormal genital development because his external genitalia are already testosterone-driven and appear normal. He may present only with the salt-wasting crisis (which is why affected males are often diagnosed later and are at higher risk of fatal crisis).
- Antenatal history: Maternal virilization, use of androgens/progestogens, anti-epileptic drugs (phenytoin), maternal CAH — to differentiate other causes of virilization
- Salt-wasting symptoms: Vomiting, poor feeding, failure to regain birth weight, lethargic, sunken fontanelle — suggest adrenal crisis
- Family history: Consanguinity (AR disorder), sibling deaths in neonatal period, sibling with CAH or ambiguous genitalia
- Newborn screening result: 17-OHP screening (if done in that center)
- In older children: Premature pubarche, rapid growth, acne, menstrual irregularity
| Feature | 21-OHD | 11β-OHD |
|---|---|---|
| Gene | CYP21A2 (chr 6p21) | CYP11B1 (chr 8q24) |
| Frequency | 90–95% | 5–8% |
| Blood pressure | Low (salt-wasting) or normal | HIGH (hypertension) |
| Electrolytes | Na↓, K↑ (salt-wasting form) | Na↑, K↓ (DOC excess) |
| Accumulated precursor | 17-OHP | 11-Deoxycortisol, DOC |
| Androgens | ↑ (virilization) | ↑ (virilization) |
| Key marker | ↑↑ 17-OHP | ↑↑ 11-Deoxycortisol |
💡 Mnemonic
11β-OHD = "11 elevates BP" — excess DOC (deoxycorticosterone) acts as a mineralocorticoid → salt retention → hypertension + hypokalemia.
21-Hydroxylase converts 17-OHP → 11-Deoxycortisol (in glucocorticoid pathway) and Progesterone → DOC (in mineralocorticoid pathway). When this enzyme is deficient:
- ↓ Cortisol → ↑ ACTH (loss of negative feedback) → adrenal hyperplasia
- ↓ Aldosterone → salt wasting, hyperkalemia, volume depletion
- ↑ 17-OHP accumulates → shunted to DHEA and androstenedione → testosterone → virilization
Key: 17-OHP is the diagnostic marker — it is grossly elevated in 21-OHD.
3β-Hydroxysteroid dehydrogenase deficiency is a rare form of CAH affecting the earliest step in all three steroid pathways (glucocorticoid, mineralocorticoid, sex steroids).
- 46,XX females: Mild virilization (DHEA has weak androgenic activity)
- 46,XY males: Undervirilization — ambiguous genitalia or feminized genitalia (paradox — because testosterone synthesis is also impaired)
- Salt-wasting crisis present
- Marker: ↑ DHEA, ↑ 17-OH-Pregnenolone
🩺 Examination — Exam Q&A
Use the Prader Classification (Stages I–V):
| Prader Stage | Appearance |
|---|---|
| I | Normal female genitalia with only mild clitoromegaly |
| II | Clitoromegaly + mild labioscrotal fusion (posterior) |
| III | Significant clitoromegaly + partial labioscrotal fusion + single perineal orifice (urogenital sinus) |
| IV | Penile clitoris + near-complete labioscrotal fusion + urogenital sinus opening at base of phallus |
| V | Male-appearing external genitalia; urogenital sinus opens at tip of phallus — cannot be distinguished from cryptorchid male |
💡 Key Point
In all Prader stages, internal genitalia (uterus, fallopian tubes, ovaries) are present and normal — because they are Müllerian-derived and are not androgen-sensitive.
In CAH, ↓ cortisol → ↑ ACTH (pituitary). ACTH shares a common precursor POMC (Pro-opiomelanocortin) with α-MSH (melanocyte-stimulating hormone). Excess ACTH stimulates melanocortin-1 receptors → increased melanin production → hyperpigmentation.
Hyperpigmentation is seen over the genitalia, nipples/areolae, palmar creases, and oral mucosa. It is a marker of ACTH excess and indicates inadequate cortisol replacement (or undiagnosed CAH).
- Normal male external genitalia (can be deceiving — no ambiguity)
- Hyperpigmented scrotal folds (due to ↑ ACTH)
- Signs of adrenal crisis: tachycardia, hypotension, dehydration, shock at 1–3 weeks
- If untreated (simple virilizing): By 2–4 years — premature pubic hair, penile enlargement, rapid growth but advanced bone age with early epiphyseal fusion → short final height
- Testicular volumes remain small (prepubertal) — distinguishes from true precocious puberty
- Severe dehydration: sunken eyes, sunken anterior fontanelle, dry mucous membranes, decreased skin turgor
- Tachycardia, weak thready pulses, hypotension → circulatory collapse
- Lethargy or irritability, hypotonia
- Hyperpigmentation (in primary adrenal insufficiency)
- Weight loss (>10% from birth weight)
- Hypothermia or low-grade fever
- Signs of hypoglycemia: jitteriness, seizures
| Feature | Virilized Female (CAH) | Cryptorchid Male |
|---|---|---|
| Gonads in labia/scrotum | Absent (ovaries, not descended) | May be present (undescended testes) |
| Uterus on pelvic USG | Present | Absent |
| Karyotype | 46,XX | 46,XY |
| 17-OHP | Markedly elevated | Normal |
| Testosterone | Elevated (adrenal origin) | May be normal or mildly elevated |
| HCG stimulation test | No testosterone rise | Testosterone rises (functional testes present) |
- Tall for age in childhood (advanced bone age due to excess androgens)
- Then short adult stature (early epiphyseal fusion)
- Premature pubic and axillary hair (premature adrenarche)
- Acne, oily skin
- Penile/clitoral enlargement
- Advanced bone age on X-ray (bone age > chronological age)
- Small testes in males (not the source of androgens — distinguishes from true precocious puberty)
TARTs are benign, ACTH-responsive adrenal-like cells that are present in the testes of males with CAH (due to ectopic adrenal rest tissue). In poorly controlled CAH, chronic ACTH excess causes these rests to hypertrophy, forming bilateral intratesticular masses.
- Palpable as testicular masses — may be mistaken for testicular tumor
- Can cause obstructive azoospermia and infertility
- Seen on testicular ultrasound as bilateral hypoechoic lesions adjacent to the mediastinum testis
- Treatment: Optimize glucocorticoid to suppress ACTH; may regress with good control
🔬 Investigations — Exam Q&A
Serum 17-Hydroxyprogesterone (17-OHP) — the substrate that accumulates due to 21-hydroxylase block.
| Form | Basal 17-OHP level |
|---|---|
| Normal | < 2 nmol/L (in child) / < 6 nmol/L (neonatal, first 24hr — transiently high) |
| Non-classic CAH | 2–10 nmol/L basally; rises to >30 nmol/L after ACTH stimulation |
| Classic Simple Virilizing | >30–100 nmol/L |
| Classic Salt-Wasting | >300 nmol/L (markedly elevated) |
⚠️ Caution
17-OHP is physiologically elevated in premature neonates and in the first 24–48 hours of life due to stress. Always interpret with gestational age and postnatal age-specific nomograms.
Characteristic electrolyte profile:
- Hyponatremia (Na <130 mEq/L) — aldosterone deficiency → renal sodium wasting
- Hyperkalemia (K >6 mEq/L) — aldosterone deficiency → failure to excrete potassium
- Hypoglycemia — cortisol deficiency → decreased gluconeogenesis
- Metabolic acidosis — decreased H⁺ excretion by kidney (aldosterone also exchanges Na⁺/H⁺)
- Elevated plasma renin activity (PRA) — volume depletion stimulates renin (renin is elevated while aldosterone is low)
💡 Mnemonic: "Salt-Wasting = HypoNa + HyperK + HypoGlucose"
This triad in a sick neonate should always prompt suspicion of CAH.
Urgent (first 24–48 hours):
- Serum 17-OHP (most urgent)
- Serum electrolytes, blood glucose, blood gas
- Serum cortisol and ACTH
- Karyotype (FISH for SRY gene for rapid sex determination within 24–48 hours; conventional karyotype in 5–7 days)
- Pelvic and abdominal USG — presence of uterus, ovaries, or undescended testes
Follow-up investigations:
- Serum testosterone, DHT, LH, FSH
- Plasma renin activity (PRA) and aldosterone
- Urinary steroid profile (by GC-MS) — gold standard for enzymatic diagnosis
- CYP21A2 genotyping for confirmation and family counseling
- Genitogram (retrograde contrast injection into urogenital sinus) — defines anatomy before surgery
Synthetic ACTH (Synacthen/Tetracosactide) 250 mcg IV/IM is given; serum 17-OHP (and cortisol) is measured at 0 and 60 minutes.
Interpretation (17-OHP at 60 min):
| Result | Interpretation |
|---|---|
| <30 nmol/L | Normal / Unaffected carrier (usually) |
| 30–300 nmol/L | Non-classic CAH (heterozygous borderline) |
| >300 nmol/L | Classic CAH (21-OHD confirmed) |
Use: Diagnosing non-classic CAH (where basal 17-OHP may be borderline) and distinguishing carriers from affected individuals. Not needed in acute salt-wasting crisis — diagnosis is clinical + basal 17-OHP.
Newborn screening for CAH measures 17-OHP from a dried blood spot (DBS/heel-prick) on a filter paper card (part of the national newborn screening panel in many countries).
- Done on day 2–4 of life (after 48 hours to avoid physiologic spike)
- A positive screen requires confirmatory serum 17-OHP
- Advantage: Detects affected males (who have no genital ambiguity) before they develop salt-wasting crisis, thus preventing mortality
- Limitation: High false-positive rate in premature neonates; 17-OHP is elevated with prematurity, illness, and in the first 24–48 hours
X-ray of the left hand and wrist (Greulich-Pyle atlas) to assess skeletal maturity.
- In poorly controlled/untreated CAH: Bone age > Chronological age due to androgens advancing skeletal maturation
- If bone age is >2 years advanced: Risk of early epiphyseal fusion → reduced final adult height
- Monitoring bone age helps assess adequacy of treatment — well-controlled CAH has bone age appropriate for age
| Parameter | Target / Goal |
|---|---|
| Serum 17-OHP | 2–10 nmol/L (avoid complete suppression; over-treatment indicates too much steroid) |
| Androstenedione | Normal for age and sex |
| Plasma Renin Activity (PRA) | Normal (elevated PRA = insufficient fludrocortisone) |
| Electrolytes | Normal Na and K |
| Growth velocity | Normal for age |
| Bone age | Consistent with chronological age |
| Blood pressure | Normal (avoid over-mineralocorticoid-replacement) |
💡 Aim for Good Control without Over-Suppression
Very low 17-OHP (<1 nmol/L) indicates over-treatment with glucocorticoid → risk of iatrogenic Cushing syndrome and growth suppression.
💊 Management — Exam Q&A
🚨 This is a MEDICAL EMERGENCY — Do not delay treatment for investigation results
Step 1 — Secure IV Access and immediate bloods: Electrolytes, glucose, 17-OHP, cortisol, ACTH, blood gas (take blood before giving hydrocortisone if clinically stable, but do NOT delay treatment in shock).
Step 2 — Fluid Resuscitation: Normal saline (0.9% NaCl) bolus 10–20 mL/kg IV over 20–30 minutes for hypovolemic shock. Repeat if needed. Avoid hypotonic fluids.
Step 3 — Hydrocortisone (Stress dose):
- Hydrocortisone sodium succinate: 50–100 mg/m² IV/IM stat (approximately 25–50 mg in a neonate as a stress dose) — corrects glucocorticoid deficiency and has mineralocorticoid activity at high doses
- Then maintenance: 50–100 mg/m²/day in 4–6 divided doses IV, tapering to oral as condition improves
Step 4 — Correct Hypoglycemia: 10% Dextrose 2 mL/kg IV bolus if hypoglycemic; add dextrose to maintenance fluids.
Step 5 — Correct Hyperkalemia: Usually corrects with hydrocortisone and fluids. ECG monitoring. If severe: calcium gluconate, insulin-glucose, sodium bicarbonate.
Step 6 — Once oral feeding established: Transition to oral hydrocortisone + fludrocortisone + NaCl supplements.
Drug of choice in children: Hydrocortisone (short-acting, allows normal growth — avoids growth suppression of long-acting steroids).
- Dose: 10–15 mg/m²/day in 3 divided doses (higher dose in morning, mimics diurnal cortisol rhythm — or equal doses TID in infants)
- Route: Oral
- Avoid prednisolone or dexamethasone in growing children — cause growth suppression
- Adults may use prednisolone (2.5–7.5 mg/day) or dexamethasone (0.25–0.5 mg OD nocte) — better compliance with once/twice daily dosing
💡 Why not Dexamethasone in children?
Dexamethasone has no mineralocorticoid activity, long half-life, and significantly suppresses growth axis. Reserved for adult CAH or specific indications.
- Drug: Fludrocortisone (9α-fluorohydrocortisone) — a synthetic mineralocorticoid
- Dose: 0.05–0.2 mg/day orally in a single daily dose (infants may need up to 0.3 mg/day due to physiologic aldosterone resistance in neonates)
- Additionally: Sodium chloride supplementation (1–2 g/day = 17–34 mEq/day) in infants under 12 months — breast milk and formula are low in sodium
- Monitor: Serum electrolytes, BP, PRA (target normal PRA)
- Elevated PRA = underdose; suppressed PRA + hypertension = overdose
Patients with CAH cannot mount a normal cortisol stress response. During physiological stress (illness, surgery, trauma), they require increased glucocorticoid doses to prevent adrenal crisis.
| Situation | Action |
|---|---|
| Mild illness (low-grade fever, minor infection) | Double or triple the usual oral hydrocortisone dose for the duration of illness |
| High fever (>38.5°C), vomiting, moderate illness | Triple dose + IM hydrocortisone if vomiting prevents oral intake |
| Surgery (minor) | Hydrocortisone 50 mg/m² IM/IV at induction, then 50–100 mg/m²/day for 24–48 hours |
| Major surgery / ICU admission | Hydrocortisone 100 mg/m²/day IV continuous infusion or q6h doses |
| Vomiting / inability to take oral | IM hydrocortisone injection at home (parents trained to give) — 25–50 mg IM STAT then hospital |
🚨 Important
Parents of children with CAH must be educated in stress dosing and given a medical alert bracelet and a hydrocortisone emergency injection kit with instructions.
Feminizing genitoplasty is considered for significantly virilized females (Prader III–V) after parental counseling.
- Clitoral reduction/recession: Reduces penile clitoris to normal female size while preserving neurovascular bundle — preserving sensation (clitorectomy is now abandoned)
- Vaginoplasty: Creates or enlarges vaginal opening — separates the urogenital sinus; may require second procedure at puberty
- Timing: Traditionally 2–6 months of age for clitoral surgery; vaginal surgery often deferred to puberty when tissue is more estrogen-primed. There is ongoing debate — some advocate deferring all surgery until the patient can consent
- Labioplasty: Reconstruction of labia minora/majora to female appearance
💡 Ethical Note
Current debates recommend deferring irreversible cosmetic genital surgery until the child can participate in the decision. Early surgery should be reserved for functional indications (obstruction to urine/secretion drainage).
Due to the disease (undertreatment / poor control):
- Short adult stature (advanced bone age, early epiphyseal fusion)
- Precocious puberty (central, triggered by androgens)
- Polycystic ovarian syndrome (PCOS) in females — menstrual irregularities, infertility
- Testicular adrenal rest tumors (TARTs) in males → infertility
- Adrenal crises (life-threatening)
Due to treatment (overtreatment with glucocorticoids):
- Iatrogenic Cushing syndrome (obesity, striae, hypertension)
- Growth suppression (major concern in children)
- Osteoporosis
- Adrenal suppression — cannot taper steroid abruptly
- 46,XX females with CAH are raised as female — they have normal female internal genitalia, ovarian function, and can bear children with adequate treatment
- Sex assignment should involve a multidisciplinary team (MDT): pediatric endocrinologist, urologist/surgeon, psychologist, social worker, ethicist
- Parents need thorough counseling about the condition, treatment, and prognosis — gender identity in CAH females is overwhelmingly female
- Psychological support throughout childhood and adolescence is essential
- Do not delay sex registration — karyotype result is available in 24–48 hours (FISH); conventional karyotype in 5–7 days
🔭 Recent Advances — Exam Q&A
Prenatal Diagnosis:
- Indicated when both parents are known carriers (heterozygotes) of CYP21A2 mutations
- Chorionic villus sampling (CVS) at 10–12 weeks or amniocentesis at 15–18 weeks for CYP21A2 genotyping + karyotype
- Elevated 17-OHP in amniotic fluid is also diagnostic
Prenatal Treatment (Dexamethasone):
- Dexamethasone (20 mcg/kg/day in 3 divided doses) given to the mother from 6–7 weeks gestation — crosses the placenta and suppresses fetal ACTH → reduces androgen production → prevents virilization of a 46,XX fetus
- Treatment continued if fetus is 46,XX and affected; stopped if male or unaffected female
- Controversy: 7 in 8 fetuses treated unnecessarily; maternal side effects include hypertension, weight gain, glucose intolerance, striae; long-term fetal neurocognitive safety is debated. Currently used selectively; considered experimental by some guidelines.
Conventional hydrocortisone is given 3× daily, but does not replicate the natural circadian cortisol peak (highest in early morning). The large midnight-to-morning window allows ACTH to rise, driving androgen excess overnight and early morning.
Modified-Release (Chronocort / Plenadren):
- Chronocort: A delayed-release hydrocortisone capsule designed to be taken at bedtime — releases hydrocortisone in a pulsatile manner replicating the physiologic morning surge
- Plenadren: Once-daily modified-release tablet; better cortisol profile in adults
- Advantage: Better suppression of overnight ACTH → lower androgens, lower HbA1c, improved metabolic profile, potentially better growth outcomes
- Currently being studied for pediatric use; FDA/EMA approvals for adults
Since excess glucocorticoid causes side effects, several non-glucocorticoid approaches are being studied:
- CRH antagonists / ACTH inhibitors: Crinecerfont (NBI-74788), a CRF1 receptor antagonist — reduces ACTH and androgen production without supraphysiological glucocorticoid doses. Phase 3 trials show promise in adults and children (ACROBAT trial)
- Abiraterone acetate: CYP17A1 inhibitor that blocks androgen synthesis — being studied as an adjunct to reduce androgen excess while reducing glucocorticoid doses
- Aldosterone synthase inhibitors + fludrocortisone regulation
- Gene therapy: AAV-mediated delivery of functional CYP21A2 gene into the adrenal gland — in preclinical and early human trials
- Adrenal stem cell/organ transplantation — experimental
CAH-X syndrome results from a contiguous gene deletion at chromosome 6p21.3 that involves both CYP21A2 (causing CAH) and the adjacent TNXB gene (encoding Tenascin-X, a connective tissue protein).
- Tenascin-X deficiency → Ehlers-Danlos syndrome-like features: joint hypermobility, skin hyperextensibility, easy bruising
- Seen in ~7–10% of CAH patients
- Important to recognize as these patients may have connective tissue complications beyond endocrine management
Traditional newborn screening for CAH uses immunoassay for 17-OHP on dried blood spot (DBS). This has high false-positive rates especially in premature and sick neonates.
Tandem Mass Spectrometry (LC-MS/MS):
- Can measure a steroid profile on the same DBS — including 17-OHP, 21-deoxycortisol, androstenedione, and cortisol simultaneously
- The 17-OHP / cortisol ratio and presence of 21-deoxycortisol significantly improve specificity, reducing false positives
- Allows differentiation of CAH from prematurity-related 17-OHP elevation
- Being adopted in many national newborn screening programs as second-tier testing
⚡ Key Points — Quick Revision
One-Liners for Exam
- Most common CAH: 21-Hydroxylase deficiency (CYP21A2) — 90–95%
- Inheritance: Autosomal Recessive
- Classic forms: Salt-Wasting (75%) and Simple Virilizing (25%)
- Key biochemical marker: ↑↑ Serum 17-OHP
- Electrolytes in crisis: Hyponatremia + Hyperkalemia + Hypoglycemia
- Why no virilization in 46,XY males: Male genitalia already androgen-driven; males identified only by crisis or newborn screening
- Prader staging: Grade I (mild clitoromegaly) → Grade V (fully male-appearing) for virilized females
- Hyperpigmentation: Due to ↑ ACTH acting on melanocortin receptors (shared POMC precursor with α-MSH)
- 11β-OHD: 2nd most common CAH — hypertension + hypokalemia (DOC excess, unlike salt-wasting in 21-OHD)
- Adrenal crisis Rx: 0.9% NaCl bolus + IV Hydrocortisone 50–100 mg/m² stat + Dextrose for hypoglycemia
- Long-term glucocorticoid: Hydrocortisone 10–15 mg/m²/day in 3 doses (NOT dexamethasone in children — causes growth suppression)
- Mineralocorticoid: Fludrocortisone 0.05–0.2 mg/day + NaCl supplements in infants
- Stress dosing: 2–3× usual hydrocortisone dose during fever/illness/surgery
- Bone age: Advanced (> chronological age) in poorly controlled CAH → short final stature
- Gold standard diagnosis: Serum 17-OHP (basal) + ACTH stimulation test for non-classic form
- Newborn screening: Dried blood spot 17-OHP (day 2–4); LC-MS/MS second-tier test reduces false positives
- Supracristal VSD risk analogy: Supracristal VSD → AR; Non-classic CAH → late-onset mild symptoms; don't confuse these
- TARTs: Testicular adrenal rest tumors in males with poor control → infertility; bilateral hypoechoic lesions on USG
- Prenatal Rx: Maternal dexamethasone from 6–7 weeks if known carrier couple — prevents virilization of 46,XX fetus; controversial
- Newer therapy: Crinecerfont (CRF1 antagonist) — reduces ACTH/androgen without high-dose glucocorticoid; Phase 3 trials
🧠 Comparison: CAH Types at a Glance
| Enzyme | Cortisol | Aldosterone | BP | Androgens | Key Marker |
|---|---|---|---|---|---|
| 21-OHD (Classic SW) | ↓↓ | ↓↓ | Low | ↑↑ | 17-OHP ↑↑↑ |
| 21-OHD (Simple Virilizing) | ↓ | Near normal | Normal | ↑↑ | 17-OHP ↑↑ |
| 11β-OHD | ↓ | ↓ (aldosterone) | High | ↑↑ | 11-Deoxycortisol ↑↑ |
| 3β-HSD | ↓ | ↓ | Low | ↑ DHEA (weak) | 17-OH-Pregnenolone ↑ |
| Non-classic 21-OHD | Normal | Normal | Normal | Mildly ↑ | 17-OHP elevated on ACTH stimulation |