Guideline 4.12 — Congenital Hypothyroidism & Congenital Adrenal Hyperplasia

KEY TAKEAWAYS

Both are newborn-screening triumphs — infants are usually asymptomatic at birth, and screening prevents catastrophe (intellectual disability in CH; fatal salt-wasting crisis in CAH).
Congenital hypothyroidism (CH): treat fast to protect the brain. Start levothyroxine as soon as diagnosis is confirmed (ideally within the first ~2 weeks) — early treatment yields normal cognitive development; delay causes irreversible impairment.
CH is TSH-based screening (high TSH, low free T4 in primary CH) — but TSH-only screening misses central (secondary) hypothyroidism.
Congenital adrenal hyperplasia (CAH): 21-hydroxylase deficiency is ~95% of cases, screened by 17-hydroxyprogesterone (17-OHP).
The CAH danger is the salt-wasting crisis (~day 7–14): vomiting, dehydration, shock, hyponatremia, hyperkalemia, hypoglycemia — treated emergently with IV fluids + stress-dose hydrocortisone.
Watch the CAH boys: males with salt-wasting CAH have normal-appearing genitalia (no clue), so they're the ones who present in undiagnosed crisis.

1. Clinical Overview

Clinical Overview

Two of the most important newborn-screening conditions are endocrine, both silent at birth and both catastrophic if missed. Congenital hypothyroidism is the leading preventable cause of intellectual disability: the neonatal brain depends on thyroid hormone, and because maternal thyroxine partly protects the fetus, affected infants usually look normal at birth — making screening and prompt levothyroxine the difference between normal development and permanent impairment. Congenital adrenal hyperplasia (most often 21-hydroxylase deficiency) impairs cortisol (and often aldosterone) synthesis while driving androgen excess; its severe salt-wasting form can kill a newborn in an adrenal crisis within the first weeks — which screening (and clinical vigilance, especially in boys) exists to prevent.

2. Definitions

Term	Meaning
Congenital hypothyroidism (CH)	Inadequate thyroid hormone from birth (most commonly thyroid dysgenesis; also dyshormonogenesis, central, transient).
CAH	Group of autosomal-recessive adrenal steroidogenesis defects; 21-hydroxylase deficiency ≈ 95%.
Salt-wasting CAH (SW-CAH)	Severe classic CAH with cortisol and aldosterone deficiency → salt-wasting crisis.
Simple-virilizing CAH (SV-CAH)	Classic CAH with androgen excess but sufficient aldosterone to avoid overt salt-wasting.
17-OHP	17-hydroxyprogesterone — the CAH newborn-screening marker (accumulates behind the 21-hydroxylase block).

3. PART A — Congenital Hypothyroidism

PART A — Congenital Hypothyroidism

Pathophysiology & causes

Thyroid dysgenesis (agenesis, hypoplasia, ectopy) — the most common cause.
Dyshormonogenesis (inherited defects in hormone synthesis).
Central (secondary/tertiary) — pituitary/hypothalamic (rare; missed by TSH-only screening).
Transient — maternal antithyroid drugs, iodine deficiency/excess, maternal TSH-receptor–blocking antibodies.

Clinical presentation (often absent early — why screening matters)

Usually asymptomatic at birth (maternal T4 protection). If undiagnosed: prolonged jaundice, lethargy, poor feeding, constipation, hypotonia, large fontanelle, macroglossia, umbilical hernia, hoarse cry, dry skin, hypothermia, coarse features.

Diagnosis

Newborn screening (TSH ± T4). Confirm with serum TSH (high) and free T4 (low) for primary CH.
Imaging (thyroid ultrasound/scintigraphy) can define etiology but must not delay treatment.

Management

Levothyroxine (L-T4), started as soon as diagnosis is confirmed — ideally within the first ~2 weeks of life. Typical starting dose is high on a per-kg basis (commonly ~10–15 mcg/kg/day) to normalize thyroid status rapidly.
Monitor TSH and free T4 and titrate; ensure consistent administration (crushed tablet; avoid soy/iron/calcium co-administration that impairs absorption).
Early, adequate treatment → normal neurodevelopment; delay → irreversible cognitive loss.

4. PART B — Congenital Adrenal Hyperplasia (21-hydroxylase deficiency)

PART B — Congenital Adrenal Hyperplasia (21-hydroxylase deficiency)

Pathophysiology

21-hydroxylase (CYP21A2) deficiency blocks conversion of precursors to cortisol and aldosterone → cortisol deficiency removes negative feedback → ACTH rises, driving adrenal hyperplasia and shunting precursors into the androgen pathway.
Result: cortisol ± aldosterone deficiency plus androgen excess.
Forms: classic salt-wasting (~75% of classic — cortisol + aldosterone deficiency), classic simple-virilizing (~25%), and non-classic (mild, later).

Clinical presentation

Females (classic): virilized/ambiguous genitalia at birth (a visible clue that prompts evaluation).
Males (classic salt-wasting): normal-appearing genitalia → no clue → high risk of presenting in undiagnosed salt-wasting crisis.
Salt-wasting crisis (~day 7–14, up to ~day 20): vomiting, poor feeding, dehydration, hypotension/shock, with hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis.

Diagnosis

Newborn screening: 17-OHP (elevated) — note a high false-positive rate (prematurity/stress); second-tier LC-MS/MS steroid profiling improves specificity.
Confirm: elevated 17-OHP, electrolytes (hyponatremia + hyperkalemia in salt-wasting), elevated adrenal androgens; ACTH-stimulation and genetic testing as needed.

Management

Acute salt-wasting crisis (endocrine emergency):
IV isotonic fluids (restore volume; correct hyponatremia/hypovolemia).
IV stress-dose hydrocortisone (glucocorticoid replacement — the priority).
Dextrose for hypoglycemia; treat hyperkalemia.
Maintenance:
Glucocorticoid replacement (hydrocortisone).
Mineralocorticoid (fludrocortisone) + sodium chloride supplementation in infancy for salt-wasters.
Stress dosing of glucocorticoid during illness/surgery (lifelong).
Ambiguous genitalia: multidisciplinary team (endocrinology, urology, psychology), careful sex-assignment discussion, and avoidance of rushed surgery.

5. Monitoring

Monitoring

CH: serial TSH/free T4, growth, and development; titrate levothyroxine.
CAH: growth, electrolytes, adrenal androgens/17-OHP, blood pressure, and signs of over/under-treatment (growth suppression vs virilization); ongoing stress-dosing education for families.

6. Complications

Complications

CH (if delayed/untreated): irreversible intellectual disability, growth failure, delayed development.
CAH: fatal salt-wasting crisis (untreated); over-/under-treatment effects (growth suppression from excess glucocorticoid; virilization, precocious puberty, and early growth-plate closure from androgen excess); adrenal crises during illness if not stress-dosed.

7. Safety Warnings

Safety Warnings

⚠️ Start levothyroxine promptly in confirmed CH — don't delay for imaging.
⚠️ TSH-only screening misses central hypothyroidism — keep it in mind clinically.
⚠️ CAH salt-wasting crisis is an emergency — IV fluids + stress-dose hydrocortisone first; don't wait for confirmatory hormone results if the infant is crashing with hyponatremia/hyperkalemia.
⚠️ Watch the boys — normal genitalia means no warning sign for salt-wasting CAH.
⚠️ Stress-dose glucocorticoids during illness/surgery for life.
⚠️ Don't rush genital surgery in ambiguous genitalia — multidisciplinary, shared decision-making.

8. Common Mistakes

Common Mistakes

Delaying levothyroxine in CH (pursuing imaging first).
Assuming normal TSH screen excludes central hypothyroidism.
Treating a CAH crisis without stress-dose hydrocortisone (or waiting for labs).
Missing salt-wasting CAH in a male (no genital clue).
Forgetting fludrocortisone + salt for salt-wasters.
Not teaching families stress dosing.
Rushed genital surgery without a multidisciplinary team.

9. Clinical Pearls

Clinical Pearls

💡 CH: the brain can't wait — levothyroxine early, high per-kg dose, protect development.
💡 High TSH + low free T4 = primary CH; normal TSH doesn't rule out central disease.
💡 CAH crisis chemistry: low sodium, high potassium, low glucose — plus shock.
💡 Fluids + hydrocortisone save the CAH infant — glucocorticoid is the priority.
💡 Virilized girl → CAH is obvious; "well" boy who crashes at 1–2 weeks → think salt-wasting CAH.
💡 17-OHP screens have false positives (prematurity/stress) — confirm.

10. Summary Table

Summary Table

Domain	Congenital Hypothyroidism	CAH (21-hydroxylase deficiency)
Screen marker	TSH ± T4	17-OHP (2nd-tier LC-MS/MS)
Confirm	↑TSH, ↓free T4 (primary)	↑17-OHP; ↓Na, ↑K (salt-wasting)
Danger	Irreversible intellectual disability if delayed	Salt-wasting adrenal crisis (~day 7–14)
Presentation	Often asymptomatic; later: prolonged jaundice, constipation, hypotonia, macroglossia	Females: ambiguous genitalia; males: normal genitalia (missed)
Treatment	Levothyroxine ~10–15 mcg/kg/day, start ASAP	Crisis: IV fluids + stress-dose hydrocortisone + dextrose; maintenance: hydrocortisone + fludrocortisone + salt
Pitfall	TSH-only misses central CH	Missed salt-wasting CAH in boys; needs lifelong stress dosing

11. Step-by-Step Bedside Algorithm

POSITIVE NEWBORN SCREEN (or clinical suspicion)
        │
        ├───────────────► CONGENITAL HYPOTHYROIDISM (↑TSH screen)
        │                     │
        │                     ▼
        │           Confirm serum TSH (high) + free T4 (low)
        │                     │
        │                     ▼
        │           START LEVOTHYROXINE ASAP (~10–15 mcg/kg/day)
        │           (don't delay for imaging; imaging defines etiology)
        │                     │
        │                     ▼
        │           Monitor TSH/free T4 + growth/development; titrate
        │
        └───────────────► CAH (↑17-OHP screen) — or infant in crisis
                              │
                              ▼
                     UNWELL / crisis (vomiting, dehydration, shock,
                     ↓Na, ↑K, ↓glucose)?
                              │ Yes → EMERGENCY:
                              │   IV isotonic fluids + STRESS-DOSE IV HYDROCORTISONE
                              │   + dextrose; treat hyperkalemia
                              │ (don't wait for confirmatory labs if crashing)
                              ▼
                     Confirm: 17-OHP, electrolytes, androgens (± ACTH stim/genetics)
                              │
                              ▼
                     MAINTENANCE: hydrocortisone + (fludrocortisone + salt for salt-wasters)
                     + lifelong STRESS DOSING education
                              │
                     Ambiguous genitalia → multidisciplinary team; no rushed surgery

12. References to Verify

Confirm each against the primary source before clinical or published use.

1.CAH guideline: Speiser PW, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(11):4043–4088. (Screening + management — verify.)
2.CH screening/management: AAP / pediatric endocrine society guidance on newborn screening and management of congenital hypothyroidism. (Verify levothyroxine dosing/timing.)
3.Newborn-screening panels (RUSP): confirm CH and CAH are on your jurisdiction's panel and the local algorithm. (Verify.)
4.CAH screening accuracy: 17-OHP false positives (prematurity/stress) and second-tier LC-MS/MS. (Verify.)
5.Adrenal-crisis management: stress-dose hydrocortisone / emergency protocols. (Verify dosing with endocrinology.)

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Chapter 4.12 — Congenital Hypothyroidism & Congenital Adrenal Hyperplasia