Congenital Adrenal Hypoplasia

Also see Ambiguous Genitalia

CARA is 17 but has no menses.
CARA-17 is for the critical sample: Cortisol, ACTH, renin, Aldo, 17ohp.
17 and no menses (Amenorrhea) indicates the phenotype of this deficiency in a girl.
(Boys are incompletely virilized)

Glucocorticoid (cortisol)
Mineralocorticoid (aldosterone)
Sex Steroi (DHEA, others)

* hypergonadotropic hypogonadism (boys are incompletely virilized or
pseudohermaphrodite, girls look normal but failure of puberty
(mnemonic, still no menses at 17)
** decr delta-4-androstinedione (boys are incompletely virilized),
incr DHEA, OHP, pregnenolone girls are mildly virilized

An enzymatic block results in decreased cortisol (similar across all
forms of CAH) and loss of negative feedback, so increased ACTH, caused
adrenal hyperplasia. The metabolites which aren't blocked are
increased in production. The type of enzyme deficiency determines
which of the adrenal hormones are deficient vs excessive.

5 Enzyme deficiencies can manifest as CAH:

• 21-alpha-Hydroxylase (>90%), milder form presents in childhood/adolescence.
• 11-beta-Hydroxylase (5-8%)
• 3-beta-Hydroxysteroid dehydrogenase (<1%)
• 17-alpha-Hydroxylase (<<1%)
• Steroidogenic Acute Regulatory Protein (StAR)

The most important glucocorticoid is cortisol and deficiency can cause
hypotension and hypoglycema. The most important mineralocorticoid is
aldosterone and deficiency can produce hyperkalemia and hyponatremia
(salt-wasting). The enzymatic block in 17 causes elevated DOC, which
has mineralocorticoid activity and Na retention, hypokalemia and
volume hypertension. Among the sex steroids, DHEA is an important one.

To test a full differential of all causes of adrenal insufficiency, a
critical sample should be drawn before therapy:
- cortisol, ACTH, renin, aldosterone, 17-OHP (in the newborn)
- also draw chem-8
- if hypertensive 11-DOC (elev in 11-beta)
- karyotype (not critical)

If hypovolemic as in 21 due to salt-wasting, renin will be high. If
hypertensive as in 11 and 17, renin will be low.

Acute management:
- draw critical sample
- NS 20/kg
- replete hypoglycemia with D10W 2 cc/kg in neonate (5 cc/kg in children)
- D5W or D5NS at 2x maint (3200 cc/m2/d) without potassium
If elevated potassium
- 10% calcium gluconate 1/2 cc/kg over 10 min (=1/2 to 1 meq/kg)
- then sodium bicarb 1 meq/kg over a 10-30 min
- in extreme cases, insulin 0.1 to 0.2 U/kg/hr in D10W
- start kayexalate

Other workup
- pelvis US, urogenitography

Acute Therapy
- stress dose glucocorticoid: 50-100 mg/m2/day hydrocortisone IV div
q6h. High doses of hydrocortisone also have mineralocorticoid effect
(so this is preferred over methylprednisone (10-20 mg/mg2) or dex 1-2
mg/m2))
- mineralocorticoid: fludrocortisone (Florinef). There is no IV form.
Dosing does not depend on weight: 0.05 to 0.2 mg PO qd
- Na supplement 1-5 meq/kg/d

Chronic therapy
- same as above, except hydrocortisone lowered to 10-25 mg/m2/d.
Prednisone or dex may be given to reduce freq of dosing, but more
growth retardation occurs.

During acute illness at home
- for mild illness, t>38, double PO dose
- for severe illness, triple PO dose
- if vomits within 1-2 hours of dose, repeat dose. If vomit again,
give IM hydrocortisone sodium succinate as instructed by endo