Pocket ObGyn – Congenital Adrenal Hyperplasia (CAH)

Dec 8, 2019 admin PHỤ KHOA, SẢN KHOA, SINH DỤC 0

Pocket ObGyn – Congenital Adrenal Hyperplasia (CAH)
See Abbreviations

Definition and Epidemiology
  • Autosomal recessive disorders of cortisol &/or aldosterone biosynthesis, result in cortisol deficiency, ± aldosterone deficiency, & androgen excess. There are two forms:
  • Classic CAH (sev form, 1/15–16000 live births)
  • salt wasting (67%)
  • nonsalt losing (simple virilizing; 33%)
  • NCAH (mild or late onset); asymptomatic or postnatal
Pathology & Pathophysiology
  • Caused by a mut in cortisol producing
  • ­ corticotrophin ® adrenal hyperplasia
  • ­ cortisol precursors which are diverted to the biosynthesis of sex hormones ® androgen excess ® ambiguous genitalia in newborn girls, rapid postnatal growth in both sexes
  • Aldosterone deficiency ® salt wasting ® FTT, hyponatremic hypovolemia, shock
  • HyperK

Classic CAH – abn cortisol, sex hormone, ± aldosterone production NCAH – nml cortisol & aldosterone, but mild to mod ­ sex hormones

•   Muts:

CYP21 (CYP21A2; 95% of cases; codes for adrenal 21-hydroxylase) ® CYP21 mut

® 21-hydroxylase deficiency ® inadeq cortisol synthesis ® inadeq negative feedback to hypothalamus & pituitary ® increased ACTH secretion ® adrenal gland hyperplasia. Adrenal steroids are converted to adrenal androgens.

CYP11B1 mut ® 11b-hydroxylase deficiency ® ­ 11-deoxycortisol &

11-deoxycorticosterone ® salt retention ® hypervolemia, HTN.

HSD3B2 mut ® 3b-hydroxysteroid dehydrogenase deficiency ® sev adrenal insuf- ficiency, ­ ACTH ® ­ pregnenolone, 17-hydroxypregnenolone, & DHEA ® mild virilization, ± salt wasting.

Clinical Manifestations
  • Salt-losing adrenal crisis in neonat period for 3/4ths newborns w/ classic
  • 46 XX female pseudohermaphroditism: Nml uterus, fallopian tubes & ovaries but varying levels of ambiguous genitalia depending on degree & type of enzyme deficiency
  • Ambiguous genitalia: Classic CAH – newborn ambiguous genitalia (clitoral hypertrophy, labioscrotal fusion – partial or complete, common urogenital sinus). Boys have no overt sx except hyperpigmentation & penile NCAH – presents in adolescence; rapid growth, premature pubic or axillary hair, hirsutism.
  • Hyperandrogenism: Hirsutism, acne, oligomenorrhea/amenorrhea, polycystic ovaries, precocious
  • Infertility: 80% women w/ simple virilizing & 60% women w/ salt-wasting CAH are (Endocrinol Metab Clin North Am 2001;30:207)
  • Metabolic syn/insulin resistance/obesity
  • Short stature: Untreated, long-term sex hormone exposure leads to advanced skeletal age & premature epiphyseal Mean adult height = 10 cm below nml pop.
  • Issues of gender & sexuality (Endocrinol Metab Clin North Am 2001;30:155)
  • Iatrogenic Cushing syn
Workup
  • Serum electrolytes, aldosterone, & plasma renin: HyperK, ¯ aldosterone, hyperreninemia (use age-specific reference for renin).
  • Random 17-OHP: >242 nmol/L (nml 3 nmol/L) at 3 d in full-term False positives in premature infants. Use weight & gestational age–based reference ranges.
  • Corticotrophin-stimulation test: 250 mg cosyntropin followed by measurement of 17-OHP 60 min 17-OHP level >10 ng/mL (30.3 nmol/L)
  • Early morning (before 0800 h) 17-OHP: >5 nmol/L in children & >6 nmol/L in women during follicular phase r/o NCAH
  • Genetic analysis, neonat screening or gene-specific prenatal dx

Treatment
  • Glucocorticoids (short acting in children to avoid growth suppression). Stress dosing during febrile illness, Surg, trauma, (Double or triple daily dose.) Hydrocortisone 12–18 mg/m2 divided into 2 or 3 doses. Longer-acting glucocorti-

coids can be used in adults.

Prednisone 5–7.5 mg QD in 2 doses or dexamethasone 0.25–0.50 mg QHS. Good in Preg (does not cross the placenta). Goal early morning 17-OHP 12–36 nmol/L.

  • Mineralocorticoides
  • Fludrocortisone 100–200 mg QD; adjust to maintain plasma rennin in midnormal range
  • NaCl suppl (salt-losing CAH) 1st 6–12 mo of life
  • Infertility ® ovulation induction
  • Hirsutism ® antiandrogens (w/ OCPs as antiandrogens are teratogens)
  • Prenatal rx: Mat dexamethasone suppresses fetal HPA axis & ¯ genital ambiguity Start prior to 8 w of gest when masculinization of external genitalia begins CVS or amniocentesis for gender, if male or unaffected female ® d/c steroids

85% of prenatally treated female infants are born w/ nml or slightly virilized genitalia

  • Neonat rx: Hydrocortisone dose £25 mg/m2 Monit weight, length, adrenal steroid conc, plasma renin, & electrolytes.
  • Surgical mgmt of ambiguous genitalia (controversial): Age 2–6 mo in virilized girls; technically easier than at later ages (std of care) later ages when psychosexual identity is established.

See Abbreviations

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