Adrenal hyperplasia Notes

NOTES NOTES ADRENAL HYPERPLASIA CONGENITAL ADRENAL HYPERPLASIA osms.it/congenital-adrenal-hyperplasia PATHOLOGY & CAUSES ▪ Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive metabolic disorders characterized by defects in certain genes resulting in a partial/total lack of an enzyme involved in steroidogenesis within the adrenal cortex ▫ ↓ steroid hormone production → compensatory ↑ ACTH → adrenal hyperplasia ▫ ↓ cortisol → cortisol precursor accumulation → steroid precursors shunted to overproduction of other ACTH-dependent adrenal steroids TYPES 21-hydroxylase deficiency ▪ Defective gene: CYP21A2 ▪ Most common type of CAH ▫ Classic: neonatal/early infancy genital ambiguity in females, adrenal insufficiency; classic non-salt-losing (simple virilizing): female fetus virilization; classic salt-losing ▫ Non-classic (late onset): presents later in life (child-adult) with androgen excess signs; non-salt-losing 17-alpha hydroxylase deficiency ▪ Defective gene: CYP17A1 ▪ Rare ▪ Steroid precursors for testosterone, cortisol synthesis shunted to aldosterone 11-beta-hydroxylase deficiency ▪ Defective gene: CYP11B1 ▪ 7% of CAH cases ▪ Lack of enzyme prevents conversion of 11-deoxycortisol to cortisol ▪ 11-deoxycortisol (aldosterone precursor) has mild mineralocorticoid effect → biphasic effect on mineralocorticoid balance SIGNS & SYMPTOMS 21-hydroxylase deficiency ▪ Varies by subtype 17-alpha hydroxylase deficiency ▪ ↓ cortisol → corticosterone presence prevents adrenal crisis ▪ Mineralocorticoid excess → secondary hypertension; hypokalemic alkalosis ▪ Gonadocorticoid deficiency (males: mildly underdeveloped genitalia, hypergonadotropic hypogonadism; females: abnormal pubertal sexual development, infertility) 11-beta-hydroxylase deficiency ▪ Androgen excess → external genitalia virilization, sexual ambiguity (females) ▪ Biphasic mineralocorticoid balance → possible salt-wasting crisis in early infancy; secondary hypertension and hypokalemia in childhood and adult life OSMOSIS.ORG 73

TREATMENT MEDICATIONS Figure 12.1 Clitoromegaly with normal labia and introitus in a biologically female individual with 21-hydroxylase deficiency. DIAGNOSIS ▪ Clinical presentation ▫ Steroid imbalance evidence ▪ Most cases identified via newborn screening SURGERY LAB RESULTS ▪ Address complications (e.g., fluid, electrolyte imbalance) ▪ Monitor ▫ Serum 17-hydroxyprogesterone, renin, electrolytes ▫ Blood pressure ▫ Bone age and density ▫ Tanner staging ▫ Weight ▫ Growth velocity Serum hormone levels ▪ 21-hydroxylase deficiency ▫ ↓ sodium (salt-losing type), ↑ potassium (salt-losing type) ▫ Serum markers: ↑↑ serum 17-hydroxyprogesterone, ↑ 21-deoxycortisol) ▪ 17-alpha hydroxylase deficiency ▫ ↑ sodium, ↓ potassium ▫ Serum markers: ↑ pregnenolone, ↑ progesterone, ↑ 11-deoxycorticosterone, ↑ 11-deoxycortisol ▪ 11-beta-hydroxylase deficiency ▫ ↑ sodium, ↓ potassium ▫ Serum markers: ↑ 11-deoxycorticosterone, ↑ 11-deoxycortisol) Genetic testing Prenatal diagnosis ▪ By chorionic villus sampling at 10–12 weeks 74 ▪ 21-hydroxylase deficiency ▫ Exogenous glucocorticoid (hydrocortisone), mineralocorticoid (fludrocortisone) ▪ 11-beta-hydroxylase deficiency ▫ Exogenous glucocorticoid (hydrocortisone), antihypertensives ▪ 17-alpha hydroxylase deficiency ▫ Exogenous glucocorticoid (hydrocortisone), sex steroid replacement beginning at puberty, antihypertensives ▪ If CAH diagnosed prenatally ▫ Dexamethasone OSMOSIS.ORG ▪ Potential atypical genitalia correction OTHER INTERVENTIONS

Chapter 12 Adrenal Hyperplasia OSMOSIS.ORG 75