In 21-hydroxylase deficiency, excessive androgenic activity causes signs of masculinization in females, ranging from clitoral hypertrophy and pseudohermaphroditism in infants to oligomenorrhea, hirsutism, and acne in postpubertal girls. In males, androgen excess is associated with enlargement of the external genitalia and other evidence of precocious puberty in young patients. Most men with CAH are fertile but some have failure of Leydig cell development and oligospermia. In approximately one-third of individuals with 21-hydroxylase deficiency, the enzymatic defect is severe enough to produce aldosterone deficiency, with resultant salt (sodium) wasting. Concomitant cortisol deficiency places individuals with CAH at risk for acute adrenal insufficiency (discussed later).
CAH should be suspected in any neonate with ambiguous genitalia. Severe enzyme deficiency in infancy can be a life-threatening condition, with vomiting, dehydration, and salt wasting. In the milder variants, women may present with delayed menarche, oligomenorrhea, or hirsutism. In all cases, an androgen-producing ovarian neoplasm must be excluded. Treatment of CAH is with exogenous glucocorticoids, which, in addition to providing adequate levels of glucocorticoids, also suppress ACTH levels, thereby decreasing the excessive synthesis of the steroid hormones responsible for many of the clinical abnormalities. Mineralocorticoid supplementation is required in the salt-wasting variants of CAH.
Theadrenalcortexcansecreteexcessandrogensineitheroftwosettings:adrenocorticalneoplasms(usuallyvirilizing carcinomas)orcongenitaladrenalhyperplasia(CAH).
CAHconsistsofagroupofautosomalrecessivedisorderscharacterizedbydefectsinsteroidbiosynthesis,usuallycortisol;themostcommonsubtypeiscausedbydeficiencyoftheenzyme21-hydroxylase.
ReductionincortisolproductioncausesacompensatoryincreaseinACTHsecretion,whichinturnstimulatesandrogenproduction.Androgenshavevirilizingeffects,includingmasculinizationinfemales(ambiguousgenitalia,oligomenorrhea,hirsutism),precociouspubertyinmales,and,insomeinstances,salt(sodium)wastingandhypotension.
Bilateralhyperplasiaoftheadrenalcortexischaracteristic.
Adrenocortical insufficiency, or hypofunction, may be caused by either primary adrenal disease (primary hypoadrenalism) or decreased stimulation of the adrenals resulting from ACTH deficiency (secondary hypoadrenalism). Primary adrenocortical insufficiency may be acute (called adrenal crisis), or chronic (Addison disease).
Table20.7CausesofAdrenalInsufficiency
APS1, APS2, Autoimmunepolyendocrinesyndrometypes1and2;AIRE, autoimmuneregulatorgene.
Acute adrenocortical insufficiency occurs most commonly in the clinical settings listed in