Statistically most virilized females have CAH; 90% of these females have 21-hydroxylase deficiency. The diagnosis is established by measuring the plasma concentration of 17-hydroxyprogesterone and androstenedione (see Chapter 178), which typically is hundreds of times above the normal range. Other enzymatic defects also may be diagnosed by quantifying circulating levels of the adrenal steroid precursor proximal to the defective enzyme block.
Establishing an accurate diagnosis is more difficult in underdeveloped males. When certain types of adrenal hyperplasia coexist with defects in androgen production of the testes, excessive ACTH secretion elevates substantially levels of specific adrenal steroid precursors, allowing a diagnosis. If the defect is restricted to testosterone biosynthesis, the measurement of testosterone and its precursors in the basal state and after stimulation by hCG may be required. Patients with normal levels of testosterone either have persistent androgen resistance or have had an interruption of normal morphogenesis of the genitalia. Abnormalities of the sex chromosomes may be associated with dysgenetic gonads, which may be associated with persistence of müllerian structures.
Treatment consists of replacing deficient hormones (cortisolin adrenal hyperplasia or testosterone in a child with androgen biosynthetic defects who will be raised as male), surgical restoration to make the individual look more appropriatefor the gender of rearing, and psychological support of thewhole family. Gonads and internal organs discordant forthe gender of rearing are often removed. Dysgenetic gonadswith Y-genetic material always should be removed because gonadoblastomas or dysgerminomas may develop in theorgan. Reconstructive surgery is usually performed by 2 yearsof age so that genital structure reflects gender of rearing. Thisrecommendation for reconstructive surgery is controversial;some advocate that surgery not be performed in infancy orearly childhood so that the child or young adolescent can be involved in the decision. A decision for gender of rearing isrecommended from birth; however the knowledge that theperson with a DSD may change gender later on is shared withparents from the outset.
The adrenal gland consists of an outer cortex, which is responsible for the synthesis of steroids, and an inner medulla derived from neuroectodermal tissue, which synthesizes catecholamines. The adrenal cortex consists of three zones: an outer glomerulosa (end product is the mineralocorticoid aldosterone, which regulates sodium and potassium balance), a middle fasciculata (end product is cortisol), and an inner reticularis (synthesizes sex steroids). The general scheme of these synthetic steps is shown in Figure 178-1.
Hypothalamic corticotropin-releasing hormone (CRH)stimulates the release of pituitary adrenocorticotropic hormone (ACTH, corticotropin), derived by selective processingfrom pro-opiomelanocortin. ACTH governs the synthesisand release of cortisol and adrenal androgens. Primary adrenal insufficiency or cortisol deficiency from any defect in theadrenal gland results in an oversecretion of ACTH; cortisoldeficiency also may occur from ACTH (secondary) or CRH (tertiary) deficiency, causing low serum ACTH concentrations and low cortisol. Endogenous (or exogenous) glucocorticoids feed back to inhibit ACTH and CRH secretion. The renin-angiotensin system and potassium regulate aldosterone secretion; ACTH has little effect on aldosterone production except in excess, when it may increase aldosteronesecretion.