Laboratory Studies

Based on the excess precursors formed by the enzyme deficiency, diagnosis is made by measuring 11-deoxycortisol.^[13]

Random levels of 11-deoxycortisol are markedly elevated (to several thousand ng/dL) in the classic form. In subjects with the late-onset (nonclassic) variants, random levels of 11-deoxycortisol may be normal; thus, an ACTH stimulation test to demonstrate elevated poststimulation values is then indicated (see Adrenocorticotropin [ACTH] and Dexamethasone/Corticotropin-Releasing Hormone Test).

In the classic form, other hormones that may be elevated include deoxycorticosterone (DOC), urinary 17-ketosteroids, urinary tetra hydrometabolites, adrenal androgens (including dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEA-S], and androstenedione), and testosterone.^[14]

Because DOC and other precursors associated with 11-beta-hydroxylase deficiency have mineralocorticoid activity, plasma renin activity is suppressed. Neonates may lack the diagnostic features of hypertension and suppressed renin.

Mild to moderate elevations of 17-hydroxyprogesterone may be observed (see 17-Hydroxyprogesterone, Serum and 17-Hydroxyprogesterone, Urine); thus, a diagnosis of 11-beta-hydroxylase deficiency may be missed in neonates if 11-deoxycortisol is not specifically measured. Although 17-hydroxyprogesterone levels are not markedly elevated, an erroneous diagnosis of 21-hydroxylase deficiency is possible.

In contrast to other forms of CAH, carriers of 11-beta-hydroxylase deficiency (heterozygotes) do not have elevated metabolite precursors.

Once a case has been identified, additional familial cases can be found by using biochemical or genetic markers.

Increased understanding of the genetic basis of this condition has enabled the medical community to establish the diagnosis prenatally.^{[15, 16, 17]} Techniques include estimating amniotic fluid 11-deoxycortisol and oligonucleotide hybridization of deoxyribonucleic acid (DNA) obtained from chorionic villus biopsies. DNA analysis is used routinely in Israel, where the single His R448H mutation is prevalent.

In addition to enabling genetic counseling, prenatal diagnosis of 11-beta-hydroxylase deficiency offers the opportunity to consider prenatal treatment with dexamethasone in order to prevent virilization of the external genitalia of XX fetuses.^{[15, 16, 18]}

In patients with a mild (nonclassic) variant of 11-beta-hydroxylase deficiency, ACTH-stimulated levels of 11-deoxycortisol should be 5 times the normal level.

Imaging Studies

Pelvic or testicular ultrasonography is useful to visualize adnexal structures in the pelvis of females, to check for normal gonads, and to exclude testicular masses.

Testicular adrenal rest tumors (ectopic adrenal tissue) have been described in males. The tumors usually are bilateral, located in the mediastinum testes, and detected by ultrasonography.

Abdominal computed tomography (CT) scanning may be useful for evaluating the adrenal glands, excluding mass lesions, and diagnosing adrenal hyperplasia, which typically is symmetrical and bilateral (and may also be nodular in long-standing cases). Occasionally, adrenal rests can also be found in ectopic retroperitoneal locations.

Treatment & Management

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