The 2010 Endocrine Society guidelines conclude that prenatal dexamethasone therapy should be pursued only through institutional review boards’ approved protocols at centers capable of collecting sufficient outcome data (182).
In a small percentage of patients with CAH, hypertension, rather than mineralocorticoid deficiency, develops. The hypertension responds to corticosteroid replacement (183–186). Many of these patients have a deficiency in 11β-hydroxylase (184,185). In most populations, 11β-hydroxylase deficiency accounts for 5% to 8% of the cases of CAH, or 1 in 100,000 births (187). A much higher incidence, 1 in 5,000 to 7,000, was described in Moroccan Jewish immigrants (186).
Two 11β-hydroxylase isoenzymes are responsible for cortisol and aldosterone synthesis, respectively, CYP11-B1 and CYP11-B2. They are encoded by two genes on the middle of the long arm of chromosome 8 (187–189).
Inability to synthesize a fully functional 11β-hydroxylase enzyme causes a decrease in cortisol production, a compensatory increase in ACTH secretion, and increased production of androstenedione, 11-deoxycortisol, 11-deoxycorticosterone, and DHEA. The diagnosis of 11βhydroxylase-deficient late-onset adrenal hyperplasia is determined when 11-deoxycortisol levels are higher than 25 ng/mL 60 minutes after ACTH(1–24) stimulation (190).
Patients with 11β-hydroxylase deficiency may present with either a classic pattern of the disorder or symptoms of a mild deficiency. The severe classic form is found in about two-thirds of the patients with mild-to-moderate hypertension during the first years of life.
In about one-third of the patients it is associated with left ventricular hypertrophy, with or without retinopathy, and occasionally death is reported from cerebrovascular accident (183). Signs of androgen excess are common in the severe form and are similar to those seen in the 21-hydroxylase deficiency.
In the mild, nonclassic form, children have virilization or precocious puberty but not hypertension. Adult women will seek treatment for postpubertal onset of hirsutism, acne, and amenorrhea.