Taylor_Speroff's Clinical Gynecologic Endocrinology and Infe

272 Section II • Clinical Endocrinology

and even total clitoral amputation generally do not have an impaired erotic response or decreased capacity for orgasm. When necessary, vaginal reconstruction is best postponed until after puberty when mature compliance is possible. In patients with severe classical CAH, bilateral adrenalectomy offers the potential advantage of preventing adrenal hyper androgenism, but also increases the risk for developing adre nal crisis. 260–262 Treatment in Adults For older adolescent and adult women with classical CAH, the goal of treatment is to lower and maintain serum concen trations of adrenal precursors (17-OHP) and androgens to the upper limits for normal women. After epiphyseal closure is complete, treatment with long-acting glucocorticoids (e.g., dexamethasone, prednisone) generally is preferred. When administered at bedtime in a dose ranging between 0.25 and 0.75 mg, ACTH is effectively suppressed for most or all of the following day. Bedtime treatment effectively inhibits the peak of ACTH secretion, which occurs between 2:00 a.m. and 10:00 a.m. 240 To avoid the risks of osteoporosis and developing Cushing syndrome, dosage must be adjusted to the needs of the individual patient. Alternative treatment regimens include prednisone (median dose 7 mg/ day; range 4–10 mg/day) or single or divided doses of hydro cortisone (median 30 mg/day; range 15–40 mg/day). 263 Supplemental doses of glucocorticoid, generally involving a two- to threefold increase in the usual daily dose, are indi cated during times of stress such as febrile illness, surgery, and trauma; normal exercise does not require stress doses of glucocorticoids. 236 As in children with classical CAH, mineralocorticoid treatment in adults is provided with fludrocortisone , in the dose required to maintain normal serum sodium and potassium concentrations and plasma rennin activity, usu ally ranging between 0.1 and 0.2 mg/day. When mineralo corticoid treatment is optimized, the dose of glucocorticoids can be minimized. 244,245 Inadequate treatment can result in chronic volume depletion that promotes excess produc tion of renin and angiotensin II, which, in turn, can stimu late increased adrenal androgen synthesis. 246 Patients with the simple virilizing form of classical CAH who exhibit increased plasma renin activity and aldosterone concentra tions can benefit from mineralocorticoid treatment, which helps in controlling 17-OHP levels. 264,265 Treatment should be monitored by periodic measure ments of bone density, and serum 17-OHP, DHEA-S, andro stenedione, and testosterone concentrations, remaining alert to the development of signs or symptoms of Cushing syndrome. In those who require mineralocorticoid treat ment, plasma renin activity should be monitored and maintained near the upper limit of normal. Many women with classical CAH who underwent recon structive surgery during childhood later require further reconstructive surgery during late adolescence or early

advanced bone age. 248,249 Patients with classical CAH have an increased risk for developing central precocious puberty due to poor control of adrenal androgen production; in those who do, treatment with a long-acting GnRH agonist may be needed. 250 Illness can precipitate adrenal crisis in children with classical CAH unless they receive adequate glucocorticoid treatment. Signs and symptoms suggesting the possibility include hypotension, electrolyte imbalance (hyponatremia, hyperkalemia, hypoglycemia), and vomiting and diarrhea that sometimes can be accompanied by abdominal pain, fever, loss of appetite, and weight loss. In children with mild illness, the maintenance dose of glucocorticoid gener ally should be increased by two- to threefold. When illness is associated with diarrhea or vomiting and reduced oral intake, intravenous glucocorticoids, saline, and glucose may be required. In children with severe illness or who require major surgery, intravenous hydrocortisone should be admin istered in a dose appropriate for age; for those 12 years of age or older, a one-time dose of 100 mg should be adminis tered, followed by 100 mg/day. During recovery, stress doses of hydrocortisone can be gradually decreased, by approxi mately 50% per day. 229 Children with classical CAH are at increased risk for early puberty and short stature because high levels of sex steroids promote premature epiphyseal closure. In treated patients with classical CAH, adult height usually is lower than in reference populations, by an average of approxi mately 10 cm, independent of the level of control of adrenal androgen concentrations, which suggests that treatment with exogenous glucocorticoids also suppresses growth. 251,252 The effectiveness of treatment during the first 2 years of life and during puberty appears to have the most important influence on final height. 253–255 Treatment with growth hormone and a long-acting GnRH agonist can help to maximize growth and adult height. 256,257 Obesity is a common complication of glu cocorticoid treatment in children with classical CAH; body mass index correlates with the dose of prescribed medica tion. 258 In obese children, the incidence of hypertension also is increased. 259 The surgical management of the genital abnormalities in virilized female children with classical CAH is quite com plicated. Traditionally, surgery has been performed in the first few years of life, when the child is still too young to remember the procedure, to avoid any psychological prob lems associated with having abnormal external genitalia. However, the wisdom and outcomes achieved with early surgery recently have been challenged, and many now advocate delaying unnecessary surgery until the child is older and can participate in the decision. 115 The contro versy is discussed in a later section of this chapter devoted to the management of ambiguous genitalia. If clitoroplasty is performed, the clitoral recession procedure, conserv ing the glans and its innervation, should be employed. It is important to know that women who undergo clitoroplasty

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