Taylor_Speroff's Clinical Gynecologic Endocrinology and Infe

Chapter 8 • Normal and Abnormal Sexual Development 271

glucocorticoids. 147,229,236 The goal of treatment is to promote normal growth and development by providing sufficient hormone to minimize adrenal sex steroid production while avoiding the consequences of glucocorticoid excess. Usually, that can be achieved by treatment with hydro cortisone (cortisol) in a dose of 12–18 mg/m 2 daily, 139,229,236 which still exceeds normal daily cortisol secretion in chil dren and adolescents (6–9 mg/m 2 /day). 237–239 Whereas long acting glucocorticoids (e.g., prednisone, dexamethasone) also can be used, their longer duration of action and greater potency also increase the risk of overtreatment, which can adversely affect growth before closure of the epiphy ses. 148,240,241 Normal growth has been observed in some stud ies of children treated with prednisone (approximately 1 mg/ m 2 /day) 242 or dexamethasone (approximately 0.27 mg/m 2 / day), 243 but hydrocortisone remains the treatment of choice during childhood. 229,236 Mineralocorticoid treatment with fludrocortisone is required for children having classical 21-hydroxylase deficiency , regardless whether they have the salt-wasting or simple virilizing form of the disorder. The goal of treatment is to maintain normal serum sodium and potassium concen trations while avoiding the consequences of overtreatment or undertreatment. Excessive mineralocorticoid treatment can cause hypertension and hypokalemia and may impair growth. 244 Inadequate treatment can result in poor growth because it increases the glucocorticoid requirement 244,245 and may increase adrenal androgen production, because chronic volume depletion causes increased production of renin and angiotensin II, which can stimulate steroidogen esis. 246 In children, fludrocortisone is administered in a dose ranging between 0.05 and 0.2 mg daily. 229 Salt supplemen tation can be discontinued as the child begins to eat table food, but may be needed during hot weather or strenuous exercise. The effectiveness of treatment generally should be moni tored approximately every 3 months in infants and every 4–12 months in children, 229 by measuring the serum concen trations of 17-OHP, androstenedione, plasma rennin activity, growth velocity, and skeletal maturation, comparing results to normative data for age and sexual maturation. 139 Ideally, serum hormone measurements should be obtained in the morning when results will reflect peak concentrations. 147,229,236 Serum 17-OHP levels generally should be maintained in a range between 400 and 1,200 ng/dL, but care must be taken to avoid undertreatment of hyperandrogenism and the consequences of iatrogenic hypercortisolism. 247 Plasma rennin activity should be kept within the normal range for age by adjusting treatment with fludrocortisone and salt supplementation, before adjusting the level of glucocorti coid treatment. When necessary, a brief 7–10-day course of treatment with dexamethasone can effectively suppress high androstenedione levels that may result from poor compli ance. Bone age and growth rate should be monitored every 6 months, with the goal of avoiding a decrease in growth and

Positive hCG

Begin dexamethasone treatment

Chorionic Villus sampling

Sex determination

Genotyping

Male

Unaffected

Discontinue dexamethasone treatment

II

FIGURE 8.9

0.9% saline) and correction of any significant hypoglycemia (2–4 mg/kg 10% dextrose); hyperkalemia should be corrected by administering glucose and insulin, if necessary. After a blood sample is obtained for measurement of steroid hormones (17-OHP primarily), a stress dose of hydrocorti sone should be administered (50–100 mg/m 2 intravenously, typically 25 mg), followed by 50–100 mg/m 2 daily in divided doses (every 4 hours). Additional stress doses of hydrocorti sone are administered until the infant is stable and feeding normally. Immediate mineralocorticoid replacement is not necessary but will be required if a diagnosis of salt-wasting CAH is confirmed. Initially, doses of fludrocortisone up to 0.3 mg daily and sodium chloride supplementation (1–3 g daily; 17–51 mEq daily) are required. In infants having a positive neonatal screening test for CAH, the diagnosis should be confirmed with a second blood sample for measurement of 17-OHP and electrolytes. While awaiting the results, electrolytes should be monitored closely if the infant is not treated empirically with gluco corticoids and mineralocorticoids. Again, the urgent need is to identify infants with salt-wasting CAH before they develop adrenal crisis, which can occur anytime within the first few days or weeks after birth without treatment. 147,229 Treatment in Children Ideally, the medical, surgical, and psychological manage ment of children with CAH should be guided by a multi disciplinary team, including pediatric endocrinologists, surgeons, urologists, geneticists, and psychologists. 229 Children with classical or symptomatic nonclassi cal 21-hydroxylase deficiency require treatment with

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