Taylor_Speroff's Clinical Gynecologic Endocrinology and Infe

290 Section II • Clinical Endocrinology

XX Virilization

SRY +

SRY –

SRY translocation

17-hydroxyprogesterone 17-hydroxypregnenolone

Elevated

Normal

Congenital adrenal hyperplasia 21-hydroxylase deficiency 11 β -hydroxylase deficiency 3 β -HSD deficiency P450 oxidoreductase deficiency

Imaging

Normal

Abnormal

AMH

Maternal androgen exposure or virilization during pregnancy Luteoma Theca-lutein cysts P450 aromatase deficiency

Male

hCG stimulation test

Normal male testosterone response

Ovotesticular DSD SOX9 duplication

FIGURE 8.14

AMH mutations typically have normal male external genita lia, variable testicular descent, and persistent müllerian ducts. When the serum AMH level is normal or imaging reveals testes, disorders of androgen synthesis (steroid 5 α -reductase, 17 β -HSD, and P450 oxidoreductase deficiencies), LH recep tor defects, incomplete androgen insensitivity, and AMH receptor defects must be considered. In patients with steroid 5 α -reductase deficiency, the testosterone/DHT ratio typically is greater than 10. In those with 17 β -HSD deficiency, the serum testosterone concentration often is in the lower normal range, but the serum androstenedione level is elevated severalfold and the testosterone/androstenedione ratio usually is less than 0.8. 587 In patients with LH receptor defects, LH levels are high, testosterone concentrations are low, and androstenedione lev els are not elevated. An hCG stimulation test helps to better define and distinguish suspected enzyme deficiencies from incomplete androgen insensitivity and LH receptor defects. The test involves measurements of serum hCG, LH, FSH, tes tosterone, androstenedione, and DHT on days 1 (basal), 3, and 6, with exogenous hCG (1,500 IU/m 2 ) administered on days 1 and 3. A normal response is a twofold increase in the testoster one level on day 3 and a fourfold rise on day 6, a testosterone/ DHT ratio less than 10, 366 and a testosterone/androstenedi one ratio greater than 0.8. 587 However, because endocrine evaluation may not distinguish clearly between patients with 17 β -HSD deficiency and those with LH receptor defects, geno typing may be required to establish the correct diagnosis. In patients exhibiting normal basal and stimulated andro gen levels, the remaining possibilities include incomplete

androgen insensitivity, an AMH receptor defect, and prena tal exposure to an endocrine disruptor. Sequencing of the AR gene will identify some, but not all, patients with incomplete AIS; a demonstrable mutation will be found in fewer than half of those in which the diagnosis is suspected, 464 and other pos sibilities (e.g., SF1 mutation) must then be considered. Those having an AMH receptor mutation typically have normal male external genitalia and cryptorchid testes. Occasionally, ambig uous genitalia may result from prenatal exposure to phenytoin, phenobarbital, or an environmental exposure 588 (Figure 8.15) . Mixed Sex Chromosome Pattern The differential diagnosis of a mixed sex chromosome pat tern includes only a few disorders associated with genital ambiguity, such as mixed gonadal dysgenesis, ovotesticular DSD, and chimerism. Patients with mixed gonadal dysgen esis typically exhibit external genital asymmetry, and those with ovotesticular DSD generally can be expected to have a low serum AMH level. Clinical Management of Children with Ambiguous Genitalia The management of children born with ambiguous genitalia focuses initially on stabilization, averting the possibility of adrenal crisis in infants with salt-wasting forms of CAH being the most urgent medical issue. Thereafter, management deci sions regarding the sex of rearing must consider a great many interacting and sometimes conflicting factors. Recent years

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