Introduction

Pediatric urologic emergencies fortunately remain rare occurrences within the emergency department of a hospital or ambulatory care center. More commonly, congenital anomalies noted at birth, or benign lesions that prompt significant parental anxiety (such as benign scrotal conditions), often result in a visit to the emergency department for evaluation. These urgencies nonetheless require both the appropriate investigations and management in order to allay patient and parental concern. The objective of this chapter is to there-

Gynecologic Preteen
Fig. 8.1. Phenotypic appearance of a newborn 46, XX female with moderate virilization secondary to CAH
Table 8.1. Classification of intersex disorders

Category

Gonadal histology

Genotype

Phenotype

Female pseudohermaphro-ditism

Histologically normal ovaries

46, XX

Variable degrees of virilization

True hermaphroditism

Ovarian and testicular tissue

Variable, most commonly mosaic 46,XX/ 46,XY or 47,XXX/46XY

Variable appearance, depending on amount of viable testicular tissue

Male pseudohermaphro-ditism

Histologically normal testes

46, XY

Partial or complete failure ofmas-culinization

Pure or mixed gonadal dysgenesis

Dysplastic gonads with abundant fibrous stroma

Usually both XY and XO cell lines

Variable appearance, depending on amount of viable testicular tissue

Cholesterol

Cholesterol

IStAR P450see

Aa Pregnenolone 17"0H

S Progesterone

21-OH

Co rti cosieron a I 18-OH

18- OH Cortlcosterone

18-oxldase

[Aldosterone]

■ 17-OH Pregnenolone- 1DehydroeplandrostBrene

17. 20-Lyase

17-OH Progesterone-'-"» Androslenedlone

J 21-OH

11 Desoxycortlsol 11 beta-OH

ICortlMll i- Aromatase iTcstPStcronôl Estrone

17 beta -HSD

i- Aromatase iTcstPStcronôl Estrone

17 beta -HSD

170-HSD

170-HSD

So-reductase Dlhydrolesi osle rone] |Eslradlol|

Fig. 8.2. Steroidogenic cascade demonstrating the various adrenal enzymes involved in miner-alocorticoid, glucocorticoid, and androgen production tween the 7th and 14th weeks of gestation and, depending on the underlying etiology, may have profound effects on the ultimate phenotypic appearance of the genitalia (Fig. 8.1).

Intersexuality is most conveniently classified according to gonadal histology. Four main categories have been identified that effectively enable the appropriate diagnosis and prognosis of these children with respect to sexual assignment, potential fertility as well as future gender identity (Table 8.1).

Congenital adrenal hyperplasia (CAH) is the most common underlying cause of sexual ambiguity and, if not recognized, may lead to death in the neonatal period. Although other causes of intersexuality, such as mixed gonadal dysgenesis or true hermaphroditism, may cause distress to the family in the newborn period secondary to inability to assign appropriate gender, only patients with CAH affected by the salt-wasting form represent a true urologic emergency. Consequently, the scope of this section will concentrate on the management of the infant with CAH, bearing in mind that the initial evaluation is similar for all infants with ambiguous genitalia.

CAH is caused by an inherited defect in cortisol metabolism occurring in 1 in 10,000 to 1 in 15,000 live births (Perry et al. 2005) (Fig. 8.2). Although numerous enzymatic defects have been identified, deficiencies in 21-hydroxylase account for more than 90% of cases (Forest 2004). Deficient 21-hydroxylase activity leads to an overproduction of the weak adrenal androgens, an-drostenedione and dehydroepiandrosterone, while preventing appropriate mineralocorticoid and gluco-corticoid production. These weak androgens are subsequently converted to testosterone and dihydrotestoste-rone, resulting in virilization in the female fetus. The salt-wasting form affects two-thirds of CAH patients, where mineralocorticoid and glucocorticoid deficiencies lead to severe dehydration, hyponatremia, and hy-perkalemia. This in turn can lead to fatal cardiac arrhythmias and hypovolemic shock (Lee and Donahoe 1997). If not recognized immediately postpartum, patients with the salt-wasting form typically present 7-10 days following birth with lethargy, poor feeding, vomiting, or even subsequent to near-miss SIDS episodes (Gassner et al. 2004).

Other potential causes of female pseudohermaphroditism include maternal ingestion of androgenic medications during pregnancy, placental aromatase deficiency, or, rarely, hormonally active maternal ovarian

Virilization
Fig. 8.3. Severe virilization of a 46, XX female with 21-hydroxy-lase deficiency. As do most CAH patients with significant virilization, this patient presented with the salt-wasting variety

or adrenal tumors (Ludwig et al. 1998; McClamrock and Adashi 1992). Therefore, a careful history, particularly ascertaining potential maternal drug exposure, is important for elucidating the potential underlying etiology for virilization. A family history of neonatal death or sexual ambiguity may also identify potential cases.

Acute resuscitative measures are obviously indicated for those infants presenting with signs of shock and dehydration. Physical examination will reveal various degrees of virilization, from mild clitoral hypertrophy, to a fully developed phallus, rugated scrotum and impalpable gonads (Fig. 8.3). In general, patients with salt-wasting tend to present with more severe virilizati-on. Laboratory investigations are directed toward determining the underlying cause and typically include serum electrolytes, glucose, gonadotropin, testosterone, dihydrotestosterone, androstenedione, dehydroe-piandrosterone, as well as chromosomal analysis. As the vast majority of females with CAH will harbor a defect in the 21-hydroxylase enzyme, they will demonstrate significantly elevated levels of that enzyme's substrate, namely 17-hydroxyprogesterone. If 17-hydroxy-progesterone levels are not elevated, other rare enzymatic defects may be present such as 11-betahydroxy-lase, 20,22-desmolase, or 3B-hydroxysteroid dehydrogenase (Dacou-Vouteakis et al. 2001).

Abdominal and pelvic ultrasound (US) is important to document the presence of a uterus and ovaries as well as rule-out any upper urinary tract anomalies. Furthermore, fluoroscopic genitography will demonstrate the confluence of the urogenital sinus, urethra,

Fig. 8.4. Urogenital sinogram demonstrating the confluence of the vagina posteriorly and the anteriorly oriented urethra, bladder neck, and bladder and vagina as well as assess for vesicoureteral reflux (Fig. 8.4).

These patients require lifelong mineralocorticoid and glucocorticoid replacement and their optimal management involves a multidisciplinary health care team consisting of pediatric urology, gynecology, endocrinology, genetics, as well as psychiatry and social work. As the vast majority with CAH can appropriately be reared as females (46, XX) with potential fertility, lifelong follow-up of these unique patients is imperative in order to address not only medical, but psychosocial issues as well, which may arise during growth into adulthood.

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