Ambiguous Genitalia: Etiology, Treatment, and Nursing Implications Leslie A. Parker, RNC, MSN, ARNP

Transcription

1 Ambiguous Genitalia: Etiology, Treatment, and Nursing Implications Leslie A. Parker, RNC, MSN, ARNP = The infant presenting with ambiguous genitalia is a challenge to both the medical and nursing staff. The birth of any infant with ambiguous genitalia is considered a physical and psychologic emergency requiring prompt recognition and treatment for a positive outcome. A review of the etiology, presentation, diagnosis, and treatment of ambiguous genitalia is presented. The important aspects of family care also are discussed. JOGNN, 27,15-22; Accepted: May 1996; Updated August The birth of an infant with ambiguous genitalia is a medical and psychosocial emergency requiring rapid diagnosis and management. A delay in diagnosis can result in a life-threatening situation or cause undue emotional stress for the family (Aaronson, 1992). Early recognition is imperative to ensure the psychologic, social, and sexual health of the infant. It is emotionally devastating for the child and family if genital ambiguity goes unrecognized, leaving the infant with abnormally appearing genitalia and possibly the appearance of incongruent secondary sex characteristics at puberty. The nurse is often the first and sometimes the only clinician to perform an in-depth physical examination on the newborn infant and must therefore be adept at recognizing potential genital ambiguity. This article presents a comprehensive overview of the etiology, presentation, diagnosis, and management of the infant with ambiguous genitalia. Literature Review Nomzal Sexual Differentiation To completely understand the development of abnormal sexual differentiation, one must be fa- miliar with the sequence of normal embryologic development. Before 8 weeks gestation, no differences exist in internal or external genitalia of male and female embryos. Each has the capability to develop either male or female characteristics. This development is based solely on the presence or absence of the hormone testosterone, which is secreted by the testes (McGillivray, 1992a). There are three distinct steps in the process of normal sexual differentiation. These steps involve (a) differentiation of the gonads, (b) differentiation of the internal duct system, and (3) differentiation of the external genitalia (Walsh, 1978). Differentiation of the gonad into either a testicle or an ovary is directed by the chromosomal karyotype of the embryo. If a Y chromosome is present, testes will develop. If there is no Y chromosome, ovaries will develop (Brown, 1980). The internal duct system develops from bilateral primordial ducts. These are the wolffian ducts in the male and the mullerian ducts in the female. Under the stimulation of testosterone, the wolffian duct system develops into the epididymis, vas deferens, and seminal vesicle. Without the influence of testosterone, the wolffian structures will regress, and these structures will not develop. The testicles also secrete mullerian-inhibiting substance, which causes regression of the mullerian ducts. If no mullerian-inhibiting substance is present, the mullerian ducts will remain and develop into the fallopian tubes, uterus, and upper vagina (Moore & Persaud, 1993). Before 10 to 15 weeks gestation, the external genitalia in the male and female fetuses are identical. These structures include a urogenital sinus, a genital tubercle, genital folds, and genital swellings. Differentiation again is directed by the presence or absence of testosterone. Under the influ- JanuarylFebruary 1998 JOGNN 15

2 ence of testosterone, the urogenital sinus forms the prostate, the genital tubercle becomes the glans penis, the genital folds develop into the urethra and the penile shaft, and the scrotum develops from the genital swellings. Without testosterone, feminization of the external genitalia occurs. The urogenital sinus becomes the lower vagina, the genital tubercle forms the clitoris, the genital folds develop into the labia minora, and the labia majora develops from the genital swellings. If an abnormal level of testosterone is present, ambiguity of the external or internal system may result (Moore & Persaud, 1993). Classification of Intersexuality Any deviation in the normal steps of sexual differentiation can result in a disorder of intersexuality and subsequent ambiguous genitalia. To simplify the discussion of intersex, it is necessary to classify the disorders of sexual differentiation. Izquierdo and Glassberg (1993) proposed the following classification system: (a) true hermaphrodite (ovary plus testes); (b) female pseudohermaphrodite (ovary only); (c) male pseudohermaphrodite without mullerian structures (testicle only); and (d) male pseudohermaphrodite without mullerian regression (dysgenic testes or streak gonads) (see Table 1). True Hermaphrodite The definition of a true hermaphrodite is an individual with both ovarian and testicular tissue. This may be in the form of a testes on one side and an ovary on the other, bilateral ovotestes, or a combination of ovotestes with either a testes or an ovary. Phenotype may range from normal male to normal female, although some type of genital ambiguity usually is pres- TABLE 1 Classifications of Intersexuality True Hermaphrodite Female pseudohermaphrodite Congenital adrenal hyperplasia Exogenous exposure Male pseudohermaphrodite without mullerian structures Defects in testosterone synthesis Inability to convert testosterone to dihydrotestosterone Androgen receptor defects Male pseudohermaphrodite with mullerian structures Mixed gonadal dysgenesis Dysgenic male pseudohermaphrodite ent. Diagnosis must be made through laparotomy exhibiting both ovarian and testicular tissue (Izquierdo & Glassberg, 1993). Female Pseudohermaphrodite Female pseudohermaphroditism is the most common disorder of sexual differentiation, accounting for 60% to 70% of all cases. These infants always have a normal female karyotype (46XX) and a normal uterus, fallopian tubes, ovaries, and upper vagina. Their external genitalia become virilized or made more masculine from intrauterine exposure to androgens (Izquierdo & Glassberg, 1993). The most common form of female pseudohermaphroditism is congenital adrenal hyperplasia (CAH). This involves an inborn error in the biosynthesis pathway of cortisol in the adrenal cortex. An enzyme necessary for the formation of cortisol is deficient, resulting in either an absence or a decreased level of cortisol. This decreased level of cortisol then stimulates an increase in adrenocorticotropin hormone (ACTH) and subsequent adrenal hyperplasia. The precursors of cortisol also accumulate at increased levels in the blood and have androgenic actions or are converted to androgens, which lead to virilization of the external genitalia (Brown, 1980; Izquierdo & Glassberg, 1993; McGillivray, 1992a). nital virilization in the infant with congenital adrenal hyperplasia is the result of an increased level of serum androgens. Deficiencies in three different enzymes may be responsible for genital ambiguity in the female pseudohermaphrodite (see Figure 1). By far, the most common is 21-hydroxylase deficiency, which accounts for 90% of all female CAH. This may be a life-threatening condition because 21-hydroxylase also is required in the synthesis of aldosterone. If the condition is untreated, one half to two thirds of patients with 21-hydroxylase deficiency will develop salt-losing tendencies, possibly resulting in hyponatremia, hypokalemia, dehydration, acidosis, vascular collapse, and death during the first few weeks of life (Aaronson, 1992). Much less common is 11 betahydroxylase deficiency, which presents with hypertension due to increased mineralocorticoid levels and subsequent severe water retention (Lee, 1991). The third enzyme whose deficiency can lead to CAH is 3 16 JOGNN Volume 27, Number 1

3 Mineraiocorticoid Pathway GlumoRicoid Pathway Androgen Pathway cholesterol OE 17-oH 17,200ES pregnenolone 1 1 -b 170H pregnenolone -b dehydroepiandrosterone 3 F D 3 F D JES progesterone -b 170H pregesterone,-+ androstenedlone deoxycortlcostemne deoxycortisol corticostemne cortisol testosterone i aldosterone FIGURE 1 Pathways of adrenal biosynthesis. 17-OH 17 alpha-hydroxylase 17,20-DES desmolase 3 p-hsd 3 beta-hydroxystwroid dehydrogenase 210H 21 hydroxyiasw tlp-oh 11 beta-hydroxylase 17p-HSD 17 beta-hydroxysteroid dehydrogenase DES desmolase beta-hydroxysteroid dehydrogenase. This is a rare condition resulting in mild virilization and salt wasting (Aaronson, 1992). Diagnosis of 21-hydroxylase deficiency is through elevated serum levels of 17-alphahydroxyprogesterone, which is a precursor of cortisol that accumulates at increased levels in the blood. The other enzyme deficiencies are diagnosed with increased serum levels of other cortisol precursors (Lee, 1991). The infant with female pseudohermaphroditism may present with variable degrees of genital ambiguity ranging from a slightly enlarged clitoris to normally appearing male genitalia without palpable gonads (see Figure 2). The degree of virilization is based on magnitude, duration, and timing of androgen exposure (Brown, 1980). Because CAH can result in death from hyponatremia, dehydration, and vascular collapse, initial treatment consists of rehydration and correction of electrolyte imbalances. To prevent the adrenal insufficiency and the subsequent productions of virilizing androgens, supplemental glucocorticoid (cortisol) is administered. Mineralocorticoid in the form of the drug fludrocortisone will be required to prevent hyponatremia (Meyers-Seifer & Charest, 1992). Surgically, clitoroplasty, vaginoplasty, and labioscrotal reduction will be required for normally appearing and functioning female genitalia (McGillivray, 1992a). With prompt diagnosis, the patient with CAH has an excellent prognosis for health, prospects for a satisfactory sexual life, and the potential to bear children (Brown, 1980). Male Pseudohermaphrodite Without Mullenati Structures The infant with male pseudohermaphroditism without mullerian structures always has a normal male (46XY) karyotype and normally functioning testes. Genital ambiguity is the result of an abnormal testosterone level or a decreased tissue response to testosterone leading to decreased masculinization of the external genitalia. The etiology of male pseudohermaphroditism can be categorized into three major groups: (a) defects in the biosynthesis of testosterone, (b) inability to convert testosterone to dihydrotestosterone (DHT), and (c) androgen receptor defects (Izquierdo & Glassberg, 1993; Lee, 1991). Defects in the biosynthesis of testosterone are related to a deficiency in one of the five enzymes required JanuarylFebruary 1998 JOG" 17

4 FIGURE 2 The genitalia of a female pseudohermaphrodite. Note. From Pathology of the Neonate (slide presentation) (1 992). Reprinted courtesy of Dr. David A. Clark and Wyeth-Ayerst Laboratories, Philadelphia. for the biosynthesis of testosterone from cholesterol. These enzymes include 17,20-desmolase, 20,22-desmolase, 17 alpha-hydroxylase, 3 beta-hydroxysteroid dehydrogenase, and 17 beta-hydroxysteroid dehydrogenase (see Figure 1). This deficiency leads to a diminished testosterone level and genital ambiguity. Three of these enzymes also are necessary for the synthesis of cortisol, with a deficiency resulting in adrenal hypertrophy and potential salt wasting (Aaronson, 1992). Diagnosis can be ascertained by determining there are decreased serum testosterone levels with an increased level of steroid precursors before the enzyme blockage (Brown, 1980). Dihydrostestosterone, a more potent masculine hormone than testosterone, is responsible for virilization of the external genitalia and development of male secondary sex characteristics at puberty (Griffen & Wilson, 1980). This hormone is converted from testosterone in certain tissues by the enzyme 5 alpha-reductase. A deficiency of 5 alpha-reductase will lead to inadequate virilization of the male external genitalia (Glassberg, 1987). Infants with this condition have normal levels of testosterone and mullerian-inhibiting substance; the internal genitalia are masculinized, and only the external genitalia appear to be predominantly female. Diagnosis is made by determining that there is an increased level of testosterone compared with that of DHT (Griffen & Wilson, 1980). Both testosterone and DHT must bind to receptor sites located in the cytoplasma of peripheral tissue. If an androgen receptor defect is present, hormonal effects are not produced, and feminization of both the internal duct system and the external genitalia occurs (Aaronson, 1992; Izquierdo & Glassberg, 1993). Diagnosis is made by examination, finding increased serum levels of testosterone and abnormal binding of DHT to androgen receptors in fibroblasts obtained from genital skin (Griffen & Wilson, 1980). The male pseudohermaphrodite may present with varying degrees of genital feminization ranging in appearance from normal female with a blind vagina to normal male with a hypospadias (see Figure 3) (Izquierdo & Glassberg, 1993). In infants with normally appearing female genitalia, the condition may not be suspected until puberty and the development of male secondary sex characteristics or lack of breast development and presence of amenorrhea (Glassberg, 1987). Male Pseudohermaphrodite With Persistent Mullerian Structures This category is differentiated into four types. Only two, mixed gonadal dysgenesis and dysgenic male pseudohermaphroditism, exhibit ambiguous genitalia in the newborn and are included in this discussion (Izquierdo & Glassberg, 1993). The patient with mixed gonadal dysgenesis has a normal testis on one side and a gonadal streak on the other. A streaked gonad is an undifferen- 18 JOGNN Volume 27, Number 1

5 FIGURE 3 The genitalia of a male pseudohermaphrodite. Note. From Pathology of the Neonate (slide presentation) (1 992). Reprinted courtesy of Dr. David A. Clark and Wyeth-Ayerst Laboratories, Philadelphia. tiated gonad characterized by white streaks of connective tissue (Lee, 1991). In dysgenic male pseudohermaphroditism, the patient exhibits bilateral dysgenic testes, which can be described as bilateral undifferentiated gonads. In both disorders there are varying degrees of genital ambiguity. Because mullerian-inhibiting substance is not secreted from the testes, a uterus, vagina, and at least one fallopian tube will be present (Izquierdo & Glassberg, 1993). Evaluation and Differential Diagnosis Although most of the infants discussed in this article have genitalia that are undeniably ambiguous, some present with only a slight aberration. Because a delay in diagnosis results in consequences regarding the medical condition and psychosocial health of the infant and family, health care providers performing physical examinations of newborn infants must be on the alert for these conditions. When performing a detailed examination of the genitalia, it is helpful to keep a mental checklist of normal physical findings. In all male infants, one should be able to palpate bilateral testes. In the full-term male, the testes should be descended at least into the upper scrotum (McGillivray, 1992b). The stretched penis should be equal to or longer than 2.5 cm measured from the pubic ramus to the tip along the dorsum (McGillivray, 1992b; Meyers-Seifer & Charest, 1992). There should be a midline fusion line of the scrotum just below the phallus, no hypospadias or chordee, and only one perineal opening. Normal female anatomy should consist of a clitoris shorter than or equal to 1 cm, two separate perineal openings, and no fusion of the labia (Mc- Gillivray, 1992b). Genitalia that must be considered ambiguous until proven otherwise are (a) hypospadias with no palpable gonads, (b) hypospadias with 1 palpable gonad, (c) small penis or clitoral hypertrophy with no palpable gonads, and (d) partial fusion of labioscrotal skin (Castiglia, 1989). A cardinal rule is that when an infant has one major genital abnormality or more than one minor abnormality, a problem of sexual differentiation should be assumed until it is proven otherwise (Brown, 1980). When sexual ambiguity is suspected, the following evaluation is warranted. History The family should be questioned about spontaneous abortions, stillbirths, and early neonatal deaths. Because many of these defects are autosomal recessive, a positive family history may be revealed (McGillvray, 1992 b). Physical Examination The most important aspect of the genital examination is the presence or absence of palpable gonads in JanuarylFebruary 1998 JOGNN 19

6 the labioscrotal folds or scrotum. Gonads that are predominantly ovarian never descend below the external inguinal ring (Glassberg, 1987). Therefore, a descended gonad must be a testis,' suggesting the presence of a Y chromosome and virtually excluding the diagnosis of a virilized female. The length of the penis or clitoris should be measured, and the location of the urinary meatus should be identified. The degree of penile curvature (chordee) should be assessed, and any other perineal openings should be identified. The degree of labial fusion and the presence or absence of a vagina must be noted (Mc- Gillvray, 1992b). A rectal examination should be performed to assess for the presence of a uterus, which may feel like a midline, pencil-like structure. nsidering the consequences of a delayed diagnosis, a high degree of suspicion concerning ambiguous genitalia is imperative when performing physical examinations on newborn infants. Because other congenital malformations such as renal, gastrointestinal, and neural tube anomalies are common, a complete physical examination is essential (Mc- Gillivray, ). Chromosomal Analysis A chromosomal karyotype must be performed as soon as possible. These results are rapid and should be available within 48 to 72 hours. In a more critical situation, bone marrow analysis can provide results in just a few hours. Endocrine Studies Because of the life-threatening nature of the defect, the most urgent test to perform is evaluation of the serum 17-alphahydroxyprogesterone level to assess for CAH (McGillivray, 1992b). Testosterone and testosterone precursor levels may be assessed if the diagnosis of male pseudohermaphroditism is suspected (Izquierdo & Glassberg, 1993). Radiologic Studies A pelvic ultrasound examination should be performed on all infants with ambiguous genitalia to assess for the presence of a uterus. A genitogram is also essen- tial to evaluate for the presence and placement of a vagina. This procedure is performed with a fluoroscope by injecting a water-soluble contrast medium into the urogenital orifice. Laparotomy and Lapvoscopy Although a diagnosis may be established biochemically in all female pseudohermaphrodites and some male pseudohermaphrodites, the remainder will require inspection and biopsy of the gonads through laparotomy (Aaronson, 1992). Management and Gender Assignment There are three main considerations in the process of gender assignment. In order of importance these are future unambiguous appearance of the genitalia before and after puberty, adequate sexual functioning, and fertility (Meyers-Seifer & Charest, 1992). The main goal is always the preservation of the individual's sexual self-esteem and ability eventually to have normal, enjoyable sexual relationships (Izquierdo & Glassberg, 1993). Because female pseudohermaphrodites always have a female karyotype, normal female internal structures, and potential fertility, they are consistently raised as females (Izquierdo & Glassberg, 1993). The amount of surgical reconstruction required depends on the amount of genital masculinization. Clitoroplasty, vaginoplasty, and labioscrotal reduction usually are required to construct female genitalia that appear and function normally. These procedures should be performed as soon as medically feasible, either before discharge from the hospital or within the first 3 months of life (Lee, 1991). The decision of gender assignment is much more difficult in the other three types of intersex disorders. In the male pseudohermaphrodite, the decision is based entirely on the size of the phallus. If the phallus is inadequate for appearance and future sexual function, the gender assignment will be female. If the phallus is adequate (>2.5 cm), the gender assignment will be male. It is possible surgically to produce female genitalia that appear normal and function adequately, but it is nearly impossible to reconstruct a penis and scrotum. (McGillivray, ). Female reconstruction of the male pseudohermaphrodite requires clitoroplasty, vaginoplasty, and labioscrotal reduction. The testes and any remaining wolffian duct structures are removed to prevent the formation of male secondary sex characteristics at puberty. Estrogen therapy is required at puberty to produce female secondary sex characteristics. Male reconstruction involves hypospadias repair at 9 to 12 months, vaginal resection, removal of all mul- 20 JOG" Volume 27, Number 1

7 lerian structures, and the placement of testicular tissue in the scrotum. Testosterone therapy will be required at puberty to produce male secondary sex characteristics. There is a 30% risk of malignancy in streaked or dysgenic testes; therefore, these must be removed during laparotomy (Izquierdo & Glassberg, 1993). If there is an absence of normal testes, testicular prostheses may be placed in the scrotum at puberty (Coran & Polley, 1991). In the case of the true hermaphrodite, gender assignment is based on phallic adequacy as well as the potential for sufficient hormonal production to produce normal anatomic and psychologic gender characteristics (Izquierdo & Glassberg, 1993). This is determined at laparotomy where the gonads are inspected for potential function. Genitoplasty is similar to that for male and female pseudohermaphrodites, depending on gender assignment. All incongruent gonadal tissue and duct systems are removed, and if the gender assignment is male, testicular tissue is placed into the scrotum (Izquierdo & Glassberg, 1993). A 6.2% chance of testicular malignancy exists in the true hermaphrodite; thus, careful follow-up is imperative (Glassberg, 1987). Recently there has been controversy related to genital reconstruction of infants diagnosed with ambiguous genitalia. The Intersex Society of North America (ISNA), a peer support, education, and advocacy group, has denounced the current medical practice of early gender assignment and genital reconstructive surgery ( 1994). They think genital surgery results in future emotional and psychologic distress and radically decreased sexual function. The ISNA recommends delaying surgery until the child reaches puberty and can make an informed decision after intensive family and individual counseling has been provided. Family Support The experience of having a child born with ambiguous genitalia is considered a psychologic emergency. Each family member must be treated with care and respect. The gender of the infant is often the first question asked and is considered one of the infant s most prominent features. Therefore, it is understandable that a disorder of sexual differentiation is emotionally devastating for the family (Castiglia, 1989; McGillivray, 1992a). Care of the family begins in the delivery room with the initial suspicion of an intersex disorder (McCauley, 1990). The parents should be given a brief explanation that the infant s genitalia are incompletely developed and that further diagnostic tests will be required to differentiate the gender (Pagon, 1987). They should never be told that the child has two genders or is half boyhalf girl. This could result in confusion and possible poor adaptation to the infant s future gender assignment (Izquierdo & Glassberg, 1993). upport of the family begins in the delivery room and la -9ughout hospitalization. As soon after the birth as possible, an initial conference should be held with the family. This is a critical time to initiate the process of resolution and adjustment to the infant s defects and later gender identity (Aaronson, 1992). The process of sexual differentiation should be discussed with the use of diagrams for clarification. The health care provider should explain to the parents that all fetuses initially have identical genitalia and the potential to develop into either gender. This information can help the parents discard the idea that sexes are separate and distinct entities. Examining the child s genitalia with a member of the medical team will help the parents understand and accept the genital ambiguity (Aaronson, 1992). The second formal conference should be held after all diagnostic results are available and a decision for gender assignment has been determined (Aaronson, 1992). This is a critical time for the family, because for the child to feel comfortable with his future sexual identity, the parents must completely accept the gender assignment and feel secure about their ability to raise their child with the assigned gender. At this meeting, detailed explanations of specific etiology and treatment are provided. This includes timing and nature of surgeries, possible hormonal therapy, and psychosocial development. If the disorder is of genetic origin, genetic counseling is imperative if there is a possibility of future pregnancies. Nursing Implications Nurses can play a key role in helping the family adjust to an extremely difficult situation. This is an devastating experience for the family, and family members may feel bombarded with information involving an extremely complicated condition. It is often intimidating for parents to question a physician or admit that they do not understand an explanation. The nurse can become a vital link in communication between the parents and the physician. Reinforcing information provided to the parents and answering all questions may provide immeasurable aid to these families. Nurses can also assist in some of the more practical aspects of having a child born with ambiguous JanuarylFebruary 1998 JOGNN 22

8 genitalia. Naming the child and completing the birth certificate are often immediate and critical problems encountered by the family. Deferment of both issues should be encouraged until a gender assignment has been reached (Brown, 1980). The parents also should be discouraged from giving the child an ambiguous name such as Terry or Dana and from varying the original name such as Robert to Roberta. Both of these actions will tend to disrupt the ultimate commitment to the gender assignment (Brown, 1980). The parents may need assistance in, establishing what information to divulge to friends and family. Some parents may feel more comfortable postponing announcement of the birth and, if asked, stating that the infant is critically ill and in the neonatal intensive-care unit. This will usually dissuade further questioning (McCauley, 1990). Extended family and close friends who are aware of the gender ambiguity may benefit from a condensed conference explaining the etiology, diagnosis, and treatment of the ambiguity. The nurse caring for the infant should make arrangements to admit the infant to the nursery as baby rather than baby girl or baby boy (Meyers-Seifer & Charest, 1992). A neutral name card should be placed on the crib replacing the traditional blue/pink cards (Castiglia, 1991). When discussing the infant with the family, one should refrain from using pronouns such as he/she and refer, rather, to the newborn as your infant or the child (Pagon, 1987). It is important to help parents focus on their infant as a whole rather than on the infant s condition. The nurse can emphasize the child s features that are unrelated to gender, such as what beautiful eyes the baby has or your baby has a nose just like daddy s. The nurse also can reinforce the parents nurturing abilities and encourage as much involvement in care as possible. These parents need to begin to experience a positive loving relationship with their infant. Summary Care of the infant with ambiguous genitalia may begin in the delivery room but will continue throughout life as the child matures. These individuals often require lifelong medical and psychologic treatment. Major life changes such as puberty, marriage, and the decision to adopt children may represent tremendous psychologic upheavals. Supportive family relationships can be vital to an individual s adaptation to these stressful situations. The neonatal nurse can provide the basis of a healthy parent-child relationship by assisting the family to accept their child s condition and by providing an opportunity for open communication. REFERENCES Aaronson, I. A. (1992). Sexual differentiation and intersexuality. In P. P. Kelalis, L. R. King, & A. B. Belman (Eds.), Clinical pediatric urology (pp ). Philadelphia: W. B. Saunders. Brown, D. R. (February, 1980). Disorders of sexual differentiation: Ambiguous genitalia in the infant. A practical approach for the primary physician. Minnesota Medicine, 63(7), Castiglia, P. T. (1989). Ambiguous genitalia. Journal of Pediatric Health Care, 3(6), Coran, A. G., & Polley, T. Z. (1991). Surgical management of ambiguous genitalia in the infant and child. Journal of Pediatric Surgery, 26(7), Glassberg, K. I. (1987). Intersex disorders classification and management. In A. B. Retik (Ed.), Pediatric urology (pp ). Baltimore: Williams and Wilkins. Griffen, F. E., & Wilson, J. D. (1980). The syndromes of androgen resistance. New England Journal of Medicine, 302, Intersex Society of North America. (1994). Recommendations for treatment: Intersex infants and children. San Francisco, CA: Author. Izquierdo, G., & Glassberg, K. I. (1993). Gender assignment and gender identity in patients with ambiguous genitalia. Urology, 42(3), Lee, M. M. (August, 1991). Clinical management of intersex abnormalities. Current Problems in Surgery, 28( 8), McCauley, E. (1990). Disorders of sexual differentiation and development. Pediatric Clinics of North America, 37(6), McGillivray, B. C. (1992a). Genetic aspects of ambiguous genitalia. Pediatric Clinics of North America, 39(2), McGillivray, B. C. (1992b). The newborn with ambiguous genitalia. Seminars in Perinatology, 16(6), Meyers-Seifer, C. H., & Charest, N. J. (1992). Diagnosis and management of patients with ambiguous genitalia. Seminars in Perinatology, 16(5), Moore, K. L., & Persaud, T. V. N. (1993). The developing human (5th ed.). Philadelphia: W. B. Saunders. Pagon, R. A. (1987). Diagnostic approach to the newborn with ambiguous genitalia. Pediatric Clinics of North America, 34(4), Walsh, P. C. (1978). The differential diagnosis of ambiguous genitalia in the newborn. Urology Clinics of North America, 5(1), Leslie A. Parker is an assistant professor at the University of Florida in Gainesville. Address for cowespondence: Leslie A. Parker, RNC, MSN, ARNP, Box , JHMHC, College of Nursing, University of Florida, Gainesville, FL JOG Volume 27, Number 1