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Patients with an intersex disorder of sexual development (DSD) present the urologist with complex evaluation and management challenges. The patient's phenotype, psychosexual differentiation, and chromosomal sex assignment are all important considerations. The timing of gender assignment in the patient's development should be a multidisciplinary decision that includes the patient and family members. The authors present a rare case of a female with intersex DSD due to congenital adrenal hyperplasia of the simple-virilizing (non salt-losing) form. The patient's unique presentation and challenging management, including sex assignment, are described.
KEYWORDS: Female disorder of sexual development; Congenital adrenal hyperplasia; Intersex.
CORRESPONDENCE: Professor N. K. Mohanty, M.S., M.Ch, Additional DG and Head of Department, Vardhman Mahaveer Medical College and Safdarjung Hospital, C â€“ II /124, Motibagh, New Delhi, India - 110021
CITATION: Urotoday Int J. 2010 Apr;3(2). doi:10.3834/uij.1944-5784.2010.04.06
ABBREVIATIONS AND ACRONYMS: CAH, congenital adrenal hyperplasia; DSD, disorder of sexual development; MRI, magnetic resonance image
A female with an intersex disorder of sexual development (DSD), previously known as a pseudohermaphroditism, is an individual with a 46 XX karyotype, ovaries, and a partially masculinized phenotype [1,2]. Congenital adrenal hyperplasia (CAH) is the most common cause of female intersex DSD. CAH is an autosomal recessive metabolic disorder caused by a defect in any of the 5 enzymes involved in cortisol biosynthesis. A 21-hydroxylase deficiency accounts for 95% of the reported cases of CAH [3,4,5]. The incidence of CAH has been reported to range from 1 in 5,000 to 1 in 15,000 in the USA and Europe .
Patients with CAH can be divided into 3 categories: (1) patients with virilization and aldosterone deficiency (salt wasters); (2) patients with virilization without salt wasting (simple virilizers); (3) patients without virilization or salt wasting (nonclassic). Females in the simple virilizing category present with some degree of masculinization at birth. There is clitoris enlargement, which can simulate a hypospadiac penis with bilateral undescended testes. There is varying degree of labial fusion. The vagina and urethra have a common opening into a common urogenital sinus. A magnetic resonance image (MRI) of the abdomen and pelvis will demonstrate mullerian structures along with enlarged adrenal glands. Raised serum 17 hydroxy-progesterone confirms a diagnosis of 21 hydroxylase deficiency [3,4,5].
The authors present a rare case of female with intersex DSD due to CAH of the simple-virilizing (non salt-losing) form. The patientâ€™s unique presentation and challenging management, including sex assignment, are described.
A 42-year-old male presented with ambiguous sex assignment. He lived as a female until puberty, when he developed some physical characteristics of a male. Therefore, he started to live as a male in society. In his late thirties, he married a woman. However, citing marital disharmony, his wife deserted him. He then sought medical assistance for his condition.
The patient was short-statured with a stocky build, male-pattern baldness and hair distribution, a mustache and beard, low-pitched voice, and underdeveloped breasts (Figure 1). Examination of his genitalia revealed a 1-inch elongated clitoris with a common opening below it leading to the bladder and a hypoplastic vagina. The well-developed labia majora gave the appearance of an underdeveloped scrotum with rugosities, with no palpable external gonads. The patient reported no history of cyclic menses. The family and medical history were not significant.
Routine blood and urine investigations were normal. Karyotypic analysis showed 46XX genotype (Figure 2). A genitogram revealed a small uterus with an underdeveloped vagina and a short common-passage urethra leading to a well-developed bladder. The serum 17-hydroxy progesterone was markedly elevated. The result of a 24-hour urinary 17-ketosteroid level was elevated. Serum testosterone was 3.5 ng/mL; normal range is 2-10 ng/mL. MRI of the abdomen and pelvis showed bilateral enlarged adrenals with well-developed ovaries and a rudimentary uterus. There were no testes (Figure 3a; Figure 3b).
Given the clinical diagnosis of female intersex DSD, the patient was asked for his preferred sex assignment. He indicated that he desired to live as a male, despite knowing that he could not produce sperm. Therefore, the rudimentary uterus, atrophied vagina, and both well-developed ovaries and their cord-like fallopian tubes were removed laparoscopically. The common communication with the urethra was closed.
After 3 months, the patient underwent initial clitoral and urethral lengthening to create a phallus. A third laparoscopic surgery was conducted 6 months after the patientâ€™s initial visit. The urethra was reconstructed, and bilateral silastic testicular implants were made into the labial folds. The labial folds were approximated to the midline to provide the appearance of a scrotum.
At the end of the staged surgery, the patient could achieve a total phallus length of 2.5 inches. The urethral opening was located near the tip of the ventral phallus. Together, the phallus and the bilateral artificial testes provided the patient with the external appearance of male genitalia. At his 1-year follow-up, the patient reported that he was living happily with his wife. He could have satisfactory sexual intercourse without any ejaculate. He indicated that they planned to adopt a child.
The appropriate diagnosis and management of individuals with intersex DSD is a challenging task for the urologist. Figure 4 depicts a flowchart of criteria used to evaluate and diagnose these patients. In case of a patient with the 46,XX karyotype, gender assignment is usually female . If the karyotype is 46,XY, the case is more complex and includes factors such as penile length and evidence of androgen insensitivity. Patients with the 46,XY karyotype who have complete androgen insensitivity may be appropriately assigned the female gender. Those with 5α-reductase deficiency may be more appropriately assigned the male gender. The most frequent abnormal karyotype is 45,X/46,XY mosaicism, which presents a variable phenotypic spectrum. The degree of masculinization of the external genitalia appears to vary with the amount of testicular tissue present, and gender assignment depends on the functional potential of the gonadal tissue, reproductive tracts, and genitalia [1,2,7].
Sex assignment forms an integral part of the management policy for patients with intersex DSD, and the timing of this decision can be challenging. Before deciding on the sex assignment, it is important to consider 3 stages of gender development. The first stage, gender identity, is the recognition of oneâ€™s self as male or female. The second stage, gender role, refers to the social behavior corresponding to societyâ€™s expectations for a given gender. The third stage, sexual orientation, is a personâ€™s erotic interest in male or female sexual partner .
There has been a significant change in the sex assignment protocol for patients with intersex DSD in recent years . The optimal gender policy proposed by Hampson and Money in 1956  recommended that the clinical decision for sex assignment should be made before the second year of life, so that children would not be aware of their sex history. It was hypothesized that this procedure avoided psychological distress and doubts about assigned sex. Individuals with the XX karyotype who have female pelvic organs have traditionally been assigned the female sex even when they present with extensive masculinization of the external genitalia. Using this approach, a virilized 46 XX patient with normal mullerian structures, such as the present case, would be assigned the female gender. Feminizing genital surgery would be performed, based on the potential for future fertility and receptive intercourse. However, some females with CAH are not satisfied with the assigned female sex and prefer to live as males. This dissatisfaction may be due to reduction in genital sensitivity and difficult penile-vaginal intercourse as a result of postoperative scarring  or other issues such as the development of male characteristics. Therefore, the traditional optimal gender policy has shifted to full consent policy. With the latter procedure, all medical information is provided to the patient and the parents when the patient is in later stages of gender development. Their full participation in decision-making is encouraged [9,10].
The present case belongs to the simple virilizers category of CAH due to 21-hydroxylase deficiency, which presented at a later stage. The authors used the full consent policy for sex assignment. The patient was provided with all clinical information. He decided to live as a male, knowing that he could not produce sperm. Therefore, he had a multistaged surgery to create external male genitalia. At the 1-year follow up, this patient was satisfied with his married life.
Management of a female with intersex DSD due to CAH (simple virilization form) involves more than determination of the chromosomal sex. The patient's phenotypic and psychosexual differentiation must also play an important role. Treatment of such patients presents a complex clinical situation that requires a multidisciplinary approach.
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