Editing Disorders of Sexual Differentiation (section)

== Approach to the newborn with ambiguous genitalia ==

* Team’s goal should be to make a precise diagnosis of the disorder (which can be achieved in most cases) and, with the involvement of the parents, to assign a proper sex of rearing based on the diagnosis, the status of the child’s anatomy, and the functional potential of the genitalia and reproductive tract.

=== Diagnosis and Evaluation ===

==== UrologySchool.com Summary ====
*'''<span style="color:#ff0000">History and physical exam (including stretched penile length, palpable testis, hypospadias, etc.)'''
* '''<span style="color:#ff0000">Laboratory investigations (4):'''
*# '''<span style="color:#ff0000">Karyotype'''
*# '''<span style="color:#ff0000">Serum electrolytes (rule out salt-wasting from CAH)'''
*# '''<span style="color:#ff0000">Testosterone, DHT'''
*# '''<span style="color:#ff0000">17-hydroxyprogesterone (rule out 21-OH deficiency; should not be measured until day 3-4)'''
* '''<span style="color:#ff0000">Imaging (1)'''
*# '''<span style="color:#ff0000">Pelvis US to determine presence of Mullerian-derived structures'''

==== History and Physical exam ====
*'''History'''
**'''Family history of'''
**#'''Infant death within the family might suggest the possibility of CAH'''
**#Infertility, amenorrhea, or hirsutism might also suggest possible familial patterns of intersex states
**'''Maternal use of medications, in particular steroids or contraceptives, during the pregnancy'''
*'''Physical exam'''
**'''The critical component is the presence of one or two palpable gonads. This finding effectively rules out over-masculinization [i.e. CAH] of the female.''' 
*** Because ovaries do not descend, a distinctly palpable gonad along the pathway of descent is highly suggestive of a testis.
*** '''The patient with bilateral impalpable testes or a unilateral impalpable testis and hypospadias should be regarded as having a DSD until proven otherwise, whether or not the genitalia appear ambiguous'''
****Incidence of DSD with
*****Unilateral undescended testis: 30%
******Unilateral undescened palpable: 15%
******Unilateral undescened impalpable: 50% 
*******Unilateral undescened impalpable with posterior urethral meatus: 65%
******* Unilateral undescened impalpable with anterior urethral meatus: 5-8%
*****Bilateral undescended testes and hypospadias: 32%
******Bilateral undescended palpable: 16%
******Bilateral undescended impalpable: 50%
**'''Penile size should be assessed and an accurate measure of stretched penile length recorded.'''
***Recall, the mean stretched penile length in full-term males born in the United States is 3.5 cm
**'''Presence of a uterus can be assessed by physical exam but a more precise means of assessing müllerian anatomy is by pelvic US''', which may be performed immediately in the neonatal period.
***'''In addition to defining müllerian anatomy and confirming the presence or absence of a uterus, the gonads and adrenals should be studied.'''

==== Labs (7) ====
#'''<span style="color:#ff0000">Karyotype''' 
#*Should be obtained within the immediate neonatal period
#'''<span style="color:#ff0000">Serum electrolytes'''
#*'''Should be sent immediately sent to rule out a saltwasting form of CAH'''
#'''<span style="color:#ff0000">Testosterone and DHT'''
#*'''Should be measured early'''
#'''<span style="color:#ff0000">17-hydroxyprogesterone'''
#*'''Should not be measured until day 3 or 4 to rule out 21-hydroxylase deficiency, because the stress of delivery may result in physiologic elevation of this steroid precursor in the first 1 or 2 days of life.'''
#'''hCG stimulation test'''
#*'''In the absence of palpable testes, the presence or absence of testicular tissue should be determined by documentation of a markedly elevated LH level, consistent with anorchia, or by means of an hCG stimulation test, which can demonstrate normally functioning testicular tissue.'''
#**'''In addition to ruling out anorchia, the [hCG stimulation] study can enable diagnosis of 5α-reductase deficiency (by virtue of an increased ratio of testosterone to DHT) and can help distinguish between impaired testosterone synthesis (deficient response to hCG) and androgen insensitivity (normal response to hCG).'''
#'''Serum MIS'''
#*'''Should be included as a marker of the presence of testicular tissue'''
#'''PCR characterization of the androgen receptor''' in venous blood DNA
#*May define the precise genetic abnormality responsible for a given DSD, be it abnormal androgen receptor or an enzyme abnormality.

==== Imaging ====
*'''Pelvis US to determine presence of Mullerian-derived structures'''
*'''Laparotomy or laparoscopy in this setting remains a diagnostic maneuver'''; removal of gonads or reproductive organs should be deferred until the final pathology report is available and a gender has been assigned.

=== Management ===
*'''Gender assignment'''
**Issues related to the diagnosis-specific potential for normal sexual functioning and fertility and the risk of gonadal malignancy should be addressed.
**'''In the setting of a 46,XX karyotype and masculinized female, gender assignment is usually appropriately female.'''
***In '''CAH''', cortisol suppresses the undesired androgen; and if '''maternal androgen''' is responsible for virilization, its discontinued stimulation is corrective. In both cases there are normal ovaries and müllerian-derived structure, and a '''normal reproductive potential exists.'''
**'''If the karyotype is 46,XY, the issue is a more complex one and includes factors such as penile length and evidence of androgen insensitivity'''.
**Gender role refers to aspects of behavior that distinguish males and females. The development of gender identity is poorly understood, but is influenced by prenatal and postnatal factors. Individual conflicts with gender identity are central to the concept of gender dysphoria
**'''The best predictor of adult gender identity is initial gender assignment'''
***'''Deferring the issue of gender assignment until patients reach an age at which they may declare their own gender identity is not recommended'''
*Parameters of optimal gender policy outlined in the management of ambiguous genitalia by:
**Reproductive potential (if attainable at all)
**Good sexual function
**Minimal medical procedures
**An overall gender-appropriate appearance
**A stable gender identity
**Psychosocial well-being