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History/Physical

• Family history: virilization, amenorrhea, infertility, infant death (think untreated CAH)
• Maternal medication use during pregnancy: steroids, hormonal meds
• Exam: assess general appearance, abdominopelvic masses, phallus size, palpable gonads
• Palpable gonads: ovaries do not descend, therefore any palpable gonads equal testis tissue, Ovotestis may decend but can be differentiated based on exam and US findings, bilateral nonpalpable testes or unilateral nonpalpable testis + hypospadias warrant further workup

Adjuncts

• Pelvic US: assess for evidence Mullerian structures, nonpalpable gonads, gonadal cyst (concern for ovotestis)
• Karyotype: assess presence of X + Y chromosomes
• FISH: rapidly identifies X + Y, takes hours (karyotype takes 2 days), identifies SRY gene
• Labs: consider T/DHT (may drop quickly after birth), electrolytes (salt-wasting CAH), 17OH-progesterone (wait 3-4 days due to false elevation after birth), AMH (present with testes), and LH/FSH
• Retrograde studies: can delineate connections in urogenital sinus
• Gonadal biopsy: consider only if needed for diagnosis, do not perform gonadectomy at this time

Tenets of assigning gender

• Maximize reproductive potential
• Maximize sexual function
• Minimize medical procedures
• Optimize gender-appropriate appearance
• Optimize stable gender identity
• Optimize psychosocial well-being
• Goal: avoid irreversible treatments and allow for maximal long-term function and QoL

Germ cell tumor risk

• Higher risk when Y chromosome present in non-scrotal environment (undescended testis) or gonadal dysgenesis (streak gonad)
• High risk (40-60%, gonadectomy recommended): Denys Drash, Fraiser, PAIS nonscrotal testes, gonadal dysgenesis with intraabdominal testes, StAR deficiency
• Intermediate risk (12-28%, surveillance/biopsy): Turner syndrome with Y chromosome, 17B-hydroxysteroid deficiency, PAIS or gonadal dysgenesis with scrotal testes
• Low risk (1-3%, surveillance): CAIS, ovotesticular DSD, Turner syndrome without Y chromosome

Genital Appearance	Karyotype	Gonads	Diagnosis
Female	46 XY	Testis	Complete androgen insensitivity syndrome
			5a-reductase deficiency
			StAR deficiency
		Absent	Absent testis
		Streak	Swyer syndrome
	45 X0		Turner Syndrome
Male	46 XX	Testis	46 XX with SRY+
	46 XY		Persistent mullerian duct syndrome
	47 XXY		Klinefelter syndrome
Ambiguous	46 XX	Testis	46 XX testicular DSD, SRY-
		Ovary	11B-Hydroxylase deficiency
			Excess maternal androgens
			21a-Hydroxylase deficiency
			3B-HSD deficiency
	46 XY	Testis	3B-HSD deficiency
			17B-HSD deficiency
			17-20 Desmolase deficiency
			17a-Hydroxylase deficiency
			Partial androgen insensitivity syndrome
			Leydig cell hypoplasia
	46 XY / 46 X	Testis and streak	Mixed gonadal dysgenesis
	46 XX, 46 XY, 46 XX / 46 XY	Testis and ovotestis	Ovotesticular DSD