Congenital Anomalies of the GU tract Flashcards Preview

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Flashcards in Congenital Anomalies of the GU tract Deck (24):

Features of Undervirilized Males: 

  1. Small phallus
  2. Hypospadias
  3. Cryptorchidism
  4. Bifid scrotum
  5. Absence of scrotal rugation


Features of Virilized Females (4):

  1. Clitoromegaly
  2. Common Urogenital Sinus
  3. Fused labioscrotal folds
  4. Rugated labioscrotal folds


What is the most common cause of 46 XX DSD?

Excessive fetal androgen production

  • Congenital adrenal hyperplasia:
    • 21-hydroxylase deficiency is the MOST COMMON CAUSE OF 46 XX DSD


What are other causes of 46 XX DSD?

  • Excessive maternal androgens (virilizing tumors)
  • Maternal Drugs
  • Associated with other congenital anomalies
  • Patients with Ovotesticular DSD are usually 46XX
  • XX males (presence of SRY sequences on X-chromosome)


What is the most common cause of 46 XY DSD?


  • 50% of cases of 46XY infants with ambiguous genitalia


What are other causes of 46 XY DSD?

  • Associated with syndromes of multiple congenital anomalies
  • Defect in testicular differentiation
    • Genetic defects: SRY, X-loci, autosomes
  • Defect in Sertoli Cell function: inadequate MIS
    • persistence of Mullerian ducts
  • Defect in Leydig Cell function:
    • testosterone biosynthetic defect
    • LH/HCG response defect


46 XY DSD: Pathogenesis

  1. Defect in function of androgen target tissues: 
  2. Gonadal dysgenesis: 
  3. Congenital Adrenal Hyperplasia: 

  1. Defect in function of androgen target tissues:
    • defect in dihydrotestosterone (DHT) production
      • DHT required for complete virilization before birth but not at puberty
    • defect in androgen receptor action (androgen insensitivity syndromes)
  2. Gonadal dysgenesis:
    • XY (complete or partial)
    • XY ovotesticular DSD
    • “vanishing testes”
  3. Congenital Adrenal Hyperplasia –forms that prevent testicular as well as adrenal steroidogenesis
    • 3 beta-Hydroxysteroid Dehydrogenase deficiency
    • 17-Hydroxylase/17,20 Lyase combined deficiency
    • Side Chain Cleavage deficiency


Ovotesticular DSD:

  • Definition: 
  • Karyotype: 

  • Both ovarian and testicular tissue w/ normal responsiveness to hormones 
  • Karyotype: 
    • 46XX (70%)
    • 46XY
    • 46XX/XY (20%)


Ovotesticular DSD

  • Phenotype: 

  • Gonads:
    • bilateral ovotestes, or testis on one side and ovary on other
    • In one gonad, each element may be well-defined or admixture of testicular and ovarian elements
  • Ext genitalia:
    • variable spectrum from feminine to masculine
  • Int genitalia:
    • parallels the nature of the ipsilateral gonad
  • Hormone profile:
    • testosterone levels reflect amount of testicular tissue
  • Variable MIS:
    • depends on testicular elements


What needs to be done for a Ovotesticular DSD patient?

  1. Laparoscopy with gonad biopsy as infant
  2. Surgical reconstruction to match gender assignment.
  3. Excision of organs inconsistent with gender assignment


When should you consider DSD?

  • Bilateral nonpalpable gonads
  • Severe hypodyspasias
    • Esp. w/ nonpalpable gonads
  • Clitoromegaly (maybe microphallus?)
  • Posterior fusion of vaginal opening (or undervirilized scrotum?)


What do you not do when DSD is a possible diagnosis?

  • assume cryptorchidism when it could be a female
  • assume clitoromegaly when it could be a male
  • assume hypospadias when it could be a female
  • assume you know the genetic sex based on the phenotype
  • refer to the baby as “she” or “he” until gender assignment is decided upon


List Examples of DSD:

  1. Androgen Insensitivity Syndrome
    • Complete AIS
    • Partial AIS
  2. Ovotesticular DSD
  3. Androgen Biosynthetic Defect
    • 5 αreductase deficiency
  4. Congenital Adrenal Hyperplasia
    • 21-hydroxylase deficiency


Androgen Insensitivity Syndrome

  • Where is the defect? 
  • Most common presentations: 

  • Androgen receptor defect
    • X-linked recessive, karyotype 46 XY
    • Complete and Partial forms
  • Most common presentations: 
    • CAIS:  
      • female adolescent with primary amenorrhea and breasts, no pubic hair
      • female child with testes discovered in inguinal hernia
    • PAIS: highly variable


Why may it be difficult to assign gender in PAIS?

  • Karyotype: 46XY
  • Gonads: testes vary in location. Abdominal-inguinal-scrotal
  • Ext genitalia: variable spectrum of severely undervirilizedmale
  • Intgenitalia: lack all mullerianduct structures
  • Hormone profile: Normal-High testosterone. Normal MIS.
  • Variable response to exogenous testosterone


What are the medical needs for a PAIS patient?

  • Complex surgical reconstruction depending on gender identity often delayed until puberty when patient can express input
  • Psychological support


What is the genotype and karyotype in Ovotesticular DSD?

  • Karyotype variable: 46XX (mostly), 46XY or 46XY/46XX
  • Both ovarian and testicular tissue present
    • May be bilateral ovotestes, or testis on one side and ovary on other
  • External genitalia of variable appearance: spectrum from masculine to feminine in appearance
  • Internal anatomy and endocrine function parallels the nature of the ipsilateral gonad
  • Fertility is uncommon
  • Sex of rearing can be complex decision


Example of a patient with Ovotesticular DSD:

  • 7 day old infant w/ ? genitalia
  • Karyotype: ?
  • serum testosterone: ?
  • MIS: ?
  • T:DHT ?

  • 7 day old infant w/ambiguous genitalia
  • Karyotype: 46 XX
  • serum testosterone: normal for male
  • MIS: (normal)
  • T:DHT (normal)


What are the defects of androgen biosynthesis?

  • Low androstenedione production
    • Rare forms of CAH with adrenal and gonadal enzyme defects
  • 17-ketosteroid reductase (17-KR)
    • def. (testis)
  • 5-α reductase (5α-Red)
    • def. (skin)


5α Reductase Deficiency:

  • Karyotype & Genetics: 
  • Definition: 
  • Why is DHT critical prior to birth?
  • What happens at puberty in these patients? 

  • 46 XY karyotype, autosomal recessive
  • Mutation in 5α reductase enzyme
    • converts Testosterone (T) to Dihydrotestosterone (DHT)
  • DHT is critical for virilization prior to birth, but T is critical at puberty
  • Experience surge of T at puberty, these males undergo dramatic virilization even in absence of DHT


Congenital Adrenal Hyperplasia: 

  • 46 XX DSD:
    • Defects?
  • 46 XY DSD: 
    • Defects?

  • 46 XX DSD
    • 21-OH def (CYP21)
    • 11-OH def (CYP11B)
    • 3β-HSD Def
  • 46 XY DSD
    • SCC def (CYP11A)
    • 17-OH def (CYP17)
    • 3β-HSD Def


What does CAH cause a compensatory increase in?



What is the most common form of CAH?

21-hydroxylase deficiency


CAH due to 21-hydroxylase deficiency 

  • Pathogenesis: 
  • How is it tested for? 
  • Treatment: 

  • Mild to severe virilization of female fetus due to adrenal androgen excess
  • 1:10,000 to 1:15,000 cases per live birth in severe enzyme deficiency
    • Tested by measuring level of 17-hydroxyprogesterone on state newborn screens
    • Late onset form presents in adolescent or young adult females; no congenital virilization
  • Treatment is cortisol replacement to suppress ACTH and reduce adrenal androgens