Congenital Anomalies of the GU tract Flashcards Preview

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Flashcards in Congenital Anomalies of the GU tract Deck (24)
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1
Q

Features of Undervirilized Males:

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

Features of Virilized Females (4):

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

What is the most common cause of 46 XX DSD?

A

Excessive fetal androgen production

  • Congenital adrenal hyperplasia:
    • 21-hydroxylase deficiency is the MOST COMMON CAUSE OF 46 XX DSD
4
Q

What are other causes of 46 XX DSD?

A
  • 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)
5
Q

What is the most common cause of 46 XY DSD?

A

Idiopathic

  • 50% of cases of 46XY infants with ambiguous genitalia
6
Q

What are other causes of 46 XY DSD?

A
  • 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
7
Q

46 XY DSD: Pathogenesis

  1. Defect in function of androgen target tissues:
  2. Gonadal dysgenesis:
  3. Congenital Adrenal Hyperplasia:
A
  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
8
Q

Ovotesticular DSD:

  • Definition:
  • Karyotype:
A
  • Both ovarian and testicular tissue w/ normal responsiveness to hormones
  • Karyotype:
    • 46XX (70%)
    • 46XY
    • 46XX/XY (20%)
9
Q

Ovotesticular DSD

  • Phenotype:
A
  • 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
10
Q

What needs to be done for a Ovotesticular DSD patient?

A
  1. Laparoscopy with gonad biopsy as infant
  2. Surgical reconstruction to match gender assignment.
  3. Excision of organs inconsistent with gender assignment
11
Q

When should you consider DSD?

A
  • Bilateral nonpalpable gonads
  • Severe hypodyspasias
    • Esp. w/ nonpalpable gonads
  • Clitoromegaly (maybe microphallus?)
  • Posterior fusion of vaginal opening (or undervirilized scrotum?)
  • WHENEVER GENITALIA DO NOT LOOK COMPLETELY NORMAL
12
Q

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

A
  • 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
13
Q

List Examples of DSD:

A
  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
14
Q

Androgen Insensitivity Syndrome

  • Where is the defect?
  • Most common presentations:
A
  • 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
15
Q

Why may it be difficult to assign gender in PAIS?

A
  • 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
16
Q

What are the medical needs for a PAIS patient?

A
  • Complex surgical reconstruction depending on gender identity often delayed until puberty when patient can express input
  • Psychological support
17
Q

What is the genotype and karyotype in Ovotesticular DSD?

A
  • 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
18
Q

Example of a patient with Ovotesticular DSD:

  • 7 day old infant w/ ? genitalia
  • Karyotype: ?
  • serum testosterone: ?
  • MIS: ?
  • T:DHT ?
A
  • 7 day old infant w/ambiguous genitalia
  • Karyotype: 46 XX
  • serum testosterone: normal for male
  • MIS: (normal)
  • T:DHT (normal)
19
Q

What are the defects of androgen biosynthesis?

A
  • 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)
20
Q

5α Reductase Deficiency:

  • Karyotype & Genetics:
  • Definition:
  • Why is DHT critical prior to birth?
  • What happens at puberty in these patients?
A
  • 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
21
Q

Congenital Adrenal Hyperplasia:

  • 46 XX DSD:
    • Defects?
  • 46 XY DSD:
    • Defects?
A
  • 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
22
Q

What does CAH cause a compensatory increase in?

A

ACTH

23
Q

What is the most common form of CAH?

A

21-hydroxylase deficiency

24
Q

CAH due to 21-hydroxylase deficiency

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