Week 1: Disorders of Sex Development Flashcards
(71 cards)
1
Q
Describe the genital indifferent stage
A
2
Q
Hypospadias
A
3
Q
Anterior and posterior hypospadias
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4
Q
Male epispadias
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5
Q
Typical newborn female vs clitoral hyperplasia
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6
Q
Diagnosis of Atypical genitalia
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- Newborn exam
- Newborn screening - CAH (congenital adrenal hyperplasia)
- FISH
- Karyotype
- Labs
7
Q
Labs for atypical genitalia
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- Chemistry
- FSH
- LH
- Testosterone
- Estradiol
- Mullerian inhibiting substance (MIS)
- Specific metabolites if suspecting adrenal hyperplasia
8
Q
DSD classification system
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9
Q
Sex Chromosome DSD
A
- 45, X (Turner Syndrome and variant)
- 47, XXY (Klinefelter syndrome and variants)
- 45, X/46, XY (MGD)
10
Q
Questions
A
11
Q
Turner syndrome karyotype
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- 45, XO
- One functional X chromosome
- 10% have 46, XY mosaicism -> risk for gonadoblastoma
12
Q
Pathophysiology of Turner Syndrome
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- one functional X chromosome
- Meiotic nondisjunction
- no barr body
13
Q
What is the most common cause of primary amenorrhea?
A
Turner syndrome
14
Q
What Turner Syndrome karyotype carries a risk for gonadoblastoma?
A
46, XY mosaicism (10% of cases) have risk for gonadoblastoma
15
Q
What is primary amenorrhea?
A
Menopause before menarche
16
Q
Symptoms of Turner Syndrome
A
Also,
- Pressure difference between the upper and lower extremities > 20 mmHg
- Risk of aortic dissection in pregnancy
17
Q
Turner Syndrome cardiovascular symptoms
A
18
Q
Lab values of Turner Syndrome
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- Decreased Estrogen
- Increased FSH
- Increased LH
19
Q
Streak gonads vs normal ovary
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20
Q
Sex chromosome Disorders of Sexual Development
A
- 45, X or 46, XY mosaicism Turner Syndrome
- 47, XXY Klinefelter syndrome
- X/46, XY Mixed Gonadal Dysgenesis (MGD)
21
Q
What is the most common sex chromosome disorder
A
Klinefelter Syndrome
22
Q
Klinefelter Syndrome in childhood
A
- May be a normal physical exam in childhood
- May have developmental delay
23
Q
Epidemiology of Klinefelter Syndrome
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- Most common sex chromosome disorder
- Most common chromosomal cause for hypogonadism and subfertility
24
Q
What is the most common chromosomal cause for hypogonadism and subfertility
A
Klinefelter syndrome
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Karyotype features of Klinefelter syndrome
* 47, XXY
* Extra X - inactivated -\> Barr body present
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Klinefelter Syndrome symptoms
* testis atrophy
* Androgynous body shape
* Tall with long extremities
* Gynecomastia
* Female hair distribution
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Klinefelter Syndrome Lab findings
* Testis atrophy - abnormal seminiferous tubules and abnormal leydig cell function
* Decreased inhibin B -\> increased FSH
* Decreased Testosterone -\> increased LH
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What is the second most common cause of atypical and "unclassifiable" genital appearance at birth
Mixed Gonadal Dysgenesis
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Mixed Gonadal Dysgenesis reproductive organs
Typically a streak gonad on one side and a testis, which may be undescended, on the other side
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Most common karyotype of MGD
* 45, X
* 46, XY mosaicism
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Mixed Gonadal Dysgenesis concerns
concerns for infertility and gonadoblastoma
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Karyotype of Ovotesticular DSD
46, XX
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Disorders of gonadal (ovary) development
* Gonadal dysgenesis
* Ovotesticular DSD
* Testicular DSD (eg SRY, dup SOX9, dup SOX3, RSPO1, WNT4)
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Ovotesticular DSD was previosly known as?
Previously known as true hermaphroditism
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True hemaphroditism is now known as
Ovotesticular DSD
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Ovotesticular DSD reproductive organs
* indicates that there is actual testicular and ovarian gonadal tissue
* Most common phenotype is an ovotestis on one side and ovary on other side
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Ovotesticular DSD karyotype
Most common karyotype is 46, XX
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Ovotesticular DSD most common external anatomy
Most common external anatomy resembles male with severe hypospadias
39
Question
D. Ovotestis and ovary
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Ovotesticular DSD most common external genitalia phenotype
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What is the most commonly encountered DSD is?
Congenital adrenal hyperplasia (CAH)
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46, XX DSD androgen excess pathologic mechanism
Enzyme deficiency -\> decreased steroid -\> increased metabolites and lack of ACTH suppression
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46, XX DSD androgen excess: What is the most common enzyme deficiency?
Most common enzyme deficiency is 21-hydroxylase (90%)
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46, XX DSD androgen excess: 21-hydroxylase deficiency
* Virilization in infancy
* Salt wasting in infancy
* Precocious puberty in childhood
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Steroid synthesis pathway
46
46, XX DSD androgen excess: 11-β Hydroxylase prevalence
5% of cases
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46, XX DSD androgen excess: 11-β Hydroxylase symptoms
* Virilization and hypertension
* Hypertension seconday to accumulation of DOC
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46, XX DSD androgen excess: 17α-Hydroxylase prevalence
Rare
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46, XX DSD androgen excess: 17α-Hydroxylase symptoms
* HTN and lack of sex hormones
* Male - ambiguous and undescended testes
* Female - amenorrhea, lack of secondary sex development
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External genitalia of CAH
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Question
D. 21α-hydroxylase
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Question
C. 11Desoxycortisol
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Fetoplacental androgen excess types
* Aromatase (CYP19) deficiency
* Oxidoreductase (POR) deficiency
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Placental aromatase deficiency symptoms
* Rare
* Virilization of female infants - clitoral hyperplasia
* May present with virilization of mother in 3rd trimester as fetal androgens cross placenta
* Maternal serum -\> increased testosterone, decreased estrogen
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Genitalia of Placental Aromatase deficiency
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5α-reductase deficiency inheritance pattern
Autosomal recessive
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5α-reductase deficiency pathophysiology
46, XY without conversion of T to DHT -\> ambiguous genitalia until adolescence when increase T -\> virilization and phallic growth
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5α-reductase deficiency lab values
* Testosterone normal
* Estrogen normal
* LH may be increased or normal
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5α-reductase deficiency genitalia
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Androgen insensitivity syndrome
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Androgen insensitivty syndrome types
* CAIS
* PAIS
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Androgen insensitivty syndrome: CAIS
* Defect in androgen receptor -\> typical external female genital exam
* Rudimentary vagina
* Absent internal mullerian structures
* May present with inguinal hernia in childhood
* Amenorrhea
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Androgen insensitivty syndrome: CAIS genitals
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Kallmann syndrome pathophysiology
Defect with GnRH-releasing neurons and olfactory bulbs
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Kallmann syndrome symptoms
* Hyposmia or anosmia
* Infertility in males
* amenorrhea in females
* hypogonadotropic hypogonadism
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Kallmann syndrome lab values
* Decreased FSH
* Decreased LH
* Decreased estrogen/testosterone
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What is Hyposmia or anosmia
Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected. Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. ... Lifelong hyposmia could be caused by Kallmann syndrome.
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Case
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Complete the table
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Case
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