10: Disorders of sexual development Flashcards

1
Q

What is the primary determinant of testis development in normal sexual development?
A. SRY gene on the Y chromosome
B. SRY gene on the X chromosome
C. Presence of an additional X chromosome
D. Presence of a Y chromosome

A

A. SRY gene on the Y chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

During what time frame in development are the gonadal ridge, germ cells, internal ducts, and external genitalia bipotential in both 46,XY and 46,XX embryos?
A. First trimester
B. First 6 weeks
C. Second trimester
D. Third trimester

A

B. First 6 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the term used to describe disruption of any of the three interactions of normal sexual development?
A. Normal sexual development
B. Chromosomal sex
C. Phenotypic sex
D. Disorder of sexual development (DSD)

A

D. Disorder of sexual development (DSD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Explain the three processes of normal sexual development.

A

Normal sexual development involves three processes: establishment of genotypic (chromosomal) sex, establishment of phenotypic sex, and formation of gender identity. Establishment of genotypic sex refers to the sex chromosomes an individual inherits from their parents. Establishment of phenotypic sex refers to the development of internal and external genitalia and other physical characteristics that define an individual’s biological sex. Formation of gender identity refers to an individual’s subjective sense of themselves as male, female, or somewhere in between.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does disruption of normal sexual development lead to a disorder of sexual development (DSD)?

A

Disruption of any of the three interactions of normal sexual development can lead to a disorder of sexual development (DSD). This can occur due to genetic or hormonal abnormalities, environmental factors, or a combination of factors. DSDs can lead to atypical development of the gonads, internal and external genitalia, and other physical characteristics. Additionally, DSDs can affect an individual’s gender identity and sexual orientation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What role does the SRY gene play in normal sexual development?

A

The SRY (sex-determining region Y) gene on the Y chromosome is considered the testis-determining factor in normal sexual development. Under this influence, the bipotential gonadal ridges differentiate into testes, and germ cells develop into spermatocytes. In the absence of SRY, ovarian organogenesis results. The presence or absence of the SRY gene is a critical determinant of an individual’s chromosomal and phenotypic sex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Image
FIG. 10.1 Timetable of normal sexual differentiation. Source: (From White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21(3):245-291.)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Table 10.1

Common Embryologic Origins of Genital Structures.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the primary determinant of testis formation during sexual differentiation?

A) Anti-Müllerian hormone
B) Dihydrotestosterone
C) Estrogen
D) Testosterone

A

D) Testosterone

Explanation: The SRY gene on the Y chromosome is considered the testis-determining factor, which causes the bipotential gonadal ridges to differentiate into testes. Testosterone secretion by the fetal testis Leydig cells occurs at approximately 9 weeks of gestation and promotes virilization of wolffian duct structures, the urogenital sinus, and the genital tubercle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which of the following hormones promotes Müllerian duct regression during sexual differentiation?

A) Anti-Müllerian hormone
B) Dihydrotestosterone
C) Estrogen
D) Testosterone

A

A) Anti-Müllerian hormone

Explanation: The Sertoli cells of the testis secrete anti-Müllerian hormone (AMH) at 7 to 8 weeks of gestation, which promotes Müllerian duct regression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the normal process of sexual development in the first 6 weeks of embryonic development.

A

During the first 6 weeks of embryonic development, the gonadal ridge, germ cells, internal ducts, and external genitalia are bipotential in both 46,XY and 46,XX embryos. Multiple genes are thought to determine chromosomal sex. Specifically, the SRY (sex-determining region Y) gene on the Y chromosome is considered the testis-determining factor. Under the influence of the SRY gene, the bipotential gonadal ridges differentiate into testes, and germ cells develop into spermatocytes. In the absence of SRY, ovarian organogenesis results. The wolffian ducts adjacent to the testes form the epididymis, joining with the rete testes. Distally the wolffian ducts join the urogenital sinus to develop into the seminal vesicles. In the female fetus without testosterone, the wolffian ducts regress. Without AMH, the Müllerian ducts develop into the female internal reproductive tract, including the fallopian tubes and uterus. Contact of the ducts with the urogenital sinus ultimately forms the vagina.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the role of androgens in sexual differentiation and the formation of the male external genitalia.

A

During sexual differentiation, androgens promote virilization of wolffian duct structures, the urogenital sinus, and the genital tubercle. Testosterone secretion by the fetal testis Leydig cells occurs at approximately 9 weeks of gestation. Testosterone enters target tissues by passive diffusion, and wolffian duct virilization does not occur if local androgens are not present. In some cells, testosterone is converted to dihydrotestosterone (DHT) by intracellular 5α-reductase. Testosterone or DHT then binds to an intracellular androgen receptor. DHT binds to the receptor with greater affinity and stability than does testosterone. In tissues equipped with 5α-reductase at the time of sexual differentiation (e.g., prostate, urogenital sinus, external genitalia), DHT is the active androgen. Masculinization of the external genitalia is complete by 12–13 weeks of gestation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Image
FIG. 10.2 Schematic diagram of differentiation of the male external genitalia. Source: (From Martinez-Mora J. Development of the genital tract. In: Martinez-Mora J, ed. Intersexual states: disorders of sex differentiation. Barcelona: Ediciones Doymer, 1994:53.)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Image
FIG. 10.3 Schematic diagram of differentiation of the female external genitalia. Source: (From Martinez-Mora J. Development of the genital tract. In: Martinez-Mora J, ed. Intersexual states: disorders of sex differentiation. Barcelona: Ediciones Doymer, 1994:52.)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Image
FIG. 10.4 Differentiation of the wolffian and Müllerian duct and urogenital sinus in the male and female. Source: (From Wilson JD. Embryology of the genital tract. In: Harrison HH, Gittes RF, Perlmutter AD, et al., eds. Campbell’s urology. 4th ed. Philadelphia, PA: WB Saunders, 1979:1473.)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the most widely used terminology for the conditions of abnormal sexual differentiation?
a) Difference of sex development
b) Intersex
c) Disorders of sexual development
d) Androgen insensitivity syndrome

A

c) Disorders of sexual development

Explanation: The most widely used terminology for the myriad conditions of abnormal sexual differentiation is disorders of sexual development (DSD), or disorders of sexual differentiation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the potential causes of disorders of sexual development, and how are they diagnosed?

A

Answer: Disorders of sexual development can have a variety of causes, including genetic abnormalities, hormonal imbalances, and environmental factors. In some cases, the cause may be unknown. Diagnosis of DSD involves a thorough medical history and physical examination, as well as laboratory testing to evaluate hormone levels and genetic testing to assess chromosomal abnormalities. Imaging studies may also be performed to evaluate the internal reproductive organs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the term used to describe a condition in which the individual has external female genitalia but has undescended testes instead of ovaries?
a) Turner syndrome
b) Klinefelter syndrome
c) Androgen insensitivity syndrome
d) 5-alpha-reductase deficiency

A

) Androgen insensitivity syndrome

Explanation: Androgen insensitivity syndrome (AIS) is a condition in which the individual has external female genitalia but has undescended testes instead of ovaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the difference between Turner syndrome and Klinefelter syndrome, and how do these conditions impact sexual development?

A

Turner syndrome is a genetic condition that affects females, and is caused by a missing or incomplete X chromosome. This can lead to a variety of physical and developmental abnormalities, including underdeveloped or absent ovaries, which can result in infertility and delayed or absent puberty. In contrast, Klinefelter syndrome is a genetic condition that affects males, and is caused by an extra X chromosome. This can lead to a variety of physical and developmental abnormalities, including reduced testosterone production, which can result in delayed or incomplete puberty and infertility.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the most common cause of congenital adrenal hyperplasia (CAH)?
a) Genetic mutations
b) Hormonal imbalances
c) Environmental factors
d) Unknown causes

A

a) Genetic mutations

Explanation: Congenital adrenal hyperplasia (CAH) is a genetic condition caused by mutations in genes that produce enzymes involved in the production of steroid hormones. This can lead to hormonal imbalances and a variety of physical and developmental abnormalities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the potential long-term health implications of disorders of sexual development, and how are these conditions managed?

A

The long-term health implications of disorders of sexual development can vary depending on the specific condition and its management. Some conditions may increase the risk of certain health problems, such as osteoporosis or certain types of cancer. Management of DSD typically involves a multidisciplinary approach, including medical and surgical interventions, hormone replacement therapy, and psychological support. The goal of management is to optimize physical and psychosocial outcomes, improve quality of life, and address any associated health risks.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Table 10.2

Overview of Nomenclature and Classification for Disorders of Sexual Development

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which of the following factors should be assessed in the history of a newborn with ambiguous genitalia?
a. Maternal diet during pregnancy
b. Neonatal weight
c. Prenatal testing
d. Father’s occupation

A

c. Prenatal testing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which of the following is a possible cause of ambiguous genitalia in a newborn?
a. Postnatal exposure to exogenous hormones
b. Overweight mother during pregnancy
c. High neonatal weight
d. Congenital adrenal hyperplasia

A

d. Congenital adrenal hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Family history should assess all of the following except:
a. Neonatal deaths
b. Infertility
c. History of diabetes
d. Consanguinity

A

c. History of diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is consanguinity?

A

Consanguinity refers to the degree of blood relationship between two individuals, such as first cousins or siblings. In some cultures and populations, consanguineous marriages are more common, which can increase the likelihood of certain genetic disorders being passed down through generations. A family history of consanguinity may be relevant in the evaluation of a newborn with ambiguous genitalia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is ambiguous genitalia in newborns and what are some of the possible causes?

A

Ambiguous genitalia in newborns refers to a condition in which the genitalia are not clearly male or female. This can be due to a variety of factors, including genetic abnormalities, hormonal imbalances, and environmental factors. Some possible causes include congenital adrenal hyperplasia, androgen insensitivity syndrome, and abnormalities in the production or response to hormones such as testosterone or estrogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why is a thorough history important in the diagnosis and management of newborns with ambiguous genitalia?

A

A thorough history is important in the diagnosis and management of newborns with ambiguous genitalia because it can provide important information about possible causes and guide further testing and management. Factors such as level of prematurity, exposure to exogenous hormones by mother, and prenatal testing such as fetal karyotype or appearance of genitalia on sonogram can all provide important clues. Family history is also important, as certain conditions such as congenital adrenal hyperplasia may be inherited and may affect multiple family members.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are some of the factors that should be assessed in the family history of a newborn with ambiguous genitalia?

A

In the family history of a newborn with ambiguous genitalia, it is important to assess for a variety of factors that may provide important clues to the underlying cause. These may include neonatal deaths (suggestive of congenital adrenal hyperplasia [CAH]), urologic diagnoses in children or adults, precocious puberty, infertility, amenorrhea, hirsutism, or consanguinity. By assessing these factors, healthcare providers may be able to better identify possible causes and guide further testing and management.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Which of the following is highly suggestive of the presence of a testicle in a newborn with ambiguous genitalia?
A. A nonpalpable gonad
B. A palpable gonad in the abdomen
C. A palpable gonad in the inguinal canal or scrotum
D. A palpable gonad in the labioscrotal folds

A

C. A palpable gonad in the inguinal canal or scrotum is highly suggestive of the presence of a testicle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What should be assessed during phallic examination of a newborn with ambiguous genitalia?
A. The degree of rugation and pigmentation of the labioscrotal folds
B. The number and location of perineal orifices
C. The presence of a uterus
D. Stretched penile length

A

D. Stretched penile length should be measured during phallic examination.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How can the presence of a uterus be determined on physical exam in a newborn with ambiguous genitalia?
A. By visual inspection of the external genitalia
B. By palpation of an anterior midline cordlike structure on rectal examination
C. By measuring stretched penile length
D. By assessing the degree of rugation and pigmentation of the labioscrotal folds

A

B. The presence of a uterus can sometimes be determined on physical exam by palpation of an anterior midline cordlike structure on rectal examination.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the significance of a nonpalpable testicle or a unilateral nonpalpable testis in the presence of any degree of hypospadias in a newborn with ambiguous genitalia?

A

Bilaterally nonpalpable testicles or a unilateral nonpalpable testis in the presence of any degree of hypospadias should be treated as disorders of sexual development (DSD) until proven otherwise. This is because these findings suggest an underlying hormonal or genetic abnormality that may require further evaluation and management.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What other dysmorphic features should be noted during the physical examination of a newborn with ambiguous genitalia?

A

In addition to genital examination, it is important to note other dysmorphic features suggestive of genetic disorders, such as short, broad neck associated with Turner syndrome. This is because DSD can be associated with various genetic disorders and other systemic abnormalities that may require further evaluation and management.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How is the presence of an ovotestis diagnosed in a newborn with ambiguous genitalia?

A

An ovotestis is a rare condition in which both ovarian and testicular tissue are present in the same gonad. In some cases, an ovotestis may undergo descent and be palpable in the inguinal canal or scrotum. However, the diagnosis of an ovotestis usually requires histological examination of the gonad after surgical removal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Which of the following is NOT included in the immediate serum laboratory evaluation for newborns with ambiguous genitalia?
a. Karyotype
b. Serum electrolytes
c. 17-hydroxyprogesterone
d. Prostate-specific antigen (PSA)

A

d. Prostate-specific antigen (PSA)

Explanation: The immediate serum laboratory evaluation for newborns with ambiguous genitalia includes karyotype, serum electrolytes, 17-hydroxyprogesterone, testosterone, LH, and FSH. PSA is not part of the evaluation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the purpose of the human chorionic gonadotropin (hCG) stimulation test in newborns with ambiguous genitalia?
a. To determine the presence of testicular tissue
b. To determine the presence of Müllerian structures
c. To evaluate for functional anorchia
d. To evaluate for salt-wasting form of CAH

A

a. To determine the presence of testicular tissue

Explanation: The hCG stimulation test is used to determine the presence or absence of testicular tissue in newborns with ambiguous genitalia. A failure to respond to hCG in combination with other laboratory findings can indicate functional anorchia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Which imaging modality can be helpful in determining the presence of Müllerian structures and/or gonads in newborns with ambiguous genitalia?
a. X-ray
b. Pelvic ultrasound
c. Computed tomography (CT)
d. Magnetic resonance imaging (MRI)

A

d. Magnetic resonance imaging (MRI)

Explanation: Pelvic ultrasound or MRI can be helpful in determining the presence of Müllerian structures and/or gonads in newborns with ambiguous genitalia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the role of karyotyping in the evaluation of newborns with ambiguous genitalia?

A

Answer: Karyotyping is an important part of the evaluation of newborns with ambiguous genitalia, as it can help to identify X and Y chromosome material and determine the genetic sex of the baby. This information can be used to guide further evaluation and management.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the most common presentation of DSD in the newborn?
a) Abnormal reproductive tract development
b) Ambiguous genitalia
c) Undescended testicles
d) Delayed puberty

A

Answer: b) Ambiguous genitalia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Which of the following specialties should be included in the multidisciplinary team for management of DSD in the newborn?
a) Urologist
b) Endocrinologist
c) Geneticist
d) Psychiatrist/Psychologist/Social worker
e) All of the above

A

e) All of the above

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are the initial goals of care for a newborn with suspected DSD?
a) Psychological stabilization
b) Diagnosis
c) Reproductive tract development
d) Sex reassignment surgery

A

b) Diagnosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How is sex of rearing determined for a newborn with DSD?
a) Based on the parent’s preference
b) Based on the child’s gender identity
c) Based on diagnosis, anatomy, and functional potential of the genital and reproductive tract
d) Based on the child’s external appearance

A

c) Based on diagnosis, anatomy, and functional potential of the genital and reproductive tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are the most common causes of DSD in the newborn, and how are they diagnosed and managed?

A

The most common causes of DSD in the newborn are congenital adrenal hyperplasia (CAH), androgen insensitivity syndrome (AIS), and 5-alpha-reductase deficiency. Diagnosis involves a combination of clinical examination, imaging studies, and laboratory testing. Treatment of CAH involves hormone replacement therapy, while AIS and 5-alpha-reductase deficiency may require surgery to reconstruct the external genitalia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Image
FIG. 10.5 Diagnostic algorithm for DSD based on number of gonads palpated. 17-OHP, 17-Hydroxyprogesterone; AMH, anti-Müllerian hormone; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; FSH, follicle-stimulating hormone; hCG, human chorionic gonadotropin; LH, luteinizing hormone; MRI, magnetic resonance imaging.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Table 10.3

Clinical Presentation for Disorders of Sexual Development After the Newborn Period

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the most common major abnormality of sexual development?
a) Turner syndrome
b) Klinefelter syndrome
c) Congenital adrenal hyperplasia
d) Androgen insensitivity syndrome

A

b) Klinefelter syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the classic karyotype associated with Klinefelter syndrome?
a) 47,XXX
b) 46,XX
c) 47,XY
d) 47,XXY

A

d) 47,XXY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the most common cause of infertility in Klinefelter syndrome?
a) Low testosterone levels
b) Elevated estradiol levels
c) Seminiferous tubules degeneration
d) Hyaline replacement of testicles

A

c) Seminiferous tubules degeneration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the recommended management for gynecomastia in Klinefelter syndrome?
a) Androgen supplementation
b) Reduction mammoplasty
c) Both a) and b)
d) Intracytoplasmic sperm injection

A

c) Both a) and b)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the retrieval rate for sperm in microdissection testicular sperm extraction in nonmosaic Klinefelter syndrome patients?
a) 10%-20%
b) 20%-30%
c) 40%-50%
d) 50%-60%

A

c) 40%-50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the pathophysiology of Klinefelter syndrome?

A

Klinefelter syndrome is characterized by the presence of at least one Y chromosome and at least two X chromosomes. This results in testicular dysgenesis, where seminiferous tubules degenerate and are replaced by hyaline, leading to small and firm testicles. The decreased testosterone levels and increased estrogen levels result in gynecomastia, breast carcinoma, and extragonadal germ cell tumors. The majority of patients are infertile with azoospermia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are the clinical manifestations of Klinefelter syndrome?

A

Patients with Klinefelter syndrome may present with small and firm testicles, gynecomastia, reduced body hair, decreased libido, and infertility. They are also at an increased risk for breast carcinoma, extragonadal germ cell tumors, and Leydig/Sertoli cell tumors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

How is Klinefelter syndrome diagnosed and evaluated?

A

The diagnosis of Klinefelter syndrome is confirmed by a karyotype analysis, which typically shows a 47,XXY chromosomal pattern. The serum testosterone levels are low-normal, while the gonadotropins and estradiol levels are elevated. Imaging studies, such as testicular ultrasound or magnetic resonance imaging, may reveal small and firm testicles.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is the recommended management for Klinefelter syndrome?

A

Treatment for Klinefelter syndrome includes androgen supplementation to improve libido and reduce gynecomastia. Reduction mammoplasty may also be necessary for severe cases of gynecomastia. Assisted reproductive technology, such as microdissection testicular sperm extraction and intracytoplasmic sperm injection, may be used for nonmosaic patients who desire to have children. Patients should also undergo regular surveillance for breast carcinoma and other malignancies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What does nonmosaic mean?

A

Nonmosaic patients are those with Klinefelter syndrome who have the same chromosomal pattern in all of their cells. In contrast, mosaic patients have more than one chromosomal pattern in their cells, meaning that only some cells in their body have the extra X chromosome. The distinction between mosaic and nonmosaic Klinefelter syndrome can impact the severity of the condition and the success of treatments such as assisted reproductive technology.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the hypothesized mechanism for 46,XX male development?
A. Deletion of SRY on the Y chromosome
B. Translocation of Y chromosome material, including SRY, to the X chromosome
C. Mutation of SRY on the X chromosome
D. Overexpression of SRY on the X chromosome

A

B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the endocrinologic profile of individuals with 46,XX male?
A. High testosterone and low LH and FSH levels
B. Low testosterone and high LH and FSH levels
C. High estrogen and low LH and FSH levels
D. Low estrogen and high LH and FSH levels

A

A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the role of hormonal treatment in individuals with 46,XX male?
A. It can induce fertility and sperm retrieval
B. It can correct the external genitalia abnormalities
C. It can correct the endocrinologic imbalances
D. It has no role due to lack of germ cells

A

C

60
Q

What is the pathophysiology of 46,XX male and how does it present clinically?

A

What is the pathophysiology of 46,XX male and how does it present clinically?
46,XX male is a disorder of gonadal differentiation and development characterized by testicular development in individuals with no Y chromosome. The hypothesized mechanism is translocation of Y chromosome material, including SRY, to the X chromosome. This leads to the expression of SRY, which is responsible for initiating male gonadal differentiation. Most individuals with 46,XX male have normal male external genitalia or hypospadias, but all are infertile due to lack of germ cells.

61
Q

How is 46,XX male diagnosed and what is the endocrinologic profile of affected individuals?

A

Diagnosis of 46,XX male is based on karyotyping, which reveals the presence of two X chromosomes and no Y chromosome. In terms of endocrinologic profile, individuals with 46,XX male have high testosterone levels and low LH and FSH levels, similar to Klinefelter syndrome.

62
Q

What is the management of 46,XX male and why is hormonal treatment important?

A

The management of 46,XX male involves correcting the endocrinologic imbalances through hormonal treatment, which is similar to the treatment of Klinefelter syndrome. Testosterone replacement therapy can be used to maintain normal male secondary sexual characteristics and bone health. However, because of the lack of germ cells, there is no role for sperm retrieval. Hormonal treatment is important for long-term health and well-being of individuals with 46,XX male.

63
Q

What is the pathophysiology of Turner syndrome?
A. One normal functioning X chromosome and one abnormal Y chromosome
B. Two normal X chromosomes and one abnormal Y chromosome
C. One normal functioning X chromosome and the other sex chromosome may be absent, abnormal or with mosaicism
D. Two abnormal X chromosomes and one normal Y chromosome

A

C

64
Q

What is a hallmark of Turner syndrome?
a. Lack of development of secondary sex characteristics.
b. Early onset of puberty.
c. Development of male secondary sex characteristics.
d. Normal development of secondary sex characteristics.

A

a. Lack of development of secondary sex characteristics.

65
Q

What is the risk of gonadoblastoma in patients with Turner syndrome?
a. Less than 5%.
b. 10-12%.
c. 20-25%.
d. More than 30%.

A

b. 10-12%.

66
Q

Describe the pathophysiology of Turner syndrome.

A

Turner syndrome is characterized by one normal functioning X chromosome and one absent, abnormal, or mosaic sex chromosome. By birth, gonads are mostly devoid of oocytes, resulting in characteristic streak gonads. The lack of oocytes and the absence of estrogen production lead to a lack of pubertal development of the external genitalia and lack of development of secondary sex characteristics.

67
Q

What are the common manifestations of 45,X type in Turner syndrome?

A

Manifestations of 45,X type may include short stature, broad chest, widespread nipples, webbing of the neck, peripheral edema at birth, short fourth metacarpal, hypoplastic nails, multiple pigmented nevi, coarctation of the aorta, bicuspid aortic valve, and renal anomalies.

68
Q

How is Turner syndrome diagnosed?

A

The diagnosis should be considered in any infant with lymphedema or young woman with short stature, lack of secondary sex characteristics, or primary amenorrhea. Karyotype analysis is required to confirm the diagnosis.

69
Q

What is the risk of gonadoblastoma in patients with Turner syndrome, and how is it managed?

A

Risk of gonadoblastoma is estimated at 12%–20% and has been reported as early as 5 months of age. Determination of Y chromosome material in Turner syndrome is critical because it predisposes to masculinization and gonadoblastoma. Prophylactic gonadectomy in the Y mosaic Turner syndrome patient is advised but not required in the 45,XO patient.

70
Q

What is the management of Turner syndrome?

A

Endocrinologic evaluation is needed. Growth hormone or sex hormones may be needed for growth and development. Although spontaneous fertility is rare, pregnancy is a possibility for some patients with spontaneous menses. Regular follow-up and monitoring of cardiac and renal function is also recommended.

71
Q

Image
FIG. 10.6 Gross appearance of streak gonad during diagnostic laparoscopy. Source: (Courtesy of D. Diamond, MD.)

A
72
Q

What is the main characteristic of 46,XX “pure” gonadal dysgenesis?
a. Male external genitalia
b. Absence of Müllerian ducts
c. Elevated serum gonadotropins
d. Presence of wolffian structures

A

c. Elevated serum gonadotropins

Explanation: Patients with 46,XX “pure” gonadal dysgenesis have normal female external genitalia, normal Müllerian ducts with the absence of wolffian structures, normal height, and bilateral streak gonads. Due to the presence of streak gonads, they have elevated serum gonadotropins. Management involves estrogen and progesterone replacement and gonadectomy is not recommended.

73
Q

What is the recommended management for 46,XX “pure” gonadal dysgenesis?
a. Testosterone replacement
b. Gonadectomy
c. Androgen blockers
d. Estrogen and progesterone replacement

A

d. Estrogen and progesterone replacement

Explanation: Management of 46,XX “pure” gonadal dysgenesis involves estrogen and progesterone replacement since there is no Y chromosome material and gonadectomy is not recommended.

74
Q

What is gonadal dysgenesis and what are its types?

A

Gonadal dysgenesis refers to a group of conditions characterized by abnormal gonadal development. There are several types of gonadal dysgenesis, including:

45,X (Turner syndrome)
46,XY gonadal dysgenesis
46,XX gonadal dysgenesis
46,XX/46,XY gonadal dysgenesis (mixed gonadal dysgenesis)

75
Q

What is the second most common cause of ambiguous genitalia in the neonatal period?
A. Turner Syndrome
B. Klinefelter Syndrome
C. Mixed Gonadal Dysgenesis
D. Androgen Insensitivity Syndrome

A

C. Mixed Gonadal Dysgenesis

76
Q

What is the risk of gonadoblastoma or dysgerminoma in patients with mixed gonadal dysgenesis?
A. 5%-10%
B. 15%-35%
C. 40%-60%
D. 70%-80%

A

B. 15%-35%

77
Q

What syndrome is associated with nephropathy, genital ambiguity, and Wilms tumor in patients with mixed gonadal dysgenesis?
A. Denys-Drash Syndrome
B. Klinefelter Syndrome
C. Turner Syndrome
D. Frasier Syndrome

A

A. Denys-Drash Syndrome

78
Q

Define Mixed Gonadal Dysgenesis (MGD). What is the pathophysiology and presentation of MGD?

A

Mixed Gonadal Dysgenesis (MGD) is a disorder of sexual development characterized by a unilateral testis, a contralateral streak gonad, and persistent Müllerian structures associated with varying degrees of masculinization. Most patients with MGD have a 45,XO/46,XY karyotype. MGD can also present with phenotypic internal asymmetry, where a dysgenetic or streak gonad on one side will be associated with an ipsilateral uterus and fallopian tube, and a testicle on the contralateral side can be associated with wolffian duct structures (e.g., epididymis, vas deferens). This underscores the effects of local testosterone and AMH secretion. MGD is the second most common cause of ambiguous genitalia in the neonatal period.

79
Q

What is the risk of gonadoblastoma or dysgerminoma in patients with mixed gonadal dysgenesis? What syndromes are associated with mixed gonadal dysgenesis?

A

The risk of gonadoblastoma or dysgerminoma in patients with mixed gonadal dysgenesis is 15%-35%. Denys-Drash syndrome and Frasier syndrome are associated with mutations in the Wilms tumor suppressor gene and are associated with mixed gonadal dysgenesis. Denys-Drash syndrome is associated with nephropathy, genital ambiguity, and Wilms tumor. The risk of gonadal tumor in patients with Denys-Drash syndrome is up to 40%. Frasier syndrome is not associated with an increased risk of Wilms tumor but a 60% risk of gonadoblastoma in the presence of Y chromosome material.

80
Q

What are the primary considerations for the management of mixed gonadal dysgenesis? What are the screening recommendations for patients with mixed gonadal dysgenesis?

A

Sex assignment, gonadectomy if indicated, and screening for Wilms tumor are the primary considerations for the management of mixed gonadal dysgenesis. If male gender is selected and the testicle can be brought to the scrotum, physical exam and ultrasound screening for gonadoblastoma must be weighed against prophylactic gonadectomy and androgen replacement. Screening recommendations for patients with mixed gonadal dysgenesis include regular abdominal ultrasounds for Wilms tumor and periodic evaluation of sex hormone levels.

81
Q

Which of the following is a characteristic of partial gonadal dysgenesis?
a) 46,XX karyotype
b) Only one dysgenetic testis
c) Low risk of gonadal malignancy
d) None of the above

A

b) Only one dysgenetic testis

82
Q

What is the estimated risk of gonadal malignancy in individuals with partial gonadal dysgenesis by 40 years of age?
a) Less than 10%
b) Around 20%
c) More than 40%
d) No risk of malignancy

A

c) More than 40%

83
Q

What is the management approach for partial gonadal dysgenesis?

A

d) Similar to mixed gonadal dysgenesis

84
Q

What is partial gonadal dysgenesis and what karyotype is typically present in affected individuals?

A

Partial gonadal dysgenesis is a disorder of gonadal differentiation and development that is characterized by two dysgenetic testes and variable phenotypic presentation. Individuals typically have a 45,X/46,XY or 46,XY karyotype.

85
Q

What are the clinical features of partial gonadal dysgenesis?

A

The phenotype of partial gonadal dysgenesis is variable, depending on the production of anti-Müllerian hormone (AMH) and testosterone. Some common features include ambiguous genitalia, undescended testes, and infertility. Other features may include shortened stature, hearing loss, and skeletal abnormalities.

86
Q

What is the risk of gonadal malignancy in individuals with partial gonadal dysgenesis and how is it managed?

A

The risk of gonadal malignancy has been estimated to be more than 40% by 40 years of age. Therefore, regular monitoring with physical examination, imaging studies, and tumor markers is recommended. The management approach is similar to that of mixed gonadal dysgenesis, which may involve surgical removal of the dysgenetic testes. Hormonal replacement therapy may also be necessary. Genetic counseling is recommended for affected individuals and their families.

87
Q

What is the definition of Swyer Syndrome?
a. Lack of testis formation despite a Y chromosome, with bilateral streak gonads, normal female genitalia, and well-developed Müllerian structures.
b. A condition in which a person has both male and female reproductive organs.
c. A genetic disorder that affects the development of the reproductive system in males.

A

a. Lack of testis formation despite a Y chromosome, with bilateral streak gonads, normal female genitalia, and well-developed Müllerian structures.

88
Q

What is the common presentation of Swyer Syndrome?
a. Delayed puberty and amenorrhea.
b. Ambiguous genitalia and sexual infantilism.
c. Precocious puberty and breast development.

A

a. Delayed puberty and amenorrhea.

89
Q

What is the risk of germ cell tumors in Swyer Syndrome?
a. 10%
b. 25%
c. 35%

A

c. 35%

90
Q

Describe the pathophysiology of Swyer Syndrome.

A

Swyer Syndrome is a disorder of gonadal differentiation and development. It is characterized by a lack of testis formation despite having a Y chromosome. Bilateral streak gonads are present, and the individual has normal female genitalia and well-developed Müllerian structures. The absence of testis formation is due to mutations in genes that regulate the differentiation and development of the gonads.

91
Q

What are the common clinical features of Swyer Syndrome?

A

The majority of individuals with Swyer Syndrome present in adolescence with delayed puberty and amenorrhea. There is no genital ambiguity, but there is sexual infantilism. High levels of serum gonadotropins are observed, which can lead to elevated androgen levels and clitoromegaly in some individuals. In addition, there may be other associated features such as short stature and osteoporosis.

92
Q

What is the management of Swyer Syndrome?

A

The risk of germ cell tumors in Swyer Syndrome is up to 35% by 30 years of age. Therefore, management includes gonadectomy and cyclic hormone replacement therapy. The gonads are removed to prevent the development of tumors. Hormone replacement therapy is given to induce puberty and to replace the hormones that are normally produced by the gonads. Counseling and support may also be necessary to help individuals cope with the psychological and social issues associated with the disorder.

93
Q

What is the etiology of Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome?
A) Genetic mutation
B) Trauma
C) Infection
D) None of the above

A

A) Genetic mutation, teratogen, or bilateral testicular torsion

Explanation: The etiology of Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome is postulated to be caused by a genetic mutation, teratogen, or bilateral testicular torsion.

94
Q

What is the phenotype range of patients with Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome?
A) Only typical female
B) Only ambiguous
C) Only male
D) Range from typical female to ambiguous to male

A

D) Range from typical female to ambiguous to male

Explanation: The phenotype range of patients with Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome ranges from typical female to ambiguous to male.

95
Q

How is diagnosis made for Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome?
A) Physical examination
B) Imaging studies
C) Karyotype, castrate levels of testosterone, and elevated gonadotropins during mini-puberty from 2-6 months of age
D) Blood tests

A

C) Karyotype, castrate levels of testosterone, and elevated gonadotropins during mini-puberty from 2-6 months of age

Explanation: Diagnosis for Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome can be made with karyotype, castrate levels of testosterone, and elevated gonadotropins during mini-puberty from 2-6 months of age.

96
Q

What is the treatment for Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome?

A

C) Individualized

Explanation: Treatment for Embryonic Testicular Regression and Bilateral Vanishing Testes Syndrome is individualized.

97
Q

Image
FIG. 10.7 Human intraoperative photographs (A) Intraabdominal testis at internal ring. (B) High intraabdominal testis. (C) Normal ovary. (D) Streak gonads in a patient with XY gonadal dysgenesis. (E) Ovotestis in ovotesticular syndrome.

A
98
Q

What is ovotesticular DSD?

A

Ovotesticular DSD is a condition where individuals have both testicular and ovarian tissue. The gonads may take the form of one ovary and one testis, or more commonly, one or two ovotestes. The chromosomal makeup in order of frequency is 46,XX, mosaicism with Y chromosome material, and 46,XY.

99
Q

What is the presentation of ovotesticular DSD?

A

The differentiation of both the external and internal genitalia is variable and related to the function of the ipsilateral gonad. In most, the genitalia are ambiguous. The ovary, most commonly found on the left side, is usually orthotopic. Testes and ovotestes, more commonly found on the right side, can lie anywhere in the path of testicular descent. Fallopian tubes are consistently present along with the ovary, and vas deferens alongside the testis. Ovotestes can have fallopian tube, vas deferens, or both structures. In most patients, a uterus is present. Frequently, the ovarian portion of an ovostestis is normal while the testicular component is dysgenetic.

100
Q

What is the management of ovotesticular DSD?

A

Although both gonadoblastoma and dysgerminoma have been described, the incidence is low. Gender assignment is based on functional potential of external and internal genital

101
Q

Image
FIG. 10.8 Steroid biosynthetic pathway for mineralocorticoid, glucocorticoid, and sex steroid hormone production.

A
102
Q

Which of the following is the most common cause of ambiguous genitalia in newborns?
a) 46,XX DSD
b) Congenital adrenal hyperplasia
c) Increased maternal androgens
d) Aromatase deficiency

A

b) Congenital adrenal hyperplasia

Explanation: Congenital adrenal hyperplasia is the most common cause of ambiguous genitalia in newborns.

103
Q

What is the most common enzymatic defect responsible for congenital adrenal hyperplasia?
a) 5α-reductase deficiency
b) 17α-hydroxylase deficiency
c) 21-hydroxylase deficiency
d) 11β-hydroxylase deficiency

A

c) 21-hydroxylase deficiency

Explanation: A deficiency in 21-hydroxylase is responsible for 95% of cases of congenital adrenal hyperplasia.

104
Q

What is the main treatment for congenital adrenal hyperplasia?
a) Androgen supplementation
b) Mineralocorticoid treatment
c) Hydrocortisone administration
d) Surgery

A

c) Hydrocortisone administration

Explanation: Treatment of congenital adrenal hyperplasia consists of hydrocortisone administration in childhood and adolescence.

105
Q

Which of the following is a potential source of increased maternal androgens leading to 46,XX DSD?
a) Maternal ingestion of progestins or androgens
b) Aromatase deficiency in the mother
c) Maternal tumor with virilizing effects on a female fetus
d) All of the above

A

d) All of the above

Explanation: Maternal ingestion of progestins or androgens, aromatase deficiency in the mother, and maternal tumor with virilizing effects on a female fetus are all potential sources of increased maternal androgens leading to 46,XX DSD.

106
Q

What is 46,XX DSD and how does it present?

A

46,XX DSD is a phenotypic abnormality of sexual development in which individuals with no chromosomal abnormalities and ovaries have some degree of external masculinization and ambiguous genitalia. The condition presents with variable degrees of clitoromegaly and labial fusion in females, and a common urogenital sinus. Müllerian structures are usually normal.

107
Q

What is congenital adrenal hyperplasia (CAH) and how does it present?

A

CAH is caused by a defect in one of five enzymes involved in the cortisol biosynthetic pathway, resulting in impaired production of hydrocortisone and a compensatory increase in secretion of adrenocorticotrophic hormone (ACTH). A deficiency in 21-hydroxylase is responsible for 95% of cases, while a deficiency in 11β-hydroxylase accounts for approximately 5% of cases. The most common presentation of CAH is ambiguous genitalia in the newborn, with varying degrees of virilization in females. Patients with 21-hydroxylase deficiency exhibit one of three presentations: salt wasting and virilization, simple virilization without salt wasting, and those without evidence of either. In the salt-losing variant, failure to regain birth weight, weight loss, and dehydration occur in the first few weeks of life, and in severe cases, adrenal crises can occur within the first 10-21 days of life. In males with CAH, there is sexual precocity within the first 2-3 years of life.

108
Q

How is congenital adrenal hyperplasia evaluated and managed?

A

Evaluation of CAH includes testing for serum electrolytes, serum renin, and cortisol levels. Pelvic ultrasound may be used to demonstrate Müllerian structures in classic 21-hydroxylase deficiency. Management of CAH consists of hydrocortisone administration in childhood and adolescence. Those with the salt-wasting variant require increased salt intake and mineralocorticoid treatment indefinitely. Surgical management in CAH patients is controversial and can include urethroplasty and vaginoplasty to create separate orifices and enlarge the vaginal introitus, clitoroplasty with reduction in size and creation of a clitoral hood, and feminizing vulvoplasty/labioplasty. Proper hormonal supplementation can lead to long-term fertility in males and feminization and menstruation in females.

109
Q

What is 46,XX DSD secondary to increased maternal androgens and how is it treated?

A

46,XX DSD secondary to increased maternal androgens is a rare diagnosis, historically caused by maternal ingestion of progestins or androgens, aromatase deficiency in the mother, or a maternal tumor with virilizing effects on a female fetus. The diagnosis is recognized postnatally by a normal hormonal profile, and genital reconstruction, if desired, is the only treatment.

110
Q

Table 10.4

Enzyme Deficiencies Involved in Congenital Adrenal Hyperplasia

A
111
Q

Image
FIG. 10.9 Urogenital sinus in a patient with intersex.

A
112
Q

Image
FIG. 10.10 Pure urogenital sinus abnormality.

A
113
Q

Image
FIG. 10.11 Classification by Prader of the various degrees of masculinization of the external genitalia in females with congenital adrenal hyperplasia that has been applied by some authors to intersexual states in general. Source: (From Prader A. Die Haufigkeit der kongenitalen androgenitalen Syndroms. Helv Pediatr Acta 1958;13:426.)

A
114
Q

Image
FIG. 10.12 (A to C) Schematic illustration of three presentations of persistent Müllerian duct syndrome. Source: (From Hutson JM, Grover SR, O’Connell M, Pennell SD. Malformation syndromes associated with disorders of sex development. Nat Rev Endocrinol 2014;10(8):476-487.)

A
115
Q

Which of the following enzymes are required for testosterone biosynthesis?
A. 5α-reductase type II isoenzyme
B. Cholesterol side-chain cleavage enzyme
C. 3β-hydroxysteroid dehydrogenase
D. 17α-hydroxylase
E. All of the above

A

E

Explanation: All of the mentioned enzymes are required for testosterone biosynthesis. Deficiencies in any of these enzymes not only result in abnormal testosterone production but also impaired production of glucocorticoids and mineralocorticoids.

116
Q

Which of the following disorders is characterized by 46,XY karyotype, bilateral testes, female-appearing external genitalia, and absence of Müllerian derivatives?
A. Leydig cell aplasia
B. Syndrome of complete androgen insensitivity (CAIS)
C. Syndrome of partial androgen resistance (PAIS)
D. Mild androgen insensitivity syndrome (MAIS)
E. Persistent müllerian duct syndrome (PMDS)

A

B

Explanation: Syndrome of complete androgen insensitivity (CAIS) is characterized by 46,XY karyotype, bilateral testes, female-appearing external genitalia, and absence of Müllerian derivatives (due to AMH secretion). A mutation in the gene for the androgen receptor is identified in 95% of cases.

117
Q

What is the recommended management of Persistent Mullerian Duct Syndrome (PMDS)?
A. Removal of Müllerian structures to prevent vas injury
B. Preservation of Müllerian structures to prevent vas injury
C. Orchiopexies for male gender assignment
D. None of the above

A

B

Explanation: Management of Müllerian structures in PMDS is controversial, as the vasa deferentia are in close proximity to the uterus and proximal vagina, and preservation of structures to prevent vas injury has been recommended. However, malignancies have been reported in up to 8% of Müllerian remnants, supporting careful excision.

118
Q

What is Leydig cell aplasia and how is it diagnosed and managed?

A

Leydig cell aplasia is a rare autosomal recessive trait in males that yields absence of Leydig cells or abnormalities of the LH receptor on Leydig cells. The phenotype varies with bilateral testes. Absent rise of serum testosterone after hCG stimulation is characteristic. Histology of the testicles shows absence of Leydig cells with normal Sertoli cells. The diagnosis is made through genetic testing and hormonal evaluation. Management of Leydig cell aplasia is variable and dependent on the enzymatic abnormality determined by genetic testing.

119
Q

What is 5α-reductase deficiency and how does it affect gender assignment?

A

5α-reductase deficiency is caused by an autosomal recessive mutation in the 5α-reductase type II isoenzyme, which catalyzes conversion of testosterone to DHT. This mutation is expressed at high levels in the prostate and external genitalia. The phenotype of 5α-reductase deficiency ranges from female, to ambiguous genitalia, to penoscrotal hypospadias. The diagnosis is made through genetic testing and hormonal evaluation. Individuals with 5α-reductase deficiency have normal plasma testosterone but low DHT. After hCG stimulation, the testosterone/DHT ratio increases markedly (20:1). This diagnosis is associated with gender reversal at puberty, specifically in a pedigree study from the Dominican Republic, individuals known as guevedoces (“testicles at 12,” or “penis at 12”). Male gender assignment is usually favored, but studies supporting this were performed in a unique sociologic environment.

120
Q

Which of the following is NOT a common presentation of Mayer Rokitansky Küster hauser syndrome (MRKH)?
a. Primary amenorrhea
b. Infertility
c. Cyclic abdominal pain
d. Irregular menstrual cycles

A

d. Irregular menstrual cycles

Explanation: The primary presentation of MRKH is primary amenorrhea, which means the individual has not experienced menstruation by the age of 16. Infertility, cyclic abdominal pain, or dyspareunia may also occur.

121
Q

What is the pathophysiology of MRKH?
a. Absence of the ovaries and uterus in a 46,XY individual with male phenotype
b. Absence of the uterus and vagina in a 46,XY individual with male phenotype
c. Absence of the uterus and vagina in a 46,XX individual with female phenotype and normal secondary sexual characteristics
d. Absence of the ovaries and uterus in a 46,XX individual with female phenotype and normal secondary sexual characteristics

A

d. Irregular menstrual cycles

Explanation: The primary presentation of MRKH is primary amenorrhea, which means the individual has not experienced menstruation by the age of 16. Infertility, cyclic abdominal pain, or dyspareunia may also occur.

122
Q

What is the pathophysiology of MRKH?
a. Absence of the ovaries and uterus in a 46,XY individual with male phenotype
b. Absence of the uterus and vagina in a 46,XY individual with male phenotype
c. Absence of the uterus and vagina in a 46,XX individual with female phenotype and normal secondary sexual characteristics
d. Absence of the ovaries and uterus in a 46,XX individual with female phenotype and normal secondary sexual characteristics

A

c. Absence of the uterus and vagina in a 46,XX individual with female phenotype and normal secondary sexual characteristics

Explanation: MRKH is associated with congenital absence of the uterus and vagina in a 46,XX individual with female phenotype and normal secondary sexual characteristics. Normal ovaries and fallopian tubes are present, but only uterine remnants remain, along with a shallow vaginal pouch.

123
Q

What upper tract urinary anomalies may occur in MRKH?
a. Renal cell carcinoma
b. Bladder cancer
c. Renal agenesis, pelvic kidney, and horseshoe kidney
d. Cystitis

A

c. Renal agenesis, pelvic kidney, and horseshoe kidney

Explanation: Upper tract urinary anomalies occur in one third of patients with MRKH, including renal agenesis, pelvic kidney, and horseshoe kidney.

124
Q

What is Mayer Rokitansky Küster hauser syndrome (MRKH)? What are the common presentations of this condition?

A

Mayer Rokitansky Küster hauser syndrome (MRKH) is a congenital disorder that is associated with the absence of the uterus and vagina in a 46,XX individual with female phenotype and normal secondary sexual characteristics. Normal ovaries and fallopian tubes are present, but only uterine remnants remain, along with a shallow vaginal pouch. Upper tract urinary anomalies occur in one third of patients, including renal agenesis, pelvic kidney, and horseshoe kidney. The primary presentation of MRKH is primary amenorrhea, which means the individual has not experienced menstruation by the age of 16. Infertility, cyclic abdominal pain, or dyspareunia may also occur.

125
Q

How is MRKH evaluated and managed?

A

MRKH is evaluated using abdominal ultrasound or MRI to demonstrate an absent uterus. Hormonal profile can also be used to demonstrate normal female parameters. Management of MRKH involves the creation of a neovagina with dilation or surgery. If present, a hemiuterus should be removed or hormonally suppressed. Upper tract urinary anomalies may also require further management. Psychological counseling and support may also be beneficial for individuals with MRKH.

126
Q

Describe the role of androgens in sexual differentiation and the formation of the male external genitalia.

A

During sexual differentiation, androgens promote virilization of wolffian duct structures, the urogenital sinus, and the genital tubercle. Testosterone secretion by the fetal testis Leydig cells occurs at approximately 9 weeks of gestation. Testosterone enters target tissues by passive diffusion, and wolffian duct virilization does not occur if local androgens are not present. In some cells, testosterone is converted to dihydrotestosterone (DHT) by intracellular 5α-reductase. Testosterone or DHT then binds to an intracellular androgen receptor. DHT binds to the receptor with greater affinity and stability than does testosterone. In tissues equipped with 5α-reductase at the time of sexual differentiation (e.g., prostate, urogenital sinus, external genitalia), DHT is the active androgen. Masculinization of the external genitalia is complete by 12–13 weeks of gestation.

127
Q

Kidneys produce urine at week ___ of development

A

12

128
Q

Kidneys develop from ___derm

A

meso

129
Q

____ develops into the collecting system & ureter

A

ureteric bud

130
Q

Kidneys begin to ascend around week ___ of development

A

6

131
Q

Failure of contact between ureteric bud & metanephros leads to ____

A

renal agenesis

132
Q

Abnormal contact between ureteric bud & metanephros leads to ____

A

dysplastic kidney

133
Q

Multicystic dysplastic kidney is associated with other GU anomalies such as ___, ___, and ___

A

VUR, seminal vesicle cysts, Gartner’s duct cysts

134
Q

Ureteric bud misplacement leads to ___ or ___

A

VUR or ectopic ureter

135
Q

Ureteric bud duplications leads to _____

A

duplicated collecting system

136
Q

The effect of ___ allows gonads to descend below inguinal ring

A

testosterone

137
Q

At week ___, SRY gene flips the switch to allow for male differentiation

A

6

138
Q

Sertoli cells secrete _____ during development

A

MIS (mullerian inhibiting substance)

139
Q

____ is necessary for wolffian duct development

A

Testosterone

140
Q

External genitalia are undifferentiated until week ___ of development

A

8

141
Q

CAH is due to defect in _____

A

21-hydroxylase

142
Q

CAH leads to virilization in genotypic, ____, individuals

A

46XX

143
Q

Bilateral testes, female external genitalia

A

AIS (Androgen Insensitivity), 46XY

144
Q

One testis & one ovary, various external genitalia

A

46XX, ovotesticular dysgenesis

145
Q

46XX, normal external genitalia, bilateral streak gonads

A

pure gonadal dysgenesis