reproductive pathology 1 Flashcards
Sex chromosome disorders - mechanism and types
Aneuploidy (abnormal number of chromosomes) most commonly due to meiotic nondisjunction
- Klinefelter syndrome 2. Turner syndrome
- Double Y males 4. Ovotesticular disorder of sex development
Klinefelter syndrome - sex and karyotype
male - 47, XXY
Klinefelter syndrome - The extra chromosome is retained because of
- nondisjunction meiosis I (maternal or paternal)
- nondisjunction event during meiosis II (maternal)
- -> mosaicism possible (mitotic error)
Klinefelter syndrome –> presentation
- Testicular atrophy 2. eunuchoid body shape
3. Long extremities 4. gynecomastia 5. female hair distribution 6. Devopmental delay
Klinefelter syndrome - lab/endocrine profile - mechanism
- presence of inactivated X chromosome (Barr body)
- High FSH (dysgenesis of seminiferous tubuls –> low inhibin B)
- high estrogen (abnormal Leydig function –> low testosterone –> high LH –> upregulation of aromatase)
- Common cause of hypogonadism seen in infertility work-up
Klinefelter syndrome - high estrogen - mechanism
abnormal Leydig function –> low testosterone –> high LH –> upregulation of aromatase
MCC of amenorrhea
Turner
Turner syndrome - sex and karyotype
female - 45,XO
Turner syndrome - mechanism
absence of one complete or partial copy of the X chromosome in some or all the cells (mosaicism possible –> mitotic error)
Turner syndromes - findings/clinical characteristics (outside and in the body)
- Short stature (if untreated)
- ovarian dysgenesis (streak ovary)
- shield chest
- bicuspid aortic valve
- coartraction (femoral less than branchial pulse)
- Lymphatic vessels defects (a. cystic hygroma or wedded neck, b. lymphadema in feet or hands)
- horseshoe kidney
- amenorrhea (menopause before menarche)
Turner syndrome - urogenital system
- ovarian dysgenesis (streak ovary)
2. horseshoe kidney
Turner syndrome - cardiovascular
- bicuspid aortic valve
- coarctation aorta(femoral less than branchial pulse)
- Lymphatic vessels defects (a. cystic hygroma or wedded neck, b. lymphadema in feet or hands)
Turner syndrome - lab/endocrine profile
- no Barr body
2. low estrogen –> high LH, FSH
Turner syndrome - pregnancy
possible is some cases (IVF, exogenous estradiol-17β and progesterone) (+donation of an egg or embryo)
Double Y - sex and karyotype
males - XYY
Double Y - presentation
- Phenotypically normal (usually undiagnosed)
- very tall
- may be associated with severe acne
- may be associated with learning disability and autism spectrum disorders
Double Y - may associated with
- severe acne
- learning disability
- autism spectrum disorders
double Y - fertility
normal
Ovotesticular disorder of sex development - previously called
true hermaphroditism
Ovotesticular disorder of sex development (true hermaphroditism) - karyotype
46,XX > 46,XY
Ovotesticular disorder of sex development (true hermaphroditism) - manifestation
- both ovarian and testicular tissue presents (ovotestis)
2. ambiguous genitalia
Diagnosing disorders of sex hormones - high testosterone, high LH - diagnosis
defective androgen receptor
Diagnosing disorders of sex hormones - high testosterone, low LH - diagnosis
- testosterone-secreting tumor
2. exogenous steroids
Diagnosing disorders of sex hormones - low testosterone, high LH - diagnosis
1ry hypogonadism
Diagnosing disorders of sex hormones - low testosterone, low LH - diagnosis
hypognodotropic hypogonadism
Diagnosing disorders of sex hormones - testosterone/LH levels according to disease
- defective androgen receptor –> both high
- testosterone-secreting tumor –> high T, low LH
- 1ry hypogonadism –> low T, high LH
- hypognodotropic hypogonadism –> both low
- exogenous steroids –> high T, low LH
other disorders of sex development (not chromosomal) - other terms
- pseudohermaphrodite
- hermaphrodite
- intersex
other disorders of sex development (no chromosome) - types (and presentations)
- 46, XX DSD –> ovaries present, but external genitalia are virilized ambiguous
- 46, XY DSD –> testes presents, but external genitalia are female or ambiguous
46, XY DSD - presentation
testes presents, but external genitalia are female or ambigiguous
46, XY DSD - mechanism
Most common form is androgen insensitivity syndrome (Testicular feminization)
46, XX DSD - presentation
ovaries present, but external genitalia are virilized ambiguous
46, XX DSD - mechanism
due to excessive and iapproriate exposure to androgenic steroids during early gestation (eg. congenital hyperplasia or exogenous administration)
Placental aromatase deficiency - mechanism
Inability to synthesize estrogens from androgens
Placental aromatase deficiency - presentation
- masculinization of female (46, XX) infants (ambigious genitalia)
- can present with maternal virilozation during pregnancy (fetal androgens cross the placenta)
Placental aromatase deficiency - lab
high serum testosterone and androstenedione
Androgen insensitivity syndrome - karyotype/mechanism
46,XY
Defect in androgen receptor resulting in normal-appearing female
Androgen insensitivity syndrome - presentation
- normal-appearing female external genitalia with scant sexual hair, rudimentary vagina
- uterus and fallopian tubes absent
- normal functioning testes (found in labia majora)
Androgen insensitivity syndrome - testes
normal functioning testes (found in labia majora) –> surgically removed to prevent malignancy
Androgen insensitivity syndrome vs sex chromosomal disorders
Androgen insensitivity syndrome –> high LH Testosterone, and estrogen
5a-reductaes deficiency - mode of inheritance/limited to/mechanism
AR
limited to genetic males
inability to convert Testosterone to DHT
5a-reductaes deficiency - presentation
ambigious genitalia until puberty, when high testosterone causes masculinization and increased growth of external genitalia
normal internal genitalia
5a-reductaes deficiency - endocrine profile
- normal testosterone and estrogen levels
- Testosteron/DHT = 20-60
- high/normal LH
a form of hypogonadotrpic hypogonadism
Kallmann syndrome
Kallmann syndrome - mechanism
defective migration of GnRH cells and formation of oflactory bulb –> failure to complete puberty –> low synthesis of GnRH –> a form of hypogonadotrpic hypogonadism
Kallmann syndrome - presentation/findings/endocrine profile
- anosmia
- Low GnRH/FSH/LH/testosterone
- infertility
Kallmann syndrome - infertility - maechanism
- low sperm cound in males
2. amenorrhea in females
