Flashcards in 4 pathology Sex chromosome disorders of sexual development-Diagnosing disorders of sex hormones Other disorders of sex development Aromatase deficiency Androgen insensitivity syndrome (46,XY) 5a-reductase deficiency Kallmann syndrome Hydatidiform mole Deck (46):
On a blood smear of a male patient, you note a small dumbbell-shaped extension on a cell nucleus (i.e., Barr body). What does it represent?
Inactivated X chromosome, which is normal in women but indicates Klinefelter syndrome (XXY) in men
You refer a 30-year-old man and his wife for an infertility work-up. You suspect he has hypogonadism. What is a common primary cause?
Klinefelter syndrome (XXY) (incidence is 1:850)
What happens to follicle-stimulating hormone (FSH), estrogen, testosterone, and luteinizing hormone (LH) levels in Klinefelter syndrome?
Seminiferous tubule dysgenesis causes low inhibin, high FSH (abnormal Leydig cell function causes low testosterone, high LH, high estrogen)
Women with Turner syndrome tend to have ____ (menarche/menopause) before ____ (menarche/menopause).
A woman with short stature presents to your office with webbed neck and lymphedema. What is a possible diagnosis?
Turner syndrome (XO)—hugs and kisses from Tina Turner
How many Barr bodies are seen when the cells of a patient with Turner syndrome are examined under the microscope?
A young woman presents to your office with amenorrhea. What is the most common cause of primary amenorrhea?
Turner syndrome (XO), which can result from mitotic or meiotic error
A girl was recently diagnosed with Turner syndrome. What are the possible genotypes of a female patient with Turner syndrome?
45,XO (complete monosomy) or 45,XO/46,XX (mosaicism)
A woman with Turner syndrome wishes to get pregnant. What do you tell her?
It may be possible with oocyte donation and with administration of exogenous progesterone and estradiol-17β
A phenotypically normal, very tall man with acne and learning disabilities presents to your office. What additional disorder might he have?
Double Y males (XYY), in addition to acne and learning disabilities, may present with autism spectrum disorders
A woman presents to your office. You note she has ovotestis, which is a mixture of ovarian and testicular tissues. What is her condition?
True hermaphroditism (46,XX or 47,XXY), which is the presence of both ovarian and testicular tissue and ambiguous genitalia
What are the two possible karyotypes of true hermaphroditism?
46,XX and 47,XXY (also called ovotesticular disorder of sex development)
A man has the genotype XYY. What do you tell him about his fertility and the mechanism of how this happened?
Normal fertility—this is not hereditary, but just a random nondisjunction event in paternal meiosis II
A patient with an XY genotype has defective androgen receptors. What levels of testosterone and luteinizing hormone (LH) will you see?
Both testosterone and LH would be elevated (congenital androgen insensitivity)
A man has high testosterone. What lab test helps distinguish a defect in the androgen receptor from the use of exogenous testosterone?
Luteinizing hormone test, which will produce a high result with an androgen receptor defect and low result with exogenous testosterone use
A man has high testosterone. What lab test helps distinguish a defect in the androgen receptor from a testosterone-secreting tumor?
Luteinizing hormone test, which will produce a high result with androgen receptor defect and low result with testosterone-secreting tumor
How can levels of testosterone and luteinizing hormone (LH) help distinguish primary hypogonadism from hypogonadotropic hypogonadism?
Both have low testosterone, but primary hypogonadism (gonad failure) has elevated LH and hypogonadotropic hypogonadism has low LH
A man has small testicles, scarce body hair, and anosmia. He has low testosterone and luteinizing hormone. Most likely diagnosis?
Hypogonadotropic hypogonadism (specifically Kallmann syndrome)
A man lacks secondary sex characteristics (pubic/face/underarm hair). He has low testosterone/high luteinizing hormone. Diagnosis?
What is the term for a mismatch between the phenotype of internal (gonads) and external genital structures?
Pseudohermaphroditism, hermaphrodite, or intersex (a disagreement between the phenotypic [external genitalia] and the gonadal sex)
A patient has male pseudohermaphroditism. What type of internal and external sex organs are present?
Testes are present, and the external genitalia are female or ambiguous
A female with a XX genotype presents with virilized external genitalia. Ultrasound shows presence of ovaries. What is the diagnosis?
A patient presents with female pseudohermaphroditism. What in utero events can cause female pseudohermaphroditism at birth?
Excessive/inappropriate exposure to androgenic steroids in early gestation (caused by congenital adrenal hyperplasia or exogenous androgens)
A female infant (46,XX) has masculinized genitalia and increased serum testosterone and androstenedione. What is a possible diagnosis?
Aromatase deficiency, causing an inability to synthesize estrogens from androgens
A pregnant woman shows maternal virilization during pregnancy, and fetal androgens were detected in her blood. What is the likely diagnosis?
Aromatase deficiency in her fetus (fetal androgens can cross the placenta and cause maternal virilization)
A patient has androgen insensitivity syndrome. Are testes present or absent? What treatment would be needed, if any?
Testes are often found in the labia majora; surgical removal to prevent malignancy
What is the genotype and phenotype for someone with androgen insensitivity syndrome?
The genotype is (46,XY), and the phenotype is externally female
What hormone levels distinguish androgen insensitivity syndrome from sex chromosome disorders?
In androgen insensitivity, androgen, testosterone, estrogen, and LH are low—in sex chromosome disorders, testosterone and estrogen are high
What is the phenotype of the external genitalia of someone with 5α-reductase deficiency? Genotype?
It is ambiguous until puberty, at which point increased testosterone causes masculinization; internal genitalia are normal
What are the levels of testosterone, estrogen, and luteinizing hormone (LH) in a patient with 5α-reductase deficiency?
Testosterone and estrogen are normal, and LH is normal to increased (dihydrotestosterone and testosterone provide negative feedback)
What reaction is blocked in patients with 5α-reductase deficiency?
The conversion of testosterone to dihydrotestosterone (condition is autosomal recessive and limited to genetic males [46,XY])
A male lacking secondary sex characteristics and the ability to smell (anosmia) presents for his yearly physical. What is the diagnosis?
Kallmann syndrome, which is due to defective migration of GnRH cells and formation of the olfactory bulb
A young female patient failed to complete puberty and presents with amenorrhea. She has very low GnRH levels. What is a possible diagnosis?
Kallmann syndrome, which is a form of hypogonadotropic hypogonadism
A man with Kallmann syndrome would be expected to have ____ (increased/decreased) synthesis of ____ from the hypothalamus.
Decreased, GnRH (this decreases FSH, LH, and testosterone and, therefore, sperm count)
A male patient has Kallmann syndrome. What do you counsel him about his fertility?
He will have a low sperm count, contributing to infertility
A hydatidiform mole is a precursor of what malignancy?
Choriocarcinoma (more common with complete moles [2%] versus partial moles [very rare])
A partial mole ____ (does/does not) have a triploid karyotype and ____ (does/does not) contain fetal parts.
Does (69,XXY; 69,XXX; 69,XYY)—does (partial = fetal parts)
Is a patient who has extremely elevated human chorionic gonadotropin and large uterus size more likely to have a complete or a partial mole?
A complete mole (partial moles typically have milder elevations in human chorionic gonadotropin and normal uterus size)
What is the genotype of a complete hydatidiform mole? Does it contain fetal parts?
46,XX or 46,XY; no
What is the origin of the genetic material in a partial hydatidiform mole?
This type of mole has DNA from both mother and father due to the fertilization of one egg by two sperm—it can be 69,XXX, 69,XXY, or 69,XYY
How does the risk of malignancy differ between complete and partial moles?
Complete=15–20% malignant trophoblastic disease risk, 2% progress to choriocarcinoma—partial=low malignancy risk (
A patient has vaginal bleeding, enlarged uterus, preeclampsia, hyperthyroidism, and hyperemesis. Is this likely a complete or partial mole?
You observe cystic swelling of chorionic villi and proliferation of trophoblasts in the chorionic epithelium in a patient. Diagnosis?
A woman with a hydatidiform mole has only symptoms of vaginal bleeding and abdominal pain. Is this likely a complete or partial mole?
Describe the components of a complete mole.
Single sperm with an enucleated egg—subsequently results in duplicated paternal DNA