What levels of testosterone and luteinizing hormone would you expect in a patient with an XY genotype who has defective androgen receptors?
Both testosterone and luteinizing hormone would be elevated (congenital androgen insensitivity)
A patient has elevated testosterone levels; what laboratory test can help you distinguish between a defect in the androgen receptor and the use of exogenous testosterone?
An luteinizing hormone level will be elevated with an androgen receptor defect and will be decreased with exogenous testosterone; also, a patient with complete androgen insensitivity will be externally phenotypically female
What conditions can result in an elevated testosterone level and a decreased luteinizing hormone level?
The use of exogenous steroids and a testosterone-secreting tumor
How can levels of testosterone and luteinizing hormone help you distinguish between primary hypogonadism and hypogonadotropic hypogonadism?
Both have low testosterone; however, primary hypogonadism (gonad failure) has an elevated luteinizing hormone, whereas hypogonadotropic hypogonadism has a low luteinizing hormone level
What is the term for a mismatch between the phenotype of internal (gonads) and external genital structures?
Pseudohermaphroditism, a disagreement between the phenotypic (external genitalia) and the gonadal sex
What type of internal and external sex organs are present in cases of male pseudohermaphroditism?
The testes are present, but the external genitalia are female or ambiguous
What type of internal and external sex organs are present in cases of female pseudohermaphroditism?
The ovaries are present, but the external genitalia are virilized or ambiguous
What in utero events can cause female pseudohermaphroditism at birth?
Excessive exposure to androgenic steroids during early gestation; caused by congenital adrenal hyperplasia or exogenous androgens
What is the most common etiology of male pseudohermaphroditism?
Androgen insensitivity syndrome; formerly known as testicular feminization
A normal-appearing female presents to your office with secondary sex characteristics but no sexual hair, and on exam she has a blind pouch vagina and no palpable uterus; what condition should you suspect?
Androgen insensitivity syndrome, a mutation in the androgen receptor leading to no response to androgens
How can one distinguish between androgen insensitivity syndrome and sex chromosome disorders?
In androgen insensitivity syndrome testosterone, estrogen, and luteinizing hormone will all be elevated, while in sex chromosome disorders testosterone and estrogen are low
You diagnose a patient with androgen insensitivity syndrome; what should be done to prevent malignancy?
Surgical removal of the testicles
In someone with androgen insensitivity syndrome, where in the body are the testes often found?
Most commonly in the labia majora; they can also be found in the abdomen or pelvis
What is the genotype and phenotype for someone with androgen insensitivity syndrome?
The genotype is (46,XY), and the phenotype is externally female
What is the phenotype of the external genitalia of someone with reductase deficiency?
It is ambiguous until puberty (Penis )
What are the levels of testosterone, estrogen, and luteinizing hormone in a patient with reductase deficiency?
Testosterone and estrogen are normal; luteinizing hormone is normal to increased (dihydrotestosterone and testosterone provide negative feedback)
Why do individuals with reductase deficiency undergo genital growth at puberty?
Increased levels of testosterone at puberty trigger growth of the external genitalia despite the lack of reductase
What reaction is blocked in patients with reductase deficiency?
The conversion of testosterone to dihydrotestosterone, which is needed for secondary sex characteristics
What is the histologic appearance of a hydatidiform mole? What is the appearance on gross pathology?
Cystic swelling of the chorionic villi and the proliferation of the chorionic epithelium (trophoblast); grossly, it has a honeycombed uterus or cluster of grapes appearance
A hydatidiform mole is the most common precursor of what malignancy?
What is the genotype of a complete hydatidiform mole?
46,XX (or 46,XY)
A woman presents with abnormal uterine bleeding, highly elevated human chorionic gonadotropin, and an abnormally enlarged uterus; what would you expect to see on sonogram?
Hydatidiform mole, which classically has a snowstorm appearance with no fetus on ultrasound
Which type of hydatidiform mole has chromosomes that are triploid or tetraploid: a partial mole or a complete mole?
A partial mole will commonly have a 69, XXY genotype
Which type of hydatidiform mole may contain fetal parts: a partial mole or a complete mole?
A partial mole
(remember: PARTial mole contains 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 origin of the genetic material in a complete hydatidiform mole?
A complete mole contains exclusively paternal DNA; two sperm fertilize an empty egg
What is the origin of the genetic material in a partial hydatidiform mole?
This type of mole has DNA from both the mother and the father due to the fertilization of one egg by two sperm; it can be 69,XXX or 69,XXY
What is the treatment for hydatidiform mole?
Dilatation and curettage; human chorionic gonadotropin level is checked frequently and methotrexate is used if choriocarcinoma develops
How does the risk of malignancy differ between complete and partial moles?
Complete moles have a 15% to 20% risk for malignant trophoblastic disease and progress 2% of the time to choriocarcinoma; partial moles have a low risk of malignancy () and rarely progress
What is the most common cause of recurrent miscarriages in the first weeks of pregnancy?
Low progesterone levels associated with no response to ;-human chorionic gonadotropin
What is the most common cause of recurrent miscarriages in the first trimester?
Chromosomal abnormalities, such as a robertsonian translocation
What is the most common cause of recurrent miscarriages in the second trimester?
Bicornuate uterus, resulting from incomplete fusion of the paramesonephric ducts during uterine development
A pregnant woman is noted to have a blood pressure of 140/90, swollen ankles and eyes, and protein in her urine; what is the diagnosis?
This is classic triad of preeclampsia (hypertension, proteinuria, and edema) which affects 7% of pregnancies
What condition should you think of when a pregnant woman who has been monitored for preeclampsia develops seizures?
How can you distinguish between preeclampsia and a molar pregnancy in a pregnant woman with new-onset hypertension?
Preeclampsia occurs from 20 weeks gestation to 6 weeks postpartum; symptoms before 20 weeks may be due to a molar pregnancy
Name four conditions that predispose a woman to preeclampsia or eclampsia.
Hypertension, chronic renal disease, diabetes, and autoimmune disorders
A pregnant woman is seen in the emergency room with elevated blood pressure, a platelet count of 90, elevated liver function tests, and elevated indirect bilirubin; what is the diagnosis?
This is likely HELLP syndrome: Hemolysis, Elevated Liver function tests, and a Low Platelet count
What is thought to be the initial insult that leads to the increased vascular tone seen in preeclampsia?
Poor dilation of the spiral arteries causes placental insufficiency, which leads to increased vascular tone as a means of improving perfusion
What is the only definitive treatment for preeclampsia?
Delivery of the fetus
What lab findings would you expect to see in a pregnant woman with proteinuria who develops headache, blurred vision, and hyperreflexia?
Thrombocytopenia and hyperuricemia; she may have preeclampsia or eclampsia
In a stable mother with a preterm fetus that is not yet viable, what is the treatment for preeclampsia?
Bed rest, salt restriction, and treatment of hypertension
Which two drugs can be used for seizure prophylaxis or treatment in pregnant women with preeclampsia or eclampsia?
Magnesium sulfate and diazepam
The mortality associated with pregnancy-induced hypertension is most often due to what two conditions?
Cerebral hemorrhage and adult respiratory distress syndrome
A woman presents with painful vaginal bleeding in the third trimester of pregnancy and you suspect the placenta is no longer attached to the uterine wall; what is the diagnosis?
(remember: Abrupt detachment)
What are two complications of abruptio placentae?
Fetal demise and disseminated intravascular coagulation in the mother
Following delivery, a woman has massive bleeding and fails to complete the third stage (delivery of the placenta); what is the likely diagnosis?
Placenta accreta, in which the placenta is firmly attached to the myometrium and is not expelled after delivery of the fetus
What is the defect that allows placenta accreta to occur?
Implantation in the myometrium can occur where there is a defective decidua, or basal layer, of the endometrium
A woman presents with painless bleeding during pregnancy; what is the likely location of the placenta?
Painless bleeding in any trimester is consistent with placenta previa, which implants over the lower uterine segment and may occlude the cervical os
What is the most common site of an ectopic pregnancy?
The fallopian tubes, although it also occurs in the abdomen, cervix, or ovaries
A sexually active 20-year-old woman presents with sudden severe lower abdominal pain and a history of pelvic inflammatory disease. If tests reveal an increased human chorionic gonadotropin level, what diagnosis is likely?
Name two risk factors for placenta previa.
Prior pregnancy or prior cesarean section
Name three risk factors for placenta accreta.
Prior cesarean section, inflammation (such as Asherman's syndrome), or placenta previa
Name three risk factors for abruptio placentae.
Smoking, hypertension, and cocaine use
Name four risk factors for ectopic pregnancy.
Pelvic inflammatory disease (salpingitis), tubal surgery, rupture of the appendix, and history of infertility
If a fetal anomaly has caused polyhydramnios, what process is likely failing to occur?
An inability to swallow amniotic fluid results in an increased amount of amnion
Knowing that a fetus unable to swallow results in polyhydramnios, name two congenital conditions associated with increased amniotic fluid.
Esophageal or duodenal atresia and anencephaly
If a fetal anomaly has caused oligohydramnios, what process is likely failing to occur?
Oligohydramnios is a result of decreased urine excretion due to a disorder in the perfusion, function, or excretion of urine from the urinary tract
Name three congenital conditions that are associated with oligohydramnios.
Placental insufficiency (decreased renal perfusion), bilateral renal agenesis (no urinary tract), and posterior urethral valves (obstructed urinary excretion)
What fetal syndrome is associated with chronic low amounts of amniotic fluid?
Oligohydramnios can result in Potter's syndrome due to the space restriction from a lack of amniotic fluid, leading to characteristic facies and other abnormalities
On histology, where would you expect to see the initial stages of cervical dysplasia or carcinoma in situ ?
At the basal layer of the squamocolumnar junction; dysplasia begins basally and progressively extends to the apical surface
What cancer, seen only among women, can be prevented by the use of a vaccine?
Cervical cancer, which is caused by the human papillomavirus (typically types 16 and 18) and is usually squamous cell carcinoma
What characteristics of cervical cancer make it amenable to screening and effective intervention?
Cervical cancer develops slowly and has identifiable precursor lesions, meaning it can be located and removed in an early stage before developing to invasive carcinoma
Which area of the cervix is particularly susceptible to human papillomavirus infection and dysplasia leading to cervical cancer?
The squamocolumnar junction
Name four risk factors for cervical cancer.
Multiple sexual partners, early sexual intercourse, HIV infection, and smoking
A previously healthy 40-year-old woman who was recently diagnosed with cervical carcinoma now has oliguria and a creatinine of 4.0 mg/dL. What is the likely cause?
Lateral invasion of the carcinoma resulting in obstruction of the ureters
On laparoscopy, a woman with chronic pelvic pain has multiple lesions that appear like chocolate cysts on her ovaries. She asks if this means she has cancer; what do you tell her?
Cancer is unlikely; these lesions are classic for endometriosis, the nonneoplastic placement of endometrium in abnormal locations
A woman has been unable to conceive for several years and complains of severe pain during her periods; what diagnosis should you consider?
Endometriosis: ectopic endometrial tissue commonly on the peritoneum or ovaries
How are chocolate cysts formed?
Cyclic bleeding (menstruation) of the ectopic endometrial tissue results in cysts filled with blood that have a chocolate appearance
What processes are thought to lead to the ectopic endometrial implantation in endometriosis?
Retrograde menstrual flow or ascending pelvic infection
What is adenomyosis?
Adenomyosis occurs when endometrial tissue develops within the myometrium
What happens to the endometrium when it is exposed to excessive or continuous estrogen stimulation?
Endometrial hyperplasia, the abnormal proliferation of endometrial glands
A woman who is postmenopausal presents with vaginal bleeding; what two conditions should immediately come to mind?
Endometrial hyperplasia, or the more worrisome endometrial carcinoma
Name four risk factors for endometrial hyperplasia.
Hormone replacement therapy, anovulatory cycles, granulosa cell tumors, and polycystic ovarian syndrome (think: increased estrogen exposure)
What is the most common gynecologic malignancy?
A woman who is 60 years of age presents with vaginal bleeding and has a distant history of endometrial hyperplasia; what should be in your differential?
Endometrial carcinoma; peak occurrence is between 55-65 years of age
Name six risk factors for endometrial carcinoma.
Endometrial hyperplasia, late menopause, nulliparity, hypertension, diabetes, obesity, and prolonged estrogen without progestins (think: increased estrogen exposure)
What histologic finding best determines the prognosis of a woman with newly diagnosed endometrial cancer?
Increased myometrial invasion portends a poorer prognosis
A 30-year-old black female comes to your office with abnormal uterine bleeding and you note she has a history of several miscarriages. What benign neoplasm could be responsible?
Leiomyomas, or fibroids
What genetic background predisposes women to both fibroids (leiomyomas) and leiomyosarcoma?
Fibroids are at least twice as common in women of African genetic background
On average how long does it take for a leiomyoma, which is benign, to progress to leiomyosarcoma?
Never; leiomyomas do not progress to leiomyosarcoma or undergo malignant transformation
A woman has a hysterectomy for severe fibroids that caused her to have iron-deficiency anemia due to bleeding; what histology would confirm this diagnosis?
Bundles of smooth muscle in a whorled pattern
Leiomyomas are sensitive to what hormone? What is the clinical significance?
Estrogen, meaning leiomyomas grow with pregnancy and shrink with menopause
How can leiomyosarcoma be distinguished from leiomyoma based on gross tumor appearance?
Leiomyosarcomas are irregularly shaped bulky tumors, frequently with hemorrhagic or necrotic areas, whereas leiomyomas are well demarcated and often multiple
A middle-aged woman with known fibroids has developed a leiomyosarcoma; what are the chances of cure and how did this likely develop?
Leiomyosarcoma is highly aggressive and often recurs following treatment; it develops de novo, not from a prior fibroid
Rank the following types of gynecological tumors according to their incidence from most to least common: ovarian, cervical, endometrial.
Endometrial ; ovarian ; cervical (US data; cervical tumors are the most common worldwide)
Rank the following types of gynecological tumors according to their prognosis, from worst to best: endometrial, ovarian, cervical.
Ovarian ; cervical ; endometrial
What distinguishes premature ovarian failure from menopause?
Menopause occurs after the age of 40 years, whereas premature ovarian failure occurs between puberty and the age of 40 years (normal reproductive age)
How are the causes and symptoms of premature ovarian failure and menopause related?
Both present with the same signs (menopause) and are caused by the atresia of ovarian follicles
You suspect a woman has premature ovarian failure; what would you expect to see on blood labs?
Decreased estrogen and increased follicle-stimulating hormone and luteinizing hormone
Name two causes of anovulation that are due to increased levels of circulating estrogens.
Polycystic ovarian syndrome and obesity
Name four endocrine abnormalities that can cause anovulation.
Thyroid disorders, Cushing's syndrome, adrenal insufficiency, hyperprolactinemia
What cause of anovulation may be seen in a woman who has had several episodes of pelvic inflammatory disease?
Asherman's syndrome (due to postinflammatory adhesion formation)
What might be a cause of anovulation in a 30-year-old woman who is experiencing hot flashes, irregular menstrual cycles, and dyspareunia?
Premature ovarian failure
Disrupting what endocrine signaling system may cause anovulation?
The hypothalamus-pituitary-ovary axis (such as in Kallmann syndrome, where there is a failure of gonadotrope cells in the pituitary)
You are seeing an obese woman who notes she has irregular menstrual cycles but a negative pregnancy test and has developed dark hair above her lips and on her chest; what is the cause of her infertility?
Polycystic ovarian syndrome, which causes anovulation due to elevated luteinizing hormone levels
What is the etiology of the increased serum testosterone level in a woman with polycystic ovarian syndrome?
The elevation in luteinizing hormone acts on theca cells resulting in altered steroid synthesis and increased androgen secretion
You order labs on a woman with polycystic ovarian syndrome; what do you expect the relative levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and glucose to be?
Increased luteinizing hormone, suppressed follicle-stimulating hormone via negative feedback, increased testosterone, and often increased glucose (insulin resistance)
A woman with polycystic ovarian syndrome is at increased risk for what type of cancer?
Endometrial cancer; remember there is prolonged exposure to estrogens
Name three treatments for polycystic ovarian syndrome that act by interfering with the elevated secretion of luteinizing hormone.
Oral contraceptive pills, gonadotropin analogs, and clomiphene (a selective estrogen receptor modulator) all modulate feedback to the hypothalamus and decrease luteinizing hormone levels
What are two nonpharmaceutical treatments for polycystic ovarian syndrome?
Weight loss and surgery (ovarian wedge resection or laparoscopic drilling)
What is an ovarian cyst that consists of an unruptured, distended graafian follicle called?
A follicular cyst
A woman with endometrial hyperplasia and anovulatory cycles is determined to have an ovarian cyst; what is the most likely type?
A follicular cyst, which can be associated with endometrial hyperplasia and elevated estrogens
What is the prognosis for a woman who has a cyst caused by bleeding into a persistent corpus luteum?
This is a corpus luteum cyst, which often regress spontaneously
What is the cause of a chocolate cyst?
This is an endometrioma, a common result of endometriosis, which varies with the menstrual cycle and forms by bleeding into a cyst cavity
What type of cyst is most likely to form in the presence of elevated gonadotropins?
Theca-lutein cysts, which respond to gonadotropins and are thus often multiple and bilateral
What type of cysts are associated with choriocarcinoma and moles?
Name a rare but malignant germ cell tumor that has large hyperchromatic syncytiotrophoblast cells on histopathology.
What tumor, associated with theca-lutein cysts, can occur in either the mother or fetus during pregnancy?
What serum marker is used as a tumor marker for choriocarcinoma?
Human chorionic gonadotropin
How can serum markers help to distinguish between choriocarcinoma and dysgerminoma?
Both express human chorionic gonadotropin, but a dysgerminoma will also cause elevated lactate dehydrogenase
What tumor is the female correlate to the seminoma in males?
The dysgerminoma, although it is much rarer, comprising only 1% of germ cell tumors
On histology, a _____ (dysgerminoma/endodermal sinus) tumor will have sheets of uniform cells, whereas a _____ (dysgerminoma/endodermal sinus) tumor will have Schiller-Duval bodies that look like glomeruli.
Dysgerminoma; endodermal sinus (yolk sac tumor)
What germ cell tumor is very aggressive and appears as a yellow, friable mass on gross pathology?
An endodermal sinus tumor (yolk sac tumor)