Male Repro- 1 Flashcards
Answer D
The temporal association between this patient’s arguments with his wife and subsequent onset of erectile dysfunction (ED) makes psychogenic factors the most likely cause of his ED. The presence of spontaneous nocturnal erections is another important diagnostic clue as this demonstrates the integrity of neurologic reflexes and corpus cavernosa blood flow. Loss of normal nocturnal erections occurs in men with organic ED but is not seen with psychogenic etiologies.
ED can be caused by organic factors, psychogenic factors, or a combination of both. Psychogenic causes include performance anxiety, depression, sexual trauma, and/or relationship problems and are typically associated with an abrupt onset triggered by stress, as in this patient. In contrast, men suffering from organic causes of ED (eg, vascular insufficiency) tend to have a slower progression of symptoms, with intermittent ED later becoming more persistent in nature (Choice E).
(Choice A) There tends to be an increase in the incidence of ED with advancing age. However, the sudden onset of this patient’s dysfunction during a time of relationship and work stress makes a psychogenic cause more likely.
(Choices B and C) Antidepressants, particularly selective serotonin reuptake inhibitors, have been associated with sexual dysfunction. However, the norepinephrine-dopamine reuptake inhibitor bupropion has not been associated with sexual dysfunction. Of the antihypertensive agents, thiazide diuretics and sympathetic blockers (eg, clonidine, methyldopa) have the greatest risk for ED. Angiotension-converting enzyme inhibitors (eg, lisinopril) and calcium channel blockers (eg, amlodipine) have the least risk.
Educational objective:
Psychogenic causes of erectile dysfunction include performance anxiety, depression, sexual trauma, relationship problems, and stress. Important clues include sudden-onset and normal nocturnal erections.
Answer A
This patient has a history of recurrent pneumonia, digital clubbing, azoospermia, and bilateral absence of the vas deferens; this is most likely due to cystic fibrosis (CF). Patients with CF have variable severity of lung and pancreatic function. Although most patients have recurrent sinopulmonary infections and pancreatic insufficiency, some patients may have mild disease depending on their underlying mutation. Regardless of lung or pancreas function, virtually all adult men with CF have azoospermia and infertility. Although spermatogenesis is usually normal, almost all males with CF are unable to secrete semen due to congenital bilateral absence of the vas deferens (CBAVD). CFTR mutations are likely responsible for abnormal development of Wolffian structures, resulting in vasal agenesis and defective sperm transport.
A diagnosis of CF can be based on elevated sweat chloride levels. If the sweat chloride test is equivocal, measurement of nasal transepithelial potential difference and genetic testing for CFTR mutations should be performed to confirm the diagnosis.
(Choice B) Although, primary ciliary dyskinesia (eg, Kartagener syndrome) can cause recurrent pulmonary infections and digital clubbing, infertility in Kartagener syndrome is usually due to immotile spermatozoa. Abnormal nasociliary motility is a nonspecific finding that is seen most commonly in patients with primary ciliary dyskinesia and in some patients with CF (due to abnormally thick mucus). A more specific test for CF is the nasal transepithelial potential difference. In addition, CBAVD is virtually pathognomonic for a CFTR mutation.
(Choice C) Low serum alpha-1 antitrypsin (AAT) is associated with AAT deficiency and not with CF. AAT deficiency is typically associated with panacinar emphysema and chronic liver disease. Infertility is not seen in these patients.
(Choices D and F) FSH, LH, and testosterone levels are usually normal in patients with CF. A low testosterone level in the setting of decreased FSH and LH is seen in hypogonadotropic hypogonadism (eg, Kallmann syndrome).
(Choice E) Primary humoral deficiencies usually manifest as recurrent upper and lower respiratory tract infections due to impaired antibody production. However, most patients with selective IgA deficiency are asymptomatic.
Educational objective:
CFTR gene mutations are the most common cause of congenital bilateral absence of the vas deferens (CBAVD). Patients with CBAVD have azoospermia and infertility but normal levels of FSH, LH, and testosterone. Elevated sweat chloride levels are diagnostic of cystic fibrosis.
Answer A
This patient has an elevated testosterone level, but his gynecomastia and sparse facial and pubic hair suggests lack of the expected physiologic response. Androgen insensitivity syndrome (AIS) is caused by loss-of-function mutations of the androgen receptor (AR) gene on the X chromosome. Complete AIS is characterized by female body habitus and external genitalia (but with absence of internal Mullerian derivatives) and cryptorchid testes. In contrast, partial AIS has a variable phenotype; typical findings include:
Undervirilization of the external genitalia, ranging from phenotypically female to phenotypically male (often with microphallus and hypospadias)
Decreased facial, axillary, and pubic hair (which is driven by androgens in both males and females)
Oligospermia
Gynecomastia
Dysfunction of the AR in the hypothalamus and pituitary leads to loss of feedback inhibition of gonadotropin-releasing hormone (GnRH), FSH, and LH. This results in the following hormonal findings:
GnRH induces increased LH secretion, which leads to increased testosterone production in the testes.
FSH secretion is increased by GnRH but suppressed by inhibin from the seminiferous tubules and is often normal.
Estrogen, which is derived by aromatization of testosterone, may be normal or elevated.
(Choices B and E) Testicular disorders can affect the Leydig cells, seminiferous tubules, or both. The Leydig cells are the primary site of testosterone production; reduced Leydig cell function can cause gynecomastia and elevated LH but would be associated with low (not high) testosterone. Injury to the seminiferous tubules leads to loss of inhibin feedback of FSH secretion and an elevated FSH.
(Choice C) Ejaculatory duct obstruction can be caused by congenital defects or infection (eg, Chlamydia trachomatis). Sperm counts are low but testicular endocrine function (ie, testosterone level) is typically normal.
(Choice D) Abuse of exogenous androgens can reduce spermatogenesis (due to reduced local testicular testosterone levels) and cause gynecomastia (due to aromatization of excess androgens to estrogens). However, this would be associated with suppression of LH levels.
Educational objective:
Androgen receptor dysfunction in patients with partial androgen insensitivity syndrome leads to decreased facial, axillary, and pubic hair; oligospermia; gynecomastia; and undervirilization of external genitalia (eg, microphallus). Loss of feedback inhibition of gonadotropin-releasing hormone results in elevated LH and testosterone levels.
Answer B
Patients with chronic conditions often have unaddressed psychosocial concerns. This patient was recently diagnosed with amyotrophic lateral sclerosis, which involves physical impairment. Although his clinical condition and mood are stable, he confides that he has “felt distant” from his wife.
The best next step is to validate the patient’s feelings (eg, “Many patients with this condition experience changes with intimacy and sex”). Then the physician should elicit the patient’s specific concerns (eg, “is there anything you would like to talk about?”).
The patient could be referring to a new lack of emotional intimacy with his wife or a decline in sexual well-being, which also adversely affects quality of life but may remain unaddressed due to embarrassment. For example, a common concern is decreased libido; partners of patients with physical impairment may also be worried about hurting their partners during intercourse. Therefore, physicians should have a low threshold for inquiring about emotional and sexual well-being in patients who raise relationship concerns. If the patient chooses to raise such issues, additional education on condition-specific interventions can be discussed. In addition, regular reassessment is recommended.
(Choice A) This statement validates potential relationship difficulties following a new medical diagnosis. However, recommending that the patient “continue monitoring” his feelings is an inadequate response because it does not explore his specific concerns.
(Choice C) This response prematurely focuses on couples therapy without eliciting the reasons for the patient’s distance from his wife, which could be related to his chronic condition and may benefit from medical intervention.
(Choice D) Normalizing relationship difficulties can be validating. However, a generalization such as “it may take time” is dismissive, and the response does not explore the nature of the patient’s concern.
Educational objective:
Patients with chronic conditions often have unaddressed psychosocial concerns such as lack of emotional intimacy or decline in sexual well-being that can adversely affect quality of life. Therefore, physicians should regularly evaluate patients with chronic conditions for emotional and sexual well-being to allow them to raise concerns without embarrassment.
Answer D
Early in normal gestation, the testes are located in the retroperitoneal region and subsequently descend into the scrotum before birth. During descent, they are accompanied by an evagination of the peritoneum called the processus vaginalis, which then obliterates after descent is complete.
Failure of obliteration of the processus vaginalis leads to a persistent connection between the scrotum and the peritoneal cavity through the inguinal canal. If the opening is small and allows for fluid leakage only, a communicating hydrocele develops. Diagnosis is made clinically through transillumination of the scrotum; a scrotal ultrasound would reveal fluid surrounding the affected testicle.
If the communication between the peritoneal cavity and the scrotum is large enough to allow for the passage of abdominal organs, an indirect inguinal hernia develops. Indirect inguinal hernias are common in children. They pass through the deep inguinal ring, are covered by internal spermatic fascia, and are located lateral to the inferior epigastric blood vessels. Hydroceles and indirect inguinal hernias both can present as an asymptomatic scrotal mass that increases in size during Valsalva maneuvers.
(Choice A) Direct inguinal hernias are an acquired protrusion of abdominal contents through a weakness of the abdominal wall (Hesselbach triangle). Direct inguinal hernias do not pass through the inguinal canal and are located medial to the inferior epigastric blood vessels.
(Choice B) Femoral hernias are an acquired protrusion of abdominal contents through a weakness of the femoral canal. They are the least common type of hernia.
(Choice C) Hypospadias occurs due to incomplete fusion of the urethral folds and presents as a ventrally located urethra.
(Choice E) Orchitis is a non-specific inflammation of the testes that is classically associated with mumps. In young adults and adolescents, it is commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae. In older patients, Escherichia coli is the most common causative agent.
(Choice F) Testicular torsion is a rotation of the testes around the spermatic cord leading to acute testicular pain. Trauma or a congenitally-horizontal positioning of the testes (“bell clapper deformity”) facilitates torsion.
Educational objective:
Communicating hydroceles and indirect inguinal hernias are caused by an incomplete obliteration of the processus vaginalis. The resultant connection between the scrotum and abdominal cavity can allow for fluid leakage (hydrocele) or the passage of abdominal contents (indirect inguinal hernia).
Answer E
Differentiation and development of the external genitalia occurs during weeks 8-15 of gestation. In females, the urethral (urogenital) folds do not fuse and ultimately form the labia minora and the vestibule of the vagina. In males, the urethral folds fuse to form the ventral aspect of the penis and the penile raphe, which serve as the anterior wall of the urethra.
Incomplete fusion of these folds in a male would result in an abnormal opening of the urethra at a location proximal to the distal tip of the glans penis. Depending on the degree of nonunion, the urethral opening can be anywhere from the perineum to just proximal to the glans penis. This condition is known as hypospadias and can generally be repaired surgically to allow normal urination and sexual activity.
(Choice A) A bifid scrotum (two separate sacs) results from malunion of the labioscrotal folds. In females, the labioscrotal swellings form the labia majora.
(Choice B) Cryptorchidism is failure of a fetal testis to descend into the scrotum. Most undescended testes will descend spontaneously by the time the infant is 4 months old.
(Choice C) The genital tubercle becomes the glans penis in males and the clitoris in females. Epispadias is an abnormal opening of the urethra on the dorsal surface of the penile shaft that results from faulty positioning of the genital tubercle in the fifth week of gestation.
(Choice D) The processus vaginalis is a projection of the peritoneal cavity that accompanies the descending testis into the scrotum and ultimately forms the tunica vaginalis of the testis. Hydrocele is development of a fluid-filled peritoneal sac within the scrotum that results from incomplete obliteration of the processus vaginalis.
Educational objective:
In males, incomplete fusion of the urethral (urogenital) folds results in hypospadias, an abnormal opening of the urethra proximal to the glans penis along the ventral shaft of the penis.
Answer E
Lymphatic drainage of the scrotum occurs via the superficial inguinal lymph nodes. These lymph nodes drain nearly all cutaneous lymph from the umbilicus to the feet, including the external genitalia and anus (up to the dentate line). The exceptions are the testis, glans penis, and the cutaneous portion of the posterior calf. Lymph from the testes drains directly into the para-aortic (retroperitoneal) lymph nodes (Choice D). Lymph from the glans penis and the cutaneous portion of the posterior calf drains into the deep inguinal lymph nodes. The superficial inguinal lymph nodes also drain into the deep inguinal lymph nodes.
(Choice A) The common iliac nodes are located alongside the common iliac artery and drain the internal and external iliac nodes. The external iliac nodes receive lymph from the deep inguinal lymph nodes.
(Choice B) The inferior mesenteric nodes drain the structures supplied by branches of the inferior mesenteric artery (eg, the left colic, sigmoid, and superior rectal arteries). Thus, these nodes drain the descending and sigmoid colon as well as the upper part of the rectum, and their efferents drain into the pre-aortic nodes.
(Choice C) Infraclavicular lymph nodes are found beside the cephalic vein between the pectoralis major and deltoid, immediately below the clavicle. They drain lymph from portions of the upper limb and breast.
Educational objective:
Due to its intra-abdominal origin, lymphatic drainage of the testis is to the para-aortic lymph nodes. In contrast, lymph drainage from the scrotum goes into the superficial inguinal lymph nodes.
Answer A
Finasteride is a 5-alpha reductase inhibitor and it inhibits the conversion of testosterone to dihydrotestosterone. It acts on the epithelial components of the prostate gland and produces improvement of symptoms as well as reduction in the size of the gland. There are various histological patterns of BPH. Some patients have predominant epithelial hyperplasia and others have predominant stromal hyperplasia. Those with stromal hyperplasia may have collagen or smooth muscle predominance. Patients with epithelial predominance best respond to treatment with finasteride.
(Choice B, C & D) Alpha-1 blockers produce symptomatic improvement in patients with BPH by their action on smooth muscles present in prostate and bladder base. Patients with smooth muscle predominance best respond to treatment with alpha-1 blockers. Patients with collagen predominance respond neither to finasteride nor to alpha-1 blockers.
Educational objective:
Finasteride acts on epithelium and alpha-1 blockers act on smooth muscles of prostate and bladder base.
Answer B
This patient’s painless testicular lesion, necrotic mass on ultrasound, and elevated serum alpha-fetoprotein (AFP) level raises strong suspicion for testicular cancer, the most common solid organ malignancy in men age 15-35. Most cases (>95%) arise from pluripotent germ cells that normally differentiate into sperm (germ-cell tumors), which are categorized as follows:
Non-seminomatous germ cell tumors (NSGCT) contain undifferentiated or partially differentiated germ cells (eg, embryonal carcinoma, yolk sac tumor, choriocarcinoma). They often generate abnormal hormones (human chorionic growth [hCG] hormone) or proteins (AFP) that can be measured in the blood to aid diagnosis and evaluate for recurrence following treatment.
Seminomas contain large uniform germ cells that retain the phenotypic features of spermatogonia. They do not produce AFP but some seminomas secrete limited quantities of hCG.
Lactate dehydrogenase (LDH), a marker of tissue injury and cell turnover, is also often elevated in patients with germ cell tumors but is less sensitive and specific than hCG or AFP.
(Choice A) Leydig cells secrete testosterone and are found in the testicular stroma. Leydig cell tumors often produce estrogen or testosterone, leading to feminization (eg, gynecomastia) or precocious puberty, respectively. They do not generate AFP or hCG.
(Choice C) Sertoli cells nourish sperm and secrete inhibin, which moderates pituitary gonadotropin release. Sertoli cell tumors are sometimes associated with the excessive production of estrogen but do not typically elevate AFP.
(Choice D) Teratomas are terminally differentiated germ cells that may contain skin or gastrointestinal epithelium, cartilage, and/or neuronal tissue. They are often malignant in adults and may be part of some nonseminomatous germ cell tumors. However, terminally differentiated cells are not generally able to produce AFP or hCG; therefore, these tumor markers are usually not elevated.
(Choice E) Primary testicular lymphoma is uncommon and usually occurs in men age >60. Although lymphoma can be associated with elevated LDH, AFP is almost always normal.
Educational objective:
Most cases of testicular cancer are either seminomatous or nonseminomatous germ cell tumors. Nonseminomatous germ cell tumors are composed of partially differentiated germ cells, which often retain the ability to secrete human chorionic growth hormone and alpha-fetoprotein (serum tumor markers). Serum lactate dehydrogenase, a marker of tissue injury and cell turnover, is also frequently increased.
Answer E
This patient with external male genitalia has a 46,XX karyotype, discordant findings suggestive of a disorder of sex development. Virilized genitalia in genotypic females (XX) are usually caused by androgen overproduction by the adrenals (eg, congenital adrenal hyperplasia) or gonads. However, this patient’s internal male genital ducts (eg, seminal vesicles, vas deferens) and testes along with the absence of internal female genital ducts are more consistent with translocation of the sex-determining region of the Y chromosome (SRY gene) onto an X chromosome.
In normal early gestation, the embryo has undifferentiated gonads and precursors of both male and female internal genital ducts (wolffian and müllerian ducts, respectively). In genotypic males (XY), the gonads differentiate into testes due to testes-determining factor, a protein encoded by the SRY gene. The testes produce testosterone (promotes development of internal male genital tract and external male genitalia) and antimüllerian hormone (causes regression of müllerian ducts that form the fallopian tubes and uterus). This same process occurs in genotypic females (XX) who have an SRY gene translocation.
Therefore, patients have a male phenotype but are usually diagnosed after a karyotype is performed for:
Infertility: Because normal spermatogenesis relies on other Y chromosome genes that are not translocated with the SRY gene, patients have azoospermia.
Hypogonadism: Without spermatogenesis, the postpubertal testes remain small and testosterone levels remain relatively low (as compared to expected levels in a postpubertal male). Reduced negative feedback from testosterone on the hypothalamus and pituitary result in high FSH and LH (hypergonadotropic hypogonadism), as seen in this patient. Increased estradiol relative to testosterone stimulates breast tissue development (gynecomastia).
(Choice A) Affected patients with 5-alpha reductase deficiency have testes (due to the SRY gene) but develop external female genitalia due to inability to convert testosterone to dihydrotestosterone. Moreover, a karyotype would show 46,XY.
(Choice B) Dysfunctional androgen receptors in affected patients with androgen insensitivity syndrome lead to external female genitalia with no internal genital ducts (normal antimüllerian hormone/absent testosterone effect), findings not seen in this patient. A karyotype would show 46,XY.
(Choice C) Aromatase deficiency (inability to convert androgens to estrogens) in genotypic females (XX) leads to virilized (ambiguous) genitalia due to excessive androgens. However, testes would not be present and female genital ducts would be expected due to absence of the SRY gene.
(Choice D) Gynecomastia and small testes are seen in Klinefelter syndrome. However, a karyotype would show 47,XXY.
Educational objective:
In patients with a 46,XX karyotype, translocation of the sex-determining region of the Y chromosome (SRY gene) leads to development of fetal testes. Affected patients have a male phenotype with small testes, gynecomastia, and infertility (azoospermia).
Answer D
Erectile dysfunction (ED) is characterized by an inability to initiate or maintain an erection adequate for sexual intercourse. Causes can be categorized as organic (eg, hypogonadism, arterial insufficiency, neurologic impairment) or psychogenic.
Psychogenic ED is common in patients with preexisting mood or anxiety disorders but can also occur abruptly following a stressful precipitating event:
Prolonged illness: Patients may be hesitant or unsure how to initiate sexual activity.
Severe, acute illness: Patients may believe the illness can be caused or worsened by sexual activity. This is especially common in those with cardiovascular disease (eg, stroke, myocardial infarction), who are often concerned that sexual activity may strain the heart and lead to further cardiac events.
Surgical procedures: Patients may be embarrassed by their appearance (eg, surgical scar) or body odor (eg, incontinence, colostomy).
Loss of loved one: Patients may experience survivor guilt or feel fearful about the future.
Psychogenic ED is often situational, with normal erections at night or during masturbation but impaired erections when with a partner. This patient has situational ED despite normal libido following an acute, severe illness, suggesting psychogenic sexual dysfunction (ie, performance anxiety) rather than an organic etiology.
(Choice A) Organic ED is common in patients with cardiovascular disease due to systemic arterial insufficiency and comorbid conditions (eg, diabetes) that impair erectile function. However, onset typically occurs gradually, rather than abruptly following a stressful event, and nocturnal erections are impaired as well. In addition, aortoiliac occlusion is often associated with pain in the buttocks, posterior thigh, or calf during exercise; this patient has normal exercise tolerance.
(Choice B) Bladder neck obstruction (eg, benign prostatic hyperplasia [BPH]) can reduce semen volume. Laxity of the musculature at the bladder outlet, which can occur following surgical repair of BPH, can lead to retrograde ejaculation of semen into the bladder. However, erections are typically normal unless the patient is taking a 5-alpha reductase inhibitor (eg, finasteride).
(Choice C) Some cardiovascular medications, such as beta blockers (eg, metoprolol) and thiazide diuretics, can cause ED, but nocturnal/nonsexual erections are also affected.
(Choice E) Testosterone deficiency causes ED with decreased libido and loss of nocturnal erections. This patient’s normal libido suggests adequate testosterone levels.
Educational objective:
Psychogenic erectile dysfunction often begins abruptly following severe medical (eg, myocardial infarction) or emotional stressors. The symptoms are often situational, with normal erections at night or during masturbation but impaired with a partner. Libido is often normal.
Answer C
This patient has signs of bladder outlet obstruction (eg, urinary hesitancy, need to strain) most likely due to benign prostatic hyperplasia (BPH), a condition that is present in >90% of men age >80. The diagnosis is based on history of urinary symptoms and digital rectal examination showing a smooth, homogenously enlarged prostate. The prostate is located just anterior to the anal canal (Choice D) and posterior to the symphysis pubis (the above CT image is just superior to the joining of the left and right pubic bones).
BPH may cause static urinary obstruction (androgen-mediated enlargement of the prostate) or dynamic obstruction (prostate smooth muscle contraction via α-adrenoceptors). 5-α reductase inhibitors (eg, finasteride) inhibit the action of androgens on the prostate gland, preventing the conversion of testosterone to dihydrotestosterone and thereby limiting further prostate enlargement. α-adrenergic blockers (eg, tamsulosin) relax the smooth muscle in the bladder neck and prostate gland and are also used to control symptoms of BPH.
(Choice B) The distal end of the anterior bladder wall may or may not be visible at this level depending on patient positioning and bladder filling.
Educational objective:
The prostate is located between the pubic symphysis and the anal canal and is visible on inferior sections of the pelvis on CT scan. Benign prostatic hyperplasia is a common, age-related condition that causes urinary symptoms (eg, hesitancy, straining, incomplete voiding). It can be medically treated with α-adrenergic blockers and 5-α reductase inhibitors.
Answer E
This patient has features of testosterone deficiency (ie, hypogonadism), including erectile dysfunction, low libido, and gynecomastia. His tall stature and small, firm testes are consistent with Klinefelter syndrome (KS), which causes hypogonadism due to hyalinization and fibrosis of the testes. Patients who develop hypogonadism prior to puberty, including patients with KS, often have a eunuchoid habitus, sparse body hair, and high-pitched voice, whereas these features are much less pronounced in those who develop hypogonadism later in life.
Primary hypogonadism can be confirmed with low serum testosterone associated with elevated LH. Management of male hypogonadism includes testosterone therapy, which can improve libido and erectile function, increase bone density, and facilitate muscle development.
(Choice A) Aromatase inhibitors decrease the conversion of androgens to the corresponding estrogens (eg, testosterone to estradiol). Although some experts use aromatase inhibitors as supplemental therapy in KS, the primary defect is inadequate testosterone production, so testosterone therapy should be initiated first.
(Choice B) hCG has bioactivity analogous to that of LH and can be used to stimulate testosterone production in patients with secondary/central hypogonadism (ie, low endogenous LH). However, patients with KS have primary hypogonadism, so gonadotropin therapy is not useful.
(Choice C) Phosphodiesterase 5 inhibitors (eg, sildenafil) can assist in the treatment of erectile dysfunction but would not improve this patient’s hormone levels or libido.
(Choice D) Selective estrogen receptor modulators (eg, tamoxifen) are sometimes used to minimize breast enlargement in adolescents with KS. However, nonsurgical interventions are not useful in adults with established gynecomastia.
Educational objective:
Management of male hypogonadism includes testosterone therapy, which can improve libido and erectile function, increase bone density, and facilitate muscle development.
Answer E
This patient’s decreased libido, erectile dysfunction, and testicular atrophy are indicative of hypogonadism. These findings, in combination with hyperpigmentation of the skin, elevated glucose/diabetes mellitus, and hepatomegaly, are strongly suggestive of hereditary hemochromatosis (HH).
HH is an autosomal recessive disorder characterized by excessive intestinal iron absorption and accumulation in various tissues. Secondary hypogonadism occurs in HH due to deposition of iron in the pituitary gland, resulting in decreased gonadotropin secretion and subsequent testicular failure. In women, HH is often not diagnosed until after menopause, as premenopausal women have ongoing menstrual blood loss that usually prevents significant iron overload and symptom development; therefore, amenorrhea is a rare finding in women with HH.
(Choice A) Atherosclerotic disease is a common cause of erectile dysfunction in older men, especially those with a history of smoking, but it typically would not affect libido and would not cause hyperpigmentation or hepatomegaly.
(Choice B) Autoimmune adrenalitis is a common cause of primary adrenal insufficiency (ie, Addison disease). Hyperpigmentation is common due to increased cosecretion of melanocyte-stimulating hormone with ACTH, but patients typically have orthostatic hypotension (due to loss of mineralocorticoid) and hypoglycemia (not hyperglycemia).
(Choice C) Ectopic ACTH secretion causes paraneoplastic Cushing syndrome (eg, small cell lung cancer). Patients may develop hyperpigmentation and hyperglycemia but also often have hypertension and proximal muscle weakness. Small testes are not seen.
(Choice D) Testicular fibrosis is a common manifestation of Klinefelter syndrome (KS). Hypogonadism due to KS is typically apparent at puberty and is often associated with a eunuchoid habitus, sparse body hair, and high-pitched voice. Hepatomegaly is not common.
Educational objective:
Hereditary hemochromatosis can cause secondary hypogonadism due to deposition of iron in the pituitary gland, resulting in decreased gonadotropin secretion. Patients who develop secondary hypogonadism are also at risk for deficiencies in other pituitary hormones (eg, central hypothyroidism).
Answer A
This patient has acute, severe, progressive scrotal pain with a high-riding scrotal mass, findings concerning for testicular torsion. Torsion is caused by twisting of the spermatic cord and its contents, leading to venous congestion, ischemia, and necrosis of the testis if untreated.
Classic presentation is an adolescent or young adult male with sudden onset of unilateral scrotal pain, usually with associated nausea and vomiting. Poor testicular perfusion can also cause reactive scrotal edema and discoloration (eg, erythema) on examination. Because the cremaster muscle lies within the spermatic cord, an absent cremasteric reflex (testicular elevation when stroking the ipsilateral inner thigh) is highly suggestive of testicular torsion. The testicle itself is often transverse (due to inadequate fixation of the lower pole of the testis to the tunica vaginalis) and high riding (due to cord shortening with rotation).
Diagnosis can be clinical with classic findings or may require ultrasound evaluation. Twisting of the spermatic cord and/or decreased testicular perfusion on ultrasound confirms the diagnosis.
(Choice B) Increased abdominal pressure (eg, cough, Valsalva maneuver) can lead to bulging within the groin or scrotum due to an inguinal hernia. If incarcerated, a hernia can lead to acute scrotal pain, but a high-riding testicle would not be expected.
(Choice C) Varicocele, which is characterized by a scrotal mass with a “bag of worms” texture, increases in size when standing as compared with supine positioning. This dilation of the pampiniform plexus may cause a dull ache, but not acute, severe pain.
(Choice D) Epididymitis caused by infection (eg, Neisseria gonorrhoeae) or trauma causes acute scrotal pain that is relieved with manual elevation of the testicle. In contrast to this case, urinary symptoms (eg, dysuria, frequency, urgency) are typical, and a high-riding testicle would not be seen.
(Choice E) Hydrocele is a fluid collection within the tunica vaginalis that transilluminates on examination and causes scrotal enlargement but not acute pain.
Educational objective:
Testicular torsion presents with acute, severe, progressive unilateral scrotal pain. Classic examination findings include scrotal edema and discoloration, a high-riding testicle, and an absent cremasteric reflex (ie, absence of testicular elevation when stroking the ipsilateral thigh).
Answer E
This elderly man with new back pain, urinary symptoms, and osteoblastic lesions in the lumbar spine likely has prostate cancer with metastases to the bone. After regional lymph nodes, liver, and lungs, the skeletal system is the fourth most common site of metastases, which usually disseminate hematogenously. Cancers of the pelvis, including the prostate, spread to the lumbosacral spine via the vertebral venous plexus (VVP). The VVP communicates with a number of venous networks, including the prostatic venous plexus, which receives the venous supply from the prostate, penis, and bladder. It runs up the entire spinal column and connects with the venous supply of the brain via a valveless system, which allows for bidirectional flow and regulation of intracranial pressure. This venous connection to the cerebral circulation may help explain the propensity of tumors to metastasize to the brain.
(Choices A and F) The VVP also communicates with the azygos vein in the chest, which explains in part why breast and lung cancers frequently metastasize to the thoracic spine. Similarly, due to pulmonary venous drainage into the left side of the heart, lung tumors often spread systemically via the arterial system.
(Choices B and D) Although lymph nodes are the most common sites of metastasis in general, lymphatic spread to the skeletal system is very rare.
(Choice C) The pampiniform plexus receives venous drainage from the testis, epididymis, and ductus deferens and drains into the testicular veins.
Educational objective:
The skeletal system is a common site of metastasis due to hematogenous seeding. Cancers of the pelvis, including the prostate, spread to the lumbosacral spine via the vertebral venous plexus, which in turn communicates with a number of venous networks, including the prostatic venous plexus.
Answer B
This patient has priapism (persistently painful erection caused by engorgement of the corpora cavernosa), a frequent complication of sickle cell disease (SCD); with priapism, the corpus spongiosum often remains flaccid (soft glans penis), unlike a normal erection.
Normal penile erection and detumescence (ie, penile relaxation) occurs via the following mechanisms:
Flaccid state: A predominance of sympathetic input causes arterial and trabecular smooth muscle to be tonically contracted. This minimizes the volume of the cavernous tissue (sponge-like regions of erectile tissue) and limits blood flow into the vascular channels of the penis.
Erect state: Increased parasympathetic stimulation leads to a rise in nitric oxide and cyclic GMP production, causing smooth muscle relaxation. The resulting increase in penile blood flow fills the relaxed sinusoids, engorging the corpora cavernosa. Subsequent compression of the venous sinuses reduces venous outflow and helps maintain the erection.
Priapism most often occurs due to ongoing obstruction of the venous sinuses (low-flow priapism); the resulting impaired penile venous outflow prevents normal detumescence. Patients with SCD are at elevated risk due to increased sensitivity to vasodilators such as adenosine (released by ischemic tissue) that maintain corpora cavernosa engorgement. Persistent venous obstruction eventually results in penile ischemia (similar to compartment syndrome); blood gas analysis will show hypoxia, hypercarbia, and acidosis. Priapism is a medical emergency because events lasting more than 12 hours can result in permanent erectile dysfunction.
(Choice A) Fibrosis of the tunica albuginea occurs in Peyronie disease. The excessive fibrous scar tissue often causes painful erections and abnormal penile curvature. Persistent erection does not occur in this condition.
(Choices C and E) Parasympathetic activity stimulates erection, whereas sympathetic activity promotes detumescence. Impaired parasympathetic activity and/or increased sympathetic activity would result in a flaccid penis, not priapism.
(Choice D) Rarely, a pathologic increase in penile arterial inflow (eg, trauma, atrioventricular fistula) can cause high-flow (nonischemic) priapism characterized by aspiration of bright red blood with normal pH, oxygen, and carbon dioxide levels. However, this patient’s penial blood gas analysis is indicative of low-flow (ischemic) priapism, which occurs far more frequently than high-flow priapism (particularly in patients with SCD).
Educational objective:
Engorgement of the corpora cavernosa during erection compresses the venous sinuses, which reduces penile venous outflow to help maintain an erection. Priapism most often occurs due to persistent obstruction of the venous sinuses that prevents normal detumescence. Blood aspiration from the corpora cavernosa reveals penile ischemia due to the low-flow state.
Answer A
This patient has benign prostatic hyperplasia (BPH). BPH is due to the effects of dihydrotestosterone on prostatic epithelial cells and is characterized by progressive prostatic enlargement with age, leading to bladder outlet obstruction and incomplete bladder emptying. Typical symptoms include urinary frequency, nocturia, hesitancy, and weak urinary stream. The bladder outlet obstruction is made up of a dynamic component (smooth muscle tone in the bladder neck, prostate capsule, and prostatic urethra) and a fixed component (structural effects of the enlarged prostate).
Alpha adrenergic antagonists (eg, terazosin, tamsulosin) are smooth muscle relaxants that work on the dynamic component of bladder outlet obstruction. They work within days to weeks. However, these drugs do not significantly affect prostate volume (Choice D). 5-alpha reductase inhibitors (eg, finasteride, dutasteride) inhibit the conversion of testosterone to dihydrotestosterone and address the fixed component of bladder outlet obstruction. Over time, they reduce prostate volume but can take up to 6-12 months to achieve maximal effect.
(Choice B) Phenazopyridine is a urinary analgesic that provides symptomatic relief of dysuria in urinary tract infections. It is not effective for BPH and does not affect prostate volume.
(Choice C) Tadalafil is a phosphodiesterase-5 inhibitor that is primarily used to treat erectile dysfunction. Although some studies have shown symptom improvement in BPH, tadalafil does not significantly decrease prostate volume.
(Choice E) Antimuscarinics (eg, tolterodine) are used to treat overactive bladder symptoms (eg, urinary frequency, urgency, incontinence). They can cause urine retention and are normally used in BPH only once another drug has addressed the bladder outlet obstruction. They do not affect prostate volume.
Educational objective:
5-alpha reductase inhibitors (eg, finasteride, dutasteride) block the conversion of testosterone to dihydrotestosterone in the prostate. These drugs reduce prostate volume in patients with benign prostatic hyperplasia and relieve the fixed component of bladder outlet obstruction.
