A 25-year-old Caucasian man is undergoing evaluation for azoospermia. The patient has been monogamous with his long-term girlfriend and does not use contraception during sexual intercourse. They have been trying to conceive for the past year with no success. The patient has a past medical history of recurrent pneumonia with frequent hospitalizations for antibiotic treatment. He takes no medications and does not use tobacco, alcohol, or illicit drugs. The patient has no allergies and his immunizations are up-to-date. His family history is unknown as he was adopted as an infant. Physical examination shows digital clubbing. A transrectal ultrasound shows bilateral absence of the vas deferens. Which of the following tests would most likely confirm the underlying diagnosis of this patient's condition?

Question

A 25-year-old Caucasian man is undergoing evaluation for azoospermia.  The patient has been monogamous with his long-term girlfriend and does not use contraception during sexual intercourse.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia with frequent hospitalizations for antibiotic treatment.  He takes no medications and does not use tobacco, alcohol, or illicit drugs.  The patient has no allergies and his immunizations are up-to-date.  His family history is unknown as he was adopted as an infant.  Physical examination shows digital clubbing.  A transrectal ultrasound shows bilateral absence of the vas deferens.  Which of the following tests would most likely confirm the underlying diagnosis of this patient's condition?

Quizplus · Accepted Answer

11ec160b_377e_c959_9249_b188795a94a9_MD0001_00 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. __________ References: Management of male infertility due to congenital bilateral absence of vas deferens should not ignore the diagnosis of cystic fibrosis. (http://www.ncbi.nlm.nih.gov/pubmed/22390181) CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/22081250)

A 25-Year-Old Caucasian Man Is Undergoing Evaluation for Azoospermia