If you’re preparing for the United States Medical Licensing Examination® (USMLE®) Step 1 exam, you might want to know which questions are most often missed by test-prep takers. Check out this example from Kaplan Medical, and read an expert explanation of the answer. Also check out all posts in this series.
A 23-year-old woman comes to the physician because she has never had a menstrual period. Physical examination shows absent pubic and axillary hair, small breasts and no palpable uterus. Karyotypic results show 46,XY. Surgical resection of gonadal structures is performed. Examination of tissue obtained shows seminiferous tubules with normal Leydig cells. A loss-of-function mutation of the androgen receptor (AR) gene is found.
Which of the following sets of laboratory findings in serum was most likely in this patient prior to surgery?
A. High testosterone; high LH.
B. High testosterone; low LH.
C. Low testosterone; high LH.
D. Low testosterone; low LH.
E. Normal testosterone; normal LH.
The correct answer is A.
DNA analysis shows that this patient is a genotypic male with an abnormality of the androgen receptor molecule; the patient has complete androgen insensitivity syndrome.
The androgen receptor molecule normally combines with testosterone inside the cell. The complex then binds with chromatin, resulting in the synthesis of messenger RNA. Because the target tissues contain defective androgen receptor protein, they are unable to respond to testosterone. Androgen insensitivity during the fetal period means that male sexual development is impaired and female external genitalia are formed.
Choice B: High testosterone and low luteinizing hormone (LH) would not be expected in androgen insensitivity syndrome. Cells of the pituitary and hypothalamus also contain the androgen receptor protein. Feedback suppression of LH secretion occurs when the molecular complex is present in the hypothalamus and pituitary.
Choice C: Testosterone is low and LH is high in primary hypogonadism due to defective gonadal steroid synthesis. The reduced testosterone results in feedback elevation of LH secretion by the pituitary.
Choice D: Low LH, resulting in depressed levels of testosterone secretion, is characteristic of a defect in hypothalamic or pituitary function (hypogonadotrophic hypogonadism).
Choice E: Because the androgen receptor in hypothalamic and pituitary tissue is also defective, normal testosterone suppression of pituitary gonadotropins, such as LH, is absent. As a result, serum levels of gonadotropins are elevated, resulting in increased production of testosterone by Leydig cells.
Testosterone and LH levels can help distinguish between different causes of abnormal sexual development:
- High testosterone and high LH: defective androgen receptor (androgen insensitivity syndrome).
- High testosterone and low LH: testosterone-secreting tumor.
- Low testosterone and high LH: primary hypogonadism.
- Low testosterone and low LH: hypogonadotrophic hypogonadism.
For more prep questions on USMLE Steps 1, 2 and 3, view other posts in this series.
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