A 16-year-old girl comes to the office for a routine health maintenance examination. The patient is in high school, is performing well academically, and plays on the tennis team. She has no concerns today. The patient has not reached menarche, but she says that her mother did not start menstruating until this age. The patient recently started wearing contact lenses for myopia and uses an over-the-counter cream for acne. She is at the 70th percentile for height and 25th percentile for weight. Blood pressure is 120/70 mm Hg and pulse is 60/min. Breast development is sexual maturity rating (Tanner stage) 4. Pelvic examination shows sexual maturity rating (Tanner stage) 4 pubic hair development and normal external genitalia. Speculum examination demonstrates a well-rugated vagina but no cervix. FSH level is within the normal pubertal range. Karyotype is 46,XX. Pelvic ultrasonography reveals that the uterus is absent. Which of the following is the best next step in management of this patient?
Show Explanatory Sources
This patient has normal secondary sexual characteristics (eg, breasts, external genitalia), but the uterus and cervix are absent, findings consistent with müllerian agenesis (ie, Mayer-Rokitansky-Küster-Hauser syndrome), or abnormal paramesonephric (müllerian) duct development. The ovaries and external genitalia develop independently of the müllerian duct system; therefore, patients have normal FSH levels (ie, normal ovarian function), normal external genitalia, and the lower two-thirds of the vagina (ie, blind vaginal pouch).
In contrast, the internal genitalia derive from the intermediate mesoderm, which develops into the paramesonephric (müllerian) and mesonephric (wolffian) ducts.
Because of their common embryologic source and synchronous development in the first trimester, internal genital anomalies and renal abnormalities are often concurrent. Therefore, patients with müllerian agenesis should undergo evaluation of the renal tract (ie, ureters, kidney) with renal ultrasonography. Common abnormalities include unilateral renal agenesis, pelvic kidneys, and duplications of the collecting system.
(Choice A) Echocardiography is performed in patients with Turner syndrome to evaluate for cardiac malformations (eg, bicuspid aortic valve, aortic coarctation). This patient has a normal karyotype and FSH level (ie, normal ovarian function), making Turner syndrome unlikely.
(Choice B) Dihydrotestosterone and testosterone levels are measured to diagnose 5-alpha reductase deficiency and androgen insensitivity syndrome (AIS). In 5-alpha reductase deficiency, genotypic males (46,XY) appear phenotypically female until puberty; elevated testosterone levels at puberty then cause virilization (eg, clitoromegaly) and lack of breast development, which are not seen in this patient. In AIS, genotypic males appear phenotypically female through puberty and have breast development. In contrast to this patient, those with AIS have no or minimal acne or pubic hair development due to an abnormal androgen receptor.
(Choices C and D) TSH and prolactin levels are measured in patients with primary amenorrhea who have a uterus and a low or normal FSH. MRI of the head is indicated in patients with a low or normal FSH, high prolactin, or visual field defects to evaluate hypothalamic and pituitary causes (eg, sellar mass).
Educational objective:
Müllerian agenesis causes primary amenorrhea due to failed development of the uterus, cervix, and upper third of the vagina. Urogenital structures develop from a common embryologic source; therefore, renal malformations are common, so patients require evaluation with renal ultrasonography.