A 15-year-old girl is brought to the office for a routine well child visit. The patient has been healthy, and her only concern is that she has not yet had a menstrual period. She wears corrective glasses for myopia. Her father's height is 180 cm (5 ft 11 in), and her mother's height is 170 cm (5 ft 7 in). On examination, the patient's height is below the 3rd percentile and weight is at the 40th percentile. BMI is 22.5 kg/m2. Blood pressure is 140/90 mm Hg in the right upper arm and 90/40 mm Hg in the lower extremities. The thyroid gland is not enlarged. Multiple pigmented nevi are scattered on the face and chest. She is Tanner stage 1 for pubic hair and breast development. Pelvic examination shows no abnormalities. There are no palpable masses. A urine pregnancy test is negative. If untreated, which of the following complications is this patient most at risk of developing?
Comorbidity screening in Turner syndrome | |
Cardiovascular |
|
Renal |
|
Musculoskeletal |
|
Vision & hearing |
|
Autoimmune |
|
*Aortic coarctation, bicuspid aortic valve. **High risk in pregnancy. BP = blood pressure; HbA1c = glycosylated hemoglobin; LFT = liver function test; | |
This patient has primary amenorrhea with short stature and signs of aortic coarctation (blood pressure differential), findings concerning for Turner syndrome (TS), or loss of an X chromosome (45,X karyotype). Other characteristic findings include scattered pigmented nevi (as seen in this patient), a webbed neck, and a broad chest.
Patients with TS typically have ovarian dysgenesis causing "streak ovaries" (fibrotic ovaries without follicles) and primary ovarian insufficiency. Lack of ovarian-produced estrogen leads to:
Pubertal delay: Minimal or no breast development—as seen in this 15-year-old patient who is Tanner stage 1—and amenorrhea.
Increased risk for osteoporotic fracture: Estrogen inhibits osteoclast-mediated bone resorption; therefore, patients with TS have increased bone resorption and decreased bone mineral density. Comorbid vitamin D deficiency can also contribute to fracture risk.
Increased risk for cardiovascular comorbidities: Because estrogen promotes vasodilation via nitric oxide production, patients with TS are predisposed to elevated vascular resistance and aortic stiffness. Hyperlipidemia is also associated with estrogen deficiency and increases the risk for hypertension and coronary artery disease.
Estrogen therapy is indicated to promote sexual maturation and reduce the risk for osteoporotic fractures and cardiovascular complications.
(Choice A) High, unopposed estrogen levels (as in polycystic ovarian syndrome) increase the risk for endometrial hyperplasia. This patient's lack of breast development is inconsistent with elevated estrogen, and low estrogen levels in TS are likely protective against endometrial hyperplasia.
(Choice B) TS increases the risk for certain neurocognitive impairments, such as social difficulties, specific learning disabilities, or attention deficit hyperactivity disorder. However, most patients with TS have normal intelligence.
(Choice C) Mitral valve prolapse is common in connective tissue disorders (eg, Marfan syndrome), which are often associated with tall stature and do not cause menstrual abnormalities. Common cardiac comorbidities in TS include bicuspid aortic valve, coarctation of the aorta, and aortic dilation/dissection.
(Choice E) Visual field defects (eg, bitemporal hemianopsia) can occur when a prolactinoma compresses the optic chiasm. Excess prolactin causes galactorrhea and suppresses GnRH, resulting in amenorrhea; however, a prolactinoma would not explain this patient's short stature and blood pressure differential. In addition, although refractive errors (eg, myopia) and strabismus are common in TS, visual field defects are not.
Educational objective:
Short stature, amenorrhea, and aortic coarctation are features of Turner syndrome. Patients are at increased risk for osteoporotic fracture due to estrogen deficiency from ovarian dysgenesis.