A 6-year-old girl is evaluated in the pediatric endocrinology clinic for recent episodes o… — USMLE Step 2 CK

A $6$ -year-old girl is evaluated in the pediatric endocrinology clinic for recent episodes of vaginal spotting and bilateral breast enlargement. Her parents report an unusually rapid growth spurt over the last $8$ months. Her medical history is notable for a recent nondisplaced right femur fracture after a minor trip and fall, which was attributed to a localized lytic bone lesion on radiographs.

Physical examination shows Tanner stage $3$ breast development and Tanner stage $1$ pubic hair. A large, flat, hyperpigmented skin macule with irregular, jagged margins is present on her left lateral trunk. Bone age radiography reveals a skeletal age of $10$ years.

Laboratory evaluation:

Test	Patient Value	Normal Prepubertal Range
Serum estradiol	$145 \text{ pg/mL}$	$< 15 \text{ pg/mL}$
Basal luteinizing hormone (LH)	$0.1 \text{ mIU/mL}$	$< 0.3 \text{ mIU/mL}$
Basal follicle-stimulating hormone (FSH)	$0.2 \text{ mIU/mL}$	$< 0.3 \text{ mIU/mL}$
Peak LH (after GnRH stimulation)	$0.2 \text{ mIU/mL}$	$< 0.3 \text{ mIU/mL}$

Pelvic ultrasound reveals a $3.5\text{-cm}$ unilateral ovarian cyst.

Which of the following pharmacologic mechanisms is most appropriate to halt the progression of this patient's pubertal development?

A
Continuous stimulation of pituitary gonadotropin-releasing hormone receptors
B
Suppression of pituitary adrenocorticotropic hormone secretion
Inhibition of the enzyme aromataseCevap
D
Competitive antagonism at the androgen receptor
E
Inhibition of thyroid peroxidase and peripheral deiodination

Cevap

Inhibition of the enzyme aromatase

This patient presents with the classic triad of McCune-Albright syndrome: peripheral precocious puberty, polyostotic fibrous dysplasia (lytic bone lesion and fracture), and café-au-lait macules with irregular, "coast of Maine" borders. The syndrome is caused by a somatic activating mutation in the

GNAS

gene, leading to continuous G-protein receptor activation. In the ovaries, this results in autonomous estrogen production and cyst formation. Because the puberty is peripheral (gonadotropin-independent)—as evidenced by the high estradiol but suppressed, GnRH-unresponsive LH levels—central suppression with GnRH agonists is completely ineffective. Management requires peripheral blockade of estrogen synthesis or action. This is most commonly achieved using aromatase inhibitors (e.g., letrozole), which inhibit the conversion of androgens to estrogens, or selective estrogen receptor modulators/antagonists (e.g., tamoxifen, fulvestrant).

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Analyze the clinical triad

The patient has precocious puberty, a lytic bone lesion causing a fracture (polyostotic fibrous dysplasia), and a jagged hyperpigmented macule (café-au-lait spot).

Identifying these three findings confirms the diagnosis of McCune-Albright syndrome.

Interpret the laboratory and imaging findings

High estradiol with suppressed, non-responsive LH/FSH indicates peripheral (gonadotropin-independent) precocious puberty driven by the autonomous ovarian cyst.

Differentiating central from peripheral precocious puberty is required to select the correct therapeutic target.

Determine the appropriate pharmacologic intervention

Because the estrogen production is autonomous (independent of pituitary LH), central suppression will fail. The treatment must directly block estrogen synthesis or action.

Aromatase inhibitors (e.g., letrozole) prevent the conversion of androgens to estrogens in the ovary, halting the pubertal progression.

Anahtar Kavram

McCune-Albright syndrome causes peripheral precocious puberty via autonomous ovarian estrogen production, which must be treated with peripheral blockade (e.g., aromatase inhibitors) rather than central suppression (GnRH agonists).

Tahmini Süre:1m 45s

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