Clinical Scenario:
A 6-year-old girl presents with recurrent episodes of painless vaginal bleeding and breast development. She has several café-au-lait macules with irregular “coast of Maine” borders that respect the midline. She has progressive enlargement of the left thigh, and radiographs demonstrate fibrous dysplasia of the femur. Laboratory evaluation during an episode of breast development shows markedly elevated estradiol with suppressed LH and FSH. Which of the following is the most likely diagnosis?
A. Congenital adrenal hyperplasia
B. McCune-Albright syndrome
C. Central precocious puberty
D. Ovarian granulosa cell tumor
E. Peutz-Jeghers syndrome
Correct answer & Explanation:
Answer: B. McCune-Albright syndrome
Discussion
The combination of fibrous dysplasia, café-au-lait pigmentation, and gonadotropin-independent precocious puberty is characteristic of McCune-Albright syndrome (MAS). MAS results from a postzygotic activating mutation of the GNAS gene, producing constitutive activation of the Gsα–cAMP signaling pathway. Because the mutation is mosaic, the clinical manifestations vary between individuals and genetic testing from peripheral blood may be negative.
In girls, the most common endocrinopathy is peripheral precocious puberty caused by autonomous ovarian activity, often associated with estrogen-producing ovarian cysts. This produces episodes of breast development and vaginal bleeding. During active episodes, estradiol may be markedly elevated while LH and FSH remain suppressed, reflecting the gonadotropin-independent nature of the process.
Central precocious puberty would be associated with activation of the hypothalamic-pituitary-gonadal axis and pubertal LH secretion. An ovarian granulosa cell tumor can produce estrogen and cause peripheral precocious puberty, but it does not explain the characteristic combination of fibrous dysplasia and café-au-lait pigmentation.
Congenital adrenal hyperplasia produces excess adrenal androgens rather than an estrogen-dominant picture with recurrent vaginal bleeding and breast development. Peutz-Jeghers syndrome can be associated with sex-cord tumors and mucocutaneous pigmentation but does not produce the classic MAS triad.
Key exam clue:
Fibrous dysplasia + café-au-lait macules + peripheral precocious puberty → McCune-Albright syndrome.
Mechanistic pearl:
In MAS, autonomous ovarian estrogen → high estradiol → suppression of hypothalamic/pituitary gonadotropins. Therefore, high estrogen with suppressed LH/FSH indicates peripheral precocious puberty, not central precocious puberty.
