CENTRAL PRECOCIOUS PUBERTY , OR MCCUNE-ALBRIGHT SYNDROME, OR ?

QUESTION-Our daughter will be 7 in January and is ½ Asian, ½ Caucasian.  Her BMI is below average.  Recently (late September), she developed breast buds (T2).  Initially this was unilateral but they are now bilateral.  As per her pediatric and endocrinology examinations, she has no other signs of puberty.  She does have a very large/irregular café au lait spot.  Bone scan was completed and there is no evidence of fibrous dysplasia.  Bone age is 7.  CBC/CMP/TSH/IGF-1/IGFBP3 results are all within the normal range.  MRI of the brain with contrast and thin cuts through the pituitary has been ordered, but not completed as of yet.  A pelvic ultrasound and GnRHa stim test were completed with the results included below.  From my reading of the literature, her estradiol response is pubertal, but the LH peak is significantly below what would be found in most cases of CPP.  I would appreciate any input you could provide. Thanks, MDGnRH (Leuprolide) stimulation test:
24 hr    3 hr      2 hr      1 hr      0 hr

Estradiol (pg/mL)        80        18                                2

FSH (mIU/mL)             ND       14.12   10.64   7.65     0.99

LH (mIU/mL)               ND       1.26     1.62     1.29      <0.02
There is a prepubertal uterus appearance measuring 3.4 x 0.9 x 1.3 cm in size.  The endometrial stripe thickness is 0.2 cm.  There is slight free fluid in the cul-de-sac. The ovaries look normal by grayscale imaging as well as by color and spectral Doppler imaging including arterial and venous systems.  Small follicular cysts are seen at both ovaries. Right ovary measures 2.8 x 1.0 x 1.6 cm in size.  Left ovary measures 2.6 x 1.1 x 1.0 cm in size.  Urinary bladder looks normal.  Bowel gas obscures other areas of the pelvis. Scanning of the adrenal glands shows no abnormality sonographically.
Conclusion:  Prepubertal uterine appearance and pre/peripubertal ovarian appearances.
RESPONSE- I have read the information presented for your daughter and believe that she is having a very appropriate evaluation.  I am unable to diagnose or advise you without seeing her as a patient and evaluating her in person, but can give you my interpretation of the information you have presented.  I am very suspicious about her large irregular care au lait spot in the setting of her breast development and gonadotropin results that, after stimulation, appear prepubertal.  While the classic presentation of McCune Albright syndrome is with the triad of precocious puberty, bone fibrous dysplasia, and the presence of café au lait spot(s), the absence of the bone lesions does not rule out the presence of the G protein mutations in granulosa cells of some of her follicles.  These mutations are somatic cell mutations occurring in somatic tissue rather than germline.  They can occur in only follicles, skin, bone, or endocrine tissues or in combinations of these different tissues.  Gonadotropin dependent precocious puberty (i.e., originating in the hypothalamus as premature activation) is usually idiopathic but baseline LH levels should be higher than baseline FSH levels and with GnRH agonist stimulation there should be a higher response of LH than of FSH.  For that reason, my interpretation of the data is that this is not central precocity and may well be a form of McCune Albright syndrome.  Despite this, the MRI of her head will help rule out other central causes and is a good idea.  Richard H. Reindollar, M.D.