What is McCune-Albright Syndrome (MAS)?

MAS is a rare disorder characterized by the classic triad of fibrous dysplasia of bone, café-au-lait skin pigmentation, and precocious puberty. It is caused by a somatic (not inherited) mutation affecting multiple tissues.

Classic Triad:

• 1. Fibrous Dysplasia (FD): Abnormal bone development → bone pain, fractures, deformities; often affects skull, femur, tibia
• 2. Café-au-Lait Spots: Large, irregular brown skin patches with "coast of Maine" borders
• 3. Precocious Puberty (PP): Early sexual development (especially girls); due to autonomous ovarian cysts producing estrogen

Endocrine Manifestations (Various Glands Hyperfunction):

• Precocious Puberty (85% of girls, rare in boys): Menses, breast development before age 8
• Hyperthyroidism (20-40%): Nontoxic or toxic nodules
• Growth Hormone Excess (20%): Gigantism or acromegaly
• Cushing Syndrome (5-10%): Autonomous adrenal cortisol production
• Hypophosphatemia/Rickets: From FGF23 excess (fibrous dysplasia secretes FGF23)

Genetics:

• GNAS Gene Mutation (Somatic, Postzygotic): Not inherited; occurs early in development
• Mosaic Pattern: Only some cells affected → variable severity
• Not Passed to Offspring

Diagnosis:

• Clinical: Classic triad or 2 of 3 features
• Imaging: X-rays, bone scans show fibrous dysplasia
• Endocrine Testing: Based on symptoms (sex hormones, thyroid, GH/IGF-1, cortisol)
• Genetic Testing: Difficult (mosaic mutation; may need affected tissue biopsy)

Treatment:

• Precocious Puberty: Aromatase inhibitors (letrozole, anastrozole) or tamoxifen to block estrogen
• Fibrous Dysplasia: Bisphosphonates for bone pain; surgery for fractures/deformities
• Hyperthyroidism: Methimazole, surgery, or radioiodine
• GH Excess: Surgery (pituitary), somatostatin analogs
• Cushing's: Surgery (adrenalectomy)
• Hypophosphatemia: Phosphate supplements, calcitriol