What is the management approach for McCune-Albright syndrome?

Management of McCune-Albright Syndrome

McCune-Albright syndrome (MAS) requires a multidisciplinary management approach with treatment tailored to the specific manifestations present, focusing on bisphosphonates for fibrous dysplasia, appropriate endocrine therapies for associated endocrinopathies, and surgical intervention only for specific complications or significant deformities.

Overview and Diagnosis

McCune-Albright syndrome is a rare genetic disorder (prevalence between 1/100,000 and 1/1,000) characterized by the clinical triad of:

• Fibrous dysplasia of bone (FD)
• Café-au-lait skin spots
• Precocious puberty

The diagnosis is established when at least two of these manifestations are present 1. MAS results from somatic activating mutations in the GNAS gene that occur during early embryonic development 1, 2.

Comprehensive Management Approach

Fibrous Dysplasia Management

• First-line treatment: Bisphosphonates are recommended as the first-line medical treatment for symptomatic fibrous dysplasia 3

  • Benefits include pain reduction, improved cortical thickness, and decreased risk of pathological fractures
  • Regular monitoring with radiological evaluation every 6-12 months is necessary

• Surgical interventions should be reserved for:

  • Circumscribed symptomatic lesions: curettage, cryotherapy, and bone grafting
  • Extensive lesions with deformity: corrective osteotomies, rigid internal fixation
  • Pathological fractures or impending fractures
  • Progressive scoliosis
  • Cranial base lesions with neurological compromise 3

• Physical therapy: Strengthening exercises are recommended to maintain musculature around affected bones and minimize fracture risk 1

Endocrine Manifestations Management

1. Precocious puberty:

   • Girls: Aromatase inhibitors or selective estrogen receptor modulators
   • Boys: Testosterone synthesis inhibitors or androgen receptor blockers 4

2. Growth hormone excess:

   • Surgical approach for pituitary adenomas when present
   • Medical therapy with somatostatin analogs or GH receptor antagonist (pegvisomant) 4
   • Pegvisomant can effectively normalize IGF-1 levels and suppress growth velocity 4

3. Hyperthyroidism:

   • Antithyroid medications
   • Radioactive iodine or surgery for definitive treatment in selected cases

4. Cushing syndrome:

   • Adrenal enzyme inhibitors
   • Surgical intervention when indicated

5. Renal phosphate wasting:

   • Phosphate supplements
   • Vitamin D analogs

Special Considerations

• Avoid radiation therapy in patients with MAS due to increased risk of sarcomatous transformation 3

• Skull base fibrous dysplasia: Requires careful monitoring and potential surgical intervention if there is compression of neural structures 3

• Regular monitoring: More frequent follow-up for patients with active or symptomatic disease 3

Multidisciplinary Care Pathway

Evidence shows that a multidisciplinary care pathway significantly improves quality of life and reduces pain in patients with FD/MAS 5. The team should include:

• Endocrinologist
• Orthopedic surgeon
• Neurosurgeon (for craniofacial involvement)
• Radiologist
• Pain management specialist
• Physical therapist
• Genetic counselor

Prognosis and Follow-up

• Long-term follow-up is essential due to the risk of progression, recurrence, or malignant transformation (though malignant transformation occurs in less than 1% of cases) 1

• Regular clinical and radiological evaluation every 6-12 months is recommended, with more frequent monitoring for patients with active or symptomatic disease 3

• Quality of life assessment should be incorporated into routine follow-up, as all FD subtypes may induce pain and reduced quality of life 5

Conclusion

Management of McCune-Albright syndrome should focus on controlling symptoms, preventing complications, and improving quality of life. Early referral to specialized centers with multidisciplinary expertise in MAS is strongly recommended, as this approach has been shown to improve outcomes even in patients with limited disease extent 5.