Patients may have one or many of these features, which may occur in any combination. As such, the clinical presentation of patients with McCune Albright syndrome varies greatly depending on the disease features. Various endocrine diseases may present in McCune–Albright syndrome due to increased hormone production.
Precocious puberty: The most common endocrinopathy is precocious puberty, which presents in girls with recurrent estrogen-producing cysts leading to episodic breast development, growth acceleration, and vaginal bleeding. Precocious puberty may also occur in boys with McCune–Albright syndrome, but is much less common.
Testicular abnormalities: Testicular abnormalities are seen in a majority of boys with McCune–Albright syndrome.
Hyperthyroidism: Hyperthyroidism occurs in approximately one-third of patients with McCune Albright syndrome. Many others may suffer from other kinds of thyroid involvement.
Growth Hormone Excess: GNAS mutation in the anterior pituitary can result in excess growth hormone secretion and is found in approximately 10–15% of patients.
Cushing's Syndrome: In McCune–Albright syndrome, Cushing's syndrome is a very rare feature that develops only in infancy.
Genetics
Genetically, there is a spontaneous postzygotic mutation of the gene GNAS, on the long arm of chromosome 20 at position 13.3, which is involved in G-protein signaling. This mutation, which occurs only in the mosaic state, leads to constitutive receptor signaling and inappropriate production of excess cAMP. The mutation that causes McCune–Albright syndrome arises very early during embryogenesis. Because all cases of the syndrome are sporadic, it is believed that the mutation would be lethal if it affected all cells in the embryo. Mutant cells can only survive when they are intermixed with normal cells. There are no known risk factors for acquiring McCune–Albright syndrome, and no exposures during pregnancy that are known to either cause or prevent the mutation from occurring. The disease cannot be inherited and occurs equally among all ethnic groups.
Diagnosis
McCune–Albright syndrome has different levels of severity. For example, one child with McCune–Albright syndrome may be entirely healthy, with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age, and have no unusual skin pigmentation. Diagnosis may be made only after decades. In other cases, children are diagnosed in early infancy, show obvious bone disease, and obvious increased endocrine secretions from several glands.
Skeletal abnormalities
Patients with fibrous dysplasia may have bone fractures, pain, and deformities. Patients may also develop low blood phosphate levels due to overproduction of the protein fibroblast growth factor 23. CT scan of the skull is the most useful test for craniofacial fibrous dysplasia. Regular hearing and vision screening is recommended. X-rays are usually sufficient to reveal fibrous dysplasia of the appendicular skeleton, but CT and/or MRI scans can reveal microfractures. Regular screening for scoliosis should also be undertaken.
Endocrine abnormalities
is more common in females, but may occur in males as well. Drugs such as letrozole and anastrozole can be used to prevent short stature in both males and females. In males, drugs such as spironolactone and flutamide can be used to treat the behavioral issues associated with androgen excess. Males with McCune–Albright syndrome may present with benign testicular tumors, though testicular cancer appears to be rare. Annual ultrasounds of testicular masses should be performed to screen for cancer. Hyperthyroidism is found in about 38% of patients. Medications such as thioamides are useful in treating these symptoms. However, as thyroid symptoms in this disorder almost never resolve spontaneously, surgery or radiation are more definitive treatments. Annual thyroid ultrasounds should be performed to screen for thyroid cancer. Hyperparathyroidism secondary to Vitamin D deficiency is common, and may worsen fibrous dysplasia. Levels of calcium and parathyroid hormone should be periodically assessed.
Treatment
Treatment is dictated by both the tissues affected and the extent to which they are affected.
Skeletal abnormalities
Surgical management of skeletal abnormalities has evolved over the years. Surgical intervention may be necessary for some skeletal abnormalities. Bisphosphonates are helpful in relieving bone pain, but it is no longer believed that they prevent progression of the disease. Denosumab has been found successful in reducing bone pain and decreasing tumor growth. Muscle strengthening exercises are important for preventing bone fractures; cycling and swimming are recommended in order to reduce the risk of fracture during exercise.
Endocrine abnormalities
In one study, 18% of McCune–Albright patients had hypophosphatemia due to kidney involvement. High doses of oral phosphate and calcitriol should be given for treatment. Pituitary hormone abnormalities may occur. Growth hormone excess may worsen craniofacial dysplasia; treatment with somatostatin analogues or pegvisomant may be effective. Surgery may be an option, but may be complicated by the cranial abnormalities associated with the disorder. Excessive prolactin secretion may also occur; this is treated with dopamine agonists such as cabergoline. Cushing syndrome is a rare but potentially fatal complication that can occur in the first year of life. Adrenalectomy is the treatment of choice. Metyrapone may also be used for treatment.
Epidemiology
McCune–Albright syndrome is estimated to occur at a frequency between 1 person in 100,000 to 1 person in 1,000,000 individuals worldwide.
Notable cases
Lauren Ruotolo is an author and involved in advocacy for McCune–Albright syndrome.
Mauricio Saravia was an artist and graphic designer with severe McCune–Albright syndrome.
