Overview
What are features of McCune-Albright syndrome (MAS)?
What are the manifestations of McCune-Albright syndrome (MAS)?
Which lab tests are performed in the workup of McCune-Albright syndrome (MAS)?
Which imaging studies are performed in the workup of McCune-Albright syndrome (MAS)?
Which studies may be considered in the workup of McCune-Albright syndrome (MAS)?
How is precocious puberty treated in McCune-Albright syndrome (MAS)?
How is polyostotic fibrous dysplasia (PFD) treated in McCune-Albright syndrome (MAS)?
How is hyperthyroidism treated in McCune-Albright syndrome (MAS)?
How are endocrine abnormalities treated in McCune-Albright syndrome (MAS)?
What is the role of surgery in the treatment of McCune-Albright syndrome (MAS)?
What is McCune-Albright syndrome (MAS)?
Which endocrine syndromes are associated with McCune-Albright syndrome (MAS)?
What is the role of genetics in the etiology of McCune-Albright syndrome?
How is McCune-Albright syndrome diagnosed?
Which specialist consultation is beneficial to patients with McCune-Albright syndrome?
What is the pathophysiology of McCune-Albright syndrome (MAS)?
Which conditions are associated with McCune-Albright syndrome?
Which malignancies are associated with McCune-Albright syndrome?
What causes McCune-Albright syndrome (MAS)?
What causes the classic triad of features in McCune-Albright syndrome?
What is the prevalence of McCune-Albright syndrome (MAS)?
At what age is McCune-Albright syndrome (MAS) typically diagnosed?
At are the sexual and racial predilections of McCune-Albright syndrome (MAS)?
What is the prognosis of McCune-Albright syndrome (MAS)?
What is included in patient education about McCune-Albright syndrome (MAS)?
Presentation
What is the focus of clinical history in the evaluation of McCune-Albright syndrome (MAS)?
Which clinical history findings are characteristic of McCune-Albright syndrome (MAS)?
Which physical findings are characteristic of McCune-Albright syndrome (MAS)?
Which physical findings are characteristic of precocious puberty in McCune-Albright syndrome (MAS)?
Which physical findings are characteristic of endocrine disorders in McCune-Albright syndrome (MAS)?
What are the possible complications of precocious puberty in McCune-Albright syndrome (MAS)?
What are the possible complications of endocrine disorders in McCune-Albright syndrome (MAS)?
What are the possible cardiac complications of McCune-Albright syndrome (MAS)?
DDX
Why should McCune-Albright syndrome (MAS) be considered in patients with recurrent fractures?
Which conditions are included in the differential diagnoses of McCune-Albright syndrome (MAS)?
What are the differential diagnoses for McCune-Albright Syndrome?
Workup
What are the initial studies in the workup of McCune-Albright syndrome (MAS)?
What is the role of hormone measurement in the diagnosis of McCune-Albright syndrome?
What is the role of blood and urinary chemistries in the diagnosis of McCune-Albright syndrome?
What is the role of thyroid testing in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of ACTH measurement in the diagnosis of McCune-Albright Syndrome?
What is the role of serum growth hormone testing in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of plain radiography in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of ultrasonography in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of CT scanning in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of MRI in the diagnosis of McCune-Albright syndrome (MAS)?
What is the role of bone scanning in the workup of McCune-Albright syndrome (MAS)?
What is the role of bone biopsy in the diagnosis of McCune-Albright syndrome (MAS)?
Which histologic findings are characteristic of McCune-Albright syndrome (MAS)?
Treatment
How is McCune-Albright syndrome (MAS) treated?
What is the role of surgery in the treatment of hyperthyroidism in McCune-Albright syndrome (MAS)?
Which dietary modifications are used in the treatment of McCune-Albright syndrome (MAS)?
Which specialist consultations are beneficial to patients with McCune-Albright syndrome (MAS)?
What is included in the long-term monitoring of patients with McCune-Albright syndrome (MAS)?
What is included in the long-term monitoring of hyperthyroidism in McCune-Albright syndrome (MAS)?
Medications
What is the role of medications in the treatment of McCune-Albright syndrome (MAS)?
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Base of the skull computed tomography scan showing extensive fibrous dysplasia in McCune-Albright syndrome. Note the asymmetrical affectation, with near-total obliteration of various neural foramina at the base of the skull. This degree of fibrous dysplasia can result in multiple cranial nerve compression neuropathies, of which blindness and deafness (from involvement of cranial nerves II and VIII) are among the most disabling.
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Café au lait spot. This is a fairly large, irregular-edged ("coast-of-Maine" variety) lesion. It presents as a brownish, otherwise-asymptomatic macule/patch. The degree of pigmentation is fairly uniform.
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Fibrous dysplasia of a long bone characterized by focal bony expansion, patchy areas of sclerosis, and bony cyst formation in McCune-Albright syndrome.
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Plain skull radiograph in a typical McCune-Albright syndrome case shows marked macrocrania, frontal bossing, and markedly thickened bony table in patchy areas, particularly at base of skull and occiput. Skull also shows hair-on-end appearance, which needs to be differentiated from similar radiologic appearances in Paget disease or poorly controlled hemoglobinopathy (eg, beta-thalassemia, sickle cell disease).
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Large café-au-lait patches around shoulder in child with McCune-Albright syndrome.
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Lucency characteristic of polyostotic fibrous dysplasia in patient with McCune-Albright syndrome.
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McCune-Albright syndrome case showing café-au-lait pigmentation. Lesion does not cross midline, which is typical of pigmented lesions in this syndrome.
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Adrenal hyperplasia with nodular elements in adrenal gland isolated from infant with infantile Cushing syndrome in the context of McCune-Albright syndrome. DNA isolated from nodular tissue was determined to have activating Gs alpha mutation (GNAS1), whereas DNA isolated from surrounding tissue did not contain this mutation.
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The G protein cycle begins with ligand binding to a 7-transmembrane domain G protein-coupled receptor (GPCR). Binding of the cognate ligand forms a ligand-receptor complex, which then stimulates an exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the alpha subunit of the stimulatory G protein (Gs alpha). This activates the alpha subunit, which subsequently stimulates adenylyl cyclase (AC) to increase production of cyclic adenosine monophosphate (cAMP). The alpha subunit contains intrinsic guanosine triphosphatase (GTPase) activity, which cleaves a phosphate group from GTP, converting it to GDP, and thus inactivates the alpha subunit. The inactivated alpha subunit is now ready to be reactivated by ligand-receptor binding, so that the next cycle of signal transduction can occur.
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Mutations in McCune-Albright syndrome inactivate intrinsic guanosine triphosphatase (GTPase) activity, thus preventing inactivation of the "turned-on" Gs alpha subunit. Once activated, the mutated Gs alpha subunit is able to continuously stimulate adenylyl cyclase, even in absence of ligand binding to its cognate GPCR receptor. The result is elevation of intracellular cyclic adenosine monophosphate (cAMP) and continual stimulation of downstream cAMP signaling cascades.
