Endocrine Abstracts

The McCune–Albright syndrome is a rare condition of variable severity that typically presents in childhood and is characterized by the triad of fibrous dysplasia (FDP), endocrinopathy and café-au-lait spots. The syndrome was independently described by Donovan McCune (1902–1976) and Fuller Albright (1900–1969) approximately 70 years ago and is now recognized to be the result of post-zygotic somatic constituently activating mutations of the alpha subunit of the stimulatory G protein. The activating nature of the mutations cause endocrine hyperfunction which, most commonly, manifests as gonadotrophin-independent precocious puberty (girls more frequently than boys), hyperthyroidism, GH hypersecretion causing gigantism and acromegaly, and Cushing’s syndrome, secondary autonomous adrenal hyperplasia.

Fibrous dysplasia can occur in any bone but most commonly affects the long bones, rib and skull and is a cause of much morbidity. The spectrum of associated problems varies from asymptomatic abnormalities detected on isotopic bone scans to disfiguring lesions, to pathological fractures or comprehension neuropathies, for example resulting in deafness or blindness.

Precocious puberty can present as early as infancy, with signs such as vaginal bleeding or breast development, and is difficult to control as it does not respond to GnRH agonists, although aromotase inhibitors have been shown to be of some benefit. Hyperthyroidism responds to the conventional treatment options. Surgical management of the associated pituitary problems can be complicated by FDP of the skull although acromegaly can be medically treated with somatostatin analogues and the GH receptor antagonist pegvisomant.

The combination of precocious puberty-related premature epiphyseal fusion, FDP and hypophosphatemic osteomalacia (due to decreased reabsorption of phosphate by the renal tubule) can result in short stature.