Which conditions are associated with McCune-Albright syndrome?

Updated: Jan 17, 2019
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Answer

Approximately 30 cases of FD associated with single or multiple intramuscular or juxtamuscular myxomas (Mazabraud syndrome) have been documented. [2, 3] This syndrome has been associated with precocious puberty and café-au-lait spots and occurs in association with MAS. The myxomas associated with this condition can occur in virtually any location in the muscular system. The exact etiopathogenesis of the syndrome is unclear, because no activating mutations of the GNAS1 gene have been demonstrated in this clinical variant.

Simple myxomas typically are benign and solitary, with peak incidence in the sixth and seventh decades. The age of peak incidence for this syndrome is young adulthood, and the tumors commonly are multiple. The main sites of involvement are the large muscles of the thighs, buttocks, and shoulders. They often are located close to FD lesions but typically remain separate from them. They commonly recur, even after attempts at surgical resection.

Hypophosphatemic rickets is a potential complication that may worsen the bone disease associated with PFD. It is due to a tubulopathy and characterized by hyperphosphaturia. In patients with MAS, hyperphosphaturia may be due to a phosphatonin similar to that seen in patients with tumor-induced osteomalacia, which appears to be fibroblast growth factor 23 (FGF-23). While MAS patients with hypophosphatemic rickets are typically managed with calcitriol and phosphorus supplements, they must be monitored closely for hypercalcemia, excessive hypercalciuria, nephrocalcinosis, and progressive loss of renal function, as well as the development of secondary hyperparathyroidism.

Hepatic abnormalities range from mild elevation of hepatic transaminases to severe neonatal jaundice and chronic cholestasis. Although some liver biopsies appear normal, others reveal mild biliary abnormalities or fatty liver. One case report described fatty liver in an infant with Cushing syndrome, suggesting that the fatty liver may have been secondary to glucocorticoid excess. Elevated transaminases in this infant, however, persisted long after the glucocorticoid excess had been corrected with adrenalectomy.

A study by Wood et al indicated that a wide range of gastrointestinal (GI) tract and pancreatic abnormalities occur in patients with MAS, with the investigators pointing out that GNAS mutations are not only responsible for MAS but are also found in association with several GI and pancreatic neoplasms. GI abnormalities in the study’s seven patients included gastric heterotopia/metaplasia, gastric hyperplastic polyps, fundic gland polyps, and a hamartomatous polyp, with endoscopic ultrasonographic findings in the pancreas suggesting the presence of intraductal papillary mucinous neoplasms (IPMNs). [20]

In a cross-sectional study of 54 patients with MAS, Robinson et al found radiographic GI abnormalities in 30 (56%) of them. IPMNs occurred in 25 (46%) patients, with 14 individuals having IPMNs alone and 11 also having abnormal hepatobiliary imaging. In addition, the investigators reported that, compared with the rest of the cohort, more fibrous dysplasia (as evaluated using skeletal burden scores), as well as a greater prevalence of acute pancreatitis and diabetes mellitus, was present in the patients with MAS-associated GI pathology. [21]

Many case reports describe sudden deaths, mostly occurring in patients with multiple endocrine and nonendocrine manifestations of MAS. Persistent tachycardia has been observed in addition to mild-to-moderate cardiomegaly, even in the absence of hyperthyroidism. Although the cause of death in these patients is unclear, it is presumed to be secondary to cardiac arrhythmia.


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