Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome

J Clin Endocrinol Metab. 2018 Nov 1;103(11):4293-4303. doi: 10.1210/jc.2018-01022.

Abstract

Context: McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic gain-of-function mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Somatic GNAS mutations have been reported in intraductal papillary mucinous neoplasms (IPMNs) and various gastrointestinal (GI) tumors. The clinical spectrum and prevalence of MAS-associated GI disease is not well established.

Objective: Define the spectrum and prevalence of MAS-associated GI pathology in a large cohort of patients with MAS.

Design: Cross-sectional study.

Setting: National Institutes of Health Clinical Center and The Johns Hopkins Hospital.

Methods: Fifty-four consecutive subjects with MAS (28 males; age range, 7 to 67 years) were screened with magnetic resonance cholangiopancreatography (MRCP).

Results: Thirty of 54 subjects (56%) had radiographic GI abnormalities. Twenty-five (46%) of the screened subjects had IPMNs (mean age of 35.1 years). Fourteen of the 25 had IPMNs alone, and 11 had IPMNs and abnormal hepatobiliary imaging. The 30 patients with MAS-associated GI pathology had a higher prevalence of acute pancreatitis, diabetes mellitus, and skeletal disease burden of fibrous dysplasia than patients without GI disease.

Conclusions: A broad spectrum of GI pathology is associated with MAS. IPMNs are common and occur at a younger age than in the general population. Patients with MAS should be considered for screening with a focused GI history and baseline MRCP. Further determination of the natural history and malignant potential of IPMNs in MAS is needed.

Trial registration: ClinicalTrials.gov NCT00001727.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Child
  • Cholangiopancreatography, Magnetic Resonance
  • Chromogranins / genetics
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus / epidemiology*
  • Diabetes Mellitus / genetics
  • Female
  • Fibrous Dysplasia, Polyostotic / complications*
  • Fibrous Dysplasia, Polyostotic / genetics
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • Gain of Function Mutation
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Intraductal Neoplasms / diagnostic imaging
  • Pancreatic Intraductal Neoplasms / epidemiology*
  • Pancreatic Intraductal Neoplasms / genetics
  • Pancreatitis / diagnostic imaging
  • Pancreatitis / epidemiology*
  • Pancreatitis / genetics
  • Prevalence
  • Rare Diseases / diagnostic imaging*
  • Rare Diseases / genetics
  • Young Adult

Substances

  • Chromogranins
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs

Associated data

  • ClinicalTrials.gov/NCT00001727