title: McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients.
abstract: BACKGROUND
  Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation.
  
  
  OBJECTIVE
  This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly.
  
  
  METHODS
  Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features.
  
  
  RESULTS
  GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients receiving pegvisomant (10-20 mg/d).
  
  
  CONCLUSIONS
  RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, 78 rue du Général Leclercqq, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Galland
authors.forename: Peter
authors.initials: P
authors.lastname: Kamenicky
authors.forename: Hélène
authors.initials: H
authors.lastname: Affres
authors.forename: Yves
authors.initials: Y
authors.lastname: Reznik
authors.forename: Dominique
authors.initials: D
authors.lastname: Pontvert
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Bouc
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000172:Acromegaly / Q000150:complications* / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D003131:Combined Modality Therapy; D004351:Drug Resistance / Q000187:drug effects / Q000528:radiation effects; D005147:Facial Bones / Q000000981:diagnostic imaging; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications* / Q000188:drug therapy* / Q000532:radiotherapy*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007031:Hypothalamus / Q000528:radiation effects; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000528:radiation effects; D011859:Radiography; D012189:Retrospective Studies; D012886:Skull / Q000000981:diagnostic imaging; D013004:Somatostatin / Q000031:analogs & derivatives
chemical_list: D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant