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Endocr Relat Cancer. 2015 Oct;22(5):745-57. doi: 10.1530/ERC-15-0320. Epub 2015 Jul 17.

Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.

Author information

1
Departments of Endocrinology and Human GeneticsCentre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, BelgiumClinical Center of Endocrinology and GerontologyMedical University, Sofia, BulgariaDepartment of EndocrinologyKing Edward Memorial Hospital, Mumbai, IndiaAssistance Publique-Hôpitaux de ParisHôpitaux Universitaires Paris-Sud, Service d'Endocrinologie et des Maladies de la Reproduction et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Le Kremlin-Bicêtre F-94275, FranceUMR S1185Univ Paris-Sud, F-94276 Le Kremlin-Bicêtre, FranceINSERM U1185Faculté de Médecine Paris-Sud, F-94276 Le Kremlin-Bicêtre, FranceServicio de Endocrinología y NutriciónHospital Universitario La Paz, Madrid, SpainSection on Endocrinology and GeneticsProgram on Developmental Endocrinology & Genetics & Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), Bethesda, Maryland 20892, USADivision of EndocrinologyDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USADepartment of EndocrinologyGreenlane Clinical Centre, Auckland, New ZealandSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, The NetherlandsSection of Endocrinology and Internal MedicineDepartment of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, ItalyServicio de EndocrinologíaHospital Universitario Puerta De Hierro, Majadahonda, Madrid, SpainService d'endocrinologie-diabétologieCentre Hospitalier Lucien Hussel, Montée du Docteur Chapuis BP127, 38 209 Vienne cedex, FranceMurdoch Children's Research InstituteRoyal Children's Hospital, University of Melbourne, Parkville, Victoria, AustraliaDepartments of Internal Medicine and PediatricsOulu University Hospital, University of Oulu, Oulu, FinlandDepartments of Neuroen

Abstract

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases.

KEYWORDS:

X-linked acrogigantism (X-LAG) syndrome; aryl hydrocarbon receptor interacting protein gene; familial isolated pituitary adenoma (FIPA); gigantism; growth hormone; pituitary adenoma; somatotropinoma

PMID:
26187128
DOI:
10.1530/ERC-15-0320
[Indexed for MEDLINE]

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