title: Pituitary gigantism: update on molecular biology and management.
abstract: OBJECTIVE
  To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions.
  
  
  RESULTS
  Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging.
  
  
  CONCLUSIONS
  Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.
authors.affiliation: *Dr Maya B. Lodish and Dr Giampaolo Trivellin contributed equally to the writing of this article. Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Maya B
authors.initials: MB
authors.lastname: Lodish
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D005877:Gigantism / Q000235:genetics* / Q000628:therapy*; D006801:Humans