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

Liliya Rostomyan, Adrian F. Daly, Patrick Petrossians, Emil Nachev, Anurag R. Lila, Anne Lise Lecoq, Beatriz Lecumberri, Giampaolo Trivellin, Roberto Salvatori, Andreas G. Moraitis, Ian Holdaway, Dianne J. Kranenburg-Van Klaveren, Maria Chiara Zatelli, Nuria Palacios, Cecile Nozieres, Margaret Zacharin, Tapani Ebeling, Marja Ojaniemi, Liudmila Rozhinskaya, Elisa VerruaMarie Lise Jaffrain-Rea, Silvia Filipponi, Daria Gusakova, Vyacheslav Pronin, Jerome Bertherat, Zhanna Belaya, Irena Ilovayskaya, Mona Sahnoun-Fathallah, Caroline Sievers, Gunter K. Stalla, Emilie Castermans, Jean Hubert Caberg, Ekaterina Sorkina, Renata Simona Auriemma, Sachin Mittal, Maria Kareva, Philippe A. Lysy, Philippe Emy, Ernesto De Menis, Catherine S. Choong, Giovanna Mantovani, Vincent Bours, Wouter De Herder, Thierry Brue, Anne Barlier, Sebastian J.C.M.M. Neggers, Sabina Zacharieva, Philippe Chanson, Nalini Samir Shah, Constantine A. Stratakis, Luciana A. Naves, Albert Beckers

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)745-757
Number of pages13
JournalEndocrine-related cancer
Volume22
Issue number5
DOIs
StatePublished - Oct 1 2015

Keywords

  • Aryl hydrocarbon receptor interacting protein gene
  • Familial isolated pituitary adenoma (FIPA)
  • Gigantism
  • Growth hormone
  • Pituitary adenoma
  • Somatotropinoma
  • X-linked acrogigantism (X-LAG) syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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