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 Verrua & 32 others Marie 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 journalArticle

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

Fingerprint

Gigantism
Growth Disorders
Neoplasms
Mutation
Pituitary Neoplasms
Growth
Adenoma
Multicenter Studies

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
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Rostomyan, L., Daly, A. F., Petrossians, P., Nachev, E., Lila, A. R., Lecoq, A. L., ... Beckers, A. (2015). Clinical and genetic characterization of pituitary gigantism: An international collaborative study in 208 patients. Endocrine-Related Cancer, 22(5), 745-757. https://doi.org/10.1530/ERC-15-0320

Clinical and genetic characterization of pituitary gigantism : An international collaborative study in 208 patients. / Rostomyan, Liliya; Daly, Adrian F.; Petrossians, Patrick; Nachev, Emil; Lila, Anurag R.; Lecoq, Anne Lise; Lecumberri, Beatriz; Trivellin, Giampaolo; Salvatori, Roberto; Moraitis, Andreas G.; Holdaway, Ian; Kranenburg-Van Klaveren, Dianne J.; Zatelli, Maria Chiara; Palacios, Nuria; Nozieres, Cecile; Zacharin, Margaret; Ebeling, Tapani; Ojaniemi, Marja; Rozhinskaya, Liudmila; Verrua, Elisa; Jaffrain-Rea, Marie Lise; Filipponi, Silvia; Gusakova, Daria; Pronin, Vyacheslav; Bertherat, Jerome; Belaya, Zhanna; Ilovayskaya, Irena; Sahnoun-Fathallah, Mona; Sievers, Caroline; Stalla, Gunter K.; Castermans, Emilie; Caberg, Jean Hubert; Sorkina, Ekaterina; Auriemma, Renata Simona; Mittal, Sachin; Kareva, Maria; Lysy, Philippe A.; Emy, Philippe; De Menis, Ernesto; Choong, Catherine S.; Mantovani, Giovanna; Bours, Vincent; De Herder, Wouter; Brue, Thierry; Barlier, Anne; Neggers, Sebastian J C M M; Zacharieva, Sabina; Chanson, Philippe; Shah, Nalini Samir; Stratakis, Constantine A.; Naves, Luciana A.; Beckers, Albert.

In: Endocrine-Related Cancer, Vol. 22, No. 5, 01.10.2015, p. 745-757.

Research output: Contribution to journalArticle

Rostomyan, L, Daly, AF, Petrossians, P, Nachev, E, Lila, AR, Lecoq, AL, Lecumberri, B, Trivellin, G, Salvatori, R, Moraitis, AG, Holdaway, I, Kranenburg-Van Klaveren, DJ, Zatelli, MC, Palacios, N, Nozieres, C, Zacharin, M, Ebeling, T, Ojaniemi, M, Rozhinskaya, L, Verrua, E, Jaffrain-Rea, ML, Filipponi, S, Gusakova, D, Pronin, V, Bertherat, J, Belaya, Z, Ilovayskaya, I, Sahnoun-Fathallah, M, Sievers, C, Stalla, GK, Castermans, E, Caberg, JH, Sorkina, E, Auriemma, RS, Mittal, S, Kareva, M, Lysy, PA, Emy, P, De Menis, E, Choong, CS, Mantovani, G, Bours, V, De Herder, W, Brue, T, Barlier, A, Neggers, SJCMM, Zacharieva, S, Chanson, P, Shah, NS, Stratakis, CA, Naves, LA & Beckers, A 2015, 'Clinical and genetic characterization of pituitary gigantism: An international collaborative study in 208 patients', Endocrine-Related Cancer, vol. 22, no. 5, pp. 745-757. https://doi.org/10.1530/ERC-15-0320
Rostomyan, Liliya ; Daly, Adrian F. ; Petrossians, Patrick ; Nachev, Emil ; Lila, Anurag R. ; Lecoq, Anne Lise ; Lecumberri, Beatriz ; Trivellin, Giampaolo ; Salvatori, Roberto ; Moraitis, Andreas G. ; Holdaway, Ian ; Kranenburg-Van Klaveren, Dianne J. ; Zatelli, Maria Chiara ; Palacios, Nuria ; Nozieres, Cecile ; Zacharin, Margaret ; Ebeling, Tapani ; Ojaniemi, Marja ; Rozhinskaya, Liudmila ; Verrua, Elisa ; Jaffrain-Rea, Marie Lise ; Filipponi, Silvia ; Gusakova, Daria ; Pronin, Vyacheslav ; Bertherat, Jerome ; Belaya, Zhanna ; Ilovayskaya, Irena ; Sahnoun-Fathallah, Mona ; Sievers, Caroline ; Stalla, Gunter K. ; Castermans, Emilie ; Caberg, Jean Hubert ; Sorkina, Ekaterina ; Auriemma, Renata Simona ; Mittal, Sachin ; Kareva, Maria ; Lysy, Philippe A. ; Emy, Philippe ; De Menis, Ernesto ; Choong, Catherine S. ; Mantovani, Giovanna ; Bours, Vincent ; De Herder, Wouter ; Brue, Thierry ; Barlier, Anne ; Neggers, Sebastian J C M M ; Zacharieva, Sabina ; Chanson, Philippe ; Shah, Nalini Samir ; Stratakis, Constantine A. ; Naves, Luciana A. ; Beckers, Albert. / Clinical and genetic characterization of pituitary gigantism : An international collaborative study in 208 patients. In: Endocrine-Related Cancer. 2015 ; Vol. 22, No. 5. pp. 745-757.
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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.",
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T2 - An international collaborative study in 208 patients

AU - Rostomyan, Liliya

AU - Daly, Adrian F.

AU - Petrossians, Patrick

AU - Nachev, Emil

AU - Lila, Anurag R.

AU - Lecoq, Anne Lise

AU - Lecumberri, Beatriz

AU - Trivellin, Giampaolo

AU - Salvatori, Roberto

AU - Moraitis, Andreas G.

AU - Holdaway, Ian

AU - Kranenburg-Van Klaveren, Dianne J.

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AU - Palacios, Nuria

AU - Nozieres, Cecile

AU - Zacharin, Margaret

AU - Ebeling, Tapani

AU - Ojaniemi, Marja

AU - Rozhinskaya, Liudmila

AU - Verrua, Elisa

AU - Jaffrain-Rea, Marie Lise

AU - Filipponi, Silvia

AU - Gusakova, Daria

AU - Pronin, Vyacheslav

AU - Bertherat, Jerome

AU - Belaya, Zhanna

AU - Ilovayskaya, Irena

AU - Sahnoun-Fathallah, Mona

AU - Sievers, Caroline

AU - Stalla, Gunter K.

AU - Castermans, Emilie

AU - Caberg, Jean Hubert

AU - Sorkina, Ekaterina

AU - Auriemma, Renata Simona

AU - Mittal, Sachin

AU - Kareva, Maria

AU - Lysy, Philippe A.

AU - Emy, Philippe

AU - De Menis, Ernesto

AU - Choong, Catherine S.

AU - Mantovani, Giovanna

AU - Bours, Vincent

AU - De Herder, Wouter

AU - Brue, Thierry

AU - Barlier, Anne

AU - Neggers, Sebastian J C M M

AU - Zacharieva, Sabina

AU - Chanson, Philippe

AU - Shah, Nalini Samir

AU - Stratakis, Constantine A.

AU - Naves, Luciana A.

AU - Beckers, Albert

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

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KW - Familial isolated pituitary adenoma (FIPA)

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KW - Somatotropinoma

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