Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study

被引：269

作者：

Daly, Adrian F. ^{[1
]}

Tichomirowa, Maria A. ^{[1
]}

Petrossians, Patrick ^{[1
]}

Heliovaara, Elina ^{[3
,4
]}

Jaffrain-Rea, Marie-Lise ^{[5
,6
]}

Barlier, Anne ^{[7
]}

Naves, Luciana A. ^{[8
]}

Ebeling, Tapani ^{[9
]}

Karhu, Auli ^{[3
,4
]}

Raappana, Antti ^{[10
]}

Cazabat, Laure ^{[12
]}

De Menis, Ernesto ^{[13
]}

Fajardo Montanana, Carmen ^{[14
]}

Raverot, Gerald ^{[15
]}

Weil, Robert J. ^{[16
,17
]}

Sane, Timo ^{[18
]}

Maiter, Dominique ^{[19
]}

Neggers, Sebastian ^{[20
]}

Yaneva, Maria ^{[21
]}

Tabarin, Antoine ^{[22
]}

Verrua, Elisa ^{[23
]}

Eloranta, Eija ^{[9
]}

Murat, Arnaud ^{[24
]}

Vierimaa, Outi ^{[11
]}

Salmela, Pasi I. ^{[9
]}

Emy, Philippe ^{[25
]}

Toledo, Rodrigo A. ^{[26
]}

Isabel Sabate, Maria ^{[27
]}

Villa, Chiara ^{[28
,29
,31
]}

Popelier, Marc ^{[32
]}

Salvatori, Roberto ^{[33
]}

Jennings, Juliet ^{[34
,35
]}

Ferrandez Longas, Angel ^{[36
]}

Labarta Aizpun, Jose Ignacio ^{[36
]}

Georgitsi, Marianthi

Paschke, Ralf ^{[37
]}

Ronchi, Cristina ^{[23
]}

Valimaki, Matti ^{[18
]}

Saloranta, Carola ^{[18
]}

De Herder, Wouter ^{[20
]}

Cozzi, Renato ^{[38
]}

Guitelman, Mirtha

Magri, Flavia ^{[29
,31
]}

Lagonigro, Maria Stefania ^{[29
,30
]}

Halaby, Georges ^{[39
]}

Corman, Vinciane ^{[40
]}

Hagelstein, Marie-Therese ^{[2
]}

Vanbellinghen, Jean-Francois ^{[2
]}

Barra, Gustavo Barcelos ^{[41
]}

Gimenez-Roqueplo, Anne-Paule ^{[42
]}

机构：

[1] Univ Liege, CHU Liege, Dept Endocrinol, B-4000 Liege, Belgium

[2] Univ Liege, CHU Liege, Dept Mol Genet, B-4000 Liege, Belgium

[3] Univ Helsinki, Biomedicum Helsinki, Mol & Canc Biol Program, FI-00014 Helsinki, Finland

[4] Univ Helsinki, Biomedicum Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland

[5] Univ Aquila, Dept Expt Med, I-86077 Pozzilli, Italy

[6] Ist Ricovero & Cura Carattere Sci, I-86077 Pozzilli, Italy

[7] Univ Mediterranee, Lab Biochem & Mol Biol, CHU Concept,CNRS, Ctr Rech Neurobiol Neurophysiol Marseille,UMR 623, F-13385 Marseille, France

[8] Univ Brasilia, Div Endocrinol, BR-70910 Brasilia, DF, Brazil

[9] Univ Oulu, Dept Med, FIN-90029 Oys, Finland

[10] Univ Oulu, Dept Otorhinolaryngol, FIN-90029 Oys, Finland

[11] Univ Oulu, Dept Clin Genet, FIN-90029 Oys, Finland

[12] Univ Paris 05, INSERM, U567,Fac Med, Dept Endocrinol Metab & Canc,CNRS,UMR 8104,Inst C, Rene Descartes, France

[13] Osped Gen Montebelluna, I-131044 Montebelluna, Italy

[14] Hosp Univ Ribera, Dept Endocrinol, Valencia 46600, Spain

[15] CHU Lyon, Dept Endocrinol, F-69495 Lyon, France

[16] Cleveland Clin, Brain Tumor Inst, Cleveland, OH 44195 USA

[17] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44195 USA

[18] Univ Helsinki, Cent Hosp, Dept Endocrinol, Helsinki 00029, Finland

[19] Catholic Univ Louvain, Dept Endocrinol, St Luc Univ Hosp, B-1200 Brussels, Belgium

[20] Erasmus MC, Endocrinol Sect, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands

[21] Med Univ, Clin Ctr Endocrinol & Gerontol, Sofia 1431, Bulgaria

[22] CHU Bordeaux, Dept Endocrinol, Hop Haut Leveque, F-33600 Pessac, France

[23] Osped Maggiore Policlin Mangiagalli Regina Elena, Unit Endocrinol, Fdn Inst Ricovero & Cura Carattere Sci, I-20122 Milan, Italy

[24] CHU Nantes, Dept Endocrinol, F-44093 Nantes, France

[25] Ctr Hosp Reg, Dept Endocrinol, F-45032 Orleans, France

[26] Univ Sao Paulo, Unidade Endocrinol Genet, Lab Invest Med 25, Div Endocrinol,Hosp Clin,Fac Med, BR-05403900 Sao Paulo, Brazil

[27] Austral Univ Hosp, RA-1629 Buenos Aires, DF, Argentina

[28] Univ Paris 05, Dept Neuropathol & Neurosurg, CH St Anne, INSERM,U984, F-75014 Paris, France

[29] Univ Pavia, Unit Internal Med & Endocrinol, Fdn Salvatore Maugeri, Inst Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy

[30] Univ Pavia, Ist Super Prevenz & Sicurezza, Lavoro Lab Endocrine Disruptors, I-27100 Pavia, Italy

[31] Univ Pavia, Dept Endocrinol, I-27100 Pavia, Italy

[32] Ctr Hosp, Dept Endocrinol, Serv Med A, F-78514 Rambouillet, France

[33] Johns Hopkins Univ, Div Endocrinol, Sch Med, Baltimore, MD 21287 USA

[34] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Endocrinol & Diabet, Parkville, Vic 3052, Australia

[35] Royal Childrens Hosp, Murdoch Childrens Res Inst, Ctr Hormone Res, Parkville, Vic 3052, Australia

[36] Hosp Infantil Miguel Servet, Dept Pediat, Zaragoza 50009, Spain

[37] Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany

[38] Osped Niguarda Ca Granda, Div Endocrinol, I-20162 Milan, Italy

[39] Hop Hotel Dieu, Dept Endocrinol & Metab, Beirut 166830, Lebanon

[40] Ctr Hospitalier Reg Citadelle, Dept Endocrinol, B-4000 Liege, Belgium

[41] Lab Sabin, BR-8000 Brasilia, DF, Brazil

[42] Univ Paris 05, Dept Genet, Hop Europeen Georges Pompidou, AP HP,INSERM,U770, Paris, France

[43] Greenlane Clin Ctr, Dept Endocrinol, Auckland 1051, New Zealand

[44] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany

[45] Hop La Timone, Serv Endocrinol Diabet & Malad Metab, F-13385 Marseille, France

[46] Hop La Timone, Ctr Reference Malad Rares Origine Hypophysaires, F-13385 Marseille, France

[47] Hop Bicetre, AP HP, Dept Endocrinol & Reprod Dis, F-94276 Le Kremlin Bicetre, France

[48] Univ Paris 11, F-94276 Le Kremlin Bicetre, France

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2010年 / 95卷 / 11期

基金：

芬兰科学院;

关键词：

RECEPTOR-INTERACTING-PROTEIN; GENE; EXPRESSION; GIGANTISM; PREVALENCE; DEBULKING; FEATURES; TYPE-1; AHR;

D O I：

10.1210/jc.2009-2556

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. Design: This study was an international, multicenter, retrospective case collection/database analysis. Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. (J Clin Endocrinol Metab 95: E373-E383, 2010)

引用

页码：E373 / E383

页数：11

共 48 条

[1] The Pathogenesis of Pituitary Tumors
Asa, Sylvia L.
Ezzat, Shereen
[J]. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2009, 4 : 97 - 126
[2] Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas
Barlier, Anne
Vanbellinghen, Jean-Francois
Daly, Adrian F.
Silvy, Monique
Jaffrain-Rea, Marie-Lise
Trouillas, Jacqueline
Tamagno, Gianluca
Cazabat, Laure
Bours, Vincent
Brue, Thierry
Enjalbert, Alain
Beckers, Albert
[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (05) : 1952 - 1955
[3] The clinical, pathological, and genetic features of familial isolated pituitary adenomas
Beckers, Albert
Daly, Adrian F.
[J]. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2007, 157 (04) : 371 - 382
[4] Thyrotropin-secreting pituitary tumors
BeckPeccoz, P
BruckerDavis, F
Persani, L
Smallridge, RC
Weintraub, BD
[J]. ENDOCRINE REVIEWS, 1996, 17 (06) : 610 - 638
[5] Mutations in Regulatory Subunit Type 1A of Cyclic Adenosine 5′-Monophosphate-Dependent Protein Kinase (PRKAR1A): Phenotype Analysis in 353 Patients and 80 Different Genotypes
Bertherat, Jerome
Horvath, Anelia
Groussin, Lionel
Grabar, Sophie
Boikos, Sosipatros
Cazabat, Laure
Libe, Rosella
Rene-Corail, Fernande
Stergiopoulos, Sotirios
Bourdeau, Isabelle
Bei, Thalia
Clauser, Eric
Calender, Alain
Kirschner, Lawrence S.
Bertagna, Xavier
Carney, J. Aidan
Stratakis, Constantine A.
[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (06) : 2085 - 2091
[6] Carney complex: Pathology and molecular genetics
Boikos, Sosipatros A.
Stratakis, Constantine A.
[J]. NEUROENDOCRINOLOGY, 2006, 83 (3-4) : 189 - 199
[7] Surgical treatment of pituitary tumours
Buchfelder, Michael
Schlaffer, Sven
[J]. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 23 (05) : 677 - 692
[8] Mutations of the Gene for the Aryl Hydrocarbon Receptor-Interacting Protein in Pituitary Adenomas
Cazabat, Laure
Guillaud-Bataille, Marine
Bertherat, Jerome
Raffin-Sanson, Marie-Laure
[J]. HORMONE RESEARCH, 2009, 71 (03) : 132 - 141
[9] The epidemiology of prolactinomas
Ciccarelli A.
Daly A.F.
Beckers A.
[J]. Pituitary, 2005, 8 (1) : 3 - 6
[10] The prolactinoma
Colao, Annamaria
[J]. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 23 (05) : 575 - 596

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