Familial acromegaly

被引:26
作者
Frohman, LA
Eguchi, K
机构
[1] Univ Illinois, Endocrinol Sect, Dept Med, Chicago, IL 60612 USA
[2] Hiroshima Univ, Dept Neurosurg, Hiroshima, Japan
关键词
familial acromegaly; isolated familial somatotropinomas; Carney complex; MEN-1; syndrome; endocrine neoplasia; somatotropinoma;
D O I
10.1016/j.ghir.2004.03.021
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Most pituitary tumors are sporadic, though a few occur with a familial aggregation. Three distinct syndromes have been recognized to date: multiple endocrine neoplasia, type I (MEN-1), Carney complex (CNC), and isolated familial somatotropinomas (IFS). Pituitary tumor types in MEN-1 are similar to those occurring sporadically. The largest percentage are prolactin-secreting or non-functioning and only about 10% are growth hormone (GH)-secreting (somatotropinomas). In contrast, tumors types in CNC and IFS are invariably somatotropinomas, though there are differences in both clinical and histological features. Each of the familial syndromes is associated with a tumor-suppressor gene that was initially recognized by an observed loss of heterozygosity on chromosome 11q13 in MEN-1 and IFS and on chromosome 17q in CNC. The MEN-1 gene, which codes for the nuclear protein, menin, has been identified and a large number of inactivating mutations have been recognized. The gene associated with CNC codes for the protein kinase A regulatory subunit 1, inactivation of which leads to enhanced activity of the GH-releasing hormone-induced signal transduction pathway. This pathway exerts proliferative effects in somatotropes. The gene associated with IFS is distinct from the MEN-1 gene, though it is located in close proximity, and is contained in a candidate region of similar to10 Mb. Identification of the IFS gene should provide new insight into the pathogenesis of somatotropinomas, not only in IFS but also in sporadic tumors, where there is an up to 40% allelic loss on chromosome 11q 13. (C) 2004 Published by Elsevier Ltd.
引用
收藏
页码:S90 / S96
页数:7
相关论文
共 39 条
  • [1] Acromegaly in a family without a mutation in the menin gene
    Ackermann, F
    Krohn, K
    Windgassen, M
    Buchfelder, M
    Fahlbusch, R
    Paschke, R
    [J]. EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 1999, 107 (01) : 93 - 96
  • [2] Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription
    Agarwal, SK
    Guru, SC
    Heppner, C
    Erdos, MR
    Collins, RM
    Park, SY
    Saggar, S
    Chandrasekharappa, SC
    Collins, FS
    Spiegel, AM
    Marx, SJ
    Burns, AL
    [J]. CELL, 1999, 96 (01) : 143 - 152
  • [3] Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome
    Akintoye, SO
    Chebli, C
    Booher, S
    Feuillan, P
    Kushner, H
    Leroith, D
    Cherman, N
    Bianco, P
    Wientroub, S
    Robey, PG
    Collins, MT
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (11) : 5104 - 5112
  • [4] Somatotrophinomas in multiple endocrine neoplasia type 1: A review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred
    Burgess, JR
    Shepherd, JJ
    Parameswaran, V
    Hoffman, L
    Greenaway, TM
    [J]. AMERICAN JOURNAL OF MEDICINE, 1996, 100 (05) : 544 - 547
  • [5] DOMINANT INHERITANCE OF THE COMPLEX OF MYXOMAS, SPOTTY PIGMENTATION, AND ENDOCRINE OVERACTIVITY
    CARNEY, JA
    HRUSKA, LS
    BEAUCHAMP, GD
    GORDON, H
    [J]. MAYO CLINIC PROCEEDINGS, 1986, 61 (03) : 165 - 172
  • [6] Mutations in the protein kinase A R1α regulatory subunit cause familial cardiac myxomas and Carney complex
    Casey, M
    Vaughan, CJ
    He, J
    Hatcher, CJ
    Winter, JM
    Weremowicz, S
    Montgomery, K
    Kucherlapati, R
    Morton, CC
    Basson, CT
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (05) : R31 - R38
  • [7] Positional cloning of the gene for multiple endocrine neoplasia-type 1
    Chandrasekharappa, SC
    Guru, SC
    Manickam, P
    Olufemi, SE
    Collins, FS
    EmmertBuck, MR
    Debelenko, LV
    Zhuang, ZP
    Lubensky, IA
    Liotta, LA
    Crabtree, JS
    Wang, YP
    Roe, BA
    Weisemann, J
    Boguski, MS
    Agarwal, SK
    Kester, MB
    Kim, YS
    Heppner, C
    Dong, QH
    Spiegel, AM
    Burns, AL
    Marx, SJ
    [J]. SCIENCE, 1997, 276 (5311) : 404 - 407
  • [8] DEMENIS E, 2001, PITUITARY, V5, P11
  • [9] EGUCHI K, 2002, 84 ANN M END SOC, pP3
  • [10] Clinical and anatomical articles on the theory of acromegalia
    Fraenkel, A
    Stadelmann, E
    Benda, C
    [J]. DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT, 1901, 27 : 536 - 539