Daly A F, Jaffrain-Rea M-L, Ciccarelli A, Valdes-Socin H, Rohmer V, Tamburrano G, Borson-Chazot C, Estour B, Ciccarelli E, Brue T, Ferolla P, Emy P, Colao A, De Menis E, Lecomte P, Penfornis F, Delemer B, Bertherat J, Wémeau J L, De Herder W, Archambeaud F, Stevenaert A, Calender A, Murat A, Cavagnini F, Beckers A
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium.
J Clin Endocrinol Metab. 2006 Sep;91(9):3316-23. doi: 10.1210/jc.2005-2671. Epub 2006 Jun 20.
Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).
Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA).
We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands.
Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases.
Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.
在无1型多发性内分泌腺瘤病（MEN1）和卡尼综合征（CNC）的情况下，家族性垂体腺瘤很少见。
我们的目的是描述非MEN1/CNC家族性孤立性垂体腺瘤（FIPA）的临床和系谱特征。
我们对FIPA病例的临床和系谱特征进行了一项回顾性研究，并与比利时、意大利、法国和荷兰的22家大学医院的散发性患者群体进行了比较。
共识别出64个FIPA家族，包括138名受累个体[55例催乳素瘤、47例生长激素瘤、28例无分泌功能腺瘤（NS）和8例促肾上腺皮质激素分泌肿瘤]。病例均为MEN1/PRKAR1A基因无突变。受累个体中一级亲属关系占主导（75.6%）。30个家族出现单一肿瘤表型（同质型），34个家族出现异质型表型。FIPA病例诊断时的年龄比散发性病例小（P = 0.015）；在多代家族的第一代与第二代中，肿瘤诊断更早。在异质型FIPA家族中，大腺瘤比同质型FIPA家族更常见（P = 0.036）。与散发性病例相比，异质型家族中的催乳素瘤更大，鞍上扩展更常见（P = 0.004）。生长激素瘤表现为孤立性家族性生长激素瘤病例以及异质型FIPA家族中的病例；孤立性家族性生长激素瘤病例占FIPA病例的18%，诊断时年龄比散发性生长激素瘤患者小。家族性NS病例诊断时年龄更小（P = 0.03），侵袭性肿瘤比散发性病例更常见（P = 0.024）。
在无MEN1/CNC的情况下，催乳素瘤、生长激素瘤、NS和库欣病可在家族中出现同质型和异质型表现。FIPA和散发性病例具有不同的临床特征。FIPA可能代表一种需要进一步进行基因特征分析的新型内分泌肿瘤分类。
