Clinical characterization of familial isolated pituitary adenomas.

Abstract

CONTEXT:

Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).

OBJECTIVE:

Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA).

DESIGN AND SETTING:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: A F Daly, M-L Jaffrain-Rea, A Ciccarelli, H Valdes-Socin, V Rohmer, G Tamburrano, C Borson-Chazot, B Estour, E Ciccarelli, T Brue, P Ferolla, P Emy, A Colao, E De Menis, P Lecomte, F Penfornis, B Delemer, J Bertherat, J L Wémeau, W De Herder, F Archambeaud, A Stevenaert, A Calender, A Murat, F Cavagnini, A Beckers
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 91 Issue 9 Pg. 3316-23 (Sep 2006) ISSN: 0021-972X [Print] United States
• PMID: 16787992 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
• Gonadotropins, Pituitary
• PRKAR1A protein, human
• Pituitary Hormones, Anterior
• Adrenocorticotropic Hormone
• Cyclic AMP-Dependent Protein Kinases

Topics

• Adenoma (genetics, metabolism, pathology)
• Adrenocorticotropic Hormone (metabolism)
• Adult
• Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
• Cyclic AMP-Dependent Protein Kinases (genetics)
• Female
• Gonadotropins, Pituitary (metabolism)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Pedigree
• Pituitary Hormones, Anterior (metabolism)
• Pituitary Neoplasms (genetics, metabolism, pathology)
• Prolactinoma (genetics, pathology)
• Retrospective Studies
• Sequence Analysis, DNA